Pradip Kumar Das

A Systematic Review of
Subjects for
PG Medical Entrance
Examinations
A Systematic Review of
Subjects for
PG Medical Entrance
Examinations
Pradip Kumar Das

MD (RD), PGT
IPGME&R and SSKM Hospital

Kolkata, India
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A Systematic Review of Subjects for PG Medical Entrance Examinations
2010, Pradip Kumar Das
All rights reserved. No part of this publication should be reproduced, stored in
a retrieval system, or transmitted in any form or by any means: electronic,
mechanical, photocopying, recording, or otherwise, without the prior written
permission of the author and the publisher.
This book has been published in good faith that the material provided by
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but the publisher, printer and author will not be held responsible for any
inadvertent error (s). In case of any dispute, all legal matters are to be
settled under Delhi jurisdiction only.
First Edition: 2010
ISBN 978-81-8448-865-4
Typeset at JPBMP typesetting unit
Printed at
Charis ne dhare thak ente,

Ore hobe tor joy!
Andhokar jay bujhi kete,
Ore ar nei bhoy
(Dont give up; hold tight, you will win.
The dark is fading away, fear nothing)
Rabindranath Tagore
Gitanjali, 109
To
My parents
Sri Mahadeb Das
and
Smt Gouri Das
And to my family and friends
Foreword
I am very glad to know that the book A Systematic Review
of Subjects for PG Medical Entrance Examinations by
Dr Pradip Kumar Das is coming out. Dr Das is one of
my postgraduate trainees. I have seen the manuscript and
have gone through few chapters. I found the matter of
the book is very comprehensive and especially the systematic
approach is unique. I think that this approach covers
maximum topics in minimum space and it also saves one
from unnecessary repetition of the same matter again and
again. I am sure that this book will be very helpful for
students preparing for various postgraduate medical
entrance examinations both at the national and state levels.
I wish Dr Das all the success.
Prof (Dr) PK Deb
Vice-Chancellor
West Bengal University of Health Sciences
Kolkata, India
Preface
Advances in medical knowledge have made the medical
science changing everyday. It demands hard toil and
constant vigilance to be at par with these advances.
Preparation for PG medical entrance examinations require
a firm grip on both the existing information and the new
information coming in.
While preparing for PG medical entrances, my friends
and I felt the need for a book that will contain the already
existing information, as relevant to our preparation as much
as possible. We started our preparation with the good old
technique of solving MCQs and underlining the textbooks.
At the end of this basic work, we found that many valuable
months have passed by.
Why this book
A Systematic Review of Subjects for PG Medical Entrance
Examinations aims to contain as many information as
possible, asked in previous exams or relevant to our
preparation within the bounds of two covers. This is the
result of the basic work of solving MCQs and scrutinizing
the information again and again. The information
contained herein has been gathered over several years from
various sources, some of which are mentioned at the
appendix. I have meticulously tried to verify every
information and put in only those that have been asked
or likely to be asked in various PG medical entrances.
Information from major textbooks is contained in this book.
The purpose of the book is to save time and energy
for the basic work of building up a minimum level of
knowledge base for PG entrances, to act as a readyreference for any topic and for rapid review before the
exams. This book is a complement to and not a substitute
for the textbooks; but I assure, this will save a lot of your
valuable time and effort. It is not possible to mention
references of all the information. But I have tried to believe
on only those written in any textbook as much as possible.
I realize, there may be statements that appear unlikely
and their verification has been left to the user. As for me,
x A Systematic Review of Subjects for PGMEE

I can say that I have tried to keep such disputable
information as low as possible.
How to use this book
Of the many possible ways of organizing such a book,
I have selected the systematic approach that is to take
a system at a time and discuss topics from all the subjects,
as relevant, starting from anatomy to medicine and surgery.
The benefit of this approach is that, you do not have to
read the same information again and again. As can be
appreciated, it is not possible to cover all the subjects in
one volume; this book certainly contains all the major
information. You can start with a standard question bank
and this book; take up a topic and solve the questions
from the book. At the end, I am sure that you will find
that you have covered up a great deal of information.
I sincerely hope that A Systematic Review of Subjects
for PG Medical Entrance Examinations will serve you in
your preparation the way it helped me and many of my
friends. Any kind of suggestion, correction and criticism
is cordially welcome.
Pradip Kumar Das
e-mail: dr_pradipkdas@yahoo.co.in
Acknowledgments
No word of thanks can express my gratitude to my family
members (Mahadeb Das, Gouri Das, Purabi Roy, Karabi
Sarkar, Sudeb Das, Rajen Roy, Dipak Sarkar, Sweta and
Deepro) who have always been a support to me in all
my endeavors. They have been a constant source of
inspiration for me.
Mr Sudeb Das helped me in all stages of preparing
the book; I convey my thanks and love to him. Dr Debasish
Dey was instrumental in initiation of the process; I thank
him for his support.
I am thankful to many of my friends who have read
my notes and encouraged me to bring it out as a book.
I would like to mention the names of Dr Nimai Biswas,
Dr Chinmay Nandi, Dr Susanta Bhanja, Dr Atanu Biswas,
Dr Saroj Kumar Halder, Dr Soumya Mondal, Dr Santanu
Suba, Dr Pramit Ghosh and all my friends at Calcutta
Medical College and Dr Somnath Sarkar, Dr Bhaskar
Mukherjee of NRS Medical College.
I express my gratitude to my friends Mr Rana Das and
Mr Surajit Ghosh for their support and company.
A special word of thanks goes to Miss Malabika Das.
I am grateful to my teacher Prof (Dr) PK Deb for
forwarding this book. I am also thankful to my teachers
(Prof Dr Utpalendu Das, Dr Sohini Sengupta, Dr Samiran
Samanta, Prof Dr AK Bhadra, Dr T Dhibar) and friends
at the Department of Radiology, IPGME&R and BINP,
SSKM Hospital.
Finally, I would thank all the staff of Jaypee Brothers
Medical Publishers (P) Ltd. for their effort in publishing
this book.
Contents
1. General Discussion ................................... 1
2. Gastrointestinal System .......................... 88
3. Respiratory System ............................... 164
4. Cardiovascular System .......................... 212
5. Immune System .................................... 259
6. Renal System ........................................ 309
7. Neurological Disorders .......................... 347
8. Endocrinology and Metabolism ............. 393
9. Infectious Diseases ............................... 472
10. Hematology .......................................... 637
11. Oncology .............................................. 705
12. Dermatology ......................................... 816
13. Genetics ............................................... 841
14. Nutrition ............................................... 871
15. General Pathology ................................. 901
Supplement ........................................... 930
Appendices ........................................... 957
Index .................................................... 961
GENERAL
DISCUSSION
PAIN
PAIN PATHWAY
Peripheral receptors (naked nerve endings)
Primary sensory afferents (A and C fibers)
Dorsal root ganglia in the vertebral foramina
Lateral spinothalamic tract

(along with temperature sensation)
Crosses mid-line
Thalamus (opposite side)
Somatic sensory area

I in the post-central gyrus.
II in the wall of Sylvian fissure.
Neurotransmitter
For fast pain is Glutamate.
For slow pain is substance P.
PAIN PHYSIOLOGY
Visceral Pain
Viscera are relatively insensitive to noxious stimuli under
normal circumstances. True visceral pain is produced by
distension of a hollow viscus, spasmodic contraction,
ischemia.
Cutting does not induce visceral pain (also crushing
or burning).
Neuropathic Pain
Pain produced by damage or dysfunction of the nervous
system e.g. diabetic neuropathy.
2 A Systematic Review of Subjects for PGMEE

Chronic Pain Syndrome
Sympathetically maintained.
i. Causalgia Severe burning pain produced by peripheral
nerve injury in the region innervated by the nerve.
ii. Reflex sympathetic osteodystrophy
Most common cause is Colles fracture of forearm.
Clinical feature: Pain, stiffness and swelling of hand.
The overlying skin is tense and shiny.
Treatment: Sympathetic (stellate ganglion) block.
iii. Spontaneous pain is seen in thalamic syndrome due
to damage of posterior thalamic nuclei caused by
obstruction of posterior cerebral artery.
Note: Indications of sympathectomy:
i. Hyperhydrosis (NOT anhydrosis)
ii. Causalgia
iii. Reflex sympathetic osteodystrophy
iv. Frost bite
v. Raynauds disease
vi. Thromboangiitis obliterans
vii. Claudication not very effective, but indicated to relieve
rest pain and ulceration (ischemic).
Note: Allodynia means perception of nonpainful stimulus
as painful.
Referred Pain
Pain from a viscus may be felt at some somatic structure
which may be a considerable distance away. Such referral
of pain is due to convergence of nerve fibers from the
viscus and somatic structure at the spinal cord.
For example, pain from diaphragm is referred to the tip
of the shoulder because both are supplied by phrenic nerve.
CHEST PAIN
Anginal Pain
Typically develops on exertion, after heavy meals or
emotional stress, not affected by position, respiratory
movement, etc. and resolves within 5 - 30 minutes.
Site: Substernal region, anterior mid-thorax.
Diagnosis: Pain is relieved more quickly (within 5 min) and
more completely with sublingual nitroglycerine.
General Discussion
Myocardial infarction: Similar to angina but of more

intensity and greater duration. Pain often radiates to left
arm. Not relieved by rest or nitroglycerine. Accompanied
by diaphoresis, nausea and hypotension.
Pericarditis: Pericardium is pain insensitive. Pericardial pain
is due to involvement of overlying pleura. Infectious
pericarditis, nearly always involves the pleura and is always
associated with pain. It is brought on by swallowing.
Aggravated by cough and / or deep inspiration. Relieved
in upright sitting position with body leaning forward.
HEADACHE
Pain sensitive structures in cranium are the scalp and
aponeurotica, middle meningeal artery, dural sinuses, falx
cerebri and large pial arteries.
Lumbar Puncture Headache
Occipitofrontal headache following lumbar puncture (usually within 48 hours). It is typically positional, increases on
sitting and decreases on lying down. Last for 7 10 days.
Cause Leakage of CSF.
Prevention: Using small (25 G) bore needle.
Treatment: IV caffeine sodium benzoate.
Other types of headache
See neurology section.
BACK PAIN
Disc Prolapse
Site: Between L4 L5 in lumbar spine (most common),
C5C6 in cervical spine.
Tests: To detect nerve root compression
i. Straight leg raising test.
ii. Lasegue test.
Defect:
L4 root: Weakness of extensors of the knee. Knee jerk
sluggish or absent.
L5 root: Weakness of extensor hallucis longus normal
and dorsi-flexors of foot. Ankle jerk normal.
Investigation: MRI is the investigation of choice.

Treatment:
1. Surgery Microdiscectomy is done in a case of posterolateral prolapse of disc.
2. Chemonucleosis Injection of chymopapain into the
disc.
Note: Inverted Lasegue sign is seen in lesion of L3.
Spinal Stenosis
Compression of cauda equina.
Pain radiating down the lower limbs induced by walking
and relieved by rest (pseudoclaudication).
Spinal Tumors
Most common spinal tumors are secondaries from breast
(most common), lung, prostrate, etc.
Primary tumors are usually benign
Extradural
- Osteoid osteoma
(most common
spinal tumor)
Intradural
IntramedullaryEpendymoma
Extramedullary
Meningioma
Neurofibroma
Multiple myeloma is the most common primary tumor

of spine.
Neurofibroma is the most common intradural tumor.
Note: Extramedullary tumors produce pain, early
involvement of corticospinal tract and loss of sacral
sensations. CSF protein is raised.
Sciatica
Pain radiating down the back of thigh and calf.
Cause: Degenerative arthritis, disc prolapse.
SHOULDER PAIN
Thoracic Outlet Syndrome
Cause
Cervical rib syndrome (7th cervical spine, usually unilateral,
more commonly on right side).
General Discussion
Scalenus anterior syndrome.

First thoracic rib syndrome.
Costoclavicular syndrome.
Structures compressed are:
Nerve lower trunk of brachial plexus (4th first dorsal
nerve, ulnar nerve).
Artery subclavian artery.
Clinical Feature
Neurogenic: Shoulder pain radiating down the arm,
decreased sensation on the palmar aspect of 4th and 5th
digits, weakness of the intrinsic muscles of hand.
Vascular: Pain in forearm which is induced by the use
of the arm and relived by rest. It is due to ischemic changes
in the muscles of the arm.
Test
Adsons test pain is accelerated if the arm is in raised
position at the time of exercise.
Costoclavicular compressive test.
Hyperabduction test.
Treatment
Prompt extraperiosteal excision of the cervical rib.
Brachial Plexus Disease
Lower trunk is most commonly involved. Symptoms are
as above.
Cause
1. Squamous cell Ca of lung most common (Pancoast
tumor).
2. Postradiation fibrosis (Breast Ca).
Lower trunk disease may be associated with Horners
syndrome (ptosis, miosis, anhydrosis, enophthalmos and
loss of ciliospinal reflex) due to involvement of lower cervical
sympathetic ganglion (Stellate ganglion).
Note: Deformities in brachial plexus injury:

Erbs Palsy
Cause
Injury (e.g. birth trauma) to the upper trunk.
Nerve roots involved mainly C5, partly C6.
Deformity
Arm: Adducted and medially rotated.
Forearm: Extended and pronated. This is known as
policemans tip hand or porters tip hand.
Disability
Movements lost are:
Arm: Abduction and lateral rotation.
Forearm: Flexion and supination.
Klumpices Palsy
Cause
Injury to the lower trunk. Nerve roots involved mainly
T1, partly C8.
Deformity
Claw hand hyperextension of the MCP joints and flexion
of IP joints. Horners syndrome may be present.
1. Injury to nerve of Bell
(long thoracic nerve C5, 6, 7) which supplies serratus
anterior.
Deformity: Winging of scapula.
Disability: Loss of pushing and punching actions. Inability
to abduct arm beyond 90o.
TEMPERATURE
PHYSIOLOGY
Normal body temperature is 36.8oC 0.4oC (98.2oF
0.7oF).
General Discussion
Circadian rhythm: body temperature is maximum at 6

pm and minimum at 6 am (AM nadir and PM peak).
Measurement: the following temperatures reflect the core
temperature.
i. Rectal most accurate, 0.5 1oF higher than oral
temperature.
ii. Lower esophageal.
iii. Freshly passed urine.
Regulation: By preoptic anterior (heat) and posterior (cold)
hypothalamus.
Heat acclimatization: Increase sweating to dissipate heat
and conservation of fluid otherwise (decrease renal blood
flow, increase aldosterone secretion which leads to Na+
retention and low urinary Na).
FEVER AND HYPERTHERMIA
Fever
AM temperature > 98.9oF or PM temperature > 99.9oF.
Pyrogen: Endotoxins (lipopolysaccharides), cytokines IL1, IL1, TNF, IFN, IL.
Hyperpyrexia
Temperature > 106oF.
Causes: Malaria, septicemia, encephalitis, pontine
hemorrhage, lobar pneumonia, heat stroke, datura
poisoning.
Malignant hyperthermia: Neuroleptic malignant syndrome.
Types of Fever
1. Intermittent Fever present only for several hours and
always touches the baseline.
Causes:
a. Quotidian occurs daily. E.g. Double infection
with P. vivax.
b. Tertian Fever occurs on first and third days (48
hours apart). E.g. Benign tertian malaria (P. vivax),
malignant tertian malaria (P. falciparum).
c. Quartan Fever on first and fourth days (72 hours
apart). E.g. Quartan malaria (P. malariae).

2. Continued/Sustained Fluctuation <1 o C and
temperature never touches baseline. E.g. Lobar
pneumonia, second week of typhoid fever,
Meningococcal meningitis.
3. Remittent Daily fluctuation > 2oC but never touches
baseline. E.g. Tuberculosis, viral infections and
amebic liver abscess.
4. Relapsing fever Borrelia burgdorferi.
5. PelEbstein fever fever lasting 3 10 days followed
by afebrile periods of 310 days. Classically seen in
Hodgkins lymphoma.
6. Fever of cyclic neutropenia fever occurs every 21
days and accompany the neutropenia.
Pulse-Temperature Ratio
With every 1oF rise in temperature there is increase in pulse
by 10 beats/min.
Relative bradycardia is seen in typhoid fever,
brucellosis, leptospirosis, acute rheumatic fever.
Relative tachycardia seen in TB, diphtheritic
myocarditis, PAN.
Pulse-respiration Ratio
With every 1oF rise in temperature there is increase in
respiratory rate by 23 / min.
Normal 4:1 (72:18)
Increase 12:1 (72:6) seen in narcotic poisoning.
Decrease 2:1 (72:36) seen in acute lobar pneumonia.
Drug Induced Hyperthermia
Seen in MAO inhibitors, TCAs, Amphetamines.
Malignant Hyperthermia
Inherited abnormality of skeletal muscles.
Pathology: Increased intracellular Ca++ level due to release
from sarcoplasmic reticulum leads to muscle contraction.
Precipitated by: Halothane, Succinylcholine.
General Discussion
Features: Increased temperature, muscle contraction

rigidity, rhabdomyolysis, acidosis.
Treatment: External cooling.
O2 inhalation, bicarbonate infusion, IV dantrolene.
Investigation: Increased serum CPK.
Neuroleptic Malignant Syndrome
Caused by: Chlorpromazine, Haloperidol.
Characterized by: Hyperthermia, muscle rigidity, tremor,
semi-consciousness, fluctuating BP and heart rate.
Treatment: IV dantrolene, bromocriptine.
Heatstroke
Complications: DIC, shock, hyperkalemia, hypocalcemia,
cerebellar degeneration.
HYPOTHERMIA
Core temperature 35oC
Risk factors: Extremes of age, ethanol use, Malnutrition,
Hypothyroidism.
Effects: Hypotension, bradycardia. Early tachypnea
followed by hypoventilation.
ECG QT prolongation, Osborn (J) wave,
Lactic acidosis, hypoactivity, hyperglycemia.
Complications: Atrial arrhythmias.
Treatment:
Re-warming Which should not be prompt.
Methods Extracorporeal blood warming by hemodialysis
or cardiopulmonary bypass best method.
IV warmed NS.
Neonatal Hypothermia
Signs: Bradycardia, sclerema, metabolic acidosis.
Treatment: Convection warmed incubators.
10
A Systematic Review of Subjects for PGMEE
NERVOUS SYSTEM
DYSFUNCTION
SYNCOPE
Causes
1. Decreased cerebral blood flow:
i. Vasovagal.
ii. Postural or orthostatic.
iii. Carotid sinus syncope.
2. Decreased venous return:
i. Valsalva maneuver.
ii. Cough.
iii. Micturition.
3. Decreased cardiac output:
i. Cardiac tamponade.
ii. Aortic stenosis.
4. Arrhythmias: Second and third degree AV block with
Stokes - Adams syndrome.
5. Congenital heart disease: Tetralogy of Fallot.
Treatment
1. Vasovagal syncope with normal LV systolic functions
-blockers, Disopyramide, Theophylline, Scopolamine
and ephedrine.
2. Postural syncope:
Postganglionic type: Salt loading, Fludrocortisone.
Preganglionic type: Tyramine, MAO inhibitors.
3. Carotid sinus syncope Atropine or ephedrine.
VERTIGO
The most common cause of pathologic vertigo is vestibular
dysfunction.
Mnires Disease
It is the most common cause of otogenic vertigo.
Pathology: Hydrops or distension of the endolymphatic
system.
Clinical feature: Age group affected - 3050 years.
Unilateral symptoms.
General Discussion
11
Episodic attacks of:

Rotatory vertigo, fluctuating deafness (sensorineural),
tinnitus, fullness in ear.
Investigation: Audiometry Sensorineural deafness more
in lower frequency (Cochlear).
Recruitment tests - +ve on the affected side.
Treatment:
1. Nicotinic acid (Vasodilator) increases endolymphatic reabsorption.
2. Surgery Cody tack operation.
WEAKNESS
PHYSIOLOGY OF MOTOR SYSTEM
Higher Center
The following parts of brain are involved in motor activities:
1. Cerebral cortex highest center.
Motor cortex in the precentral gyrus (Brodmann area
4).
Premotor cortex posterior ends of inferior, middle
and superior frontal gyri (Brodmann area 6 and 8).
Supplementary motor area on medial surface of
brain.
Note: In motor cortex, various parts of the body are
represented in an inverted manner. Only the facial area
is represented bilaterally. All other areas are unilateral,
controlling movements of the opposite side.
Spinocerebellum (medial) smoothens
and coordinates movements.
2. Cerebellum
Neocerebellum (lateral) planning
and organizing voluntary movements.
3. Basal ganglia Planning and programming of
movements.
Descending Tracts
A. PYRAMIDAL TRACTS: They arise from cerebral cortex and
end either on motor neurons in spinal cord or cranial
nerve nuclei in brainstem.
12
1. Corticospinal tract:
a. Lateral corticospinal tract produces an elevation
(pyramid) in midbrain. They comprise about 80
percent fibers of pyramidal system. They descend
through the internal capsule, cross midline at cervicomedullary junction and end on lateral neurons in
the ventral horn of spinal cord (on opposite side).
Action concerned with distal limb muscle and
with skilled movements (of opposite side).
b. Ventral corticospinal tract 20 percent fibers that
do not cross the midline until at the level where
they synapse with motor neurons. They end
primarily on interneurons (on the same side) which
cross the midline and end on medial neurons in
the ventral horn of spinal cord.
Action control axial and proximal limb
muscles.
2. Corticobulbar tract: From cerebral cortex to cranial
nerve nuclei in the brainstem (usually on the opposite
side). Some fibers end bilaterally e.g. those for muscles
of mastication and upper half of face.
Note: Locations of cranial nerve nuclei
Midbrain 3 and 4.
Pons 5, 6, 7 and 8.
Medulla 9, 10, 11 and 12.
B. EXTRAPYRAMIDAL (BULBOSPINAL TRACTS):
1. Ventromedial bulbospinal tracts:
a. Tectospinal originate from tectum in midbrain.
b. Vestibulospinal from the lateral and medial
vestibular nuclei.
c. Reticulospinal from the reticular formation.
Action Influence axial and proximal muscles
and are involved in maintenance of posture and
integrated movements of limbs and trunk.
2. Ventrolateral bulbospinal tract:
Rubrospinal from magnocellular portion of red
nucleus.
Action facilitate distal limb muscles.
UMN vs LMN
Upper motor neuron (UMN) neurons that contribute to
pyramidal tract (Corticospinal + Corticobulbar).
General Discussion
13
Lower motor neuron (LMN) Anterior horn cells and

related cranial motor nuclei and their axons.
Difference between UMN lesion and LMN lesions
1.
2.
3.
4.
5.
Sign
UMN lesion
LMN lesion
Atrophy
Fasciculation
Tone
Tendon reflexes
Babinskis sign
Spastic
Hyperactive
+
+
+
Flaccid
Hypoactive/absent
Note: In Friedrichs ataxia, Babinskis sign is +ve (UMN

lesion) but deep tendon reflexes are absent (LMN type).
PATHOLOGY OF MOTOR SYSTEM
Hypertonia
Causes
1. UMN lesion (clasp knife spasticity)
2. Extrapyramidal lesion except chorea (lead pipe or
cogwheel rigidity) e.g. Parkinsonism.
3. Tetanus.
4. Tetany hypocalcemia.
5. Strychnine poisoning.
Types
Spasticity in pyramidal (UMN) lesion.
Rigidity in extrapyramidal lesion.
Paratonia or Gegenhatten in frontal lobe lesion.
Hypotonia (Flaccidity)
Causes
1.
2.
3.
4.
5.
6.
7.
LMN lesion.
Tabes dorsalis (Posterior column lesion)
Chorea
Cerebellar lesion.
Myopathy.
Hypokalemia or hypercalcemia.
Others Downs syndrome, Rickets.
14
CLINICAL
Hemiplegia
Due to UMN lesion above the midcervical spinal cord.
Most common cause Thrombosis of lenticulostriate
branch of middle cerebral artery.
Investigation: CT scan, MRI.
Crossed Hemiplegia
Due to brainstem lesion.
E.g. Webers syndrome Ipsilateral third nerve palsy
(LMN type) with contralateral hemiplegia, due to midbrain
(mesencephalon) lesion.
Paraplegia
Due to intraspinal lesions at or below the upper thoracic
spinal cord level.
Cause
A. Spastic paraplegia (UMN type):
1. Cord compression most commonly due to carries
spine.
2. Motor neuron disease.
3. Multiple sclerosis.
4. Acute transverse myelitis.
5. Friedrichs ataxia.
6. Syringomyelia.
7. Lathyrism.
8. Cervical spondylosis.
B. Flaccid paraplegia (LMN type):
1. Poliomyelitis.
2. GB syndrome.
3. Progressive muscular atrophy.
4. Myasthenia gravis.
5. Myopathy.
Traumatic Paraplegia
Most common cause of paraplegia is trauma.
Site: Most common site of spinal injury is dorsolumbar
spine.
General Discussion
15
Note: Lesion above C5 is fatal due to respiratory failure.

Lesion at C5-C6 level produces quadriplegia.
Clinical feature: Flaccid paraplegia in spinal shock stage.
Spastic paraplegia later on. Often with bladder
involvement.
Investigation: MRI is the method of choice.
Complications: Negative nitrogen balance, decubitus ulcer,
hypercalcemia leads to calcium stones.
UTI most common complication.
Treatment
1. High dose corticosteroid as early as possible.
2. Bladder care Intermittent catheterization is best.
Monoplegia
Todds paralysis in epilepsy.
Note: Descending motor paralysis is caused by Diphtheria,
botulinum toxin and polio.
MOVEMENT DISORDERS
Tremor
Rest tremor Parkinsonism.
Postural tremor Hyperthyroidism.
Intention tremor Cerebellar disease.
Flapping tremor/Asterixis Hepatic failure (precoma),
uremia, respiratory failure, CO2 narcosis, renal failure.
Hemiballismus
Sudden flinging movement of limbs.
Cause: Infarction of the contralateral subthalamic nucleus
of basal ganglia.
Chorea
Rapid, jerky, irregular quasipurposive movement of basal
ganglia.
Cause: Lesion in caudate nucleus.
Sydenhams chorea Rheumatic fever.
Huntingtons Chorea most common type.
Levodopa toxicity most common cause of chorea.
16
Features: Hypotonia, pronator sign, milking sign, spooning

sign, hung up reflex, lizard tongue.
Athetosis
Lesion in Lentiform nucleus (Globus pallidus).
Note: Basal ganglia lesions produce
Hyperkinetic movements - chorea, athetosis and
ballism.
Hypokinetic movements Akinesia and bradykinesia.
Myoclonus
Cause: Lipid storage disease, Encephalitis (SSPE),
Creutzfeldt-Jakob disease, Metabolic encephalopathies.
Electrolyte imbalance.
BALANCE AND GAIT

Control
a. Head position in space Controlled by inner ear.
The utricle and saccule sense static head position
and acceleration (linear).
The semicircular canals sense rotatory motions
(angular acceleration).
Impulses pass though vestibular nerve to the vestibular
nuclei in the lower pons and upper medulla.
b. Head position relative to body: Receptors for joint
position, joint movement and muscle stretch. Impulses
are transmitted via posterior column and medial
lemniscal pathways to the cerebrum and the
spinocerebellar pathways to the cerebellum.
Ataxia
It is defined as clumsiness of movement without sensory
or motor disturbance.
Types:
a. Cerebellar ataxia.
b. Sensory ataxia due to involvement of:
i. Peripheral sensory nerves, e.g. peripheral neuropathy.
ii. Posterior nerve root Tabes dorsalis.
General Discussion
17
iii. Posterior column Multiple sclerosis, syringomyelia.

iv. Diseases of parietal lobe.
Test Positive Romberg sing.
c. Vestibular ataxia often with vertigo.
Note: Fenkels exercise is done in a case of ataxia (e.g.
Tabes dorsalis).
Abnormal Gait
1. Hemiparetic gait in cerebral stroke.
2. Paraparetic or scissoring gait in spinal cord disease
3. Stamping gait in sensory ataxia, classically in Tabes
dorsalis.
4. Steppage or Equine gait in common peroneal nerve
palsy (with foot drop). (Anterior tibial nerve injury).
5. Festinant gait Parkinsonism.
6. Waddling gait Myopathy.
7. Drunker or ataxic gait Cerebellar ataxia or acute
alcohol intoxication.
8. Apraxic gait in bilateral frontal lobe disease.
9. Astasia abasia hysterical gait disorders.
Signs of Cerebellar Disease
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Hypotonia.
Scanning speech.
Intention tremor.
Pendular knee jerk.
Dysmetria.
Ataxia.
Decomposition of movements.
Dysdiadochokinesia.
Rebound phenomenon.
Drunken or ataxic gait.
Titubation.
EPISODIC DISORDERS
Abnormal Facial Movements
1. Hemifacial spasm Often involves the muscles around
eyes and caused by paroxysmal facial nerve activity.
18
2. Facial tics Gilles de la Tourette syndrome.

3. Synkinesis, e.g. jaw winking in Bells palsy (after
recovery).
4. Tic douloureux trigeminal neuralgia.
Abnormal Limb Movements
1. Fasciculation in motor neuron disease.
2. Akathisia Parkinsonism.
3. Restless leg syndrome uremia and other neuropathies
(in middle aged females).
4. Startle syndrome or hyper-reflexias result from
mutations in glycine receptors.
Muscle Disorders
1. Myotonia Myotonic dystrophy.
Myotonia congenita AD or AR inheritance. Due to
defective Cl- channel.
2. Paramyalgia Rheumatic
Clinical feature: Stiffness and pain in shoulder and hip
in patients over age 50.
Muscle biopsy shows: muscle atrophy, CPK level is normal.
Treatment: NSAIDs and prednisolone.
Episodic Weakness
Causes:
1. Hype/hyperkalemia.
2. Hypo/hypercalcemia.
3. Hyponatremia.
4. Hypophosphatemia.
5. Hypomagnesemia.
6. Myasthenia gravis and LambertEaton syndrome.
SPEECH
PHYSIOLOGY
Language is a function of the dominant or categorical
hemisphere that is the left hemisphere in right handed
persons (Perisylvian region).
General Discussion
19
Areas:
1. Wernickes area (Area 22) Location posterior third of superior temporal gyrus.
Action Comprehension of auditory and visual
information.
2. Brocas area (Area 44) Location Posterior part of inferior frontal gyrus.
Function Speech production.
The above two areas are connected by arcuate
fasciculus.
Blood supply by middle cerebral artery.
APHASIA
Wernickes Aphasia (Sensory Aphasia)
Comprehension is impaired but fluency is normal or
increased.
There is paraphasia, neologism Jargon speech.
Cause: occlusion of inferior division of middle cerebral
artery.
Brocas Aphasia (Motor Aphasia)
Comprehension is preserved but fluency is decreased.
Others: Word finding pause (telegraphic speech).
Cause: Occlusion of superior division of the middle cerebral
artery.
Global Aphasia
Involvement of both Wernickes and Brocas areas.
Cause: Occlusion of entire middle cerebral artery (cerebral
stroke).
Prognosis: Worst.
Crossed aphasia: right hemispherical lesion in right handed
person.
Conduction Aphasia
Comprehension and fluency are preserved, but repetition
and naming are impaired.
20
Cause Lesion in arcuate fasciculus. Lesions of auditory

cortex (area 40, 41, 42).
Anomic Aphasia
Only naming is impaired. There is difficulty in understating
written language.
Cause: Lesions in angular gyrus.
Characteristically seen in head trauma, metabolic
encephalopathy, Alzheimers disease.
Pure Word Deafness
Cause: Bilateral or left sided superior temporal gyrus lesion.
Alexia
Cause: Occlusion of posterior cerebral artery.
Note: Scanning speech is seen in disseminated sclerosis.
APRAXIA
It is a disorder of initiating and planning movement.
Cause: Right sided apraxia is caused by lesion of left frontal
lobe, or the left temporoparietal region (especially the
supramarginal gyrus).
Type: Ideomotor apraxia most common type.
Gerstmanns Syndrome
Acalculia, dysgraphia, finger anomia and right-left
confusion.
Cause: Damage of inferior parietal lobe (angular gyrus)
of left hemisphere.
Balints Syndrome
Spatial disorientation caused by Oculomotor apraxia,
optic ataxia and simultanagnosia.
Cause: bilateral lesion in parietal lobe.
Dressing Apraxia
Cause: Bilateral or right sided (non-dominant) dorsal
parietal lobe lesion (also construction apraxia).
General Discussion
21
Prosopagnosia
Inability to recognize face.
Cause: Bilateral lesion in fusiform and lingual gyri of
occipitotemporal cortex.
SENSORY SYSTEM
PHYSIOLOGY
Receptors
1. Naked nerve endings.
2. Expanded nerve endings
i. Merkels discs
Slow adapting
ii. Ruffini endings
touch receptors
3. Encapsulated endings
Mechanoi. Pacinian corpuscles
receptors
ii. Meissners corpuscles Rapidly adapting
iii. Krauses end bulbs
touch receptors
Pathways
Fibers: A (large myelinated) fine touch and pressure.
A (small myelinated) Temperature and pain.
C (small unmyelinated) Pain and temperature.
Tracts: Touch Ventral spinothalamic tract.
Pain and temperature Lateral spinothalamic tract.
Touch and proprioception Dorsal column / Lemniscal
system.
Spinothalamic tracts:
Afferents from peripheral nerves enter the spinal cord
through dorsal horn
Crosses the midline and ascends as ventral or lateral

spinothalamic tracts
Project to ventral posterolateral

nucleus (VPL) of thalamus
Ultimately project to the postcentral

gyrus of parietal cortex
22
Lemniscal system:
Fibers from dorsal horn ascend in the
posterior column of the same side
First synapse in the gracile and cuneate nuclei of medulla
Second order neurons cross midline and lie medial to

medulla (medial lemniscus)
Synapse at VPL of thalamus
Third order neurons project to parietal cortex
Higher Centers
Somatic sensory area I Post-central gyrus in parietal
cortex (Brodmann area 1, 2, 3).
Somatic sensory area II in the wall of the Sylvian fissure
in parietal cortex.
Cortical Sensations
1.
2.
3.
4.
Two-point discrimination.
Touch localization.
Graphesthesia.
Stereognosis lost in parietal
cortex lesion.
Lost in ablation
of SI
PATHOLOGY
Sensory Neuropathies
Causes:
1. Diabetes.
2. Beriberi.
3. Leprosy.
4. Alcohol.
5. Vitamin B12 deficiency.
Dissociated Sensory Loss
Pain and temperature sensations are lost but touch is
spared.
Cause: Syringomyelia.
Note: Balaclave helmet type of sensory loss over face is
seen in syringomyelia.
General Discussion
23
ALERTNESS, CONFUSION
AND COMA
PHYSIOLOGY
Reticular Activating System
Wakefulness alertness is maintained my RAS.
Location Midventral portion of the medulla and
midbrain (reticular formation) + thalamus.
Brainstem RAS neurons project to thalamic relay nuclei
which in turn projects to neocortex.
Note: The reticular formation contains motor, sensory,
autonomic, all types of fibers.
Brainstem Reflexes
1.
2.
3.
4.
5.
Papillary reaction to light.

Spontaneous eye movement.
Oculocephalic reflex or Dolls eye
Oculovestibular reflex.
Corneal reflex.
Note: Normal cerebral blood flow (CBF) is 75 ml/100 g/

min in gray matter and 30 ml/100 g/min in white matter
(mean 55 ml/100 g/min).
CBF < 10 ml /100g/min produce irreversible brain
damage.
Normal O2 consumption of brain 3.5 ml/100 g/min.
PATHOLOGY
Three major groups of lesions produce confusion and
coma:
1. Supratentorial mass e.g. cerebral hemorrhage or
cerebral tumor.
2. Infratentorial lesion.
3. Metabolic disorders like hypoxia, hypercapnia,
hyponatremia, hyperosmolarity, hypercalcemia,
hypoglycemia and metabolic encephalopathies
(hepatic, renal, respiratory failures).
Supratentorial lesions produce secondary
compression of brainstem due to transtentorial
herniation.
24
CLINICAL
Signs of Brain Death
Three essential elements:
1. Widespread cortical destruction shown by deep coma
Isoelectric EEG.
2. Brainstem damage absent pupillary light reaction,
oculovestibular and corneal reflexes.
3. Medullary destruction Complete apnea.
Others:
1. No Gag reflex.
2. No motor response.
3. Pulse invariant and unresponsive to atropine.
Note: If respiration is maintained artificially heart, kidneys
and liver may continue to function normally. But after
brainstem death has occurred, cardiac arrest will follow
within 2 weeks.
Diagnosis:
1. Blood Ethanol level > 200 mg/dl causes confusion
and impaired mental activity. Level > 300 mg/dl causes
stupor.
2. CT scan and MRI
3. EEG
Alpha coma (widespread 812 Hz activity)Caused by high pontine diffuse cortical damage and
associated with a poor prognosis.
Beta coma (Fast activity) Sedatives.
Delta coma (High voltage slow waves in frontal region)
Metabolic encephalopathy.
4. CSF study.
Differential diagnosis:
1. Pontine hemorrhage Fever, pin point pupils, ocular
bobbing (diagnostic), hyperventilation, sweating,
pseudocoma.
2. Cerebellar hemorrhage Occipital headache, vomiting,
gaze paresis, inability to stand.
3. Metabolic encephalopathy Asterixis or flapping
tremor, most characteristic sign.
General Discussion
25
MEMORY
PHYSIOLOGY
1. Short-term memory:
a. Recent memory concerned with hippocampus and
perihippocampal portion of medial temporal cortex.
b. Immediate memory Perisylvian cortex, frontal lobe.
2. Long-term memory Association cortex.
AMNESIA
Types
1. Retrograde amnesia Inability to recall events preceding
the amnesic state (recent memory loss). Long-term
memory is intact.
Causes Cerebral concussion, Electroconvulsive
therapy.
2. Anterograde amnesia Inability to store, retain and
recall new knowledge.
Cause Bilateral medial temporal lobe lesion.
Other causes of short-term memory loss:
1. Brain tumor.
2. Brain infarction.
3. HS encephalitis.
4. Chronic alcoholism.
5. Degenerative dementias Alzheimers disease and
Picks disease.
Frontal Lobe Syndrome
1. Abulia Due to damage to dorsolateral prefrontal
cortex. E.g. tumor.
2. Disinhibition damage to medial prefrontal or
orbitofrontal cortex.
3. Confabulation Lesion of ventromedial portion of
frontal lobe.
Note: Personality change is seen in frontal lobe lesion.
Glabellar or palmomental reflexes are represented at frontal
lobe.
26
DEMENTIA
Loss of cognitive function (mainly memory) with clear
conscience.
Most important risk factor is increasing age.
Causes
a. Cortical dementia:
1. Alzheimers disease.
2. Picks disease.
b. Subcortical dementia:
1. Huntingtons chorea.
2. Parkinsonism.
3. Wilsons disease.
c. Vitamin deficiencies:
1. Thiamine (B1): (Wernickes encephalopathy) most
commonly due to chronic alcoholism.
2. Vitamin B12 (pernicious anemia).
3. Nicotinic acid (B3) Pellagra.
d. Endocrinal Hypothyroidism, Hypo/Hyperparathyroidism.
e. Pseudodementia Depression.
f. Head trauma Punch drunk syndrome or dementia
puglistica in Parkinsonism. Normal pressure
hydrocephalous.
g. InfectionsPrion (Creutzfeldt-Jakob disease)
HIV (AIDS dementia complex)
h. Toxic Dialysis dementia due to aluminium.
Features
Lesion in Frontal Lobe
Personality change, impaired memory, anosmia, urinary
incontinence, antisocial behavior.
Parietal Lobe
a. Dominant lobe: Aphasia, acalculia (Gerstmanns
syndrome), ideomotor apraxia, agnosia.
b. Nondominant lobe: Construction and dressing apraxia,
spatial disorientation, neglect of non-dominant side.
c. Bilateral: Balints syndrome, homonymous
hemianopia.
General Discussion
27
Temporal Lobe
Poor memory, complex hallucinations, homonymous
hemianopia.
Others Aphasia, dyslexia, loss of musical skill.
Occipital Lobe
Prosopagnosia, visual agnosia, visual hallucinations,
homonymous hemianopia, hemianopic scotoma.
EYE AND VISION

PHYSIOLOGY
Retina
Macula lutea: Yellowish pigmented spot near the posterior
pole, contains the pigment xanthophyll. Responsible for
central 10o vision.
Fovea centralis It the small pit in the center of macula.
It contains only cones. Area of maximum visual acuity.
Optic disc Lies 3 mm medial to posterior pole. Optic
nerve leaves the eye and blood vessels enter at this point.
Contains no visual pigment blind spot.
Visual Pigments
1. Rods: Operative under dim light (scotopic vision).
Contain The pigment rhodopsin which is made up
of protein called opsin and an aldehyde called 11
cis retinal (vitamin A).
On exposure to light 11cis retinal is converted to alltrans retinal and vice versa.
There are 100 million roads in human retina.
2. Cones: Operative under bright light (photopic vision).
Also responsible for color vision.
Cones contain pigments (idopsin) which respond
maximally to wavelengths 450, 535 and 565 nm (red,
green and blue vision).
There are 5 million cones in retina, maximum in
macula.
28
Ocular Reflexes
1. Light reflex: Constriction of pupil on exposure to light
(direct and consensual).
This is mediated by constrictor muscle of iris
(sphincter pupillae) which is supplied by
parasympathetic nerve via oculomotor nerve.
Pathway See later.
2. Accommodation reflex: Increase in curvature (of the
anterior surface) of lens on looking at a near object.
It is due to contraction of ciliary muscles and
relaxation of lens ligaments.
3. Near reflex: Constriction of pupil on looking at a near
object.
It is mainly initiated by medial rectus muscle which
converges eyeballs on looking at a near object.
Note:
Near response: consists of:
i. Accommodation.
ii. Convergence of visual axes.
iii. Pupillary constriction.
iv. Corneal reflex: Absent in CP angle tumors, mediated
by trigeminal nerve.
PATHWAYS
Visual Pathway
Pigment epithelium in retina Bipolar cell with its axons
(1st order neuron) Ganglion cells (2nd order neuron)
Optic nerve Crosses midline at optic chiasma (only
nasal fibers) (Optic tract) Lateral geniculate body
(Optic radiation) Visual cortex (Brodmann area 17) in
Occipital cortex around calcarine sulcus.
Note: Visual cortex is supplied by posterior and middle
cerebral arteries.
Light Reflex
Same as visual pathway up to optic chiasma pre-tectal
nuclei in midbrain EW nuclei on both sides
parasympathetic output via oculomotor nerve through
ciliary ganglion sphincter of the iris.
Note: No LGB in light reflex pathway.
General Discussion
29
PUPILLARY DEFECTS
Hippus
Alternate dilatation and contraction of pupil.
Seen in multiple sclerosis.
Argyll Robertson Pupil (ARP)
Features:
i. Absence of light reaction
ii. Presence of accommodation reflex.
iii. Miosis, irregular pupil
iv. Normal VA and optic disc
v. No response to mydriatics.
(Mnemonic: ARP accommodation reflex present).
Cause:
Lesion between pretectal nuclei and EW nuclei (Internuncial
neurons).
i. Neurosyphilis
ii. Obstructive hydrocephalus
iii. Pineal region tumors
iv. Others Diabetes, syringomyelia, multiple sclerosis,
chronic alcoholism.
Marcus-Gunn Pupil
Or relative afferent pupillary defect (RAPD).
Feature: Direct light response is less than consensual light
reflex.
Test: Swinging flash light test.
Cause: Retrobulbar optic neuritis (most common).
Adies Tonic Pupil
Unilateral dilated pupil with poor light reaction and slow
redilatation after removal of near object.
Cause: Idiopathic (most common).
Diagnosis: 0.125 percent pilocarpine test tonic pupil
constricts rapidly.
30
Miosis
Horners syndrome:
1. Miosis.
2. Pseudoptosis (due to paralysis of Mllers muscle
supplied by cervical sympathetic nerve).
3. Enophthalmos.
4. Anhydrosis.
Cause:
1. Idiopathic most common.
2. Squamous cell Ca of lung.
3. Brainstem stroke.
4. Carotid dissection.
Mydriasis
1. Oculomotor nerve palsy.
2. Injury to ciliary ganglion due to infections, trauma,
diabetes, temporal arteritis.
3. Hutchinsons pupil fixed dilated pupil in subdural
hemorrhage.
Note:
In optic disc glioma Direct reflex is absent but consensual
reflex is present (in any optic nerve lesion).
In cortical blindness (bilateral occipital lobe lesion) both
direct and consensual reflexes are present in both eyes.
COLOR VISION
Red, green and blue are primary colors.
Theories of Color Vision
The Young-Helmholtz theory postulates the presence of
3 different types of cones for 3 primary colors.
Color Blindness
Congenital
Nomenclature:
Anomaly = weakness
Anopia = blindness
Prot = Red
Deuter = Green
Tri = Blue
General Discussion
31
Cause:
Gene for blue cone is located on chromosome 7.
Genes for red and green are located on the long arm
of X chromosome.
Mutations of these genes produce congenital color
blindness.
Mutation of blue cone gene is extremely rare. Hence,
most of the cases are transmitted as X-linked recessive
and manifest in males.
Type:
Most common type is deuteranopia.
Diagnosis:
Ishiharas chart for red-green vision.
Negels anamaloscope.
Secondary
Causes:
1. Optic neuritis/macular disease.
2. Bilateral occipital lobe lesion (area V8)
Cerebral achromatopsia color blindness,
decrease VA, nystagmus, prosopagnosia.
3. Lesion in dominant occipital lobe color anomia.
4. Drugs Ethambutol, Sildenafil (Viagra).
VISUAL FIELD
Normal visual field
It is 60o above and nasally (minimum)
70-75o below and
100-110o temporal (maximum) to fixation point
(fovea).
Test Perimetry.
VISUAL FIELD DEFECTS (SCOTOMA)
Glaucoma
Selectively destroys the arcuate fibers.
i. Isopter contraction first change.
ii. Isolated paracentral scotoma earliest field defect.
iii. Seidels scotoma
iv. Arcuate (Bjerrums) scotoma - most characteristic
32
Also seen in Optic neuritis, ischemic optic

neuropathy, optic disc drusen and BRAO.
When both superior and inferior arcuate fibers are
involved it produces a ring around macula, called ring
scotoma.
v. Roennes nasal step
vi. Double arcuate scotoma last field defect, produces
tubular vision.
Altitudinal Hemianopia
Due to damage to entire upper or lower pole of optic disc.
Causes:
1. Anterior ischemic optic neuropathy (AION) - most
common cause.
Due to occlusion of short posterior ciliary arteries,
most commonly due to atherosclerosis.
Produces sudden visual loss with inferior
hemianopia.
2. Retinal vascular occlusion
3. Advanced glaucoma
4. Optic neuritis.
Ceco-central Scotoma
Due to damage to papillomacular fibers produces
temporal pallor.
Cause:
1. Optic neuritis most common cause
2. Nutritional optic neuropathy due to deficiency of
thiamine (Vitamin B1) in heavy drinkers and pipesmokers.
3. Toxic amblyopic due to methyl alcohol, may produce
total optic atrophy. Also by Ethambutol.
4. Lebers hereditary optic neuropathy.
Scintillating Scotoma
Seen in migraine.
Ring Scotoma
Retinitis pigmentosa.
General Discussion
33
Damage to Visual Pathways

a. Tumors anterior to optic chiasm Junctional scotoma.
Cause Meningioma of tuberculum sella.
b. Compression of optic chiasm Bitemporal
hemianopia.
Cause Pituitary adenoma, meningioma,
craniopharyngioma, glioma, aneurysms.
c. Injury to post-chiasmal pathway, i.e. optic tract, LGB,
optic radiation and occipital cortex produces
homonymous hemianopia.
d. Damage to optic radiation in temporal lobe (Meyers
loop) Superior quadrantopia.
e. Damage to optic radiation in parietal lobe inferior
quadrantopia.
f. Lesion in occipital lobe due to occlusion of posterior
cerebral artery produces homonymous hemianopia
with macular sparing because tip of macula is supplied
by middle cerebral artery.
SYMPTOMATOLOGY
Painful Red Eye
1.
2.
3.
4.
5.
6.
Conjunctivitis most common cause

Blepharitis
Keratitis
Uveitis
Acute angle-closure glaucoma
Endophthalmitis.
Sudden Visual Loss

1. Transient or amaurosis fugax Central retinal artery
occlusion most commonly due to emboli (cholesterol
emboli called Hollenhorst plaque) from atherosclerotic
plaque in carotid artery. Also seen in papilledema.
2. Branch or central retinal vein occlusion.
3. Anterior ischemic optic neuropathy (AION).
4. Optic neuritis painful.
5. Lebers optic atrophy.
6. Toxic amblyopia.
7. Optic disc drusen.
8. Vitreous degeneration/hemorrhage/opacity.
34
9. Retinal detachment.
10. Classic migraine.
11. Hypertensive retinopathy.
Chronic Loss of Vision
1.
2.
3.
4.
5.
6.
7.
Cataract.
Glaucoma.
Age-related macular degeneration.
Central serous retinopathy.
Diabetic retinopathy.
Retinitis pigmentosa.
Melanoma of choroid.
Proptosis
Measured by Hertel exophthalmometer.
1. Graves ophthalmoplegia most commonly involves
the medial and inferior recti.
2. Orbital pseudotumor.
3. Tumors of orbit most commonly hemangioma.
4. Carotid cavernous fistula pulsating proptosis.
Ptosis
a. Myogenic: Lid-lag on ptosis side on down gaze.
1. Myasthenia gravis fluctuating ptosis that worsens
late in day.
2. Kearns-Sayre syndrome ptosis, retinitis
pigmentosa and heart block.
b. Neurogenic:
1. Horners syndrome (pseudoptosis) due to paralysis
of Mllers muscle pupils are miotic.
2. Oculomotor nerve palsy pupils are larger or
normal.
Test: Tensilon test
Treatment:
1. FasanellaServat operation for Horners syndrome.
2. Blaskowics levator resection.
Nystagmus
1. Optokinetic or jerk nystagmus physiological
nystagmus.
General Discussion
35
2 Congenital nystagmus Pendular or sinusoidal due

to blindness from anterior visual pathway disease early
in life.
3. Gaze evoked most common type of jerk nystagmus.
Exaggerated by myasthenia, brainstem lesion,
cerebellar lesion.
4. Vestibular nystagmus Mnires disease.
5. Downbeat nystagmus Lesions near craniocervical
junction (e.g. Chiari malformation, posterior fossa
tumor).
6. Upbeat nystagmus Phenytoin toxicity, stroke,
posterior fossa tumors.
7. See-saw nystagmus Chiasmal lesion (e.g.
craniopharyngioma).
8. Ataxic (gaze-paretic) nystagmus also called
internuclear ophthalmoplegia due to damage of
medical longitudinal fasciculus.
9. Opsoclonus bursts of consecutive saccades
(saccadonia) seen in viral hepatitis.
10. Ocular flutter seen in neuroblastoma.
11. Rotatory nystagmus seen in miners.
SMELL
PHYSIOLOGY
Olfactory receptor cells: Bipolar cells located in the olfactory
neuroepithelium in the superior 1/3rd of nasal mucosa.
Each bipolar cell has a short, thick dendrite with an
expanded end called an olfactory rod. It bears 6-8 cilia
which contain the odorant receptors.
Two characteristic of olfactory cells are that:
i. They are regularly replaced by new cells.
ii. They regenerate after injury.
Other cells in olfactory neuroepithelium are microvillar
cells, sustentacular cells and basal cells.
Olfactory Pathways
Olfactory receptor cells axons pierce cribriform plate
Olfactory glomeruli in olfactory bulb Mitral and tufted
cells (2nd order neurons) Olfactory cortex.
Note: Olfactory sensation is not relayed by thalamus.
36
Olfactory Cortex
i.
ii.
iii.
iv.
Piriform cortex
Orbitofrontal gyri in frontal lobe
Amygdala (emotional response to smell).
Entorhinal cortex (olfactory memory).
PATHOLOGY
Anosmia
Causes:
1. Head trauma most common cause in children and
young adults.
2. Viral infections most common cause in older adults.
3. Congenital anomaly Kallmanns syndrome Anosmia
and hypogonadotrophic hypogonadism.
4. Neoplasm Meningioma of frontal lobe (most
common).
5. Nutritional deficiencies of
a. Vitamin A
b. Vitamin B12
c. Zn
Note: Hallucination of bad smell Temporal lobe lesion
Parosmia Perception of bad smell.
TASTE
PHYSIOLOGY
Taste Buds
Are test receptor cells.
Types with locations:
i. Fungiform papillae On the dorsum of tongue, most
numerous at the tip.
ii. Foliate papillae along the lateral margins.
iii. Vallate papillae back of tongue.
Other locations:
Palate, epiglottis, larynx and esophagus.
General Discussion
37
Taste Pathways
Fibers carrying taste sensation:
i. From anterior 2/3 of tongue: Chorda tympani nerve.
ii. From posterior 1/3 including vallate papillae:
Glossopharyngeal nerve.
iii. Vagus nerve from other sites.
They synapse on NTS in medulla 2nd order neurons
cross midline and project to the thalamus along with fibers
in medial lemniscus 3rd order neurons project to taste
projection area in the cerebral cortex at the foot of the
postcentral gyrus.
Taste Modalities
i.
ii.
iii.
iv.
Sweet Organic substances

Salt Due to Na+
Sour due to H+
Bitter Due to cations.
Taste buds for above modalities are located in the
tongue from anterior to posterior (tip to base) in the above
order, i.e. sweet at the tip and bitter at the base.
PATHOLOGY
Hypogeusia
Diminished taste sensation is cause by captopril.
HEARING
ANATOMY AND PHYSIOLOGY
Inner Ear
It consists of two parts:
1. Cochlea involved in hearing.
2. Semicircular canal involved in equilibrium (see
above).
Structurally, it has two parts the bony labyrinth outside
and membranous labyrinth inside separated by perilymph.
38
Cochlea
It has 2 and turns.
It has 3 parts on cross-section:
1. Scala vestibuli above Reissners membrane, filled
with perilymph and connects laterally with the oval
window.
2. Scala tympani below basilar membrane, filled with
perilymph and connects to the round window.
The above two are connected through helicotrema.
3. Scala media part between the above two, filled with
endolymph, and contains the organ of Corti. This is
also called the cochlear duct.
Organ of Corti
Located on the basilar membrane in the cochlear duct.
Contains hair cells which are the auditory receptors.
Afferent neurons innervate the inner hair cells and
efferent neurons the outer hair cells.
Axons of afferent neurons form the cochlear division
of the VIII cranial nerve.
Fluids
1. Perilymph occupies the area between bony and
membranous labyrinth (perilymphatic space) and scala
vestibuli and scala tympani. It contains high levels of
Na+ and low K+.
2. Endolymph occupies the membranous labyrinth
(scala media) and contains high K+ and low Na+.
Auditory Pathway
Hair cells in the organ of Corti
cochlear division of VIII nerve
Cochlear nuclei in medulla oblongata
cross midline
Trapezoid body
Lateral lemniscus
Inferior colliculus
Medial geniculate body in the thalamus
Auditory cortex
General Discussion
39
Auditory cortex situated in the superior part of temporal cortex in the Sylvian fissure (Brodmann area 41).
TESTS OF HEARING
Rinnes Test
Using a 256 Hz tuning fork.
It compares air conduction (AC) with bone conduction
(BC).
In normal ear, AC > BC positive Rinne.
In conductive deafness, BC > AC negative Rinne.
False negative Rinne is seen in severe unilateral
sensorineural deafness. This is confirmed by Weber test.
Weber Test
Bone conduction test.
In conductive deafness sound lateralized to the deaf
ear.
In sensorineural deafness sound lateralized to the
better ear.
Absolute Bone Conduction Test
In conductive deafness ABC is normal.
In sensorineural deafness ABC is shortened
(Diagnostic).
Gelles Test
Bone conduction test.
Note:
AC signifies conduction through ossicular pathway.
BC signifies conduction through sensory neural
pathway.
AUDIOMETRY
a. Subjective
i. Pure tone audiometry
ii. Speech audiometry
iii. ABLB or Fowlers test
iv. Tests for adaptation Bekesy audiometry, Tone-Decay
test.
40
b. Objective
i. Tympanometry
ii. Brainstem evoked response audiometry (BERA or
ABR).
Pure Tone Audiometry
Most common type.
Frequencies used from 250-8000 Hz.
Response are measured in decibels (a logarithmic unit).
Interpretations:
i. Conductive deafness air-bone gap (threshold elevation
for BC > AC).
ii. Sensorineural deafness greater threshold at higher
frequencies, except in acoustic trauma (noise-induced
deafness) where there is a sudden dip at 4000 Hz.
iii. Otosclerosis conductive deafness (AB gap) with a
dip at 2000 Hz (Carharts notch).
Speech Audiometry
Response is speech discrimination at phonetically balanced
words.
i. Conductive deafness 95-100 percent speech
discrimination.
ii. In cochlear deafness 50-80 percent speech
discrimination.
iii. In retro-cochlear deafness 0-50 percent speech
discrimination.
ABLB or Fowlers Test
Test of recruitment.
The graph is called the laddergram.
In conductive deafness and in normal ear negative.
In sensorineural deafness (e.g. presbyacusis) positive.
In cochlear lesion (e.g. Mnires disease) positive.
Tone-Decay Test
A decay > 30 dB is diagnostic of retrocochlear lesion
(acoustic neuroma).
General Discussion
41
Tympanometry
Or impendence audiometry.
Test of impendence of middle ear to sound.
Graph is called the tympanogram.
Interpretations:
Type A normal.
Type B (flat or dome shaped curve) secretory otitis
media.
Type C Eustachian tube blockade.
Type D ossicular disruption.
Stapedial Reflex
This is due to contraction of middle ear muscles (tensor
tympani and stapedius).
This is absent in otosclerosis.
This is a protective reflex against loud sound.
Brainstem Evoked Response Audiometry (BERA)
Most useful test for localization of lesion in sensorineural
deafness.
DEAFNESS
Definition
Hearing loss more than 90 dB in the better ear or total
hearing loss.
Etiology
a. Conductive deafness
i. Chronic suppurative otitis media most common
cause.
ii. Secretory otitis media most common nonsuppurative cause in children.
iii. Otosclerosis most common cause in adults.
b. Sensorineural deafness
1. Childhood deafness
i. Hereditary autosomal recessive, e.g. Pendred
syndrome, trisomy 18, familial sensorineural
deafness.
ii. Meningitis most common cause of
sensorineural deafness in children.
iii. Congenital infections TORCH.
42
iv. Others unconjugated hyperbilirubinemia,

asphyxia.
2. Presbyacusis or senile deafness most common
cause.
Note: other causes of congenital deafness:
i. Alports syndrome
ii. Ushers syndrome
iii. Pendred syndrome
iv. Treacher-Collin syndrome
Tests at a glance
Normal
Cochlear
lesion
Retrocochlear lesion
Pure tone audiometry
Normal
Sensorineural
deafness
Speech discrimination
Recruitment (ABLB)
SISI (short increment
sensitivity index)
Tone decay
Stapedial reflex
BERA
90-100%
Absent
0-15%
Sensorineural
deafness
50-80%
Positive
> 70%
< 25 dB
Normal
Normal
> 25 dB
Abnormal
V wave
delayed or
absent
0-15 dB
Normal
Normal
interval
between
I and V
0-50%
Negative
0-20%
ORAL CAVITY
ORAL MUCOSA
Pigmented Lesions
1. Heavy metal poisoning (lead, mercury) blue-black
line along the gingival margin.
2. Black hairy tongue elongation of filiform papillae
due to tobacco, chromogenic agents.
3. Fordyces spot ectopic sebaceous gland, situated on
the lips.
4. Forchheimers spot (palatal petechiae) rubella,
infectious mononucleosis, scarlet fever.
General Discussion
43
White Lesion
Hairy leukoplakia HIV infection.
TONGUE
Macroglossia
Etiology
i.
ii.
iii.
iv.
v.
vi.
Downs syndrome
Pierre-Robin syndrome
Hurlers syndrome
Primary amyloidosis
Acromegaly, cretinism
Actinomycosis, tertiary syphilis.
Geographic Tongue
Benign migratory glossitis. Asymptomatic and require no
treatment.
Strawberry/Raspberry Tongue
Scarlet fever.
Bald Tongue
Xerostomia, pernicious anemia, iron deficiency anemia,
pellagra, syphilis.
PULMONARY FUNCTION
REGULATION OF RESPIRATION
Higher Center
Respiratory center is situated in the medulla.
Pre-Bottzinger complex in medulla is the respiratory
pacemaker.
Note: Expiration is passive during quiet breathing.
If brainstem is transected at the inferior border of pons,
spontaneous respiration continues but becomes irregular
and gasping.
44
CHEMICAL CONTROL OF BREATHING

Chemoreceptor
i. Carotid body situated near carotid bifurcation on
each side.
Note: blood flow to each carotid body = 2000 ml/100
gm/minute.
ii. Aortic body near the arch of aorta.
Stimulus:
i. Increased H+ ion concentration in arterial blood
acidosis.
ii. Decreased PO2 hypoxia.
Both lead to hyperventilation.
Medullary chemoreceptor: These mediate responses
produced by increased arterial PCO2 via CSF and brain
interstitial H+ concentration.
Note: CO2 is most permeable to BBB.
Effect of CO 2 : A rise of arterial PCO 2 produces
hyperventilation which washes out excess CO2. However,
when the CO2 concentration of inspired gas exceeds 7%,
there is rise of PCO2 despite hyperventilation. The resultant
hypercarbia depresses central nervous system including the
respiratory center and produces headache, confusion and
coma (CO2 narcosis).
NON-CHEMICAL CONTROL OF BREATHING
Airway and lung receptors mediated by vagus nerve.
Non-chemical control of breathing
Receptors
Location
Slow adapting Airway

(myelinated)
smooth
muscle
Rapidly
adapting
(myelinated)
Unmyelinated
C fibers
J receptors
Airway
epithelial
cells
Stimulus
Response
Lung inflation
Hering-Breur
reflex increased
duration of
expiration
Hyperpnoea,
cough, bronchoconstriction,
mucus secretion
Lung hyperinflation,
exogenous/
endogenous
substances
(histamine, PG)
Alveolar
Lung hyperApnea followed
interstitium inflation
by rapid breathing,
(juxtabradycardia and
capillary)
hypotension
(pulmonary
chemoreflex)
General Discussion
45
Effects of Exercise
i. Increased pulmonary blood flow.
ii. Increased alveolar-capillary PO2 gradient (PO2 of
pulmonary blood falls from 40 to 25 mmHg) more
O2 enter the circulation.
iii. Respiration
Initially abrupt increase due to impulses from
propioceptors in muscles, joints, tendons.
Followed after a brief pause by more gradual increase
due to humoral responses.
Mechanism increase in body temperature, increase
in plasma K+ induced by exercise.
Note: arterial pH, PCO2 and PO2 remains normal in
moderate exercise.
CLINICS
Types of Breathing
a. Vesicular breathing:
Produced by air passage through tracheobronchial tree
up to alveoli.
Variations:
i. Diminished vesicular pleural effusion,
pneumothorax, empyema.
ii. Prolonged expiration bronchial asthma, COPD.
iii. Absent pneumonia, massive effusion, collapse
with obstructed bronchus.
b. Bronchial breathing:
Air passage through tracheobronchial tree and a patent
bronchus (not in alveoli).
Variations:
i. Tubular consolidation.
ii. Cavernous cavity lung (e.g. TB)
iii. Amphoric bronchopleural fistula (open
pneumothorax).
Cheyne-Stokes Breathing
Alternate phases of apnea and hyperapnea, each phase
lasting for 30 seconds and whole cycle completed in 2
minutes.
46
Seen in:
i. Cardiac failure
ii. Uremia
iii. Narcotic poisoning
iv. Increased ICT
v. Normal in infants and adults during sleep.
Kussmauls Breathing
Deep respiration at a rapid rate.
Seen in:
i. Diabetic ketoacidosis
ii. Uremia
iii. Cerebral tumor
iv. Hepatic coma.
PERCUSSION
Normal resonant.
Dull stony dull in pleural effusion and woody dull
in consolidation.
Tympanic pneumothorax.
Hyperresonant emphysema.
Impaired thickened pleura.
PULMONARY EDEMA
Development
Two stages:
1. Interstitial edema characterized by tachypnea,
decreased gas exchange and Kerley B lines on chest
X-ray, is due to increased pulmonary vascular pressure,
increased lymphatic flow and a net gain of water in
extravascular space.
2. Alveolar edema characterized by full blown symptoms
with bilateral rales and ronchi and diffuse haziness of
lung fields on chest X-ray. This is due to disruption
of alveolar capillary membrane.
Clinical feature: Pink (blood-stained) frothy sputum.
Etiology
a. Increased PCWP
i. Cardiogenic mitral stenosis, left heart failure.
ii. Non-cardiogenic severe liver disease, nephrotic
syndrome, protein losing enteropathy.
General Discussion
47
b. Normal PCWP
i. High altitude
ii. Narcotic overdose most commonly with heroin.
iii. Pulmonary embolism
iv. Cardiopulmonary bypass.
c. Others radiation pneumonitis.
Unilateral pulmonary edema is seen in:
i. Lymphoma,
ii. Aspiration
iii. Post-pleural tap aspiration.
Note: Bat wing appearance in CXR is seen in cardiogenic
pulmonary edema.
PULMONARY HYPERTENSION
Normal pulmonary arterial pressure is 25/10 mmHg.
Pulmonary hypertension means pressure > 35/15
mmHg.
Etiology:
i. Left heart failure MS, MR, AS, AR.
ii. Congenital heart diseases ASD, VSD, PDA.
iii. Pulmonary thromboembolism
iv. SLE, PAN
v. Sickle cell anemia
vi. Progressive systemic sclerosis
vii. Toxic oil (rape seed) syndrome.
Treatment
General diuretics, anticoagulant.
Specific calcium channel blocker, endothelin receptor
antagonist (Bostenan), phophodiesterase 5 inhibitor
(sildenafil), prostacyclins (Iloprost).
COUGH
Staccato paroxysm of cough whooping cough,
chlamydia infection.
Barking or brassy cough laryngotracheobronchitis.
Hawking cough post-nasal drip.
Honking cough psychotic.
Bovine cough laryngeal paralysis.
STRIDOR
Laryngomalacia most common cause of stridor
(present at birth), intermittent in nature, increased by
crying and relieved on lying down.
48
Laryngotracheobronchitis presents at 1-5 years of age.

Acute epiglottitis
Subglottic hemangioma presents at 3-6 months of
age, increases on crying, managed by tracheostomy,
steroid and CO2 laser.
HEMOPTYSIS
Source of bleeding bronchial arteries.
Most common site of bleeding tracheobronchial tree.
Etiology:
i. Bronchitis
ii. Bronchogenic Ca
Produces
iii. Bronchiectasis
iv. Tuberculosis most common cause. massive
hemoptysis.
v. Aspergilloma
vi. Foreign body.
CYANOSIS
Produced by:
Reduced Hb > 5 gm/dl.
Sulphemoglobin > 0.5 gm/dl.
Methemoglobin > 1.5 gm/dl.
Etiology:
a. Central cyanosis:
1. Congenital heart diseases tetralogy of Fallot (most
common), Eisenmengers complex (ASD, VSD or
PDA with reversal of shunt due to pulmonary
hypertension).
2. Acute pulmonary edema (due to LVF) most
common cardiac cause.
b. Peripheral cyanosis:
1. Exposure to cold most common cause.
2. CCF.
c. Differential cyanosis:
1. Hands blue and feet red coarctation of aorta with
transposition of great vessels.
2. Hands red and feet blue PDA with reversal of shunt.
CLUBBING AND HYPERTROPHIC
OSTEOARTHROPATHY
Degrees
First degree increased fluctuation of nail bed (earliest
change) with loss of onychodermal angle (normal
120o).
General Discussion
49
Second degree first degree + increased diameter of

nail.
Third degree second degree + increased pulp tissue.
Fourth degree third degree + swelling of wrist and
ankle due to HOA.
Etiology:
a. Cardiac:
i. Congenital cyanotic heart diseases.
ii. Infective endocarditis.
iii. Aortic aneurysm.
iv. Atrial myxoma.
b. Lung:
i. Neoplasms bronchogenic Ca (most common cause),
mesothelioma.
ii. Infections empyema, lung abscess, bronchiectasis.
iii. Pulmonary fibrosis interstitial lung disease.
iv. Cystic fibrosis.
c. Ulcerative colitis and Crohns disease.
d. Biliary cirrhosis
e. Idiopathic
f. Neoplasms
g. Genetic autosomal dominant.
h. Hyperthyroidism.
Hypertrophic Osteoarthropathy (HOA)
It is subperiosteal new bone formation in the proximal
and distal diaphyses of tibia, fibula, radius and ulna. Bone
involvement is bilateral and symmetrical.
Diagnosis: Bone X-ray.
Note: HOA is most commonly seen in bronchogenic Ca.
EDEMA
Total Body Water
Water constitutes 60 percent of body weight.
2/3rd of TBW is intracellular and remaining 1/3rd is
extracellular.
ECF is distributed in interstitial fluid (75%) and plasma
(25%).
50
TBW is measured by D2O method.

Edema is an increase in fluid volume in the interstitial
space.
Pathogenesis
Two primary forces acting in vascular system regulates fluid
movement are:
i. Hydrostatic pressure which tries to drive out water
and
ii. Oncotic pressure (primarily contributed by plasma
proteins, mainly albumin) which tries to retain water.
Etiology
a. Increased hydrostatic pressure CCF most common
cause.
b. Decreased oncotic pressure (fall in plasma protein >
85%)
i. Nephrotic syndrome
ii. Cirrhosis
iii. Protein losing enteropathy.
c. Lymphatic obstruction
i. Inflammatory edema, e.g. filariasis.
ii. Neoplastic, e.g. breast Ca.
Note: In acute heart failure, there is a fall in hydrostatic
pressure in systemic capillaries due to peripheral
vasodilatation edema does not develop.
Clinical Types
Pitting edema, e.g. in CCF.
Non-pitting edema, e.g. in myxedema, filariasis and
angioneuritic edema.
Differential Diagnosis
CCF starts with edema in the dependant parts (legs).

Nephrotic syndrome starts with facial edema.
Cirrhosis starts with ascites.
Hypoproteinemia periorbital edema.
Facial edema:
Seen in nephrotic syndrome (hypoproteinemia),
trichinosis, allergic reactions, myxedema.
General Discussion
51
Idiopathic edema:
Periodic episodes of edema seen in women which is
unrelated to the menstrual cycle.
Cause: Orthostatic retention of Na+ and water (not estrogen
mediated).
Differential diagnosis: Cyclical or premenstrual edema in
which Na+ and water retention occurs secondary to high
estrogen.
Treatment: ACE inhibitors may be helpful.
SHOCK
Types
1. Hypovolemic shock most common clinical type.
Stages of hypovolemia:
i. Covert compensated most common type.
ii. Overt compensated
iii. Decompensated
2. Cardiogenic shock
Most common cause is myocardial infarction (> 40%
of LV).
Features:
SBP < 80 mmHg.
Cardiac index < 1.8 L/min/mt2.
LV filling pressure > 18 mmHg.
Pulmonary edema.
3. Distribution shock due to peripheral vasodilatation, e.g.
septic shock, anaphylactic shock.
Pathophysiology
Diagnosis
PCWP
Cardiac
output
Peripheral
vasculature
Hypovolemic shock
Cardiogenic shock
Septic shock
Decreased
Increased
Decrease/
normal
Decreased
Decreased
Increase/
normal
Constriction
Constriction
Dilatation
52
Clinical Feature
Hypotension, tachycardia, tachypnea, oliguria, metabolic
acidosis, cold and clammy skin (in septic shock, skin may
be flushed and hot due to vasodilatation).
Grading of hypovolemia:
Mild (< 20%) cold extremities, anxiety.
Moderate (20-40%) same + tachycardia, tachypnea,
decreased urine output.
Severe (> 40%) decreased BP, marked tachycardia.
Management
a. Hypovolemic shock
Fluid infusion is the main treatment.
Initial choice of fluid is crystalloids (according to
Harrison) and colloids (according to Bailey and Love).
In severe hypovolemia ionotropics (dopamine) may be
used.
b. Cardiogenic shock
Intra-aortic balloon pump, ionotropic drugs dopamine, dobutamine (drug of choice in pump
failure), amrinone, milrinone.
Monitoring
Urine output most useful method. It should be >
0.5 ml/kg/hr.
PCWP and CVP are not very helpful in determining
left ventricular function (tissue perfusion) in shock.
CARDIAC ARREST AND
SUDDEN CARDIAC DEATH
Cardiac arrest is the most common cause of sudden death.
Etiology
1. Electrical disturbance ventricular fibrillation is the
most common cause of cardiac arrest. Others are
ventricular tachycardia and asystole.
2. Decreased cardiac output acute pulmonary emboli,
ruptured aortic aneurysm, cardiac rupture after
myocardial infarction.
General Discussion
53
Structural Defect
Atherosclerotic heart disease most common cause.
Cardiomyopathy.
Conducting system disease.
Predisposing Factors
i. Hypoxia most common cause.
ii. Electrolyte disturbance Hypokalemia, hypocalcemia
(heart stops at diastole).
Management
Heimlich maneuver for dislodging an aspirated foreign
body.
Cardiopulmonary resuscitation has two components
i. Chest compression (cardiac massage) over the lower
sternum, at the rate of 80-100/minute, force to depress
sternum 3-5 cm (1.5-2 inches).
ii. Ventilation 10-12 times/minute, i.e. compression:
Ventilation ratio = 5:1 (2 in succession every 15
compression when one person is performing).
Note: Maximum cardiac index attained by external
compression is 40 percent (normal is 2.6-4.2 L/min/mt2).
Advanced life support:
i. Endotracheal intubation
ii. Defibrillation/cardioversion and/pacing adrenaline
is given if defibrillation fails. If not controlled
completely, lignocaine/procainamide/bretylium is
given.
iii. IV fluid.
iv. IV NaHCO3 in acidotic patients.
v. IV calcium gluconate in hyperkalemia, hypocalcemia, CCB therapy.
Prognosis
Those with VT carry best prognosis.
Asystole carries the worst prognosis.
54
GI FUNCTIONS
Dysphagia
a. Type of food:
To solids mechanical obstruction, e.g. malignancy.
To both solids and liquid achalasia, diffuse
esophageal spasm.
Scleroderma Dysphagia to solid unrelated to posture
and dysphagia to liquid in recumbent but not in upright
posture.
b. Duration :
Progressive dysphagia malignancy.
Episodic dysphagia lower esophageal ring.
c. Odynophagia (painful swallowing: fungal or herpetic
esophagitis or pill-induced esophagitis.
Vomiting
Mechanism:
a. Vomiting center in dorsal portion of lateral reticular
formation in medulla.
b. CTZ in area prostema of the floor of fourth ventricle.
Peripheral muscles:
1. Abdominal musculature provides the main ejection
force.
2. Diaphragm.
3. Intercostal muscles.
Clinical feature:
a. Type: Projectile vomiting in increased ICT.
b. Time: Early morning nausea early pregnancy, uremia,
alcoholic gastritis.
Shortly after taking food peptic ulcer.
4-6 hours after taking food gastric retention.
c. Character: Increased acid content gastric outlet
obstruction duet to Z-E syndrome.
Absent free HCl gastric carcinoma.
Bile obstruction below ampulla of Vater.
Complications:
i. Metabolic hypochloremic, hypokalemic, metabolic
alkalosis.
ii. Rupture of esophagus Boerhauves syndrome.
General Discussion
55
iii. Hematemesis Mallory-Weiss tear.

iv. Aspiration pneumonia in comatose patients.
a. Hiccups seen in uremia, acidosis, anoxia, systemic
infections. Cause is gastric distension.
b. Rumination seen in bulimia nervosa.
DIARRHEA
Acute
a. Watery diarrhea enteric viruses (rotavirus most
common), EPEC, cholera, protozoa, helminths.
b. Watery then bloody diarrhea campylobactor, shigella,
V. parahemolyticus.
c. Bloody diarrhea salmonella, shigella, EIEC, yersinia,
entamoeba.
Note:
Most common cause of diarrhea in neonates E. coli.
Most common cause of diarrhea in infants/children
rotavirus.
Most common cause of diarrhea in AIDS patients
Cryptosporidium.
Preformed toxins are produced by
Bacillus cereus, Staphylococcus aureus and Clostridium
perfringens (mnemonic BSC).
Chronic
a. Inflammatory ulcerative colitis, Crohns disease,
radiation, eosinophilic gastroenteritis.
b. Osmotic lactose intolerance (milk allergy), pancreatic
cholera, tropical sprue, Whipples disease, celiac sprue,
short bowel syndrome, abetalipoproteinemia.
c. Secretory (watery) Z-E syndrome, villous adenoma,
carcinoid syndrome, medullary Ca of thyroid,
cholerrheic diarrhea, and diabetes mellitus type I due
to altered motility.
Note:
Intestinal lymphangiectasia causes selective protein loss
with steatorrhea with preserved carbohydrate absorption.
56
Diagnosis
a. Inflammatory diarrhea hallmark is the presence of
blood and leukocytes in stool.
Blood is detected by Benedicts reaction.
Leukocytes are detected by Wrights or methylene
blue stain.
b. Malabsorption
i. Stool fat increased in pancreatic insufficiency.
ii. Carbohydrate d-xylose absorption test in celiac/
tropical sprue.
iii. Intestinal biopsy definitive test for malabsorption.
Diagnostic in Whipples disease, abetalipoproteinemia,
agammaglobulinemia.
iv. 1-antitrypsin assay best test for protein-losing
enteropathy.
v. Schillings test for vitamin B12 assay, done in
pernicious anemia, pancreatic insufficiency.
vi. Bacterial growth 14C-xylose breath test.
vii. Fecal osmolality to differentiate osmotic from
secretory diarrhea. Fecal osmotic gap > 50 mosmol/
kg H2O suggests osmotic diarrhea.
Treatment
a. Travelers diarrhea (ETEC) bismuth subsalicylate,
diphenoxylate + atropine, loperamide.
b. Oral rehydration for mild (5-7% of body weight) or
moderate (7.5-10% body weight) dehydration.
WHO ORS:
Principle: Glucose promotes absorption of Na+.
Composition:
Ingredient
Quantity
(in gram)
NaCl
NaHCO3
KCl
Glucose
Potable water
Or Trisodium citrate
dehydrate in place of NaHCO3
3.5
2.5
1.5
20
1 lit.
2.9
(in mmol/L)
Na +
K+
ClCitrate
Glucose
90
20
80
10
110
Total 310
Dose 75 ml/kg in the first 4 hours then 10-20 ml/

kg for each liquid stool.
General Discussion
57
Drawback when used in non-choleric diarrhea, it

produces periorbital edema due to excess Na+ absorption
(hypernatremic dehydration causes irritability).
New formula ORS: For cholera and non-cholera diarrhea.
It has low Na+ (NaCl 2.6 gm, Na+ 75 mmol/lit)
and low glucose (glucose 13.5 gm, 75 mmol/lit).
Super ORS: ORS that in addition to rehydration increases
intestinal absorption and decreases stool formation.
For example, alanine, glycine added ORS, boiled rice
best for developing countries.
c. IV rehydration for severe dehydration.
Indication: Fluid loss > 10 percent of body weight.
i. Dhaka fluid contains 5 gm of NaCl, 1 gm of KCl
and 4 gm of NaHCO3 dissolved in 1 liter of water
or 5 percent dextrose.
ii. Ringers lactate recommended by WHO. It provides
Na+ - 130 mmol/l
K+ - 4 mmol/l
Cl- - 109 mmol/l
Lactate 28 mmol/l
Total 271 mmol/l.
Dose: 30 ml/kg in the first hour and 70 ml/kg in the next
5 hours for infants < 1 year.
In older children same dose should be given in
hour and 2 hours, respectively.
d. Other drugs
Sulfasalazine in IBD.
Octreotide in carcinoid syndrome.
Clonidine in opiate withdrawal and diabetic diarrhea.
Indomethacin - in medullary Ca of thyroid and villous
adenoma.
Cholestyramine drug of choice in bile salt
malabsorption.
Metronidazole/vancomycin in pseudomembranous
colitis.
WEIGHT
Weight gain
Hypothyroidism Myxedema
Cushings syndrome
Craniopharyngioma
Insulinoma
Weight loss
Hyperthyroidism
Pheochromocytoma
Diabetes mellitus
58
GI BLEEDING
Hematemesis is vomiting of blood produced by pathology
proximal to the ligament of Treitz.
At least 60 ml of blood is required to produce a single
black stool and blood should remain for at least 8 hours
in the gut.
Etiology
Upper GI bleeding:
1. Erosive hemorrhagic gastropathy (NSAID induced)
2. Duodenal ulcer most common cause.
3. Gastric ulcer.
4. Mallory-Weiss tear.
5. Esophageal varices.
6. AV malformation.
7. Gastric tumors least common cause. Most common
gastric tumor to bleed is leiomyoma.
All the above conditions can produce both hematemesis
and melena.
Note: Most common cause of upper GI bleeding in children
is from esophageal varices due to portal hypertension.
Lower GI bleeding:
Age < 55 years
Age > 55 years
Hemorrhoids most
common cause
Colitis (IBD, infections)
Hemorrhoids, fissure
scant bleeding.
Diverticulosis most common
cause of massive bleeding.
Diverticulosis
Angiodysplasia.
They usually produce hematochezia.
Note: Most common cause of bleeding per rectum in
children is rectal polyp.
Investigation
Occult blood by card test for Hb peroxidase. False
negative test may be due to chronic ingestion of
vitamin C.
General Discussion
59
Most sensitive method to detect GI bleeding is

radiolabelled erythrocyte screening which can detect blood
as small as 0.01-0.05 ml/min.
Angiography may detect bleeding as small as 0.5
ml/min.
JAUNDICE
BILIRUBIN METABOLISM
Bilirubin is produced by catabolism of heme (the iron
porphyrin in Hb).
Heme
Synthesis
It is essentially the incorporation of ferrous ion into
protoporphyrin III the parent porphyrin in heme.
Heme synthesis occurs in mitochondria in most
mammalian cells except the RBC which does not contain
mitochondria.
The rate limiting enzyme is ALA synthetase in liver
(dependant on pyridoxal phosphate).
Note: Lead poisoning causes increased protoporphyrin in
RBC and increased ALA and coproporphyrin in urine.
Bilirubin
Heme is catabolized to bilirubin in the RE cells of peripheral
tissues through the following steps:
Hb (red) hemin (blue-purple) biliverdin (green)
bilirubin (yellow).
Note: The color change in a bruise or hematoma is due
to the above reason.
1 gm Hb yields 35 mg of bilirubin.
Daily production in human = 250-350 mg.
60
Types
Bilirubin
Water solubility
Renal excretion
Albumin binding
Van den Bergh reaction
Unconjugated
Conjugated
No
No
+++
Indirect
Yes
Yes
+
Direct
Note: Unconjugated bilirubin = total bilirubin conjugated

bilirubin (in VDB test).
Metabolism
It consists of the following steps:
1. Uptake of unconjugated bilirubin bound to albumin
by liver.
2. Conjugation with glucoronide by UDP-glucuronyl
transferase. Conjugation makes it water soluble.
3. Secretion into bile and into GI tract.
4. Intestinal circulation conjugated bilirubin is not
absorbed by intestine. In terminal ileum and colon,
it is converted to urobilinogen which is excreted in the
feces. Some urobilinogen is absorbed, taken up by the
portal vein and re-excreted by the liver (enterohepatic
circulation).
In unconjugated hyperbilirubinemia, some urobilinogen
is also excreted in urine (as in hemolysis) due to excess
production of bile pigments (acholuric jaundice).
In obstructive jaundice, conjugated bilirubin may be
present in urine without urobilinogen (choleric jaundice).
(See below)
JAUNDICE
Normal serum bilirubin level
Total = 0.3 to 1.0 mg/dl
Conjugated (direct) = 0.1 to 0.3 mg/dl.
Unconjugated (indirect) = 0.2 to 0.7 mg/dl.
Hyperbilirubinemia is bilirubin > 1.0 mg/dl.
Latent jaundice is bilirubin 1.0 2.5 mg/dl.
Clinical jaundice is bilirubin > 2.5 mg/dl.
Most common site for detecting jaundice is upper
bulbar conjunctiva.
Scleral tissue has high level of elastin which has high
affinity for bilirubin.
General Discussion
61
Classification
A. Unconjugated hyperbilirubinemia (indirect):
1. Overproduction hemolysis.
i. Rh incompatibility most common cause in
newborn.
ii. ABO incompatibility.
iii. Thalassemia.
iv. Vitamin K.
2. Decreased bilirubin conjugation (decreased hepatic
glucuronyl transferase activity).
i. Gilbert syndrome (mild deficiency).
ii. Crigler -Najjar type II (moderate deficiency) AD.
iii. Crigler-Najjar type I (absent enzyme) AR.
iv. Physiological jaundice of neonates.
v. Breast milk jaundice.
vi. Septicemia.
B. Conjugated (Direct) hyperbilirubinemia:
Direct bilirubin > 15 percent of total bilirubin.
1. Impaired hepatic excretion (intrahepatic defect)
i. Dubin-Johnson syndrome.
ii. Rotor syndrome.
iii. Hepatocellular disease hepatitis, cirrhosis.
iv. Alcoholic liver disease.
2. Extrahepatic biliary obstruction
i. CBD stones Most common cause of benign
surgical jaundice.
ii. Biliary atresia Most common cause in newborn.
iii. Others choledochal cyst, Pancreatic Ca.
Evaluation of Jaundice
Condition
Serum
bilirubin
Normal
Hemolysis
D + I
Increased I
(indirect)
Increased
D + I
Hepatitis
Obstruction Increased D
(direct)
Urine
Fecal urobilinogen
Urobilinogen Bilirubin
Mild +
Absent
Increased
Absent
(acholuric)
Decreased
+ (in micro(in microobstruction)
obstruction)
Absent
Present
(choleric)
Present
Increased
Decreased
Note: Bilirubin in urine is detected by Ehrlichs test.
62
LFT:
a. Unconjugated no enzymatic disturbance (e.g.
hemolysis)
b. Conjugated i. Hepatitis increased ALT and AST.
ii. Obstruction increased alkaline phosphatase,
5 nucleotidase and/or GGT.
NEONATAL JAUNDICE
Classification
A. Early jaundice (<10 days) unconjugated.
a. First 24 hours Rh incompatibility (Most common
cause), ABO incompatibility, others G-6PD
deficiency, Vitamin K.
b. After 24 hours - Physiological jaundice,
Cephalhematoma, Congenital hemolytic anemia
Gilbert syndrome and Crigler-Najjar syndrome,
Galactosemia.
B. Prolonged jaundice (> 10 days):
a. Unconjugated Breast milk jaundice, Septicemia.
b. Conjugated Congenital infections (TORCH, etc),
Dubin-Johnson, Rotor syndrome,
Hypothyroidism,
Extrahepatic biliary atresia,
Intrahepatic dilatation of bile duct Carolis disease.
Choledochal cyst.
Idiopathic infantile hepatitis most common cause.
EARLY JAUNDICE
Hemolytic Disease of Newborn
Due to isoimmunization (Erythroblastosis fetalis)
Rh incompatibility: Most common cause.
Mechanism: AntiD antibody (IgG) in a sensitized mother
(Rh ve) may cross the placenta and produce hemolysis
in Rh +ve fetus (not in first pregnancy).
Mechanism of sensitization APH, PPH, PIH, CS,
post-dated pregnancy.
Note: Immunization occurs when > 0.1 ml of fetal blood
enters maternal circulation.
General Discussion
63
Associated ABO incompatibility reduces the chance

of Rhimmunization.
Manifestations:
a. Hydrops fetalis Most serious form.
Diagnosis:
USG Edema of scalp, skin and pleural / pericardial
effusion, ascites (large abdomen).
X-ray Buddha position of head.
Placenta large due to hyperplasia.
b. Neonatal jaundice develops within 24 hours after
birth.
c. Congenital anemia of newborn red cell destruction
continues for up to 6 weeks.
Diagnosis:
a. Mother Quantitative assay
Maternal serum anti-D antibody level
< 4 IU/ml low risk
4-10 IU/ml moderate risk.
> 10 IU/ml severe risk.
IgG antibody detection by indirect Coombs test
Genotype of the husband
If homozygous, 100 percent

chance of affection
If heterozygous,
50 percent chance of affection
Amniocentesis
b. Amniocentesis: To assess disease progression.

Time:
i. No previous history at 30-32 weeks.
ii. Positive previous history at least 10 weeks prior to
previous stillbirth (usually before 20 weeks).
Inference: Spectophotometric analysis of amniotic fluid
shows optical density difference at 450 nm with deviation
bulge in Rh hemolytic disease.
The deviation bulge is plotted in Lileys chart. If it
falls in the
i. Low zone (zone I) continue pregnancy.
ii. Mid zone (zone II) may require termination after
34 weeks.
64
iii. High zone (zone III) severely affected child, if >

34 weeks termination, if < 34 weeks intrauterine
fetal transfusion.
c. Baby: Sensitized baby show positive direct Coombs
test.
Prevention: Administration of Rh anti-D immunoglobulin
to unsensitized (Coombs negative) mother within 72 hours
following childbirth (300 g), abortion (100 g) and ectopic
pregnancy (50 g), amniocentesis, external cephalic version.
Management: See below.
ABO incompatibility: Occurs when the mother is group
O and the baby is either group A or B.
First baby may be affected (c.f. Rh incompatibility).
Non-immune hemolysis: G6PD deficiency, vitamin K.
Note: Causes of non-immune hydrops (fetal edema)
i. Downs syndrome
ii. Congenital cardiac anomaly
iii. Beta thalassemia, G6PD deficiency
iv. Infection parvovirus, toxoplasma, rubella, syphilis.
Physiological Jaundice of Newborn
Incidence: 65 percent
Features: Appears after 30 hours (on third day). Peak level
of bilirubin maximum 12 mg/dl on day 4 or 5. Rate of
increase in bilirubin concentration < 5 mg /day. Disappears
by 7 14 days.
Aggravating factors: Prematurity, hypoglycemia, hypoxia,
dehydration, intestinal stasis.
Kernicterus
Cause: Unconjugated hyperbilirubinemia > 20 mg/dl or
serum bilirubin:protein ratio > 3:5.
Pathology: Damage to basal ganglia (most common),
hippocampus and subthalamic nuclei.
Note: Cerebral cortex is spared.
Risk factors: Prematurity, hypoglycemia, hypoxia,
hypothermia, ketoacidosis. Drugs Sulfamethoxazole,
Gentamicin, Novobiocin.
General Discussion
65
Management of Early Jaundice

1. Phototherapy:
Indications Serum bilirubin > 18 mg/dl at term.
a. Hemolytic (ABO) bilirubin level
10 at < 12 hours.
12 14 at < 18 hours.
15 at > 24 hours.
b. Non-hemolytic bilirubin level
15 at < 2 days.
18 at 2-3 days.
20 at 3-4 days.
Mechanism: Photoisomerization of bilirubin (E isomerism),
toxic 4Z-15Z bilirubin is converted to 4Z-15E bilirubin.
Blue light is most sensitive.
Complication:
i. Dehydration due to insensible water loss most
common.
ii. Diarrhea most common cause in newborn.
iii. Bronzing of skin.
iv. Retinal damage.
2. Exchange transfusion:
Indication:
a. Term baby
i. Unconjugated bilirubin > 25-28 mg/dl in nonhemolytic cases and > 18-20 mg/dl in hemolytic
cases.
ii. Serum bilirubin: Protein ratio > 3.5.
b. Erythroblastosis i. Maternal antibody titer > 1:64
ii. Baby direct Coombs positive with body weight
< 2.5 kg.
iii. Cord Hb < 10 gm/dl and cord bilirubin > 5 mg/
dl.
iv. Previous history of affected child.
Method: Rh-negative whole blood from unsensitized donors
with same ABO blood group.
Complication:
i. Hypovolemia shock (usually hypervolemia occurs).
ii. Citrate tetany.
iii. Cardiac arrest.
iv. Hypercalcemia.
66
PROLONGED JAUNDICE
Breast Milk Jaundice
Gradual onset (after 10 days).

Peak bilirubin level 25 mg/dl on 2nd or 3rd week.
Settles in 6 hours, may continue up to 4 months.
Cause pregnanediol interferes with bilirubin
conjugation.
Neonatal Cholestatic Jaundice

Etiology:
i. Idiopathic neonatal hepatitis most common cause
(50-60%).
ii. Extrahepatic biliary atresia 20 percent.
iii. 1-antitrypsin deficiency 15 percent.
Investigation:
Hepatobiliary imaging to differentiate between
intrahepatic and extrahepatic obstruction.
Liver biopsy giant hepatocytes with many nuclei.
Most specific investigation peroperative cholangiography.
Blood increased alkaline phosphatase, increased 5
nucleosidase, increased GGT (normal 5-40 IU/lit). GGT
is increased > 10 times in atresia and > 3 times in
neonatal hepatitis.
ASCITES
Ascitic Fluid
Differential diagnosis
Protein
Serum-ascites albumin
gradient (SAG)
Specific gravity
Exudate
Transudate
> 2.5 gm/dl
< 2.5 gm/dl
< 1.1 gm/dl

> 1.016
> 1.1 gm/dl

< 1.016
General Discussion
67
Etiology
a. Exudate
i. Pyogenic peritonitis
ii. Tubercular peritonitis
iii. Pancreatic ascites
iv. Malignancy.
b. Transudate
i. Cirrhosis of liver
ii. CCF
iii. Nephrotic syndrome
iv. Protein-losing enteropathy.
Diagnosis
Signs
Fluid thrill at least 2 liter of fluid should be
accumulated.
Shifting dullness -1 liter of fluid should be
accumulated.
Puddle sign can detect fluid as little as 120 ml.
USG best to detect minimal fluid.
Diagnostic paracentesis 50-100 ml of fluid is
aspirated.
1. Tuberculosis: Straw colored or hemorrhagic fluid,
exudative in nature, contains cells > 1000/mm3 (70%
of them are lymphocytes), confirmation of diagnosis
is by peritoneal biopsy.
2. Chylous ascites: Turbid, milky fluid with TG > 1000
mg/dl.
Cause: Lymphatic obstruction from trauma, tumor,
TB, filariasis, lymphoma, nephrotic syndrome.
3. Pancreatic ascites:
Cause: A leaking pseudocyst.
Exudate with increased amylase level in ascitic fluid.
4. Mucinous ascites: Pseudomyxoma peritonii due to
mucinous cystic tumors of ovary and appendix.
Colloid Ca of stomach or colon with peritoneal implant.
5. Meigs syndrome Ascites (Transudate) + hydrothorax
in a case of fibroma of ovary.
PseudoMeigs syndrome Brenners tumor of ovary.
68
RENAL FUNCTIONS
HEMATURIA
It means presence of intact RBC in urine.
Etiology
a. Surgical usually painless.
i. TB of kidney most common cause of hematuria.
ii. Renal cell carcinoma.
iii. Bladder stone terminal hematuria.
iv. Bladder Ca painless hematuria is the earliest and
most common symptom.
v. Renal trauma hematuria is the cardinal feature.
vi. Urethral rupture initial hematuria.
b. Medical causes
i. Acute glomerulonephritis most common medical
cause.
ii. Isolated hematuria IgA nephropathy, H-S purpura.
iii. HUS.
Diagnosis
Benzidine test.
Investigation
All cases of hematuria should be investigated.
Differential Diagnosis of Red Urine
Hemoglobinuria, myoglobinuria,
Ingestion of beet root, phenolphthalein,
Acute intermittent porphyria,
Drugs phenindione, clofazimine, rifampicin.
PROTEINURIA
Normal adults excrete 30-150 mg of protein per day of
which only 30 mg is albumin and remainder secreted
proteins by renal tubules (e.g. Tamm-Horsfall protein).
Proteinuria is mild (200-500 mg/day), moderate (500
mg/day to 2 gm/day) or massive (> 2 gm/day).
When it exceeds 3.5 gm/day, it is called nephrotic range.
General Discussion
69
Nephrotic range proteinuria is seen in nephrotic

syndrome (with edema) or multiple myeloma (without
edema).
Diagnosis: Albumin is detected by dipstick method.
URINARY CAST
1. RBC cast (with hematuria, subnephrotic proteinuria
and dysmorphic RBC) acute glomerulonephritis.
They are produced as RBC enters the tubules and
become trapped in cylindrical mold of Tamm-Horsfall
protein.
2. Hyaline cast usually normal, but also seen in prerenal azotemia.
They are formed in concentrated urine from the normal
constituents principally Tamm-Horsfall proteins.
3. Granular or tubular cast seen in acute renal failure.
They are pathognomonic of renal disease.
4. Waxy cast (degenerated cellular cast) seen in chronic
glomerulonephritis.
5. Broad cast seen in chronic renal failure.
6. White cell cast (with bacteruria) seen in pyelonephritis.
Note: Tamm-Horsfall protein is a normal protein
secreted by the epithelial cells of the loop of Henle.
URINE OUTPUT
Oliguria urine output < 400 ml in 24 hours.
Polyuria urine output > 3 liters in 24 hours.
MEDICAL DISORDERS DURING

PREGNANCY
PHYSIOLOGY
Weight Gain
Total weight gain during pregnancy = 11 kg.
In this, 50 percent (~ 6 kg) is reproductive weight gain
and 50 percent (~ 6 kg) is net maternal weight gain.
70
Hematological Changes
1. Blood volume: Increased to maximum 40 percent
at 3032 wks.
Plasma volume: Increased to maximum 50 percent
(Net 1.25 liters).
RBC volume: Increased to 20 30 percent - increased
O2 carrying capacity).
Due to disproportionate increase in plasma and RBC
volume, there is a state of hemodilution during
pregnancy. (Apparent in Hb concentration by 2% and
blood viscosity).
2. Protein: Total protein increased. But due to
hemodilution, plasma protein concentration falls from
7 to 6 percent.
Albumin decreased and Globulin increased.
Normal A: G ration of 1.7: 1 is decreased to 1:1.
3. Coagulation factors: Fibrinogen level increased by 50
percent.
ESR increased (4 fold increase).
All procoagulants are increased. Decreased
antithrombin III.
Increased activity of factors 2, 7, 8, 9 and 10.
Note: For above reasons, there is increased risk of
thromboembolism in pregnancy.
Decreased XI and XIII, increased plasminogen
activity.
CVS
4. Cardiac output: Increased to maximum 40 percent
at 2430 wks.
Clinical Feature:
Murmurs in pregnancy
i. Systolic murmur over apical/pulmonary area.
ii. Continuous hissing murmur over tricuspid area
mammary murmur.
3rd heart sound.
5. Blood pressure: Mid pregnancy drop to 100/70 mmHg
due to decreased peripheral resistance in pregnancy.
6. Regional circulation: To uterus is increased
from 50 ml (non-pregnant) to 750 ml near term.
Supine hypotension syndrome postural hypotension
during late pregnancy.
General Discussion
71
Metabolism
7. Protein: Positive nitrogen balance.
8. Carbohydrate: Maternal fasting hypoglycemia and
post-prandial hyperglycemia and hyperinsulinemia.
Glycosuria is normal in pregnancy.
9. Fat: increased FFA, triglycerides and ketone bodies.
Increased cholesterol and phospholipids.
10. Iron: Total iron requirement in pregnancy = 1000
mg.
Maximum: Requirement in 2nd half (67 mg/day).
11. Calcium: Daily requirement in pregnancy = 1 to 1.5
gm.
12. Kilocalories: Daily requirement 2500 (+300 from
non-pregnant state).
Renal
GFR is increased by 50 percent due to increased renal
plasma flow.
Respiratory System
VC unaltered, TV increased (+40%), RV decreased
(-20%)
Respiratory alkalosis compensated by mild acidosis.
Remember:
All are increased in pregnancy except Hb and plasma
protein (apparent fall), albumin and A:G ratio and BP,
antithrombin III.
HYPERTENSION IN PREGNANCY
Pregnancy Induced Hypertension
Pre-eclampsia
Definition:
BP > 140/90 mmHg
Edema and/or proteinuria
Pregnancy beyond 20 weeks.
Pathology: Characterized by widespread fibrin deposit due
to abnormality in endothelial integrity.
There is decreased synthesis of PGI2 (antiaggregatory
and vasodilator) from endothelium and increased sensitivity
72
to angiotensin II vasoconstriction, increased BP and

platelet aggregation.
Kidney: Fibrin deposit in basement membrane of
glomeruli.
Liver: Periportal hemorrhagic necrosis.
Blood: Hemolytic anemia, elevated LDH and low
platelets (HELLP syndrome).
Note: Physiological edema in pregnancy: Due to increased
venous pressure of the legs by gravid uterus pressing on
common iliac vein. Usually unilateral (more on night leg)
and disappears on rest.
Risk factors:
i. Primigravidae
ii. Family history
iii. Other medical disorders hypertension, hepatitis.
iv. Pregnancy complication like H. mole, multiple
pregnancy, hydramnios, Rh-incompatibility.
Clinical feature: Swelling over ankles in the morning.
Earliest sign: Rapid weight gain > 5 lb a month or 1 lb
a week.
Alarming symptoms Headache, epigastric pain, blurring
of vision due to retinal detachment.
Diagnosis:
Urine Proteinuria > 0.3 gm/lit in 24 hours.
Blood increased uric acid> 4.5 mg/dl (marker of
pre-eclampsia), increased BUN and increased
creatinine.
Increased serum LDH.
BP SBP > 30 mmHg or increased DBP > 15 mm
Hg.
Mean arterial pressure (DBP + 1/3 PP) > 90 mmHg.
If DBP>110, it is called severe PIH.
Prevention:
Low dose aspirin throughout pregnancy in high-risk
patients.
Screening test: Roll over test (at 28-32 wks).
Management:
Antihypertensive
Drugs used in pregnancy
General Discussion
73
- blockers.
- methyl dopa - drug of choice.
Hydralazine
Labetolol
Drug contraindicated ACE inhibitors.
Termination
Beyond 37 weeks.
Induction of labor by ARM - preferred method.
During labor IV ergotamine following delivering of
anterior shoulder is withheld.
Eclampsia
Definition
Pre-eclampsia complicated with convulsion and/or
coma.
Convulsion is generalized tonic-clonic in nature.
Cause: Cerebral anoxia.
Complication: Pulmonary edema (most common).
Types: Antepartum (most common), intrapartum,
postpartum within 48 hours of delivery.
Prognosis: Bad prognostic features are:
SBP > 200 mm Hg.
Oliguria and proteinuria > 5 mg/day.
Antepartum eclampsia.
Management :
a. Anticonvulsants
i. Lytic cocktail regime (of Menon) - modern regime.
Contains Chlorpromazine, Promethazine and
Pethidine.
ii. Magnesium sulphate regime (of Pritchard)
Therapeutic Mg level 4-7 mEq/l.
Monitoring is done by knee jerks, urine output and
respiratory rate.
Advantage: Least effect on neonates.
Single most effective drug.
iii. Diazepam (Lean)
iv. Phenytoin.
In status epilepticus Thiopentone sodium.
b. Obstetric: Termination to be done by ARM.
74
Gestational Hypertension
BP> 140/90 mmHg beyond 20 wks.

No features of pre-eclampsia.
Absence of any underlying cause.
BP returns to normal within 10 days following delivery.
CARDIAC DISEASE
Criteria for Diagnosis of Heart
Disease in Pregnancy
i. Diastolic murmur
ii. Loud systolic murmur with thrill.
Types
Rheumatic MS is the most common heart disease
in pregnancy.
Congenital ASD is the most common congenital
disease in pregnancy.
CCF in pregnancy occurs around 30 weeks.
Mitral Stenosis
Overall most common.
Treatment
Closed mitral valvulotomy (balloon valvuloplasty) may be
performed between 14-18 wks (Best time of surgery).
Open heart surgery is contraindicated.
Mitral Regurgitation
Well tolerated during pregnancy.
Aortic Stenosis
Worst heart disease in pregnancy.
It is a contraindication to pregnancy.
Maternal mortality of 15 percent with critical AS.
Pulmonary Hypertension
Contraindication to pregnancy.
Very high maternal mortality.
General Discussion
75
Eisenmenger Syndrome
High maternal and fetal mortality (maximum - 50%).
Treatment: S and E (absolute indication of abortion).
Pulmonary Stenosis
Well tolerated during pregnancy.
Coarctation of Aorta
Treatment: Elective CS.
Note: Contraindications to pregnancy
1. Critical AS
2. Pulmonary hypertension and Eisenmenger syndrome.
3. Marfans syndrome.
4. Chronic dilated cardiomyopathy with heart failure.
Management of Labour in Heart Disease
1. Prophylactic antibiotic.
2. Second stage: Forceps or ventouse at station O.
IV ergotamine is withheld.
3. Third stage: Oxytocin drip, IV frusemide.
Note: There is no indication of CS for heart disease. It is
done for obstetric indications, except Coarctation of aorta.
Note: Contraindications to prophylactic ergotamine:
1. Severe pre-eclampsia and eclampsia
2. Organic heart diseases
3. Suspected pleural pregnancy
4. Rh-negative mother.
DVT AND PULMONARY EMBOLISM
Causes of Increased Risk of
Thromboembolism in Pregnancy
1. Increased level of all coagulation factors (except XI
and XIII)
2. Decreased antithrombin III level
3. Decreased fibrinolytic activity.
Time
DVT is more common in postpartum (puerperium) period.
76
Management
During pregnancy IV Heparin.
[Note: Heparin does not cross the placenta. Warfarin
is contraindicated in pregnancy due to increased fetal
abnormalities (skeletal and facial anomalies)]
During puerperium
IV heparin for 7 to 10 days followed by warfarin for
36 months.
Note: Patient on oral anticoagulant should switch over
to heparin at 36 wks.
Phlegmasia Alba Dolens (Milk leg/White leg): Due to iliofemoral vein thrombophlebitis in pregnancy.
Anticoagulant in pregnancy:
Up to 12 weeks heparin,
1236 weeks warfarin,
36 weeks7 days postpartum heparin,
Lactation warfarin.
DIABETES MELLITUS
Pregnancy is diabetogenic because of:
i. Insulin resistance.
ii. Increased absorption of glucose from gut.
iii. Decreased peripheral utilization.
Glycosuria (due to decreased renal threshold) may be
normal in pregnancy.
Gestational Diabetes
This is pregnancy induced glucose intolerance.
Diagnosis: Screening Between 2428 weeks.
Method:
Fasting blood sugar levels after 50 gm oral glucose
load.
if 1 hr glucose level > 140 mg/dl.
100 gm oral glucose tolerance test is done after
overnight fasting.
A diagnosis of gestational diabetes is made if plasma
glucose level is
> 190 mg percent at 1 hour.
> 165 mg percent at 2 hours.
General Discussion
77
> 145 mg percent at 3 hour

(any 2 of above 3 values).
Potential candidates for screening:
Previous birth to a large baby
Recurrent fetal loss
Tendency to polyhydramnios.
Treatment: Diet and later insulin.
Overt Diabetes
This is pregnancy in a diabetic woman.
Complications:
Maternal
Polyhydramnios
Pre-eclampsia
Preterm labour
During labour - shoulder dystocia.
Fetal
1. Macrosomia.
2. Hairy pinna.
3. Congenital anomalies
i. Neural tube defects (anencephaly- most common
and microcephaly).
ii. Cardiac asymmetric VSD, transposition of great
vessels most common cardiac anomaly.
iii. Caudal regression - sacral agenesis most
characteristic.
Neonatal
1. Hypoglycemia - Due to hyperplasia and hypertrophy
of fetal islet cells increased fetal insulin.
2. Hypocalcemia
3. Polycythemia
4. Respiratory distress syndrome.
5. Hyperbilirubinemia
Long-term
1. Obesity
2. Diabetes
3. Mental retardation
4. Blindness.
Investigation: For early detection of fetal anomalies
1. Glycosylated HbA (HBA1C) estimation before 14 weeks
of gestation. A value > 9.5 percent suggests increased
risk.
78
2. Maternal serum -FP at 16 weeks. To detect neural

tube defects. (-FP level is increased).
3. USG at 20 weeks to detect cardiac anomalies
investigation of choice.
Treatment:
Target PP blood glucose level < 140 mg/dl.
Agent Soluble insulin is the agent of choice because
it does not cross placenta and insulin demand is
increased in pregnancy.
Note: Oral hypoglycemic agents are contraindicated
in pregnancy.
Termination of pregnancy after 37 weeks (because
chance of IUFD is increased beyond that period) by
CS.
- agonists should be avoided as tocolytics in diabetes.
Contraception:
Barrier method is ideal.
Progesterone only pill.
Glycosuria in Pregnancy
Diagnosis: Second fasting morning specimen of urine is
tested for glucose.
Glycosuria on 1 occasion before 20th week and on
2 or more occasions thereafter is an indication for oral
GTT.
Diabetes Insipidus in Pregnancy
Associated with:
1. Pre-eclampsia
2. Oligohydramnios
3. Hepatic dysfunction.
ANEMIA IN PREGNANCY
Definition
(WHO) Hb 11 gm percent,
In India, the value is 10 gm percent.
Type: Most common type of anemia in India is Dimorphic
type due to combined deficiencies of iron, folic acid and/
or vitamin B12.
Characterized by anisocytosis (micro + macrocytosis)
and hypo/normochromia.
General Discussion
79
Iron Deficiency Anemia

Total iron requirement during pregnancy is 1000 mg.
This is mostly needed in second half of pregnancy when
daily requirement of iron is 67 mg.
Anemia: Microcytic hypochromic.
Diagnosis:
MCHC < 30 percent
MCV < 75 m3
MCH < 25 pg
Decreased serum iron, decreased ferritin, increased
TIBC.
Complications:
1. Pre-eclampsia.
2. Intercurrent infection
3. Heart failure
4. Postpartum hemorrhage.
Prophylaxis: 200 mg FeSO4 (60 mg elemental iron) + 0.5
mg (500 g) folic acid daily.
Treatment: Tab. Fersolate (FeSO4) 200 mg (60 mg
elemental iron) - 1 tab 3 times daily with or after meals.
Megaloblastic Anemia
Folate deficiency is the main cause.
Daily requirement during pregnancy 300 g (normal
50 g)
Prophylaxis: 400 g daily
Treatment: 5 mg oral daily with supplementary iron with
or without IM vitamin B12 100 g/day.
Thalassemia
Prenatal diagnosis:
1. Amniocentesis (between 1416 weeks) by amniotic
fluid fibroblasts.
2. Chorion-villus biopsy (between 1012 weeks) by
trophoblasts.
3. Cordocentesis (after 18 weeks) by fetal blood.
80
JAUNDICE IN PREGNANCY
Cause
1. Viral hepatitis most common (most commonly due
to Hepatitis B).
2. Intrahepatic cholestasis.
3. Acute fatty liver of pregnancy.
Viral Hepatitis
Hepatitis B
Most common cause. (Others HDV and HCV in
association with HIV).
Risk of transmission to fetus 10 percent in first
trimester, 90 percent in third trimester.
Chance of transmission is more in HBsAg +ve mother
who are also HBeAg +ve.
Mode of transmission During the time of delivery.
Hepatitis E Associated with high internal mortality during
pregnancy.
Intrahepatic Cholestasis
Second most common cause.
Clinical feature:
Usually appear in last trimester.
Generalized pruritus is the main symptom.
Diagnosis:
Bilirubin < 5 mg percent
Markedly increased alkaline phosphatase level.
Increased AST and ALT (not more than 60 U).
Prognosis: Tends to recur in subsequent pregnancies.
Acute Fatty Liver
Microvesicular.
Diagnosis:
Bilirubin > 10 mg/dl.
Increased ALT and AST,
Increased PT.
General Discussion
81
THYROTOXICOSIS IN PREGNANCY
Management:
a. Medical Propylthiouracil is the drug of choice.
b. Surgery thyroidectomy may be done.
I131 is absolutely contraindicated.
GI TRACT
There is increased chance of cholesterol gallstones in
multiparae.
Pregnancy may cause a flare up of symptoms of
inflammatory bowel diseases.
Acute appendicitis Laparotomy should be done at
the earliest opportunity.
RENAL DISEASES
Asymptomatic Bacteriuria
Definition: Bacterial count > 105/ml in midstream
specimen of urine on two occasions without symptoms
of infection.
Incidence: 210 percent
Cause: E. coli is the most common organism.
Risk factor: Urinary tract abnormality.
Treatment: Ampicillin 500 mg QID.
Prognosis: Risk of developing chronic renal lesion in later
life.
Acute Pyelonephritis
Predisposing factors:
i. Asymptomatic bacteriuria
ii. Abnormality in renal tract.
iii. Stasis of urine.
Causative organism: E. coli (most common).
Note: Renal disorders associated with worst pregnancy
outcome are PAN and scleroderma.
82
INFECTIONS
Bacterial
1. UTI:
Most common infection during pregnancy.
Most common causative organism is E. coli.
2. Syphilis: Transplacental transmission can occur at any
stage of pregnancy, but more common in early stages.
3. Gonorrhea: Ophthalmia neonatorum occurs as a result
of infection of the fetus during delivery.
4. Gr. B streptococcus:
Most common cause of postpartum bacteremia.
5. Streptococcus pyogenes: Most common cause of
epidemic puerperal sepsis.
Viral
1. CMV most common cause of congenital viral
infection.
2. Rubella most serious viral infection in pregnancy,
produces maximum congenital abnormalities.
Most serious and maximum transmission occurs in first
trimester (Maximum in first 5-6 weeks).
Rubella vaccine is contraindicated in pregnancy.
3. HSV Mainly HSV II.
Transmission occurs during delivery.
Active HSV infection is an indication of elective CS.
Drug Acyclovir
(Indications Disseminated herpes, Chickenpox in 1st
trimester, prophylaxis in recurrent herpes.)
Neonatal infection may be
Disseminated (fatal) or
Localized (involvement of CNS, eye, mucosa)
4. HIV
Rate of transmission from mother to fetus or infant
is 30 percent.
Routes
i. Transplacental transfer
ii. Contaminated secretion and blood during delivery.
iii. Colostrum and breast milk.
Antibody testing is of limited value in infants.
5. Hepatitis B See above.
General Discussion
83
6. Chickenpox Highest risk in case of delivery within

1 week before or after the onset of maternal varicella.
Varicella zoster causes cicatrical skin lesions, limb
hypoplasia, and rudimentary digits.
Protozoal
1. Toxoplasmosis: 1st trimester lowest chance of
infection but maximum risk of fetal abnormalities.
3rd trimester highest chance of transmission but
asymptomatic in children.
The fetus is at risk only if the mother is sero-negative
2. Malaria :
Treatment: Chloroquine is the drug of choice.
Fungal
1. Candida albicans: Vulvovaginal candidiasis is more
common during pregnancy than non-pregnant state.
Note: Infections transmitted during delivery
1. Gonorrhea
2. HSV
3. Hepatitis B.
VACCINES
Contraindicated in Pregnancy
Live attenuated vaccines - Rubella, Measles, Mumps and
Varicella, Meningococcal vaccine, Typhoral.
Safe in Pregnancy
Toxoids (TT and DT), Polio, Yellow fever and inactivated
vaccines HBV, Influenza, and Pneumococcal vaccines.
Breastfeeding
Is not a contraindication to any vaccine.
SLE
a. Effect of pregnancy on SLE: May flare-up.
b. Effect of SLE on pregnancy: First trimester abortion,
lupus nephritis, recurrent DVT. PIH, prematurity, IUGR,
stillbirth.
84
c. Effect on neonate Hemolytic anemia, leukopenia,

thrombocytopenia isolated congenital heart block.
EPILEPSY
Frequency may be increased in 45 percent cases, mostly
in 1st trimester.
Treatment
Drugs contraindicated in pregnancy are:
1. Phenytoin Produces cleft lip and /or palate,
microcephaly, mental retardation, cardiac anomalies,
limb defects hypoplasia of the terminal phalanges.
2. Valproate Produces neural tube defect.
3. Carbamazepine Increased incidence of neural tube
defect.
Note: Drug safe in pregnancy is phenobarbitone.
Effect of Epilepsy on Pregnancy
More chance of stillbirth.
PUBERTY AND ADOLESCENCE

Time Period
Puberty 1016 years.
Adolescence 1021 years.
PUBERTY
Changes during Puberty
In
1.
2.
3.
4.
females
Thelarche (Development of breast) 10 years.
Puberche (Development of hair) 11 years.
Adolescent growth spurt
Menarche (First menstruation) - 13 years.
Note: Ability to be pregnant develops 12-24 months after

menarche.
Maximum growth spurt in girls is seen at menarche.
Peak height = Stage III thelarche/puberche.
Peak weight = Stage IV thelarche/puberche.
General Discussion
In
85
males
Growth in testicular volume- 11 years.
Pubic hair 12 years.
Axillary hair
Beard 16 years.
Sexuality
Homosexual experimentation is normal during adolescence.
Precocious Puberty
For girls who show thelarche < 8 years or menarche
< 10 years of age (for boys puberty <9 years).
Cause:
1. Constitutional most common cause.
2. Hypothyroidism
3. Intracranial tumor, trauma, hypothalamic hamartomas.
4. Gynaecological Granulosa cell tumor, estrogen or
androgen intake.
5. McCune Albright syndrome
6. Congenital adrenal hyperplasia in males.
Delayed Puberty
For girls who does not have breast development and/or
pubic hair by 13 years or menarche by 16 years.
Causes:
1. Hypopituitarism
2. Hypothyroidism
3. Anorexia nervosa.
McCune Albright Syndrome
Precocious puberty, polyostotic fibrous dysplasia, cystic
degeneration of long bones, caf au lait spots.
Adolescent Mortality and Morbidity
Most common cause of mortality is violence (especially
accidents).
Most common cause of morbidity is substance abuse.
86
Medico Legal Aspects

1. Criminal responsibility :
Age < 7 years no responsibility
<12 years cannot give valid consent
>18 years can give valid consent
2. Rape
Section 375, IPC.
< 15 years even if she is his own wife, <16 years
even with her consent,
3. Employment
The Factories Act, 1948
< 14 yrs Cannot be employed
1518 yrs- termed as adolescent.
4. Attainment of majority 18 years (can cast vote).
5. Marriage
18 years in females.
21 years in males.
Juvenile Delinquency
Offense by a juvenile defined as:
A boy < 16 years or a girl < 18 years.
No juvenile can be imprisoned or sentenced to death.
They are sent to juvenile homes.
Brostal for boys over 16 years.
GERIATRIC MEDICINE
Geriatric deals with people over 65 years.
Biology of Aging
Theories
1. Pleotrophic antagonism.
2. Random damage (by free radicals).
3. Telomer shortening.
4. Wear-and-tear theory.
Changes in Old Age
All are decreased with age except
ADH secretion, body fat, autoantibodies, chondroitin
sulphate in cartilages, residual volume, SBP, pulse
pressure increased
Not changed with age Hematocrit.
General Discussion
87
Diseases of Old Age

Most common problem in old age is visual impairment.
There is increased incidences of
Bone and joint disorders, Cardiovascular disorders,
Neurological disorders, Respiratory disorders,
Malignancy.
Progeria or Accelerated Aging
Seen in
Werner syndrome, Cockayne syndrome, Ataxia
telangiectasia, cutis laxa.
Epidemiology
Population over 65 years in India 3.8 percent.
Note: Life expectancy at birth in India
Male 62.8 years.
Female 63.8 years.
GASTROINTESTINAL
SYSTEM
ESOPHAGUS
ANATOMY
Length of the esophagus is approximately 25 cm (10 inches).
It extends from the lower border of the cricoid cartilage,
opposite the sixth cervical vertebra to the cardiac orifice
of the stomach, opposite the eleventh thoracic vertebra
(C6-T11).
Constrictions
Blood supply
Constrictions of esophagus
Site
1.
2.
3.
4.
Level
Cricopharyngeal sphincter
Crossing of arch of aorta
Crossing of the left bronchus
Cardiac end
C6
T4
T5
T10
Distance from upper

incisor (cm)
15
25
27
40
Cricopharyngeus sphincter is the narrowest point of

the gastrointestinal tract in adults; whereas subcricoid region
is the narrowest part in children.
i. Inferior thyroid arteries cervical part.
ii. Esophageal branches of aorta thoracic part.
iii. Esophageal branches of left gastric artery abdominal part.
iv. Others inferior phrenic artery, bronchial artery.
CONGENITAL ANOMALIES
Tracheoesophageal Fistula
Incidence: 1 in 4000 live births.
Etiology: Failure of caudal growth of tracheoesophageal
septum.
Gastrointestinal System
89
Types: 5 types1. Upper end is blind (proximal esophageal atresia) and

lower end of esophagus communicates with trachea
(distal TE fistula) - most common variety (85%).
2. Both ends open into the trachea - least common.
Clinical features:
1. Continuous drooling of saliva - the sign.
2. Choking and cyanosis.
Esophageal atresia may occur as a part of the VATER
or VACTERL group of anomalies.
V = Vertebral body segmentation defects
A = Anal atresia
C = Cardiovascular anomaly (PDA, ASD)
TE = Tracheoesophageal fistula
R = Unilateral renal agenesis
L = Radial ray hypoplasia.
Diagnosis:
Antenatal absent stomach bubble in USG.
Postnatal air bubble in stomach in X-ray.
Diagnosis is confirmed by passing a semi-rigid
nasogastric tube followed by X-ray that shows obstruction
if TE atresia is present as well as the level of the obstruction.
Dysphagia Lusoria
Dysphagia produced by compression of the esophagus by
vascular anomalies.
Etiology:
1. Vascular rings, such as double aortic arch- most
common cause.
2. Aberrant right subclavian artery.
ESOPHAGEAL RUPTURE
Etiology
1. Iatrogenic- due to instrumentation- most common
cause. Instrumental perforation is most common at
the pharyngoesophageal junction.
2. Boerhaaves syndrome- spontaneous rupture due to
increased intraesophageal pressure associated with
forceful vomiting or retching.
3. Esophageal diseases- corrosive poisoning, ulcer,
neoplasm.
90
Mallory-Weiss syndrome
Etiology: Vigorous vomiting (common in alcoholics,
pregnant females).
Pathology: Vertical tear which involves the gastric mucosa
just below the squamocolumnar junction at the cardia.
Clinical feature: A history of emesis followed by either
melena or hematemesis (which is usually not severe).
INFLAMMATORY DISORDERS
Gastro-esophageal Reflux Disease (GERD)
Factors preventing gastro-esophageal reflux:
1. Esophago-gastric angle
2. Pinchcock action of the right crus of diaphragm
3. Rosette like folds of mucous membrane at the cardia.
Etiology: Incompetence of the lower esophageal sphincter
(LES) causing gastro-esophageal reflux.
Clinical features:
1. Retrosternal burning pain (heartburn) and epigastric
pain which is aggravated by fatty foods (fatty
dyspepsia)most common.
2. Dysphagia (due to peptic stricture) and odynophagia
(painful swalloing).
3. Recurrent pulmonary aspiration may cause aspiration
pneumonia.
Diagnosis:
1. Endoscopy may show reflux esophagitis, peptic
stricture or Barretts esophagus.
2. Manometry to exclude achlasia.
3. 24 hours pH recording gold standard.
4. Barium swallow Xray.
5. Bernstein test acid infusion test.
Treatment:
a. Medical- includes antiemetics (metoclopramide), PPIs
(omeprazole).
b. Surgery- total (described by Nissen) or partial
fundoplication (laparoscopic).
Pill-Induced Gastritis
Cause: Antibiotics such as doxycycline, tetracycline and
clindamycin.
91
Barretts Esophagus
Pathology: Replacement of normal squamous epithelium
of esophagus by columnar epithelium.
Etiology: Reflux esophagitis.
Complication:
1. Columnar epithelium represents a type of intestinal
metaplasia which predisposes to adenocarcinoma
of the lower 1/3 rd of esophagus in 2-5 percent
cases.
2. Peptic ulcer and stricture.
Infectious Esophagitis
Causes of infectious esophagitis
In immunocompetent persons
HSV 1
Varicella-zoster virus
Candida
In immunocompromised patients
HSV 1or 2
Varicella-zoster virus
Candida
CMV only in immunocompromised patients
MOTILITY DISORDERS
Achalasia
Definition: A motor disorder of esophageal muscle in which
the LES does not relax properly with swallowing.
Pathology: Cause - destruction of Auerbachs (myenteric)
plexus in proximal dilated segment.
Abnormalities i. Incomplete or absent relaxation of LES
ii. Absent peristalsis of the body of esophagus the
proximal esophagus becomes dilated
(megaesophagus) and tortuous.
Clinical features: Affects both sexes at all ages (commonly
between third and fifth decades).
1. Dysphagia To both liquid and solid (more to liquid)
2. Regurgitation Aspiration pneumonia.
Diagnosis:
1. Chest X-ray shows widening of mediastinum and
a posterior mediastinal air-fluid level.
92
2. Barium swallow Shows dilated esophagus with a

tapering end at distal esophagus birds beak
deformity.
3. Manometry Most diagnostic.
Mecholyl test: Administration of cholinergic muscarinic
agonist mecholyl causes a marked increase in baseline
esophageal pressure. (Normal LES pressure is 10-25 mm
Hg.)
Findings on manometry:
i. Hypertensive LES that does not relax completely on
swallowing.
ii. Aperistlasis of the esophageal body.
iii. Increased pressure of esophagus.
Treatment:
1. Botulinum toxin maximum chance of recurrence.
2. Drugs nifedipine or nitroglycerine.
3. Balloon dilation.
4. Hellers myotomy (esophagomyotomy).
Prognosis: May lead to malignancy.
Diffuse Esophageal Spasm
Diffuse esophageal spasm is characterized by nonperistaltic
contractions, usually of large amplitude and long duration
which on Barium swallow X-ray shows Corkscrew
esophagus (multiple sacculations and pseudodiverticulae
in the wall).
Clinical feature: intermittent chest pain, non-progressive
dysphagia to both solids and liquids.
Diagnosis: Manometry is diagnostic.
An esophageal motility pattern showing hypertensive
but peristaltic contractions has been called nutcracker
esophagus.
Scleroderma of Esophagus
Pathology: Weakness of lower 2/3rd of esophagus and
incompetence of the LES.
Clinical features:
i. Dysphagia to liquids.
ii. Heartburn and regurgitation due to reflux esophagitis.
93
Diagnosis: Barium swallow X-ray dilated esophagus with

loss of peristaltic movement in the middle and distal portion
of the esophagus.
OTHER DISORDERS
Zenkers Diverticulum
Pathology: It is a pseudodiverticulum due to protrusion
through the natural weak point between the oblique and
horizontal fibers of inferior constrictor muscle (pulsion
diverticulum).
Clinical features:
1. Halitosis and regurgitation of food particles consumed
several days earlier.
2. Dysphagia and complete obstruction due to impaction
of food.
3. Lung abscess most common complication.
Treatment: Cricopharyngeal myotomy with or without
diverticulectomy.
Plummer-Vinson (Paterson-Brown Kelly)
Syndrome
Components: Hypopharyngeal webs, Iron deficiency
anemia, Angular stomatitis, Glossitis and Koilonychia.
Clinical features: Common in middle aged women.
Dysphagia (more to solids): main symptom.
Treatment: Large doses of iron and vitamins.
Prognosis: Pre-cancerous lesion (malignancy in post-cricoid
region).
Hiatus Hernia
Sliding hernia: The gastro-oesophageal junction and fundus
of the stomach slide upwards during increased intraabdominal tension most common type.
Paraesophageal (rolling) hernia: The gastro-oesophageal
junction remains in its normal position, but the pouch of
stomach rolls into the chest through esophageal
opening.
Clinical feature:Chest pain with respiratory distress.
X-ray: A gas bubble, often with a fluid level behind the
heart.
94
Complications: Volvulus, perforation and gangrene.

Diagnosis: Barium swallow is the best investigation.
Treatment: Always surgical.
ESOPHAGEAL TUMORS
Please see the chapter of oncology.
PHYSIOLOGY OF GI TRACT
DIGESTION
Digestive Enzymes
Source
Enzyme
Substrate
Products
-Amylase
Starch
Dextrins, maltose,
(rich in K +)
maltotriose
Pepsinogen(activated Protein and Cleaves peptide
by HCl to pepsin)
polypeptides bond adjacent
by chief cells
to aromatic amino
acid ( 1-4)
trypsin

Lipase
Triglycerides Fatty acid + glycerol
Proteins and Basic amino acids
Trypsinogen
enteropeptidase
polypeptides (arginine and lysine)

trypsin
lit
Chymotrypsinogen
Do
Aromatic amino
acids
chymotrypsin
Lipase
Triglycerides Monoglycerides
+ fatty acids
A number of
Polypeptides Amino acids
peptidases
Maltase
Maltose
Glucose
Lactase
Lactose
Glucose + galactose
Sucrase
Sucrose
Fructose + glucose
Saliva
pH = 7
Stomach
pH = 1.5
Exocrine
pancreas
pH = 8
Vol.=1.5
Small
intestine
Parietal cells (oxyntic cells) secrete HCl and intrinsic

factor.
Rennin (chymosin) is present in the stomach and it
coagulates milk.
Endopeptidases are pepsin, trypsin, chymotrypsin
and elastase. They break peptide bonds within a protein.
Serine proteases are trypsin, chymotrypsin, elastase.
(Note - 1 antitrypsin is a serine protease inhibitor).
95
Site of Digestion
Food
Site of digestion
Carbohydrate
Protein
Fat
Mouth and small intestine

Stomach, small intestine
Stomach (mostly by lingual lipase), duodenum
(mostly by pancreatic lipase)
ABSORPTION
1. Carbohydrate:
Site: Small intestine, mainly as hexoses.
Glucose is co-transported with Na+ by a symport called
sodium-dependant glucose transporter (SGLT). This
is a type of secondary active transport.
Glucose is also transported by facilitated diffusion by
GLUT 2 (this occurs in renal epithelium, too)
2. Proteins:
Site: mainly duodenum and jejunum (also ileum)
3. Fat:
Site: long chain fatty acids are mainly absorbed from
jejunum (also in ileum). Short chain fatty acids are
absorbed from colon.
4. Vitamins:
All vitamins are absorbed mainly from jejunum except
Vit B12 which is absorbed from terminal ileum.
5. Water and electrolytes:
i. Fluid (7000 ml secreted per day) 98 percent
reabsorbed.
ii. Na+ - upper and lower intestine, colon.
iii. Ca++ - upper intestine.
iv. Fe++ - upper intestine.
6. Bile salts:
Site: terminal ileum.
Sites of Absorption
Sites of absorption
Upper intestine
(jejunum)
Mid intestine
Terminal
intestine
Colon
All vitamins,
long chain
fatty acids and
electrolytes,
iron, calcium
Sugars,
aminoacids
Bile salts,
Vit B12,
Na +
Na + (water), short
chain fatty acids
K+ and HCO3- are
secreted in colon
(K+ content 30
mEq/lit.)
96
REGULATION OF GI FUNCTION
The Enteric Nervous System
Consists of:
1. Myenteric (Auerbachs) plexus in between outer
longitudinal and inner circular muscle layer.
2. Submucous (Meissners) plexus between circular
muscle and the mucosa.
Extrinsic Innervation
1. Parasympathetic cholinergic system - intestinal
smooth muscle tone and relaxation of sphincter
emptying.
2. Sympathetic system - smooth muscle tone with
contraction of sphincters retention.
Basic Electrical Rhythm (BER)
Pacemaking of G.I. tract, produced by interstitial cell of
Cajal (mainly at the fundus).
Migrating Motor Complex (MMC)
Cyclic motor activity that migrates from stomach to distal
ileum during fasting.
Peristalsis
Rate 2 to 25 cm/sec.
Regulation of Peristalsis:
By Myenteric plexus
antero
grade
cholinergic
fibers
retrograde
substance
cholinergic fibres
P and ACh
contraction behind the stimulus.
NO, VIP and ATP relaxation ahead of stimulus

GASTROINTESTINAL HORMONES
Gastrin
Gastrin occurs in 3 forms viz. G17, G14 and G34. G17
is the principal form that mediates gastric acid secretion.
97
Source:
1. G cells in the gastric antrum.
2. Pancreatic islets in fetal life.
3. Anterior and intermediate lobes of the pituitary gland.
Action:
1. Stimulation of gastric acid and pepsin secretion.
2. Stimulation of the growth of mucosa of the stomach
and intestine (trophic action).
3. Stimulation of gastric motility.
(Note: Normal acid level in stomach 15-20 mEq)
Regulation:
Secretion increased by
Secretion decreased by
1. Gastric content peptides

and amino acids
2. Gastric distension
3. Neural - vagal
discharge GRP
4. Blood-borne Ca++,
Epinephrine
1. Luminal acid, somatostatin

2. Blood-borne secretin,
glucagon, VIP, GIP
Cholecystokinin Pancreazymin (CCK)

Source:
1. J cells in the mucosa of upper intestine (jejunum).
2. Nerves in the distal ileum and colon.
Action:
1. Contraction of gallbladder.
2. Secretion of pancreatic juice rich in enzymes
3. Augmentation of action of secretin to produce alkaline
pancreatic juice.
4. Inhibition of gastric emptying.
Regulation:
Secretion increased by:
1. Peptides and amino acids best stimulant.
2. Fatty acids containing more than 10 C atoms.
Secretin
First hormone to be discovered by Bayliss and Starling.
Source: S cells located deep in the glands of the mucosa
of the upper small intestine (duodenum).
Action:
1. Increases secretion of HCO3 watery alkaline
pancreatic juice low in enzymes.
98
2. Augments the action of CCK.

3. Decreases gastric acid secretion and may cause
contraction of pyloric sphincter.
Regulation:
Secretion increased by products of protein digestion and
by acid bathing the gastric mucosa (acid chime).
Somatostatin
Action: Decreases gastrin and gastric acid secretion.
REGULATION OF GASTRIC SECRETION
1. Cephalic phase: Mediated by vagus nerve gastrin
by GRP
ACh
acid and pepsin
So this phase is mostly affected by vagotomy.
2. Gastric phase: Mediated by
i. Local neuronal reflex responses
ii. Gastrin
3. Intestinal phase: Mediated by neuronal and hormonal
mechanisms.
Control fats, carbohydrates and acid in duodenum
inhibit gastric acid and pepsin secretion and decrease
gastric motility.
REGULATION OF GASTRIC MOTILITY
AND EMPTYING
1. Type of food: Fatty foods decrease gastric motility.
2. Osmolality: Hyperosmolality in duodenum decreases
gastric emptying.
3. Enterogastric reflex:
Action: Decreases gastric motility.
Initiated by:
i. Products of protein digestion and H+
ii. Distension of duodenum
4. Gastroileal reflex: When food leaves the stomach,
caecum relaxes and passage through ileocaecal valve
is increased. It is associated with mass peristalsis.
5. Gastrocolic reflex: Distension of stomach by food
initiates contraction of rectum and a desire to
defecate.
99
STOMACH AND INTESTINE

ANATOMY
Size
Mean capacity of stomach at birth is one ounce (30 ml).
In adults 1 2 lit.
Stomach bed
It is formed by
i. The diaphragm
ii. Left suprarenal gland
iii. Splenic artery
iv. Left kidney
v. Pancreas
vi. Splenic flexure of colon
vii. Transverse mesocolon
(Mnemonic: Dr Sunil Sen Kills Patients Cruelly and
Mercillessly).
Duodenum
First part: Posterior relations are portal vein, bile duct
(right) and hepatic artery (left).
Third part: 10 cm long. Anterior relations are superior
mesenteric artery, root of mesentery. Posterior relations
are IVC and aorta.
Arterial supply:
Part above the opening of CBD by superior
pancreaticoduodenal artery.
Part below that by inferior pancreaticoduodenal
artery.
First part of duodenum is also supplied by right gastric
artery, supraduodenal artery and retroduodenal
branches of gastro-duodenal artery.
Duodenal fossa
Paraduodenal fossa Lodges the inferior mesenteric
vein.
PEPTIC ULCER
Duodenal Ulcer
Site: more than 95 percent of duodenal ulcers occur in
the first part of the duodenum.
100
Etiology: rare before the age of 16 years.

1. H. pylori infection.
2. Blood group O.
3. Cigarette smoking.
4. NSAIDs.
Pathology: Kissing ulcer the situation in which there
is both a posterior and an anterior duodenal ulcer.
Anteriorly placed ulcers tend to perforate.
Posteriorly placed ulcers tend to bleed due to erosion
of vessels like the gastroduodenal artery.
Diagnosis:
1. Barium meal X-ray discrete craters in proximal
duodenum Trifoliate deformity.
2. Upper GI endoscopy most accurate
3. Investigations for detection of acid production
i. Pentagastrin test best method.
ii. Kays augmented histamine test size of oxyntic
cell mass.
iii. Hollanders insulin test.
Treatment: Primary aim is to prevent complication.
1. For H. pylori infection
A. Standard triple therapy contains Bismuth
salicylate, Tetracycline and Metronidazole for 2
weeks.
B. Triple therapy with acid reduction Omeprazole,
Clarithromycin and Metronidazole or Amoxicillin
for 1 week.
2. Prostaglandins
Misoprostol is used for analgesic induced gastritis.
Side effects causes uterine contraction, so
contraindicated in women of childbearing age.
Gastric Ulcer
Site: more common on the lesser curvature, especially at
the incisura angularis.
Malignancy: gastric ulcers can turn malignant ulcer cancer
(cf. cancer ulcer or ulcerative cancer).
Diagnosis: by four quadrant biopsy (if all the quadrants
show malignancy then it is a cancer ulcer).
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Hour glass stomach: Due to cicatrical contraction of a

saddle-shaped ulcer at the lesser curvature.
Surgery for Peptic Ulcer
Rational for surgery: Aim is to exclude the damaging effects
of acid on duodenum. This has been achieved by
1. Diversion of acid away from duodenum Billroth I
and II operations.
2. Reducing the secretory potential of stomach
vagotomy.
3. Both.
Types:
1. Billroth I - gastric resection with gastroduodenal
anastomosis.
2. Billroth II- gastric resection with gastrojejunal
anastomosis.
Complication leakage from duodenal stump occurs
on 6th day (duodenal blow out due to avascular
necrosis of stump).
3. Gastrojejunostomy
It is the most commonly performed operation.
It causes a clean contaminated wound.
It has the maximum chance of recurrence.
4. Truncal vagotomy and drainage (of Dragstedt).
Drainage pyloroplasty.
5. Highly selective vagotomy - only the parietal cell mass
is denerveted.
No drainage operation is needed.
Most satisfactory operation for duodenal ulcer.
It has the least mortality rate.
Nerves of Laterjet supplying the antrum are preserved.
Complication recurrent ulcer.
6. Truncal vagotomy and antrectomy least chance of
recurrence. Maximum reduction of acidity.
Useful in recurrent ulcer.
(Note: Completeness of vagotomy is tested by
Hollanders test).
Complications of Surgery
1. Gastrojejunal and gastrocolic fistula: patient suffers from
diarrhea which is severe and follows every meal
following gastrojejunostomy.
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2. Afferent loop syndrome:

Cause: Billroth II operation
Clinical feature: abdominal bloating and pain 20
minutes to 1 hour after eating followed by nausea and
vomiting containing bile, which relieves the discomfort.
3. Dumping syndrome (Post cibal syndrome):
Cause: gastrectomy or vagotomy and drainage.
Early dumping: abdominal and vasomotor symptoms
(like palpitation, tachycardia, light headedness)
following 30 minutes after meal.
Etiology: rapid emptying of hyperosmolar gastric
contents into proximal small intestine.
Late dumping: occurs 90 minutes to 3 hours after eating
meals rich in carbohydrates.
Treatment:
i. Dietary measures limitation of sugar containing
foods and liquids.
ii. Frequent small meals.
iii. Somatostatin analogue octreotide.
4. Postvagotomy diarrhea.
5. Anemia:
Iron deficiency: most often with Billroth II.
Vitamin B12 deficiency: most common after total
gastrectomy.
(Note:Fat laden cells are seen in post-gastrectomy).
6. Anastomotic hemorrhage: after truncal vagotomy and
gastrojejunostomy.
7. Gallstone: after truncal vagotomy.
Complications of Peptic Ulcer
1. Peptic perforation:
Most common site anterior aspect of duodenum.
Chest X-ray shows gas under diaphragm.
Prognosis depends on age, duration of history,
peritonitis.
2. Hematemesis and Melena: Most common cause of
death in peptic ulcer.
3. Gastric Outlet Obstruction:
Cause
i. Pyloric stenosis secondary to peptic ulceration.
ii. Gastric cancer most common cause.
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Most common site: first part of duodenum.

Clinical feature: vomiting which is devoid of bile.
Metabolic changes: Hypochloremic, hypokalemic
(hyponatremic) metabolic alkalosis with paradoxical acidic
urine.
Management: Rehydration with IV NS and K +
supplementation.
Surgery: Truncal vagotomy with gastrojejunostomy.
GASTRITIS
Chronic Gastritis (Atrophic)
Stages:
1. Superficial gastritis
2. Atrophic gastritis
3. Gastric atrophy
Type A (Autoimmune Gastritis)
Cause: Autoantibodies against parietal cells.
Site: Fundus and body of stomach.
Pathology:
Atrophy of parietal cell mass production
of IF Pernicious anemia
Hypochlorhydria and achlorhydria
High level of gastrin from antral G cells (hypergastrinemia)
Hypertrophy of ECL cells of stomach
Carcinoid tumors
Diagnosis: Pentagastrin fast achlorhydria seen in

pernicious anemia.
Type B Gastritis
Cause: H. pylori infection.
Site: Antrum of stomach.
But in developed countries, pangastritis is more
common more prone to malignancy.
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Mntriers Disease
Characterized by large, tortuous gastric mucosal folds due
to massive foveolar hyperplasia increased mucus
production and hypochlorhydria.
Clinical feature:
Protein losing gastropathy hypoproteinemia
Anemia
It is a premalignant lesion.
NON-GASTRITIS EPITHELIAL CELL INJURY
Erosive Gastropathy
Stress Related Mucosal Injury
Features: Multiple, mostly in fundus.
Causes:
i. Mechanical ventilation
ii. Coagulopathy
iii. Sepsis and multiorgan failure
iv. Curlings ulcer
Cause: Massive injury, burn
Clinical feature: Painless GI hemorrhage
Diagnosis: Upper GI endoscopy shows superficial
erosions on gastric mucosa.
v. Cushings ulcer
Cause: Intracranial injury,
Increased intracranial tension (brain tumor, subdural
hematoma)
Clinical feature: Hemorrhage and perforation.
Sites: Esophagus, stomach and proximal duodenum.
Other Erosive Conditions
1. NSAIDs (particularly aspirin) produce hemorrhagic
erosive gastropathy most common cause.
2. Alcohol.
PEDIATRIC DISODERS
Hypertrophic Pyloric Stenosis
Pathology: Hypertrophy of the circular musculature of the
pylorus and adjacent antrum.
105
Clinical features: First-born male child is most commonly

affected. Seen within 4 weeks after birth.
Symptoms: Vomiting which is forcible and projectile
without bile.
Weight loss.
Sign: Visible peristalsis in upper abdomen.
Palpable hypertrophied pylorus: most important clinical
feature.
Metabolic effects: like GOO.
Diagnosis:
USG investigation of choice; pyloric canal appears
> 14 mm.
Treatment:
1. Rehydration with DextroseNS with K+ supplementation.
2. Ramstedts operation pyloromyotomy.
Note: Treatment of adult pyloric stenosis is pyloroplasty.
Duodenal Atresia
Most common cause of acute intestinal obstruction
of the newborn.
Duodenum is the most common site of atresia in the
GI tract.
Clinical features: Vomiting from birth; is bile-stained.
Sign Distension usually not present
Visible peristalsis.
Associated with: Downs syndrome in 30 percent cases.
Diagnosis:
Radiology Double stomach appearance due to gross
distension of stomach.
Two air-fluid levels.
Gastric aspiration >20ml at birth.
Treatment: duodenoduodenostomy.
Ileal Atresia
The child is born with abdominal distension.
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DISORDERS OF ABSORPTION
Tests for Malabsorption
1. Stool fat: Increased in steatorrhea. Diagnostic in
pancreatic insufficiency.
2. Xylose absorption: Most commonly employed test for
carbohydrate absorption. Abnormal result is found in
diseases affecting the mucosa of the proximal small
intestine such as celiac sprue and tropical sprue.
3. Schilling test: For vitamin B12 absorption. Used in
pernicious anemia and pancreatic insufficiency.
4. Intestinal biopsy:
Diagnostic in:
1. Whipples disease.
2. Abetalipoproteinemia.
3. Agammaglobulinemia.
May be diagnostic in:
1. Intestinal lymphangiectasia.
2. Giardiasis.
Not diagnostic in:
1. Celiac sprue.
2. Tropical sprue.
Causes of Malabsorption
Endocrine
1. Diabetes mellitus.
2. Hypoparathyroidism.
3. Hyperthyroidism.
Short Bowel Syndrome
Causes:
1. Massive intestinal resection following a vascular insult
to small intestine.
2. Regional enteritis (Crohns disease).
3. Jejunal bypass for morbid obesity.
4. Most common cause is mesenteric infarction.
Effect: Resection of 40-50 percent of bowel is well tolerated
provided the proximal duodenum, distal ileum and ileocecal valves are preserved.
Treatment: Diet containing at least 2500 C and consist
primarily of carbohydrate and protein with fat restricted
less than 40 gm/day.
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(Note: - All are seen in massive resection of small bowel

hypergastrinemia, Vit B12 deficiency, malabsorption,
oxalate renal stone, cholesterol gallstone, hypocalcemia,
hyperuricemia, arthritis, fatty infiltration of the liver).
Tropical Sprue
Caused by E.coli.
Features: Impaired absorption of fat, Xylose and Vitamin
B12 (at least 2 for the diagnosis).
Biopsy: Not diagnostic but characteristic.
Shows villous atrophy (also seen in Giardiasis and
Celiac sprue).
Treatment: Vitamin B12, folate and antibiotics (tetracycline).
Celiac Sprue (Non-tropical Sprue)
Pathogenesis: It is a non-infectious process. It is due to
intolerance to Gluten which is found in wheat and wheat
products, hence known as Gluten induced enteropathy.
Gluten contains gliadin.
Pathology: Impaired digestion of fat and protein (due to
decreased CCK) and consequent malabsorption.
Association: HLA DQ2 and DQ8.
Clinical features: Diarrhea with other features of
malabsorption. Vitamin B12 deficiency does not occur.
Anti-gliadin and anti-endomysial antibodies are
increased in serum.
There is increased chance of intestinal lymphoma.
Biopsy: Blunting and flattening of the mucosal surface
with either absent or broad and short villi.
Treatment: Gluten free diet (rice and maize).
Lactase Deficiency
Produces lactose or milk intolerance.
Features: Symptoms abdominal cramps, bloating or
distension and diarrhea after ingestion of milk (not in
primary variety).
Others: Stool is acidic due to production of lactic acid.
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Types:
1. Primary hereditary.
Diagnosis Measurement of breath H2 after ingestion
of 50 gm lactose.
2. Acquired due to
i. Celiac and topical sprue.
ii. Regional enteritis, ulcerative colitis.
iii. Infections Giardiasis, Shigella, Entamoeba,
Yersinia.
iv. Abetalipoproteinemia.
Whipples Disease
Causative agent: Tropheryma whippelli which is a gramnegative actinomycetee.
Features:
Usually in middle aged male.
Abdominal pain, diarrhea, malabsorption.
Arthralgia.
Memory loss or dementia most common CNS
manifestation.
Uveitis, nystagmus, ophthalmoplegia.
Hypotension.
Lymphadenopathy.
Diagnosis:
Biopsy: Presence in the mucosa of macrophages containing
large cytoplasmic granules that stain brilliant magenta with
the PAS reagent.
Treatment: Cotrimoxazole.
Intestinal Lymphangiectasia
Characterized by enteric loss of protein, hypoproteinemia,
edema, lymphocytopenia, malabsorption and abnormal
dilated lacteal.
Biopsy features
Whipple disease
Tropical sprue
Celiac sprue
Lamina propria
infiltrated with
macrophages
containing PASpositive glycogen
Same as celiac
sprue
Blunting and flattening of

mucosal surface
Villi absent or markedly
atrophied
Crypts hypertrophied
Mononuclear cell infiltration
in lamina propia.
Changes are more marked
in proximal small gut.
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Protein Losing Enteropathy

Any of the above diseases can produce protein-losing
enteropathy.
Blind Loop Syndrome
Pathology: Stasis produces abnormal bacterial flora which
prevents breakdown of foods.
Effect:
High loops (upper intestine) Steatorrhea
Low loops (lower intestine) Vitamin B12 deficiency
anemia.
Treatment: Antibiotics, Surgical extirpation.
TUMORS OF STOMACH AND DUODENUM
OTHER CONDITIONS
Trichobezoar
Hairy balls in stomach.
Complications ulceration, GI bleeding, perforation
and obstruction.
Acute Gastric Dilatation
Associated with some form of ileus.
Stomach is atonic and dilated enormously.
Clinical feature:
Patient is dehydrated with electrolyte disturbance,
Sudden massive vomiting with aspiration into the lungs.
Treatment:
Nasogastric suction.
Fluid replacement
Treatment of underlying condition.
Diverticulum of Stomach
Diverticulum is least common in stomach in the GI
tract.
110
Usually located in the posterior surface at the cardiac

end.
Mostly asymptomatic, may produce hemorrhage.
SMALL AND LARGE

INTESTIENE
ANATOMY
Ileum contains Peyers patches at the ante-mesenteric
border.
Villi leaf-like in jejunum and finger-like in ileum.
Jejunum and ileum are supplied by superior mesenteric
artery.
Appendices epiploicae are present in large intestine
except the appendix, caecum and rectum.
MEGACOLON
Hirschsprungs Disease
Also called the congenital megacolon.
Pathology: Heterogeneous genetic disorders (some are
autosomal dominant, some recessive).
Etiology: Absence of the ganglion cells in the neural plexus
of the intestinal wall (both myenteric and Auerbachs
plexuses) give rise to a contracted nonperistaltic segment
with a dilated hypertrophied segment of normal colon above
it.
Site: Rectum and lower sigmoid colon are the most
common sites.
Clinical features: More common in males.
Symptom: Delayed passage of meconium (usually within
the first 4 days of life) together with mild abdominal
distension in neonates. May also present in childhood.
Chronic constipation within first few weeks of life.
Severe constipation without soiling in otherwise healthy
children and adults.
Diagnosis:
Rectal biopsy confirmation of diagnosis depends upon
histology (aganglionosis).
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Barium enema shows a transition zone between

proximal dilated and distal constricted segments;
reversal of rectosigmoid ratio (sigmoid colon more
dilated than rectum).
Treatment:
1. Rectal saline washout.
2. Surgery temporary colostomy and definitive surgery
when the child is 10 kg.
Duhamel operation excision of the aganglionic
segment.
Swensons operation.
Soaves operation.
INFLAMMATORY BOWEL DISEASE
Ulcerative Colitis
Etiology:
1. Heredity
2. Milk allergy
3. Smoking is protective.
Pathology: Usually starts in the rectum and spreads
proximally up to 30 cm of the ileum from ileocecal junction.
It is a nonspecific inflammatory disease primarily
affecting the mucosa and superficial submucosa produce
minute ulcers.
Chronic inflammation may lead to pseudopolyps.
Features suggestive of chronicity are
Distortion of crypt architecture (cryptitis) and
mononuclear infiltrate in lamina propria (crypt
abscess).
Clinical feature: First symptom is watery or bloody diarrhea.
Complications:
1. Toxic megacolon in severe fulminant colitis a section
of colon, especially transverse colon, may become
actually dilated and the intestinal wall becomes
extremely thin.
2. Perforation Grave complication.
3. Severe hemorrhage.
4. Precancerous change more chance than Crohns
disease. Increased chance in young patients.
Investigations:
1. Barium enema shows loss of haustrations,
pseudopolyps.
112
2. Sigmoidoscopy essential for diagnosis.

3. Colonoscopy and biopsy.
Extraintestinal manifestations:
1. Arthritis migratory, most commonly at knee;
ankylosing spondylitis.
2. Skin lesions erythema nodosum, pyoderma
gangrenosum, and apthous ulcer.
3. Eye Iritis.
4. Liver Sclerosing cholangitis.
Management:
A. Medical Acute steroids, if unsuccessful cyclosporin.
Chronic sulfasalazine steroids azathioprine/6mercaptopurine.
B. Surgery
Proctocolectomy and ileostomy treatment of choice.
In emergency (e.g. perforation) total colectomy and
ileostomy.
Colectomy does not reduce the risk of sclerosing
cholangitis.
Ulcerative colitis in pregnancy: Pregnancy causes flare up
of symptoms of ulcerative colitis especially during first
trimester and in postpartum period.
Crohns Disease
It can affect any part of the GI tract from lips to anal
margin, but terminal ileum and colon are the most
common sites.
Pathology: In 60 percent cases, there are noncaseating
giant cell granulomatous ulcers.
Earliest mucosal lesions are Apthous ulcer.
All the layers are involved, leading to fibrotic thickening
of the intestinal wall.
Edema of the mucosa between the ulcers gives rise
to Cobble stone appearance.
Segments of bowel are involved with intervening normal
bowel skip lesions.
Etiology: Multiple pathogens (Salmonella, Shigella,
Clostridium difficile, Campylobacter) may initiate IBD.
Complications: Transmural inflammation leads to
1. Adhesions.
2. Crypt abscess.
3.
4.
5.
6.
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Inflammatory masses with mesenteric abscess.

Fistula enteroenteric, enterovesical, entero-cutaneous.
Have malignant potential.
Bleeding, perforation.
Diagnosis: Barium enema String sign of Kantor.

Ulcerative Tuberculosis
Cause: Secondary to pulmonary tuberculosis due to
swallowing of infected sputum.
Hyperplastic Tuberculosis
A form of secondary TB.
Site: Ileocecal region is most common.
Clinical feature: Abdominal pain and diarrhea, right iliac
fossa mass.
Radiology: Barium follow through or small bowel enema
show a long narrow filling defect in terminal ileum. Caecum
is pulled up (cephalad retraction of caecum).
Treatment: Chemotherapy
Surgery ileocaecal resection when obstruction is present.
Tuberculous Ulcer
Involves the Payers patches of terminal ileum.
Ulcers are transverse with fibrosis stenosis is
common.
Typhoid Ulcer
Most common site Payers patches of terminal ileum.
Morphology:
Gross Ulcers are along the long axis of gut. No
significant fibrosis so stenosis is uncommon.
Microscopy Erythrophagocytosis with mononuclear
cell infiltrates.
Clinical feature: Most common presentation is intestinal
bleeding.
Complications:
1. Paralytic ileus most common
2. Perforation occurs during 3rd week, less common
in children below 5 years.
3. Hemorrhage.
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Amoebic Ulcer
Site: Colon, mostly sigmoid colon.
Ulcers: Typically flask-shaped with narrow neck and broad
base.
Choleric Ulcer
The mucosa remains intact.
Pseudomembranous Colitis
Etiology: It is associated with antibiotic use particularly
clindamycin, lincomycin (also ampicillin, tetracycline and
chloramphenicol).
Organisms: Clostridium difficile.
Pathology: Production of enterotoxin A and B as well as
cytotoxin.
Endoscopy: punctate yellow exudates in colon.
Histology: small ulceration with slough.
Treatment: Vancomycin is the drug of choice (Also used
is Metronidazole).
DIVERTICULAR DISEASE
Meckels Diverticulum
Development: From Vitelo-intestinal duct.
Rule of 2: Present in 2 percent of population (most
common congenital anomaly of GI tract).
Length 2 inches
Site 2 feet (60 cm) away from ileo-caecal valve in
the antimesenteric border of ileum.
Pathology: It is a true diverticulum, as it possesses all
the 3 layers of intestine and has separate blood supply.
It contains ectopic mucosa, mainly gastric, also
pancreatic and colonic.
Complications:
1. Severe hemorrhage caused by peptic ulceration of
ectopic gastric mucosa. Ulceration may also produce
pain in periumbilical region and nausea after taking
food.
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2. Intussusception.
3. Diverticulitis.
4. Obstruction is rare due to board base. It is usually
due to band.
5. Litters hernia- Meckels diverticulum in an inguinal
or a femoral hernia.
Diagnosis:
99mTc
scan.
Colonic Diverticulum
Site: Sigmoid colon is most commonly affected. Rectum
is never affected.
Saints triad: Colonic diverticulosis, gallstone and hiatus
hernia.
Epidemiology: Diverticular disease is rare in people taking
diet containing natural fibers.
Complications:
1. Perforation.
2. Intestinal obstruction.
3. Hemorrhage important cause of hematochezia in
patients over 60 years of age. It usually produces
massive hemorrhage.
Most common site of bleeding is ascending colon (i.e.
from the superior mesenteric aretery).
4. Fistula Vesicocolic is most common.
Diverticulitis is not a precancerous lesion.
Diagnosis:
1. CT scan is diagnostic in acute phase.
2. Barium enema Saw toothed appearance.
3. Sigmoidoscopy
i. In acute phase painful to perform.
ii. Mucosa inflamed.
iii. Necks of diverticula can be seen.
4. Mesenteric angiography is both diagnostic (in localizing
bleeding site) and therapeutic in patients with severe
hemorrhage. It can detect bleeding as minimum as
0.5 ml/min.
Management:
Diverticulosis by high-residue diet.
Diverticulitis
i. Medical in acute cases.
Rest and IV Cefuroxime + Metronidazole.
116
ii. Surgery in case of obstruction Hartmanns

operartion.
VASCULAR ANOMALIES
Angiodysplasia
Pathology: Angiodysplasia is a vascular malformation
associated with aging.
The malformation consists of dilated tortuous
submucosal veins.
Site: Ascending colon and caecum most common.
Clinical feature: Age over 60 years.
Bleeding per rectum usually chronic and intermittent.
There is an association with aortic stenosis.
Investigation:
i. Barium enema is unhelpful and should be avoided.
ii. Angiography
iii. 99mTc labelled RBC confirmatory.
Treatment: Colonoscopic diathermy.
Ischemic Colitis
Most common in the splenic flexure.
X-ray Thumb printing appearance.
MESENTERIC DISORDERS
Mesenteric Adenitis
Cause:
Specific Tuberculosis
Non-specific (idiopathic) much more common.
Some cases are associated with yersinia infection.
Mesenteric Cyst
Types:
1. Chylolymphatic most common type. Arises in
congenitally misplaced lymphatics.
2. Enterogenous Arises from a sequestrated diverticulum
from the mesenteric border of intestine.
117
Clinical feature: A painless fluctuating swelling around

umbilicus which moves freely in a plane at right angles
to the attachment of mesentery.
Treatment:
Chylolymphatic cyst Enucleation.
Enterogenous cyst Resection of a segment of gut
along with the cyst followed by intestinal anastomosis.
Acute Mesenteric Ischemia
Etiology:
Occlusive arterial thrombi or embolus.
Most commonly in patients with atrial fibrillation or
atherosclerosis.
Clinical features:
Persistent vomiting and defecation.
Severe abdominal pain, often colicky.
On examination tenderness and distension of
abdomen. Bowel sounds are often normal.
Investigations: Occult blood in stool.
Blood polymorphonuclear leukocytosis.
X-ray absence of gas in the thickened small gut.
Gas bubbles in mesenteric vein (thumb printing) is
pathognomonic.
RETROPERITONEAL SPACE
Retroperitoneal Fibrosis
Etiology:
1. Idiopathic (Ormonds disease).
2. Extravasation of urine.
3. Retroperitoneal irritation by leakage of blood or
intestinal contents.
4. Trauma.
5. Drugs chemotherapeutic agents, Methysergide,
-blockers.
Idiopathic Retroperitoneal Fibrosis
It is a type of fibromatoses (others being Dupuytrens
contracture and Peyronies disease).
Extensive collagen deposits surround the ureters first
retroperitoneal structure to be affected.
118
INTESTINAL OBSTRUCTION
Types:
A. Dynamic
Intraluminal : Foreign body, gallstone
Intramural : Strictures.
Extramural : Bands and adhesions (most common
cause of intestinal obstruction), hernias, volvulus,
intussusception.
B. Adynamic
Paralytic ileus,
Mesenteric vascular occlusion,
Pseudoobstruction.
Site:
1. High small bowel vomiting is early, distension is
minimum with little fluid levels on abdominal
radiograph, causes maximum water loss (dehydration).
2. Low small bowel pain is predominant with central
distension. Vomiting is delayed. Multiple fluid levels
are seen on radiographs.
3. Large bowel distension is early, pain is minimum
and vomiting and dehydration are late.
Acute obstruction usually affects small bowel first
symptom is pain.
Chronic obstruction usually affects large bowel
symptoms are constipation and distension.
Pathology: The distension proximal to an obstruction is
produced by two factors
1. Gas appears early.
70-80 percent of intestinal gas consists of swallowed
air.
Rest by aerobic and anaerobic digestion.
2. Fluid appears late.
Source various digestive juices.
Strangulation
There is direct interference to blood flow, threatening the
viability of the bowel.
Causes:
1. External compression hernias, adhesions and bands.
2. Interruption of mesenteric blood flow by volvulus,
intussusception.
119
3. Mesenteric infarction.
4. Closed loop obstruction.
Diagnosis: Coffee bean sign.
Large Bowel Obstruction
Most common cause is malignancy.
Surgery should be considered early because of the
chance of gangrene and perforation (most commonly
at the caecum).
Adhesions and Bands
Most common cause of intestinal obstruction.
Cause: Iatrogenic most common.
Treatment: Initial management is based on IV rehydration
(with Hartmanns solution or NS) and nosogastric suction.
Enteric Strictures
Cause: TB, Crohns disease, lymphoma, radiation.
Treatment: Resection and anastomosis.
Gallstones
Classically there is impaction about 60 cm proximal to
the ileo-caecal valve.
Acute Intussusception
Etiology:
1. Idiopathic most common in children (most common
cause between 3 month 6 years of age).
Lead point Meckels diverticulum, HS purpura.
2. Adult polyp, lipoma or tumor.
Pathology: It is believed that hyperplasia of Peyers patches
in the terminal ileum may be the initiating event.
Parts:
Intussusceptum (the entering or
inner tube)
Intussuscipiens (the outer tube)
120
Clinical feature:
Most common in children between 3-9 months.
Site Ileocolic type is most common. Least common
is the multiple type.
Symptoms:
Pain is the first and most common symptom.
Stool blood and mucus are evacuated at a later
stage the red current jelly stool.
Sign No distension.
Lump may be felt.
Emptiness in the right iliac fossa- the sign of Dance.
X-ray: The Claw sign.
Treatment: Barium enema.
Superior Mesenteric Syndrome
Cause: Compression of third part of duodenum by the
superior mesenteric artery.
Clinical feature:
Most commonly seen in young females.
Features of obstruction vomiting, distension.
Weight loss, postprandial epigastric pain.
Risk factor: Weight loss (asthenic built), immobilization,
scoliosis, body cast.
Diagnosis: Barium follow through upper GI tract or
hypotonic duodenography.
Treatment: Initially conservative.
Definitive surgery is duodenojejunostomy.
Meconium Ileus
It is the neonatal manifestation of cystic fibrosis.
Inheritance: Autosomal recessive.
Pathology: Meconium is normally kept fluid by the action
of pancreatic enzymes (trypsin). The viscid meconium and
mucus fill the terminal ileum and cause neonatal
obstruction.
Diagnosis:
1. Abdominal radiograph may reveal a distended small
intestine, with mottling. Fluid levels are generally not
seen.
121
2. Absence of trypsin from stool or bile.

3. Sweat chloride > 80 mmol/lit.
Treatment: The Bishop-Koop operation.
Necrotizing Enterocolitis
Neonatal necrotizing enterocolitis develops 1-2 days after
birth.
Clinical feature: First change is non-specific bowel
dilatation.
Others - Bradycardia, blood in stool, decreased bowel
sounds.
X-ray: X-ray abdomen shows pneumatosis intestinalis
or free intraperitoneal air.
Prevention: Probiotics.
Paralytic Ileus
Varieties:
1. Postoperative for first 24-72 hours.
2. Intra-abdominal sepsis.
3. Fracture of the spine or rib, retroperitoneal hemorrhage
reflex ileus.
4. Metabolic uremia and hypokalemia.
TUMORS OF THE SMALL INTESTINE
Types
Benign:
1. Adenomas most common benign tumor of the small
gut.
Brunners gland adenoma it is not a true neoplasm,
but represents a hypertrophy or hyperplasia of
submucosal glands.
They secrete highly viscous alkaline mucus.
2. Polyps Peutz-Jeghers syndrome.
3. Lipomas most common at the distal ileum and the
ileo-cecal valve; radiolucent; intramural and asymptomatic.
Malignant:
1. Adenocarcinoma most common primary cancer of
the small gut.
Most common site is the distal duodenum.
122
Diagnosis by endoscopic biopsy.

Treatment surgical resection.
2. Lymphomas
Most common at ileum.
Mainly diffuse large cell (T cell) non-Hodgkins
lymphoma.
Immunoproliferative small intestinal disease (IPSID)
Or IgA lymphoma shows IgA with shortened alpha
heavy chain and absent light chains.
Lymphoepithelial lesions are seen.
3. Carcinoid tumors
Arise from argentaffin cells of the crypts of Liberkhn,
predominantly in the distal ileum.
Usually asymptomatic.
Peutz-Jeghers Syndrome
1. Peutz-Jeghers polyp-hamartomatous polyp affects
jejunum.
2. Melanosis of the oral mucous membrane and the lips.
TUMORS OF THE LARGE INTESTINE
Genetics in Colorectal Carcinoma
Knudsons hypothesis of adenoma-carcinoma sequence:
Loss of APC gene earliest and most common (80%)
event in sporadic Ca. It leads to increased beta catenin
and activation of MYC and cyclin D1 leading to increased
cell proliferation.
Mutation of K-RAS gene.
18q21 deletion (DCC gene) in 60 - 70 percent cases.
Loss of TP53 in 7080 percent cases.
DNA mismatch repair genes: Are involved in 10 15 percent
of sporadic cases. Inherited mutations in one of five DNA
mismatch repair genes (most commonly MLH1) leads to
hereditary nonpolyposis colon carcinoma (HNPCC).
OTHER DISORDERS
Traumatic Rupture
Cause: Blunt trauma.
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Note: in penetrating trauma, small intestine is most

commonly affected.
Site:
Least chance of rupture at ileo-caecal junction.
Sigmoid colon is ruptured most commonly during
colonoscopy.
Treatment:
1. In small intestine and sterile wounds simple closure
of the perforation.
2. In lacerated mesentery and non-viable bowel
resection.
3. In large bowel (often in gun shot injury) temporary
colostomy followed by secondary closure of wound.
Pneumatosis Cystoides Intestinalis
Gas filled cysts in the sub-serosa and sub-mucosa of small
intestine and colon.
Cause:
COPD
Necrotizing enterocolitis
Diverticulitis
Clinical feature:
Often symptom less.
May cause intestinal obstruction and rectal bleeding,
diarrhea.
Rupture of cyst may cause tension pneumoperitoneum.
Diagnosis:
Sigmoidoscopy, barium enema.
Treatment:
Conservative.
Drug Metronidazole.
Spontaneous regression may occur.
Enterocutaneous Fistula
Most common cause is previous surgery.
Colostomy
Temporary: Indications are
1. After an anterior resection.
124
2. Following traumatic injury to the rectum or colon.

3. To facilitate the operative treatment of a high fistula
in ano.
APPENDIX
Anatomy
Position: Retro-caecal is the most common type. Least
common type is preileal.
Arterial supply: Appendicular artery, a branch of lower
division of ileo-colic artery.
Development: The appendix is developed from the primitive
mid-gut.
Acute Appendicitis
Pathology:
1. Mechanism of perforation is usually due to tension
gangrene due to accumulation of secretions.
2. A mucocele of the appendix is a retention cyst.
3. Diffuse peritonitis following acute appendicitis is usually
seen when appendicular perforation occurs early (within
24 hours).
Clinical feature:
1. Pain is the earliest symptom.
2. Pain is referred to umbilicus (T10).
3. Murphys triad pain, anorexia, nausea and vomiting.
Anorexia is a constant feature.
4. Pyrexia is mild temperature over 38.3C (101F)
suggests perforation.
5. Signs
i. Pointing index sign
ii. Rovsings sign palpation of the left iliac fossa
produces pain in the right iliac fossa.
iii. Psoas sign
iv. Obturator sign.
Investigations: Diagnosis of acute appendicitis is best done
by physical examination.
Abdominal USG is useful.
Blood leukocytosis > 20,000 cells/L suggests
perforation.
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D/D of acute appendicitis: In children H-S purpura, lobar

pneumonia.
In adults tabes dorsalis, porphyria, diabetes.
Management:
A. Medical i. IV fluid
ii. Antibiotics
iii. Antipyretics.
B. Surgery
Incisions
1. Grid-Iron most commonly employed.
It is made at right angles to a line joining the anterior
superior iliac spine to the umbilicus, its centre being
along the line at McBurneys point.
Complication inguinal hernia. It has got least
complications.
2. Transverse or long (skin crease) incision.
3. Rutherford-Morrison- it is an oblique muscle cutting
incision with its lower end at McBurneys point and
extending obliquely upwards and laterally.
A Grid-Iron incision can be converted to a RutherfordMorrison incision by cutting the internal oblique and
transversus abdominis muscles in the line of incision.
Special circumstances:
1. When the base of the appendix is inflamed, it should
not be crushed but ligated close to the caecal wall
the stump is invaginated.
2. If the base is gangrenous neither crushing nor ligation
should be attempted.
3. In case of Crohns disease appendicectomy is not
done.
Postoperative complications:
1. Wound infection most common.
2. Ileus.
3. Respiratory infection.
4. Intestinal obstruction.
5. Nerve injury to iliohypogastric nerve.
6. Portal pyemia postoperative jaundice.
Management of appendicular mass (lump): Conservative
Ochsner-Sherren regimen.
126
Carcinoid Tumor of the Appendix
Appendix is the most common site of carcinoid tumor.

Carcinoid tumors arise in Argentaffin cells.
Site most commonly the distal third.
Unlike carcinoid tumors arising in other parts of the
intestinal tract, carcinoid tumor of appendix rarely gives
rise to metastasis less chance of carcinoid syndrome.
(Note: Least malignant carcinoid tumor is that of
bronchus).
Treatment:
i. Appendicectomy if the tumor size is < 2 cm
ii. Right hemicolectomy when tumor size is > 2 cm,
caecal wall is involved or lymph nodes are involved.
Pathology: On transection, carcinoid tumors appear as
solid, yellow-tan due to lipochrome deposition.
LIVER
ANATOMY
Ligamentum venosum: It is a remnant of Ductus venosus.
Falciform ligament: Contains Ligamentum teres.
Kupffers cells: Kupffers cells are derived from bone
marrow and found in liver.
Spaces of Disse: Found in liver.
Ito cells:
i. Located in Spaces of Disse.
ii. Secrete collagenous matrix responsible for
development of cirrhosis.
iii. Store the fat soluble Vitamin A.
Liver acinus of Rappaport:
It is the structural and metabolic unit of liver.
It has 3 zonesi. Inner zone (Zone 1) around the vascular back-bone
and is well oxygenated.
ii. Intermediate zone (Zone 2) moderately oxygenated.
iii. Outer zone (Zone 3) close to central vein and is
least oxygenated most susceptible to anoxic injury.
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Nutrition of liver: from 2 sources

i. Portal vein (66-75%)
ii. Hepatic artery (25-34%)
Hepatic blood flow = 30 percent of cardiac output.
Hepatic veins: Drain into IVC.
Calots triangle: It is bounded
Above and laterally, by under surface of liver.
Below and laterally, by cystic duct.
Medially by the common hepatic duct.
Development:
1. Portal vein from infra hepatic part of right and left
vitelline veins.
2. Hepatic vein from supra hepatic part of right vitelline
vein.
Line of surgical division of liver: Gallbladder bed to IVC.
Segments of liver:
Caudate lobe
Right lobe
Left lobe
Described by Couinaud.
Segment I
Segments V-VIII
Segments II-IV
PHYSIOLOGY
Bile
1. Daily production 500 ml (20 ml/hours).
2. 90-95 percent of the bile salts are absorbed from the
small intestine (mostly ileum) and undergo enterohepatic circulation.
3. Cholagogues are substances that cause contraction
of gallbladder. E.g. fatty acids and amino acids, CCK.
4. Choleretics are substances that increase the secretion
of bile, e.g. bile salts (most potent).
Note gallbladder concentrates bile 510 times.
LIVER FUNCTION TESTS
Serum Bilirubin:
Normal value 0.21.0 mg/dl
Conjugated 0.20.6 mg/dl
Unconjugated 0.20.4 mg/dl.
Serum albumin: Normal 4 6 gm/dl.
Serum alkaline phosphatase:
Normal value 313 KAU (King Armstrong Unit).
128
Very high values are obtained in post-hepatic

obstruction.
Serum transaminases:
i. ALT (Alanine Amino Transferase) or SGPT Normal
value 515 IU/L.
ALT is more sensitive indicator of parenchymal liver
disease.
ii. AST (aspartate transaminase) or SGOT. Normal
value-5-20 IU/L.
Lactate dehydrogenase (LDH):
Normal value 80-150 IU/L.
Value increased in infective hepatitis.
Obstructive jaundice.
Ca liver.
Gamma glutamyl transpeptidase (GGT):
Normal value- <30 U/L.
Increased in obstructive jaundice and alcoholic hepatitis
(most sensitive marker).
-FP:
Increased in hepatocellular carcinoma.
PT time: Is a prognostic marker of acute and chronic
hepatocellular injury (e.g. hepatitis).
HYPERBILIRUBINEMIA
Unconjugated: (Due to deficiency of Glucuronyl transferase)
1. Gilbert syndrome autosomal dominant.
i. Mild, persistent, unconjugated hyperbilirubinemia.
ii. LFTs are normal.
iii. Liver cells appear normal on L/M.
2. Crigler-Najjar syndromeConjugated:
1. Dubin- Johnson syndrome- Liver is darkly
pigmented.
2. Rotor syndrome.
Recurrent Jaundice of Pregnancy
i. Serum bilirubin levels are < 6 mg/dl.
ii. The serum alkaline phosphatase and cholesterol levels
are markedly increased.
iii. Other LFTs are only mildly deranged.
See the chapter of general discussion for more of jaundice.
129
ACUTE VIRAL HEPATITIS

All the hepatitis viruses are RNA viruses except hepatitis
B virus which is a DNA virus.
Type A Hepatitis
Picorna viridae.
Incubation period: 15-45 days.
Transmission:
By fecal-oral route.
Cases are the only source of infection. No carrier
state.
Most common sporadic cases in children.
More severe infection in adults.
Clinical feature:
Transient jaundice, spiking fever.
Recovery is slow over a period of 4-6 weeks.
Diagnosis:
Demonstration of IgM antibody in serum.
Type B Hepatitis
Hepadnaviridae.
Incubation period: 6 weeks to 6 months.
Transmission:
Sexual transmission - Most common in heterosexuals.
Blood borne.
Genetic structure:
S gene codes for envelop protein HBsAg.
C gene codes for nucleocapside proteins.
1. HBcAg core protein.
2. HBeAg nucleocapsid protein.
P gene codes for DNA polymerase which activates
DNA dependant DNA polymerase and RNA polymerase
(reverse transcriptase).
X gene HBxAg (transactivation protein).
Immune response:
1. HBsAg The first virological marker to appear after
infection (appears before the onset of symptoms). It
is a specific marker of infection.
130
HBsAg is a serological marker of disease prevalence.

Anti-HBs antibody is protective and associated with
resistance to infection.
2. HBcAg Does not appear in serum.
Anti-HBc antibody appears in pre-icteric phase and
persists for months.
It is the evidence of current or recent infection during
window period (between the disappearance of HBsAg
and appearance of anti-HBs).
3. HBeAg Related to infectivity and viral replication.
HBsAg +ve serum containing HBeAg is more likely
to be highly infectious.
90 percent of HBeAg +ve mothers but only 10-15
percent of anti-HBeAg +ve mothers transmit HBV
infection to their child.
Associations of HBV infection:
Serum sickness, glomerulonephritis and PAN.
Diagnosis:
Acute infection HBsAg, IgM anti-HBc.
Chronic infection HBsAg, IgG anti-HBc.
HBsAg is found in saliva, tears, CSF, seminal fluid,
synovial fluid, breast milk, urine.
Liver function tests: Serum AST and ALT show a variable
increase during the prodromal phase of acute infection.
But, the acute level of these enzymes does not correlate
well with the degree of liver damage.
HBV-DNA by PCR.
More sensitive marker of viral replication than HBeAg.
Use to determine the course of the disease and need
for antiviral therapy.
Special cases:
1. Carrier state: Persistence of HBsAg after acute illness;
also persistence of HBeAg for > 3 months.
i. Super carriers have HBeAg in their blood and
is highly infectious.
ii. Simple carriers more common. No HBeAg and
a low level of HBsAg in blood.
(Persistent carriers presence of HBsAg in blood for
> 9 months.)
HBsAg carrier state is associated with Downs syndrome,
leprosy, leukemia, lymphoma, PAN and chronic renal
failure on hemodialysis.
131
2. Immunization After immunization with Hepatitis B

vaccine (which contains only HBsAg), anti-HBs
antibody is the only marker to appear in blood.
Pathology:
Carrier state
HBV Ground glass hepatocytes, sanded nuclei.
Acute hepatitis
Ballooning degeneration.
Bridging necrosis.
Hepatocyte damage is due to damage of the virusinfected cells by CD8+ cytotoxic T cells.
Treatment:
Acute self-limited; no treatment required.
Chronic lamivudine is the first line drug; interferon
alpha (combination is not advantageous).
Prevention: For perinatal exposure of infants born to HBsAg
+ve mothers A single dose of HBIG 0.5 ml IM in the
thigh immediately after birth PLUS complete course of
3 injections of hep B vaccines to be started within 12
hours of birth.
(Note: Hepatitis B is not transmitted by pasteurized
albumin.)
Course: May lead to hepatocellular carcinoma most
common cause in India.
Type C Hepatitis
Flavivirus.
It is the most common cause of post-transfusion
hepatitis.
High risk of chronic liver disease and hepatocellular
carcinoma most common cause in western countries.
Associations of HCV infection: Cryoglobulinemia, MPGN,
lichen planus, autoimmune thyroiditis. Diabetes mellitus
type II is more common in hepatitis C infection.
Diagnosis:
Detection of anti-HCV during acute period is not
possible but diagnostic after that; not protective.
In early infection HCV RNA or RIBA for anti HCV.
It cannot be cultured.
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Treatment:
Acute interferon.
Chronic combination of lamivudine and interferon;
ribavarin.
Type D Hepatitis
The delta hepatitis agent requires the helper function of
HBV for its replication and expression.
Type E Hepatitis
HEV is an Alphavirus, resembles calcivirus.

They may cause epidemics.
Transmission by water-borne.
It is highly infective and fatal during pregnancy
especially in the last trimester.
In India, HEV is responsible for most of the epidemics
and sporadic hepatitis in adults.
Type G Hepatitis
Flavivirus.
Transmission by percutaneous route.
It causes chronic viremia lasting at least 10 years.
Coinfection with HIV improves survival.
CHRONIC HEPATITIS
Etiology:
1. Viral most common cause (HBV HCV, HDV).
2. Wilsons disease.
3. 1 antitrypsin deficiency.
5. Drugs -methyldopa (aldomet), methotrexate,
isoniazid.
6. Autoimmune.
Classification:
Etiological viral, autoimmune, drug-induced, etc.
Grading based on the degree of necrosis and
inflammation.
Staging based on the degree of fibrosis.
Types:
1. Chronic active hepatitis.
2. Chronic persistent hepatitis.
133
They are differentiated on histological ground.

Investigation: Liver biopsy and serum transaminase
elevation.
Treatment:
Chronic replicative hep B and hep C interferon .
Interferon is not effective in chronic HCV when there
is long-term hepatic cirrhosis.
Autoimmune hepatitis:
Type I ANA and/or Sm antibody.
Type II Anti-LKM 1 (same as chronic hepatitis C).
Type III Anti SLA/LP (soluble liver antigen).
LKM antibodies (Liver Kidney Microsomes antibody)
Anti-LKM 1
Anti-LKM 2
Anti-LKM 3
Type II autoimmune
hepatitis
Chronic hepatitis
Drug induced
hepatitis
Chronic hepatitis D
Granulomatous hepatitis:
Cause halothane, candidiasis, sarcoidosis.
Liver reaction to extrahepatic neoplasm (but not hepatic
metastases).
Morphology of Hepatitis
Acute:
Parenchymal change
Ballooning degeneration of hepatocytes.
Hepatocytic necrosis focal or centrizonal; if severe,
bridging necrosis.
Acidophilic degeneration of hepatocytes Councilman
bodies.
Inflammation predominantly mononuclear infiltrates.
Regeneration
Fatty changes in HCV.
Chronic:
Fibrosis and necrosis bridging/periportal/piece meal.
Ground glass appearance in chronic HBV.
CIRRHOSIS OF LIVER
Definition: Three characteristics
1. Bridging fibrous septa.
134
2. Parenchymal nodule.
3. Disruption of architecture of the entire liver.
Etiology:
Micronodular (<0.3 cm):
1. Alcoholic liver disease most common cause.
2. Biliary cirrhosis.
3. Hereditary hemochromatosis.
4. Wilson disease.
5. 1 antitrypsin deficiency causes cirrhosis in childhood.
Macronodular (>0.3 cm):
1. Viral hepatitis.
2. Hepatotoxins CCl4, mushroom poisoning.
3. Drugs Acetaminophen, -methyldopa.
2. Alcohol.
Others cystic fibrosis.
Childs Classification of Hepatocellular
Function in Cirrhosis
Childs classification
Bilirubin
Albumin
Ascites
Neurologic symptoms
Nutrition
< 2
> 3.5
Excellent
2 3
3 3.5
+
+
Good
> 3
< 3
+
++
Wasting
Alcoholic Liver Disease

Pathology:
1. Hepatic steatosis (fatty liver) reversible.
2. Acute hepatitis
i. Hepatic swelling (ballooning) and necrosis.
ii. Mallory bodies Hepatocytes containing
intermediate filaments. They are highly suggestive,
but not specific of alcoholic liver disease.
Also found in Primary biliary cirrhosis, Indian
childhood cirrhosis, Wilsons disease, Chronic
cholestasis, Hepatic tumor, Uncontrolled diabetes,
Morbid obesity, Jejunal bypass operation.
iii. Netrophilic infiltration.
iv. Fibrosis
135
Sinusoidal and perivenular (central hyaline

sclerosis).
Periportal fibrosis may occur in repeated bouts of
heavy alcohol intake.
3. Micronodular cirrhosis (Laennecs cirrhosis) Liver
becomes brown and shrunken Hobnail appearance.
Clinical feature:
Jaundice
Palmer erythema, spider angioma
Parotid and lacrimal gland swelling
Clubbing of the fingers
Liver enlarged, normal or decreased in size
Splenomegaly
Portal hypertension ascites, variceal bleeding
In men, decreased body hair and testicular atrophy
In women, virilization and menstrual irregularities
Dupuytrens contracture
Hepatic encephalopathy and coma
Peripheral neuropathy.
Laboratory findings:
Varying elevations of serum alkaline phosphatase.
AST is disproportionately elevated relative to ALT (c.f.
viral hepatitis) and serum AST:ALT >2 is suggestive
and > 3 is highly suggestive of alcoholic liver disease.
PT is increased.
Decreased albumin and globulin in serum.
Increased MCV (macrocytosis).
Increased GGT.
Increased CDT (carbohydrate deficient transferin).
Biliary Cirrhosis
Primary
Etiology:
Autoimmune.
Clinical feature: Pruritus is the earliest and most common
symptom; xanthomas, osteoporosis.
Diagnosis:
i. Increased serum alkaline phosphatase.
ii. Increased cholesterol
iii. An abnormal lipoprotein in RBC called Lipoprotein X.
iv. Increased IgM (antimitochondrial antibody).
136
Secondary
Due to extra-hepatic bile duct obstruction most commonly
due to stricture.
Budd-Chiari Syndrome
Etiology: Occlusion of the hepatic veins (most common)
or IVC mainly by thrombosis or venous web.
Polycythemia vera (most common) and other
myeloproliferative disorders
Pregnancy and postpartum
OCP
Paroxysmal nocturnal hemoglobinuria
Hepatocellular carcinoma
Hyperprothrombinemia (factor II)
Activated protein C resistance (factor V Leiden
mutation)
Protein C and S.
Clinical feature:
Liver is grossly enlarged and tender.
Severe intractable ascites.
Weight gain and abdominal pain.
Diagnosis:
Duplex Doppler USG.
Carolis Disease
Congenital dilatation of the intrahepatic biliary tree with
presence of intrahepatic stone formation.
Non-cirrhotic Hepatic Fibrosis
Cause:
1. Idiopathic portal hypertension.
2. Schistosomiasis.
3. Congenital hepatic fibrosis.
Non-cirrhotic Portal Fibrosis
Clinical feature:
Age 3rd or 4th decade of life.
GI hemorrhage massive hematemesis.
137
Massive splenomegaly but no hepatomegaly.

Mild ascites.
Cause:
Chronic arsenic poisoning.
Portal Vein Thrombosis
Clinical feature:
Massive hematemesis due to esophageal varices
(portal hypertension).
Moderate splenomegaly.
Normal liver functions.
Etiology: Infarct of Zahn is produced by intrahepatic
thrombosis of portal vein radicles.
Banti syndrome is subclinical thrombosis of portal vein
from neonatal omphalitis or umbilical vein catheterization.
Veno-occlusive Disease
Most commonly seen in post-bone marrow transplant
patients.
Produces centrilobular necrosis.
MAJOR COMPLICATIONS OF CIRRHOSIS
Portal Hypertension
Normal portal pressure 8-12 mm Hg (10-15 cm saline).
Portal hypertension > 30 cm saline.
Causes of portal hypertension:
Presinusoidal portal vein thrombosis, schistosomiasis.
Sinusoidal cirrhosis of liver (most common cause).
Postsinusoidal Budd-Chiari syndrome, IVC
thrombosis, venoocclusive disease.
Clinical feature:
Hemorrhage most common manifestation; usually
variceal bleeding. It is usually precipitated by minor
febrile illness. NSAIDs may accentuate it.
Splenomegaly (with hypersplenism).
Ascites.
Acute and chronic encephalopathy.
Dilatation of collaterals piles, caput medusae, etc.
138
Management of variceal bleeding:

1. Initial management i. Vigorous replacement of blood loss. Only when the
patient is hemodynamically stable should specific
diagnostic studies (endoscopy) be undertaken.
ii. Vitamin K.
iii. Balloon tamponade is done by Sengstken
Blakemore tube (3 lumen) or Minnesota tube (4
lumen) for emergency temporary hemostasis.
Pressure applied is about 40 mmHg.
2. Medical measures
i. Vasopressin (Terlipressin) acts on V1 receptors,
causes vasoconstriction.
ii. Nitroglycerin.
iii. Octreotide long acting somatostatin analogue.
3. Endoscopic sclerotherapy with 5 percent ethanolamine
oleate.
Other sclerosing agents Polydochyl, cynoacrylate,
alcohol, ethanolamine oleate.
4. Transjugular intrahepatic portosystemic stent shunt
(TIPSS) for emergency control of variceal bleeding
when drugs and sclerotherapy fail to control bleeding.
5. Esophageal stapled transection.
6. Patients with splenic or portal vein thrombosis
splenectomy and gastroesophageal devascularization.
7. Porto-caval shunt for Childs group A cirrhosis.
(Note
Most common cause of hematemesis in children is
portal hypertension.
Most common cause of portal hypertension in children
is extrahepatic obstruction.)
Ascites
Etiology:
1. Portal hypertension.
2. Hypoalbuminemia and decreased plasma oncotic
pressure.
3. Renal secondary hyperaldosteronism.
Clinical feature: Physical examination (shifting dullness)
are positive only when fluid accumulates > 500 ml.
Investigation: Minimal ascites can be detected by USG.
139
Treatment: Of refractory ascites a side-to-side portacaval

shunt.
See the chapter of general discussion for more of ascites.
Spontaneous Bacterial Peritonitis
Clinical feature: Abrupt onset of fever, chill and generalised
abdominal tenderness.
On examination:
Ascitic fluid low concentration of albumin.
Blood high white cell count.
Hepatorenal Syndrome
Characterized by Worsening azotemia with avid sodium
retention and oliguria in the absence of identifiable specific
causes of renal dysfunction.
On examination:
Renal biopsy NAD.
Urine Na+ < 5 mmol/L
Sediment nil.
Hepatic Encephalopathy (Portasystemic
Encephalopathy)
1. GI bleeding.
2. Hypokalemia, hyponatremia, hypoxia, alkalosis.
3. Diuretics.
4. Intercurrent infection.
3. Dietary protein.
4. Azotemia.
5. Constipation.
6. Drugs CNS depressants.
Clinical feature:
Disturbance of sleep and reversal of sleep-wake pattern
earliest symptom.
Asterixis most characteristic symptom.
Diagnosis:
EEG is characteristic.
Treatment:
Restriction of dietary protein.
140
Neomycin, tetracycline, ampicillin or metronidazole.

Lactulose.
INFILTRATIVE AND METABOLIC DISEASES
Fatty Liver
A. Macrovesicular B. Microvesicular
1. Alcoholic liver disease. 1. Reyes syndrome.
2. Pregnancy.
3. Obesity.
3. Drugs tetracycline.
4. Protein-energy malnutrition.
Liver Necrosis
1. Centrilobular necrosis
i. Chronic venous congestion most common cause.
ii. Hemorrhagic shock
iii. Drugs CCl 4 , halothane, acetaminophen,
rifampicin.
2. Peripheral phosphorus poisoning.
3. Mid-zonal yellow fever, eclampsia.
Reyes Syndrome
Characterized by fatty liver and encephalopathy.
Clinical feature:
Age < 15 years.
Symptom vomiting, progressive CNS damage,
hypoglycemia, tachypnea.
Onset follows an URTI especially influenza and chickenpox.
Jaundice is characteristically minimal or absent.
Etiology:
Viral Influenza, varicella, adenovirus, RSV.
Drug Salicylates.
Pathology:
Liver is enlarged.
Characteristic microvesicular steatosis in liver and renal
tubules. Glycogen depletion in hepatocytes.
Metabolic acidosis with respiratory alkalosis.
Increased serum transaminase.
Increased PT.
141
Treatment:
i. IV glucose.
ii. FFP.
iii. IV mannitol to reduce cerebral edema.
Wilson Disease (Hepatolenticular Degeneration)
Pathology: There is increased intestinal absorption and
decreased biliary excretion of copper.
There is abnormal accumulation of copper in

hepatocytes and other tissues.
Accumulation in RBCs result in hemolysis.
PCTs are affected resulting in Fanconis syndrome.
In cornea, produces K-F rings (deposition of copper
in Descemets membrane in the limbus of cornea).
Genetics:
Autosomal recessive.
It is due to mutation of chromosome 13 (ATP7B gene).
Clinical feature:
Age 6-15 years.
1. Hepatic dysfunction acute onset of jaundice and
hepatomegaly; micronodular cirrhosis.
Course may mimic chronic active hepatitis.
2. Neuropsychiatric symptoms
Basal ganglia (especially putamen) damage leads to
chorea, tremors (rest or intentional), rigidity, difficulty
in speech, abnormal posture, and dysphagia.
Note: It is a combination of features of cerebellar ataxia
and Parkinsonism.
Sensory changes never occur.
Psychosis.
3. Coombs ve hemolytic anemia.
4. Eye sunflower cataract. K-F rings do not produce
any visual impairment.
Diagnosis:
1. K-F ring in cornea On slit-lamp examination appears
brownish or gray green in descemets membrane.
2. Serum ceruloplasmin < 20 mg/dl.
3. Serum copper < 20 g/dl.
4. Increased Cu excretion in urine > 100 g/24 hour.
5. Increased Cu in liver biopsy > 250 g/gm dry weight.
142
Note: stains: Rhodanine for copper, Orcein for cuassociated protein.

Treatment:
Oral d-Penicillamine drug of choice.
Others trientine, oral Zn acetate.
LIVER INFECTIONS
Ascending Cholangitis
Cause:
Biliary tract obstruction.
Bile duct stones are common predisposing factor.
Clinical feature:
Jaundice, rigors and tender hepatomegaly.
Organ failure may occur secondary to septicemia.
Pyogenic Liver Abscess
Cause:
1. Ascending cholangitis most common cause.
2. Hematogenous spread of bacteria.
3. Local spread from contiguous structures.
Organisms:
Streptococci milleri.
E.coli.
Amoebic Liver Abscess
May rupture into pleural space.
Management conservative.
Hydatid Cyst
Treatment Indicated to prevent progressive enlargement
and rupture of the cyst.
LIVER TRAUMA
Liver is one of the most common organs to be injured
by penetrating injury.
(Other organs affected in penetrating injury are chest
and pericardium).
(Note: Blunt injury causes damage to spleen and kidneys.)
143
LIVER TUMORS
LIVER TRANSPLANTATION
Indications
1. Biliary atresia (in children).
2. Cirrhosis (alcoholic).
3. Primary sclerosing cholangitis.
4. Chronic viral hepatitis.
5. Primary hepatocellular malignancy.
Note: See also the chapter of organ transplantation.
THE GALLBLADDER
ANATOMY
The GB fossa separates the right and quadrate lobes
of liver.
Capacity of GB about 30-50 ml.
Fundus of GB projects in the angle between the lateral
border of the right rectus abdominis and 9th costal
cartilage at transpyloric plane.
The CBD is 8 cm long and 6 mm in diameter.
The ampulla of Vater is situated 810 cm distal to
the pylorus.
The supraduodenal part of CBD lies in the free margin
of lesser omentum and has following relations
i. Anteriorly liver.
ii. Posteriorly portal vein and epiploic foramen.
iii. To the left hepatic artery.
The retroduodenal part has IVC in its posterior relation.
Blood supply cystic artery a branch of right hepatic
artery.
Biliary Atresia
Clinical feature:
Jaundice which is present at birth or appear within
1 week of life.
Stools are pale.
Urine dark.
144
Prolonged steatorrhea give rise to osteomalacia (biliary

rickets).
Increased serum cholesterol.
Investigation:
i. HIDA scan.
ii. Liver biopsy.
Choledochal Cyst
It is the extrahepatic dilatation of the common bile duct.
Note: Intrahepatic dilatation of bile canaliculi is known
as Carolis disease.
Etiology: Specific weakness in a part of or the whole of
the wall of CBD.
Clinical feature:
Patient may present at any age.
Progressive Obstructive jaundice.
Cholangitis pain.
Abdominal swelling.
Investigation: USG and MRI.
Treatment: Radical excision of the cyst with reconstruction
of the biliary tract using a Roux-en-Y loop of jejunum
(hepatojejunostomy).
Gallstones
Types:
1. Cholesterol stones often solitary.
2. Mixed stones most common type.
Made up of cholesterol and calcium salts (usually
calcium-phosphate and calcium-carbonate). Often
multiple.
3. Pigment stones of calcium bilirubinate.
Cholesterol and Mixed Stones
Pathology Cholesterol stones are formed when the
concentration of cholesterol is more than bile salts and
phospholipids in bile lithogenic or supersaturated bile.
Factors
145
A. Increased bile cholesterol OCP, clofibrate, obesity.

B. Decreased bile salts
i. Estrogens.
ii. Ileal disease or resection or bypass.
iii. Cholestyramine therapy.
iv. Primary biliary cirrhosis.
v. Truncal vagotomy.
Pigment Stones
They are formed in patients with hemolysis with excess
production of bilirubin.
E.g. hemolytic anemias.
Cholecystitis
Mediator: Lysolecithin.
Investigation:
1. Oral Cholecystography: Procedure One X-ray is taken
on previous day and a tablet (containing iapanoic acid)
is given on the night before. Next day X-rays are taken
before and after a fatty meal (at least 3 pictures).
Interpretation It signifies that:
i. The tablet is absorbed properly.
ii. Liver is functioning.
iii. Concentrating power of gallbladder is normal.
iv. There is no obstruction in cystic duct.
v. Gallbladder contraction is normal after fatty meal.
Drawback It is not diagnostic of gallstone disease.
2. USG: It is the investigation of choice.
It shows
i. Presence of stones inside the gallbladder.
ii. Edema around the gallbladder wall.
iii. Impaction of stone in the infundibulum.
3. MRCP best investigation for gallstones.
4. HIDA scan: Best for visualizing biliary tree.
Management of gallstones:
1. Medical UDCA and CDCA inhibits cholesterol synthesis.
Indications Functioning gallbladder with radiolucent
stones < 15 mm in diameter.
2. Surgical
Laparoscopic cholecystectomy is the gold standard of
management of gallstone disease.
146
Indications
i. Palpable duct stones
ii. Jaundice or h/o jaundice or cholangitis.
iii. CBD is dilated.
iv. Abnormal LFT especially alkaline phosphatase
level is increased.
[Note after choledochotomy, a T-tube is placed in-situ.
It can be clamped after 10 days. Na-ditrazoite is injected
down the tube to obtain a cholangiogram after 10-14 days
to see any left over stone in the CBD. The tube can be
removed after 4 weeks].
Management of bile-duct obstruction: If the symptoms
particularly jaundice persist after cholecystectomyi. Immediate USG.
ii. If there is obstruction-immediate ERCP and removal
of stone, if present by endoscopic sphincterotomy.
iii. If there is leakage - Drain placed in the subhepatic
space and stent placed in the bile duct.
Emphysema Cholecystitis
Organisms: Gas producing anaerobes viz. Clostridium
welchii and Clostridium perfringens.
Patient profile: Elderly male, diabetic patients.
X-ray: Gas within gallbladder lumen.
Prognosis: Bad.
Gallstone Ileus
Entrance of stone into the duodenum is through a
cholecystoenteric fistula.
Impaction proximal to the ileo-cecal valve.
Treatment:
Laparotomy and removal of stone from intestine as
well as from gallbladder.
Porcelain Gallbladder
Calcium salts are deposited within the wall of a
chronically inflamed gallbladder.
Risk Chance of malignancy.
Treatment Cholecystectomy.
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Cholesterosis/Strawberry Gallbladder
Submucous deposition of cholesterol crystals and
cholesterol esters in the wall of the gallbladder.
Mucocele of Gallbladder
Distension of the gallbladder by accumulating mucus
due to obstruction of neck by gallstones.
Treatment cholecystectomy.
Complications empyema of the gallbladder,
perforation and gangrene.
STONES IN CBD
Cholangitis
Organism: E. coli.
Symptoms of cholangitis:
Charcots triad Pain, jaundice and fever with chill.
Reynolds pentad Charcots triad + shock and mental
obtundation.
Commonly associated with non-alcoholic acute
pancreatitis.
Sign: Courvoisiers law A dilated gallbladder is usually
associated with obstruction other than that caused by CBD
stones (e.g. carcinoma head of pancreas).
Diagnosis:
By cholangiography either preoperatively by ERCP or
intraoperatively at the time of operation.
Blood leukocytosis.
Treatment:
i. Preoperative ERCP with endoscopic papillotomy and
stone extraction (by Dormia busket) is preferred
method for single stone < 1.5 cm.
ii. Supraduodenal choledochotomy.
Note indications of transduodenal sphincterotomy
1. Stone impacted near the ampulla of Vater.
2. CBD dilated with multiple stones and biliary sludge.
3. Papilla is fibrosed and stenosed.
Note best suture for bile duct is non-synthetic,
absorbable.
148
OTHER CONDITIONS
CBD Strictures
Most common cause is postoperative.
Hemobilia
Cause: Traumatic or operative injury to the liver or bile
ducts.
Clinical features: Triad of biliary colic, obstructive jaundice
and melena/occult blood in stool.
Treatment:
Hepatic artery ligation.
Hepatic Artery Ligation
Indication
1. Hepatoma and liver secondaries used preoperatively
but can not cure the malignancy.
2. Hemobilia best result.
Primary Sclerosing Cholangitis
Etiology: Unknown.
Affects: The extrahepatic and intrahepatic bile ducts, may
involve gallbladder and/or pancreas.
Association: With ulcerative colitis.
Clinical feature: Jaundice, pruritus, right upper quadrant
abdominal pain or acute cholangitis.
Risk: Increased chance of cholangiocarcinoma.
MALIGNANCY
PANCREAS
ANATOMY
The posterior surface of pancreas is in relation to
i. The aorta and SMA.
ii. Left crus of the diaphragm.
iii. Left suprarenal gland.
149
iv. Left renal vessels.

v. Splenic vein (but NOT splenic artery).
Tail of the pancreas:
Lies in the lienorenal ligament.
Comes in contact with the lower part of the gastric
surface of spleen.
The endocrine part consists of only 10-20% of total
pancreatic mass.
Islets of langerhans are most numerous in the tail.
Main pancreatic duct = Wirsungs duct.
Accessory pancreatic duct = Santorinis duct.
Annular Pancreas
Associated with Downs syndrome.
Treatment Duodenojejunostomy or duodenoduodenostomy.
PANCREATITIS
Acute Pancreatitis
Etiology:
1. Alcoholism.
2. Gallstones most common cause.
3. Blunt abdominal trauma (most common cause in
children).
4. Hypercalcemia (hyperparathyroidism), hyperlipidemia.
5. Mumps.
6. Drugs- Thiazide diuretics, valproic acid, L- asparginase,
steroids, diadinosine.
7. Pregnancy.
Clinical feature:
Abdominal pain is the major symptom. Pain radiates
to back and is relieved by sitting upright.
Others fever, vomiting.
Cullens sign Faint blue discoloration around the
umbilicus.
Grey-Turners sign Bluish discoloration of the flanks.
Investigation:
1. Screening tests Serum amylase and lipase, trypsin.
The latter two are more diagnostic.
150
Serum amylase value>3 times the normal value

is highly specific. Amylase level is elevated within 24
hours and returns to normal in about 4872 hours.
Serum amylase is also elevated in
i. Pancreatic pseudocyst.
ii. Mumps.
iii. Perforated peptic ulcer.
iv. Ruptured ectopic pregnancy.
v. Ca pancreas.
vi. Intestinal obstruction.
vii. Peritonitis.
2. CT scan Investigation of choice to evaluate the
complications.
3. X-ray abdomen Generalized or local ileus (sentinel loop),
Colon cut-off sign,
Renal halo sign,
Pleural effusion in 20 percent cases,
Gasless abdomen.
Prognosis: Depends on:
Ranson Criteria
a. On admission:
i. Age > 55 years
ii. WBC count > 16,000/l
iii. Blood glucose > 200 mg/dl (11 mmol/lit)
iv. LDH > 350 U/liter.
v. SGOT > 250 U/liter.
b. During first 48 hours:
i. Hematocrit fall > 10 percent
ii. Serum calcium < 2.0 mmol/lit (8 mg%)
- worst prognostic factor
iii. Hypoxemia (PaO2)
iv. Fluid deficit > 4 liter.
Others:
Hypotension (BP < 90 mm Hg)
Note serum amylase level is not included.
Other prognostic criteria:
CECT grade of the severity index.
APACHE (Acute Physiology and Chronic Health
Evaluation) II system.
Balthazar grade of acute pancreatitis.
151
Complications:
1. Purtschers retinopathy loss of vision.
2. Pancreatic pseudocyst:
Most common complication of acute pancreatitis.
Pseudocyst because not lined by epithelium.
Cause:
i. Acute pancreatitis 90 percent
ii. Trauma 10 percent
Site: Body or tail of the pancreas.
Investigation:
1. Serum amylase is increased in 75 percent of patients.
2. USG is confirmatory.
3. CT scan is complementary to USG.
Course: Spontaneous healing may occur within 6 weeks.
Treatment: For those > 5 cm in diameter and persist for
> 6 weeks drainage operation (cystogastrostomy or
cystojejunostomy).
Excision of the cyst.
Complications:
i. Infection is the most common complication.
ii. Rupture.
iii. Hemorrhage.
iv. Abscess.
Chronic Pancreatitis
Clinical feature:
Recurrent abdominal pain may be the only symptom.
Endocrine dysfunction diabetes mellitus.
Exocrine dysfunction steatorrhea
Investigation:
CT scan/MRI Investigation of choice shows
intraductal and intraparenchymal calcification.
ERCP Chain of lakes appearance.
Treatment:
Surgery
Indications Mass in the head of pancreas.
Operation Resection of the head either by a
pancreatoduodenectomy or a Beger procedure.
152
CARCINOMA OF PANCREAS
SPLEEN
ANATOMY
Position: Spleen rests on 9th to 11th ribs on the left
side.
Axis: It is directed obliquely along the 10th rib.
Splenic notch: On superior border.
Ligaments:
1. Lieno-phrenic suspends the spleen from above
suspensory ligament of spleen.
2. Phrenico-colic supports the spleen from below
sustentaculum lienis.
Arterial supply: Only by splenic artery, branch of celiac
trunk. This is the largest branch of celiac trunk. Hence
in celiac trunk obstruction, spleen is mainly affected.
Spleen contains about 2 percent of total blood volume.
Nerve supply: Sympathetic fibers are derived from the
celiac plexus.
Development: From dorsal mesogastrium.
Function: removal of senescent RBC from the
circulation is called culling.
Portal Vein
Formation:
Splenic vein joins the superior mesenteric vein behind
the neck of the pancreas to form the portal vein.
Relations:
In front and to the right bile duct.
In front and to the left hepatic artery.
Porto-systemic shunts:
1. At lower end of esophagus Left gastric vein (portal)
+ hemi-azygos vein.
2. At rectum Superior rectal vein (portal) + middle and
inferior rectal veins.
3. At umbilicus The paraumbilical vein (portal) +
epigastric vein.
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Splenunculi (Accessory Spleen)
Sites:
i. Hilum of the spleen most common site.
ii. Greater omentum.
iii. Tail of the pancreas.
RUPTURE OF SPLEEN
Cause: Blunt trauma.
Clinical feature:
Kehrs sign pain referred to left shoulder.
Investigation:
USG.
X-ray features of splenic rupture:
1. Obliteration of splenic outline most important.
2. Obliteration of psoas shadow.
3. Indentation of the left side of gastric bubble.
4. Fracture of the ribs on left side.
5. Elevation of the left hemidiaphragm.
6. Free fluid between gas-filled intestinal coils.
Treatment:
In stable young patients and especially in children
splenectomy is not done.
Compression in vicryl mesh bag is the treatment of
choice.
Others splenectomy.
Spontaneous Rupture of Spleen
Causes:
1. Malaria most common cause worldwide.
2. Infectious mononucleosis most common cause in
USA.
SPLENOMEGALY
Causes:
a. Blood
1. Chronic leukemias (CML, CLL) and hairy cell
leukemia.
154
2. Hereditary spherocytosis.
3. Autoimmune hemolytic anemia.
4. Thalassemia.
5. Sickle cell anemia at early stages.
6. ITP.
b. Neoplastic Primary fibrosarcoma, Hodgkins
lymphoma.
c. Infections
1. Malaria.
2. Kala-azar.
Hypersplenism
Includes
1. Splenic enlargement.
2. Anemia, leucopenia or thrombocytopenia.
3. Compensatory bone marrow hyperplasia.
4. Improvement after splenectomy.
Feltys Syndrome
1. Chronic rheumatoid arthritis.
2. Leucopenia, especially neutropenia.
3. Splenomegaly.
Neoplasm
Benign most common is hemangioma.
Malignant most common is lymphoma (most
commonly small lymphocytic lymphoma).
Splenic Infarction
Causes:
1. Infective endocarditis.
2. Sickle cell anemia.
3. Hodgkins lymphoma.
4. CML.
5. PAN.
Splenic Abscess
Multiple abscesses are seen in immunosuppressive therapy.
SPLENECTOMY
Indication:
1. Trauma most common indication.
155
2. Hereditary spherocytosis at 3-4 years of age.

3. ITP.
4. Autoimmune hemolytic anemia not absolutely
indicated.
5. Thalassemia.
6. Sickle cell anemia.
7. Primary fibrosarcoma.
8. Splenic abscess.
9. Splenic vein thrombosis.
Postoperative complication:
1. Pulmonary complications most common is left basal
atelectasis.
2. Septicemia
Organism Streptococcus pneumoniae.
More chance in patients
i. Receiving chemotherapy/radiation.
ii. With thalassemia, sickle cell disease, autoimmune
anemia or thrombocytopenia.
Prevention Pneumococcal antitoxin should be given
10 days preoperatively.
All children with splenectomy should receive penicillin
till the age of 18 years.
Note after splenectomy blood shows: Howell-Joly bodies,
neutrophilia, target cells, aniso and poikilocytosis, basophil
stippling.
RECTUM
Prolapse
Partial: Only the mucosa and submucosa are prolapsed.
Treatment
i. In infants Digital reposition.
ii. In adults Excision of prolapsed mucosa.
Complete: All the layers of rectal wall are prolapsed.
Treatment:
Abdominal approach (best) Wells operation (surgery
of choice), rectopexy, Ripsteins operation.
Perineal approach in old, very young and injured
or ill patients Dolormes operation.
156
Solitary Rectal Ulcer

Situated in the anterior wall of rectum.
May cause anterior rectal wall prolapse.
Rectal Stricture
Lymphogranuloma venorum is the most common cause
of inflammatory rectal stricture.
NEOPLASMS
ANAL CANAL
ANATOMY
Length 4 cm.
Dentate/Pectinate Line
It represents the muco-cutaneous junction of anal canal
and corresponds with the position of the anal valves.
Histology
Development
Arterial supply
Lymphatic
drainage
Nerve supply
Applied
Venous
drainage
Part above the

pectinate line
Part below the

pectinate line
Simple columnar
epithelium
From endodermal
cloaca
Superior rectal artery
Internal iliac nodes
Stratified squamous
epithelium
From ectodermal
proctodeum
Inferior rectal artery
Superficial inguinal
nodes
Inferior rectal nerve
branch of pudendal
nerve
External hemorrhoids
Autonomic nerve
Insensitive to modalities
of cutaneous sensation
Distended and varicose
veins are called
internal hemorrhoids
Portal system via
superior rectal vein
Systemic vein via

inferior rectal vein.
Anorectal Ring
Made up of puborectalis part of levator ani muscle.
This is responsible for anal continence.
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CONGENITAL ANOMALY
Imperforate Anus
Radiology: Invertogram taken after 6 hours of birth.
ANAL FISSURE
Location: Mid-line posteriorly most common site.
Diagnosis: History and superficial clinical examination.
Sentinel Pile
It is a tag of edematous skin guarding (hence Sentinel)
a chronic anal fissure at the lower end.
Note there is a hypertrophied papilla at the upper
end of the fissure.
Clinical feature: Pain most common symptom, Bleeding,
Discharge.
Treatment: Approach
Conservative (preferred) if fails, dilatation under GA
if fails, surgery.
1. Conservative with G.T.N. ointment preferred.
2. Surgery Dilatation under GA.
Acute stage Lateral sphincterotomy.
Chronic/recurrent dorsal fissurectomy and
sphincterotomy.
Note digital examination is very painful and should not
be done.
HEMORRHOIDS
It means dilated veins.
External Hemorrhoids
5 day self-subsiding painful lesion is a thrombosed external
pile (perianal hematoma).
Management: Conservative.
Internal Hemorrhoids
First-degree: Hemorrhoids that bleed but do not prolapse
outside the anal-canal.
Second-degree: Hemorrhoids that prolapse on defection
but return to normal or keep in position if replaced.
158
Third-degree: Hemorrhoids that are permanently prolapsed.

Clinical feature: Painless bleeding P/R most common
cause of rectal bleeding in young adults.
On examination:
Internal hemorrhoids cannot be felt on digital
examination.
Investigation proctoscopy.
Treatment:
1. First-degree injection sclerotherapy.
2. Second-degree banding.
3. Surgery hemorrhoidectomy.
Indications of surgeryi. 3rd degree hemorrhoids.
ii. Failure of non-operative treatments in 2nd degree
hemorrhoids.
iii. Fibrosed hemorrhoids.
iv. Interoexternal hemorrhoids.
Complications of surgeryi. Acute urinary retention most common.
ii. Hemorrhage.
ANAL FISTULA
It is a tract lined by granulation tissue which connects
deeply in the anal canal or rectum and superficially on
the skin around anus.
Types:
1. Low level below the ano-rectal ring.
2. High level above the ano-rectal ring.
Intersphincteric is the most common type.
Treatment:
Low level fistulas can be laid open without fear of
permanent incontinence.
Surgery of choice is fistulotomy.
In AIDS patients seton is used.
ANO-RECTAL ABSCESS
Most common is the perineal type.
159
MALIGNANCY
HERNIAS
ANATOMY
Inguinal Canal
Length: 3.75 cm.
Formation:
Oblique canal.
Anterior wall External oblique aponeurosis. Lateral
1/3rd reinforced by internal oblique.
Posterior wall Fascia transversalis.
In the medial half Conjoint tendon which is formed
by internal oblique and transversus abdominis muscles.
Roof Arched fibers of internal oblique and transversus
abdominis.
Floor Groove of inguinal ligament.
Medially by lacunar ligament.
Inlet:
Deep inguinal ring an oval gap in fascia transversalis
above mid-inguinal point.
Triangle of Hasselbach
Bounded:
Laterally by inferior epigastric artery.
Medially by lateral border of rectus abdominis.
Below by inguinal ligament.
Contents:
1. Spermatic cord in male.
Round ligament of uterus in female.
2. Ilio-inguinal nerve- leaves the canal through superficial
ring.
Applied:
1. Indirect/oblique hernia: most common of all types.
Enters the canal through deep ring. Coverings of a
complete (which descends through superficial ring)
hernia (from outside inwards) are
i. Skin.
ii. Dartos muscle (in scrotum).
160
iii. External spermatic fascia.

iv. Cremasteric muscle and fascia.
v. Internal spermatic fascia.
vii. Extra-peritoneal fat.
viii. Peritoneum.
2. Direct: Through Hasselbachs triangle.
INGUINAL HERNIA
Indirect Inguinal Hernia
More common in young males.
More common on right side.
Direct Inguinal Hernia
More common in older people.
Strangulated Inguinal Hernia
Type:
Indirect hernias more often strangulate.
Direct hernias do not often strangulate due to wide
mouth of the sac.
Constricting agent:
Neck of the sac most common.
External inguinal ring in children.
Contents: Small intestine (more common), omentum.
Treatment:
1. Surgery Emergency. Fundus is delivered first.
2. Resuscitation with IV fluids, nasogastric suction and
antibiotics.
Surgery for inguinal hernia:
Inguinal herniotomy basic operation for all other
procedures. It is sufficient in infants, children and young
adults.
Complications injury to the ilio-inguinal nerve.
Note the most important step in hernia repair is
narrowing of the internal ring.
Sliding Hernia
Posterior wall of the sac is formed by peritoneum and
sigmoid colon and mesentery on the left side; caecum on
the right (indirect); bladder (direct).
161
Clinical feature: More common on left side.

Treatment: A sliding hernia is impossible to control with
struss. So surgery is always indicated.
SPECIAL TYPES
Littres Hernia:
When the content of the hernia is Meckels diverticulum.
Pantaloon Hernia:
When both direct and indirect inguinal hernias occur
simultaneously.
Gibbons Hernia:
Hernia with hydrocele.
Bergers hernia:
Hernia into the pouch of Douglas.
FEMORAL HERNIA
Anatomy
Femoral Canal
Length 1.25 cm.
Position It occupies the most medial compartment
of femoral sheath.
Extent femoral ring above to saphenous opening
below.
Base is directed upwards.
Femoral Ring
Boundary Anteriorly by inguinal ligament.
Posteriorly by pectineus muscle and fascia.
Medially by base of lacunar ligament.
Laterally by femoral vein.
Saphenous Opening
Situation 3 cm below and lateral to the pubic tubercle.
Covering Cribriform fascia.
Pierced by
i. Great saphenous vein.
ii. Superficial epigastric and superficial external pudendal
arteries.
162
iii. Few branches of medial femoral cutaneous nerve.

iv. Few lymph vessels.
Features
Sex more common in females.
Side more common on right side.
Most common hernia to be strangulated because of
the narrowness of the neck and its rigid surroundings.
Richters Hernia
Content only a portion of the circumference of the
intestine.
More commonly complicates the femoral hernia.
ABDOMINAL WALL HERNIAS
Umbilical Hernia (Exomphalos/Omphalocele)
Etiology: Failure of all or part of the mid gut to return
to the coelom during early fetal life.
Covering: amniotic membrane and peritoneum.
Content:
1. Defect < 4 cm (herniation of the umbilical cord)
a single loop of intestine.
2. Large defect > 4 cm any abdominal viscus.
Feature: The intestine remain freely mobile within the hernia
sac without any signs of adhesions or inflammation least
chance of obstruction.
Surgery: surgery is done soon after birth for small defects.
Paraumbilical Hernia
It is a protrusion through linea alba just above or sometimes
below the umbilicus.
Size: These may become very large.
Content:
Usually greater omentum accompanied by small
intestine.
Sometimes a portion of transverse colon.
163
Clinical feature:
More common in aged females.
Symptom dragging pain, gastrointestinal symptoms.
Treatment:
1. Epigastric herniorrhaphy for small defects (described
by Mayo).
2. Paraumbilical hernioplasty for larger defects.
Complication:
Strangulation is a frequent complication.
Treatment of complication Paul-Mikulicz method for
gangrenous transverse colon.
Epigastric Hernia
Protrusion through linea alba.
Site: Anywhere between the xiphoid process and the
umbilicus, usually midway between the two.
Origin: Thought to be due to protrusion of extraperitoneal
fat at the site where small vessels pierce the linea alba.
Content: Extra-peritoneal fat, peritoneum in true hernia.
Clinical feature:
Often symptomless.
Referred pain pain suggestive of a peptic ulcer.
Spigelian Hernia
Interparietal hernia occurring at the level of the arcuate
line lateral to the rectus muscle and below the umbilicus
(infraumbilical).
Recurrent Hernia
Causes:
Absorbable suture,
Sliding hernia,
Missed sac,
Infection.
RESPIRATORY SYSTEM
ANATOMY
BRONCHOPULMONARY SEGMENTS
Pyramidal in shape
Each segment is aereted by a tertiary or segmental
bronchus and has its own separate artery, but does
not have own vein.
Segments:
Bronchopulmonary segments
Rt. lung
Lt. lung
Upper lobe:
i. Apical
ii. Anterior
Middle lobe:
i. Medial
ii. Lateral
Lower lobe:
i. Superior
ii. Anterior basal
iii. Posterior basal
iv. Lateral basal
Upper lobe:
i. Apico-posterior
ii. Anterior
Lingular lobe:
i. Superior
ii. Inferior
Lower lobe:
i. Antero-medial basal
ii. Posterior basal
iii. Lateral basal
Arterial supply of lung

Bronchial tree upto respiratory bronchiole: bronchial
artery and pulmonary artery.
Part distal to respiratory bronchiole: pulmonary artery
alone.
PHYSIOLOGY
RESPIRATORY FUNCTION
Definitions
Different respiratory volumes
Definition
Value
Tidal volume (TD) The amount of air that
moves into the lungs with
each inspiration
0.5 L
Contd...
Respiratory System
165
Contd...
Definition
Value
Inspiratory reserve The air inspired with

3.3 L
volume (IRV)
maximum effort in excess
of TV
Expiratory reserve The volume of air
1 L
volume (ERV)
expelled by an active
expiratory effort after
passive expiration
Residual volume
The air left in lungs after
1.2 L
(RV)
a maximum expiratory effort
Vital capacity
The largest amount of air
0.5+3.3+1.0
(VC)
that can be expired after
= 4.8 L
a maximal inspiratory effort.
VC= TV+IRV+ERV
Total lung
TLC= VC+RV
4.8+1.2
capacity (TLC)
= 6.0 L
Timed vital
The rate at which air can
FEV 1 = 80%
capacity/forced
be expelled from the lungs - of VC
expiratory volume FEV1 = at 1 second;
FEV 3 = 97%
FEV3 = at 3 seconds
of VC
The maximal
Forced expiratory flow
midexpiratory flow (FEF) between 25 and
rate (MMFR)
75% of the VC, or FEF25-75%
Maximum voluntary
125-170 L mm
ventilation
Functional residual The volume of gas in
1.0+1.2= 2.2 L
capacity (FRC)
the lungs at the end of
a normal exhalation FRC= ERV+RV
Relaxation volume Lung volume at which
It is equal
intrapulmonary pressure
to FRC= 2.2 L
is 0.
Compliance:
Change in lung volume per unit change in airway
pressure. (V/P).
TLC depends upon lung compliance.
Compliance is decreased by pulmonary congestion and
interstitial lung fibrosis.
It is increased in emphysema.
Diffusing capacity:
The ability of gas to diffuse across the alveolar-capillary
membrane is ordinarily assessed by the diffusing
capacity of the lung for carbon monoxide (DLco).
DLco is decreased in interstitial lung disease,
emphysema, primary pulmonary hypertension, and
recurrent pulmonary emboli.
166
DLco is increased in CCF, alveolar hemorrhage (e.g.

Good Pastures disease).
Closing volume:
This is the volume at which the small airways tend to
collapse. It determines small airway resistance.
Measurement
1. Spirometer: Measures IRV, ERV, VC, TV but not RV,
FRC or TLC.
2. Vitalograph: measures VC and FEV.
3. N2 wash out measures RV.
4. Diffusion of CO (DLco): Diffusing capacity.
5. Helium dilution and body plethysmography - measure
RV, FRC and TLC. Body plethysmography is
particularly useful in patients with emphysematous
bullae not connected to bronchial tree.
Alterations in Ventilatory Function
Alterations in ventilatory function
Obstructive lung disease

Restrictive lung disease
TLC
RV
VC
FEV/FVC
N or
N or
PULMONARY CIRCULATION
The pulmonary circulation is a distensible low-pressure
system.
In an upright position, pulmonary arterial pressure (PAP)
is lowest at the apex of the lung and highest at the
lung base. As a result, in the upright position, perfusion
is least at the apex and greatest at the base.
Pulmonary arterial pressure = 24/9 mmHg with mean
pressure of 15 mmHg, i.e. 1/7th of systemic arterial
pressure.
Pulmonary veins are distended at the lower portion
of the lungs.
Systemic hypoxia causes pulmonary arterioles to
constrict increased pulmonary arterial pressure.
Measurement
PVR = 80(PAPPCWP)/CO
Where PVR = Pulmonary vascular resistance.
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167
PAP = Pulmonary arterial pressure.

PCWP = Pulmonary capillary wedge pressure. It
corresponds to left atrial pressure.
CO = Cardiac output.
Swan-Ganz catheter measures PAP and PCWP.
CO can be obtained by the thermodilution method.
Intraventricular pressure measurement by pulmonary
artery catheter is done at the end of expiration.
GAS EXCHANGE
Dead Space
1. Anatomical dead space: A portion (approximately 30%)
of the fresh air inspired with each breath does not reach
the alveoli but remains in the conducting airways of
the lung. This component of each breath, which is
not generally available for gas exchange, is called the
anatomic dead space component = 150 ml.
2. Physiological dead space: In a normal individual both
are equal. In certain diseases, some alveoli are ventilated
but not perfused, so that some ventilation in addition
to the anatomic dead space component is wasted. In
these conditions, physiological as well as total dead
space is increased.
The total or physiological dead space can be
measured by Bohrs equation using
Pco2 of expired air (PAco2)
Pco2 of arterial blood (Paco2) and
Tidal volume.
Ventilation and Perfusion
Ventilation barrier: The ventilation barrier is constituted
by alveolocapillary membrane made up of the pulmonary
epithelium, the capillary endothelium and their fused
basement membranes with scant pericapillary interstitial
tissue.
Values
In normal individual V/Q =1.
Ventilation per unit volume and blood flow (perfusion)
are both greater at the lung bases than at the apices;
but V/Q ratios are greater at the lung apices than at
the bases.
168
Gases
Alveolar air O2 concentration (PAo2) = 100 mmHg.
Alveolar air CO2 concentration (PAco2) =40 mmHg.
PAo2 Pao2 is usually <15 mmHg for subjects <30
years old and increases by ~3 mmHg per decade after
age 30.
Hypoxemia
It is defined as Pao2 <80 mmHg.
Causes:
1. V/Q mismatch- most common cause; it is due to airway
diseases (asthma, COPD), interstitial lung disease,
alveolar disease, pulmonary vascular disease.
2. Decrease in inspired air, e.g. due to high altitude.
3. Hypoventilation- it is due to decreased respiratory drive
or neuromuscular diseases.
4. Shunting, e.g. atelectasis, intra-alveolar filling
(pneumonia, pulmonary edema), intracardiac shunts,
vascular shunts within lungs.
Diagnosis
Respiratory failure
Pao2
Paco 2
PA-aO2
Mechanism
Causes
Type I
Type II
(<60 mmHg)
or ( 49 mmHg)
Defective oxygenation
V/Q mismatch,
Decrease in inspired air,
Shunting
(<60 mmHg)
(> 49 mmHg)
Normal
Hypoventilation
Depressed respiratory
center (e.g. brain
injury),
Respiratory muscle
weakness, Polio,
Kyphoscoliosis
Note: Hypoxemia due to V/Q mismatch and hypoventilation are correctable by 100% oxygen.
Hypoxia
Hypoxia means deficient oxygen supply to the tissues.
Hypoxic hypoxia
Most common type. The arterial PO2 is decreased leading
to stimulation of chemoreceptors and hyperventilation.
Respiratory System
169
Causes
1. Ventilation-perfusion mismatch- most common cause,
2. Ascend to high altitude.
Changes at high altitude: Rapid in PAO 2
hyperventilation PACO2 Respiratory alkalosis.
Acclimatization Increased erythropoietin secretion
Increased cortisol secretion
Reticulocytosis Increased RBC in blood.
Increased 2,3 DPG decreased O2 affinity.
CSF - Increased H+ and decreased HCO3 (acidosis)
hyperventilation.
3. Shunt- congenital cyanotic heart diseases.
4. Atelectasis or collapse of the lung.
(Note: N2 prevents atelectasis).
5. Asthma, emphysema- COPD.
i.
ii.
iii.
iv.
v.
Anemic hypoxia
Pathology:
Decreased O2 carrying of blood due to decreased Hb.
PO2 remains normal, and respiratory center is not
stimulated.
CO poisoning - produces anemic hypoxia. CO binds
to Hb to form carboxyHb (cherry-red color).
Treatment:
Hyperbaric oxygenation.
Stagnant hypoxia
Due to slow circulation (hypotension).
Hypoxia affects kidney and heart in shock and liver
and brain in CHF.
Histotoxic hypoxia
Due to cyanide poisoning inhibition of cytochrome
oxidase and inhibition of tissue oxidative process.
Hyperbaric O2 therapy
Exposure to 100% O2 at 2-3 atmospheric pressure for
5 hours.
Indications:
1. Carbon monoxide poisoning
2. Radiation injury
3. Gas gangrene
170
4. Diabetic leg ulcer

5. Decompression sickness
6. Air-embolism.
Hypoventilation
Cause
1. Bulbar poliomyelitis
2. Kyphoscoliosis
3. COPD
4. Metabolic alkalosis
5. G-B syndrome
Pathophysiology: in alveolar Pco2 (PAco2) in arterial
Pco2 (Paco2) respiratory acidosis HCO3 in plasma.
Pickwickian syndrome:
Obesity hypoventilation hypercapnia, hypoxemia
polycythemia, pulmonary hypertension, right ventricular
failure and day time somnolence.
Primary Pulmonary Hypoventilation
Etiology: Impaired ventilatory response to chemical stimuli.
Clinical features:
Common in males aged 20-50 years
Chronic hypoxemia, hypercapnia.
Diagnosis: Respiratory acidosis.
Hyperventilation
Causes:
1. High altitude
2. Pneumonia
3. CCF
4. Metabolic acidosis
5. Drugs- aspirin, -blockers
Clinical features:
1. Dyspnea- most common symptom.
2. Respiratory alkalosis - dizziness, visual impairment,
syncope, paresthesia, tetany (due to decreased Ca++),
muscle weakness (due to decreased PO42).
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171
CO2 Narcosis
When PAco 2> 7%, arterial CO 2 increases despite
hyperventilation produces CNS depression (respiratory
center is also depressed) and produces headache, confusion
and coma; fall in pH of CSF; and papilledema.
GAS TRANSPORT
O2 Transport
O2-Hb dissociation curve:
Each gram of Hb contains 1.34 ml of O2.
1 Hb molecule reacts with 4 molecules of O2 to form
Hb4O8.
Iron in Heme is in Fe++ state, and it stays in this state
in Hb4O8, so the reaction is oxygenation, not oxidation.
The curve has a sigmoid shape.
Note: PO2 of 100 mmHg in arterial blood corresponds
to 97.5% saturation of Hb or 0.3 ml/dl of dissolved
O2.
Regulation
1. Any shift to right decreases affinity and vice versa.
2. The curve shifts to right by:
i. Increase in temperature.
ii. Fall in pH.
iii. Increased 2, 3-DPG concentration.
3. The curve shifts to right in shock, RDS and CCF.
pH: Decrease in O2 affinity of Hb when pH is decreased
is called Bohr effect. It is because; deoxygenated Hb binds
H+ more actively than does oxyHb.
2, 3-DPG
It is formed from 3-phosphoglyceraldehyde in E-M
pathway.
2, 3-DPG concentration is increased ini. Exercise
ii. Ascent to high altitude
iii. Anemia
iv. Chronic hypoxia
Consequently all these conditions decrease O2 affinity.
2, 3-DPG concentration is decreased ini. Stored blood
ii. Fall in pH
iii. Fetal Hb (HbF)
172
Myoglobin
Binds only 1 molecule of O2 per mole.
Its dissociation curve has a rectangular hyperbolic
shape.
CO2 Transport
The solubility of CO2 in blood is about 20 times that
of O2.
Fate in plasma:
1. Formation of carbamino compound with plasma
proteins.
2. HydrationCO2 + H2O
CA
H2CO3
H+ + HCO3
H+ is buffered primarily by Hb, HCO3 remains as such

and CO2 is transported in blood as HCO3.
Fate in RBC
1. Formation of carbamino-Hb.
2. Hydration, H+ buffered, 70% HCO3 enters the plasma.
3. The excess HCO3 in RBC is transported to plasma
in exchange of Cl - by Band 3, a process called chloride
shift.
Amount of CO2 transported to lungs and excreted
= 200 ml/min at rest = 288 L/day.
Venous blood vs. arterial blood:
Venous blood contains
i. More Clii. More hematocrit by 3%.
DIAGNOSTIC PROCEDURES
Chest X-ray
Hilar shadow: is composed of:
i. Pulmonary arteries.
ii. Upper lobe pulmonary veins.
iii. Major bronchi.
iv. Lymph nodes.
Kerley lines:
Types i. Kerley A lines- radiate from hila.
Respiratory System
173
ii. Kerley B lines Extend from pleural surface.

Perpendicular to pleural surface.
Best seen in costophrenic angle.
iii. Kerley C lines- spider web appearance.
Cause Thickening or widening of interlobular septa.
Distension of interlobular lymphatics.
Seen in 1. Pulmonary venous hypertension i. LVF
ii. MS
2. Lymphatic obstruction i. Pneumoconiosis
ii. Lymphangiitis carcinomatosa
iii. Sarcoidosis
3. Interstitial pneumonitis.
Pulmonary nodule:
A nodule defined as solitary circumscribed density
<6 cm in diameter.
Causes of solitary pulmonary nodule
i. Congenital- hamartoma (popcorn calcification).
ii. Neoplastic- adenoma, neurofibroma.
iii. Infection- tuberculosis, hydatid cyst, lung abscess.
CT Scans
Uses:
1. Assessment of hilar and mediastinal disease.
2. Identifying and characterizing diseases close to chest
wall or spine (including pleural disease).
3. Identifying areas of fat density or calcification in
pulmonary nodules.
4. Important tool for staging of lung cancer.
Bronchoalveolar Lavage
BAL is particularly helpful in recovery of organisms
such as Pneumocystis carinii in patients with HIV
infection.
BAL is also useful in the evaluation of interstitial lung
diseases shows increased neutrophil count.
174
DISEASES OF RESPIRATORY
SYSTEM
Obstructive lung disease
Restrictive lung disease
1. Asthma
2. Chronic obstructive
pulmonary diseases
(COPD)
i. Chronic bronchitis
ii. Emphysema
3. Bronchiectasis
4. Cystic fibrosis
5. Bronchiolitis
A. Parenchymal
1. Idiopathic pulmonary fibrosis
2. Sarcoidosis
3. Hypersensitivity pneumonitis
4. Diffuse alveolar hemorrhage
syndrome
5. Pulmonary angitis and
granulomatosis
6. Lung in collagen vascular
diseases
B. Extraparenchymal
1. Neuromuscular
a. Diaphragmatic paralysis
b. Myasthenia gravis
c. G-B syndrome
d. Muscular dystrophies
e. Cervical spine injury
2. Chest wall
a. Kyphoscoliosis
b. Obesity
c. Ankylosing spondylitis
OBSTRUCTIVE LUNG DISEASES

ASTHMA
Pathogenesis
Constriction of terminal bronchioles hyperventilation
decreased PCO2.
Mediators: Histamine, bradykinin, the leukotrienes C, D
and E; PAF and PGE2, PGF2 and PGD2.
Drugs inducing asthma:
Aspirin, coloring agents (e.g. Tartrazine), - -blockers.
Aspirin sensitive respiratory syndrome - associated with
nasal polyps. Incidence - 1 to 2%.
Environmental factors:
Games like ice hockey, ice-skating provoke asthma.
Indoor swimming in heated pool is relatively safe.
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175
Clinical Features
Severe Acute Asthma:
Symptoms- triad of dyspnea, cough and wheezing (sinequa-non).
SignsExpiration is prolonged.
Tachypnea, tachycardia.
Mild systolic hypertension.
Ronchi- may be absent in very severe asthma- silent
chest.
Accessory muscles become visibly active.
Pulsus paradoxus (the last two signs indicate severity
of obstruction)
Sweating.
Cyanosis- a late sign.
The end of an episode is marked by a productive cough.
The produce takes the cast of the distal airways
(Curschmann spirals). Under microscope they show
numerous eosinophils and Charcot-Leyden crystals.
Chronic asthma: May produce Pigeon chest deformity.
Cough variant asthma: Patient presents with persistent
cough with no (or episodic) wheezing and dyspnea.
Treatment
Severe Acute Asthma (Status asthmaticus):
1. O2.
2. 2-agonists- nebulization with O2.
Drugs - sulbutamol or terbutaline.
(salmeterol- not recommended for acute episodes).
3. Systemic steroids - IV hydrocortisone or oral
prednisolone. (Inhaled steroids have no role in acute
asthma).
4. Ipratropium bromide.
Chronic Asthma:
Drug therapy 1. 2-agonists - salbutamol, terbutaline, salmeterol.
2. Methyl xanthines - theophylline, aminophylline.
3. Anticholinergics - atropine sulfate, ipratropium bromide.
4. Glucocorticoids - inhalation route preferred.
Side-effects of inhalation steroids Thrush, dyspnea, adrenal suppression, cataract
formation, decreased growth in children, purpura.
176
5. Mast cell stabilizers- sodium cromoglycate (not used

in acute asthma). They are most effective in atopic
patients who have either seasonal disease or perennial
airway stimulation.
6. Leukotriene Modifiers: Zileuton (5-lipoxygenase
synthesis inhibitor) provides protection against exerciseinduced asthma, and diminishes nocturnal symptoms,
but it has limited effectiveness against allergens.
The LTD 4 receptor antagonists (Zafirlukast and
Montelukast) - longer acting.
Monitoring: The course of the illness and the effectiveness
of therapy can be followed by measuring peak expiratory
flow rates (PEFRs) at home and/or the FEV1 in the
laboratory.
CHRONIC OBSTRUCTIVE
PULMONARY DISEASES (COPD)
Definition
Chronic bronchitis: Productive cough on most days of at
least 3 consecutive months for more than 2 successive
years.
Emphysema: Permanent dilatation of air spaces distal to
terminal bronchioles with destruction of pulmonary septa.
COPD:
Chronic obstructive pulmonary disease (COPD) is the
name of a group of chronic and slowly progressive
respiratory disorders characterized by reduced maximal
expiratory flow during forced exhalation.
COPD comprises of emphysema and chronic
bronchitis.
Airflow obstruction is characterized by FEV1 <80%
of predicted and FEV1/FVC ratio <70%.
Risk Factors
1.
2.
3.
4.
Cigarette smoking - most important risk factor.

Air pollution - especially SO2 and NO2.
Infection - rhinovirus, mycoplasmas.
1 antitrypsin deficiency - it is a serine proteinase
inhibitor; hence its deficiency leads to increased
protease activity. The disorder is transmitted as an
Respiratory System
177
autosomal recessive trait. It is associated with premature

development of severe emphysema, chronic bronchitis,
or bronchiectasis and hepatic cirrhosis.
Pathology
Chronic bronchitis: Hypertrophy of mucus-producing
glands; bilateral involvement.
Reid index: Ratio of thickness of submucosal glands to
that of bronchial wall. Normal value- 0.44 0.09
With H/O bronchitis - 0.52 0.08
Emphysema
Types1. Centriacinar (centrilobular) most common type.
Involves respiratory bronchioles but spares distal alveoli.
Most commonly associated with cigarette smoking.
2. Panacinar (panlobular) acini uniformly involved from
respiratory bronchiole to distal alveoli. Most commonly
associated with 1 antitrypsin deficiency.
3. Distal acinar (paraseptal) more striking adjacent to
pleura. Forms multiple cyst-like air spaces adjacent to
pleura. Probably cause spontaneous pneumothorax in
young adults.
Clinical Features
Differentiating features
Features
Predominant
emphysema
Predominant
bronchitis
Dyspnea
Hyperventilation
Severe
+ve (So they have
adequate oxygenation
of Hb- Pink puffers)
(35-40 mmHg)
Mild
ve (So they retain CO2.
become hypoxic and
cyanotic- blue bloters)
(50-60 mmHg)
Chronic Paco2
(Normal
40 mmHg)
Chronic Pao2
(65-75 mmHg)
(Normal
100 mmHg)
Respiratory
Uncommon
infection
Cor pulmonale
Rare
(Pul HPT+ RVF)
(45-60 mmHg)
Common
Common
178
Chest X-ray
Emphysema is manifested by an increased lucency of
the lungs. In smokers, these changes are more prominent
in the upper lobes, while in 1 antitrypsin deficiency,
they are more likely in basal zones.
In emphysema, CXR shows wide intercostals spaces.
Complications
1. Pulmonary hypertension.
2. Pneumothorax in severe long standing emphysema.
3. ECG changes most commonly supraventricular
tachycardia.
4. Acute respiratory failure indicated by a drop in Pao2
10-15 mmHg.
Management
1. Smoking cessation - most important part.
2. Bronchodilators like 2 -adrenergic agonists,
anticholinergics, and theophylline derivatives.
3. Glucocorticoids.
4. Management of exacerbations in similar way to that
of acute asthma.
BRONCHIECTASIS
Definition
Bronchiectasis is the abnormal permanent dilatation of
bronchi and bronchioles caused by destruction of muscle
and elastic supporting tissue, resulting from or associated
with chronic necrotizing infections.
Pathology
The bronchial dilatation of bronchiectasis is associated
with destructive and inflammatory changes in the walls
of medium-sized airways, often at the level of segmental
or subsegmental bronchi. The normal structural
components of the wall, including cartilage, muscle, and
elastic tissue, are destroyed and may be replaced by fibrous
tissue. The dilated airways frequently contain pools of thick,
purulent material, while more peripheral airways are often
occluded by secretions or obliterated and replaced by
fibrous tissue.
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179
Types
In cylindrical bronchiectasis the bronchi appear as
uniformly dilated tubes that end abruptly at the point
that smaller airways are obstructed by secretions.
In varicose bronchiectasis the affected bronchi have
an irregular or beaded pattern of dilatation resembling
varicose veins.
In saccular (cystic) bronchiectasis the bronchi have a
ballooned appearance at the periphery, ending in blind
sacs without recognizable bronchial structures distal
to the sacs.
Etiology
Congenital
1. Primary ciliary dyskinesia - structural abnormality of
the dyenin arms, radial spokes and microtubules;
autosomal recessive disorder.
Kartageners syndrome (immotile cilia syndrome):
Bronchiectasis (due to primary ciliar dysfunction),
sinusitis, transposition of viscera and male infertility.
2. Cystic fibrosis.
3. Panhypogammaglobulinemia is associated with
recurrent infection and bronchiectasis, patients often
also have a history of sinus or skin infections.
Acquired
In children - usually due to pneumonia following
whooping cough or measles.
In adults - organisms commonly responsible are Adenovirus and influenza virus,
Staphylococcus aureus, Klebsiella, and anaerobes,
Pseudomonas aeruginosa,
Hemophilus influenza - most common infection.
Pulmonary tuberculosis.
Clinical Features
Site: most common in left lower lobe.
Symptoms: Recurrent cough with purulent sputum,
hemoptysis.
Sign: Course crepitations over the affected area; finger
clubbing.
180
Complication
1.
2.
3.
4.
Amyloidosis.
Lung abscess.
Abscess at distant sites e.g. brain.
Arthropathy.
Note: Bronchiectasis has no malignant potential.
Investigations
1. Sputum examination.
2. High resolution CT scan - most sensitive and also the
investigation of choice. The classic appearance of a
cross-section of a thick-walled dilated bronchus next
to the accompanying pulmonary artery is the Signet
ring sign.
3. Chest X-ray - it may be normal; or may show nonspecific changes or characteristically show tram track
appearance in longitudinal view and ring shadow in
cross-sectional view.
4. Bronchography has now been replaced by CT scans.
CYSTIC FIBROSIS
Genetics
CF is an autosomal recessive disorder. The CF gene is
located on chromosome 7 and codes for a protein called
the cystic fibrosis transmembrane regulator protein (CFTR)
which acts as an ATP responsive chloride channel and
regulates other ion channels especially sodium.
Pathophysiology
Sweat glands - sweat has high concentrations of both
sodium and chloride.
Respiratory tract - The diagnostic biophysical hallmark
of CF is the raised transepithelial electric potential
difference (PD) detected in airway epithelia. This also
leads to local impairment of antibacterial defenses and
subsequent bacterial colonization and recurrent
respiratory tract infection, bronchiectasis.
Pancreas - malabsorption and progressive destruction
of the pancreas with cyst formation (fibrocystic disease
of pancreas). The islet cells too are progressively
destroyed leading to insulin deficiency and diabetes.
Respiratory System
181
Biliary tract biliary cirrhosis and associated

extrahepatic biliary stenosis.
Gut meconium ileus in neonates and the distal
intestinal obstruction syndrome in adults.
Reproductive system male infertility due to
azoospermia because of congenital bilateral absence
of the vas deferens (CABVD).
Microbiology
Respiratory infection is a chronic and serious occurrence
in CF. Staphylococcus aureus is the most common
organism in childhood whereas Pseudomonas aeruginosa
is the commonest colonizing organism after the age of
10 years. Others are Haemophilus influenzae, Burkholderia
cepacia, Aspergillus fumigatus.
Diagnosis
It is based on a combination of clinical criteria and
analyses of sweat Cl- values.
To diagnose cystic fibrosis in a child, the sweat chloride
concentration should be greater than 60 mmol/l, and
the sweat sodium concentration less than that of
chloride.
In adults Sweat Cl concentration is typically >70
mmol/l. Na concentration is also increased.
Nasal electrical potential difference is raised.
BRONCHIOLITIS
Organism: Respiratory syncytial virus (RSV).
Course: There is relationship of acute bronchiolitis and
bronchial asthma in latter life.
Clinical Features
Common age is 6 months, artificial feeding predisposes
to it.
Tachypnea, respiratory distress (retraction of IC spaces
and suprasternal notch), cyanosis, rales and ronchi.
Treatment
Humid atmosphere.
182
O2 is the mainstay of treatment.

Antibiotics have no role though antiviral ribavirin is
used.
RESTRICTIVE OR INTERSTITIAL
LUNG DISEASES
Classification
Major categories of alveolar and interstitial inflammatory lung disease
Lung response:
Lung response: Alveolitis,
Granulomatous
interstitial inflammation, and
fibrosis
Known cause
Hypersensitivity
Asbestos, Fumes, gases
pneumonitis (organic
Drugs (antibiotics, amiodarone,
dusts)
gold) and chemotherapy drugs
Inorganic dusts:
Radiation
beryllium,silica
Aspiration pneumonia
Unknown cause
Idiopathic interstitial
(lymphocytic interstitial
pneumonias
pneumonitis associated
Idiopathic pulmonary fibrosis with connective tissue
most common cause.
disease)
Desquamative interstitial
Eosinophilic pneumonias
pneumonia
Lymphangio Respiratory bronchiolitisleiomyomatosis
associated interstitial lung
Amyloidosis
disease
Inherited diseases
Acute interstitial pneumonia
(Tuberous sclerosis,
(diffuse alveolar damage)
neurofibromatosis, Nien,
Cryptogenic organizing
ann-Pickdisease,
pneumonia (bronchiolitis
Gauchers disease,
obliterans with organizing
Hermanskypneumonia)
Pudlaksyndrome)
Nonspecific interstitial
Gastrointestinal or liver
pneumonia
diseases (Crohns disease,
Connective tissue diseases primary biliary cirrhosis,
(Systemic lupus erythematosus,
chronic active
rheumatoid arthritis, ankylosing
hepatitis,ulcerative colitis)
spondylitis, systemic sclerosis,
Graft-vs.-host disease
Sjgrens syndrome,
(bone marrow
polymyositis-dermatomyositis)
transplantation;solid organ
Pulmonary hemorrhage
transplantation)
syndromes(Good pastures
syndrome, idiopathic pulmonary Sarcoidosis
hemosiderosis, isolated
Langerhans cell
pulmonary capillaritis)
granulomatosis
Pulmonary alveolar proteinosis
(eosinophilic granuloma
Lymphocytic infiltrative disorders
of the lung)
Contd...
Respiratory System
183
Contd...
Granulomatous vasculitides
Bronchocentric
(Wegeners granulomatosis,
granulomatosis
allergic granulomtosis of Churg- Lymphomatoid
Strauss)
granulomatosis
Pathology
There is diffuse thickening of pericapillary interstitium and
alveolar wall by inflammatory cells and exudates (e.g. ARDS), granulomas (e.g. - sarcoidosis), hemorrhage (e.g.
- Goodpasteurs syndrome) and/or fibrosis (e.g. - fibrosing
alveolitis).
Clinical Features
Symptoms - shortness of breath on exertion.
Sign - digital clubbing, end-inspiratory crepitations
Investigation
Bronchoalveolar lavage (BAL).
HRCT Investigation of choice.
IDIOPATHIC PULMONARY FIBROSIS/
CRYPTOGENIC FIBROSING ALVEOLITIS
Clinical Features
Exertional dyspnea, a nonproductive cough, with or without
digital clubbing. Bilateral end-inspiratory crepitations - over
the lower zones posteriorly.
Diagnosis
A surgical biopsy showing the usual interstitial pneumonia
pattern of pathology and
Major criteria
1. Exclusion of other known causes of diffuse lung disease
such as certain drug toxicities, environmental
exposures, and rheumatological diseases;
2. Abnormal pulmonary function studies that include
evidence of restriction (reduced VC often with an
increased FEV1/FVC ratio) and impaired gas exchange
(increased P(A-a)O2 at rest or on exercise or decreased
DLco);
184
3. Bibasilar reticular abnormalities with honeycombing

and minimal or no ground glass opacities on high
resolution computed tomography scans;
4. Transbronchial lung biopsy or bronchoalveolar lavage
showing no features to support an alternate diagnosis,
such as granulomas on biopsy or an excess of
lymphocytes on bronchoalveolar lavage.
Minor criteria1. Age more than 50 years;
2. Insidious onset of otherwise unexplained dyspnea on
exertion;
3. Duration of illness more than 3 to 6 months;
4. Bibasilar, inspiratory crackles on chest auscultation.
The presence of all of the following major diagnostic
criteria as well as at least three of the four minor criteria
increases the likelihood of a correct clinical diagnosis
of cryptogenic fibrosing alveolitis.
SARCOIDOSIS
Multisystem disorder characterized by:
1. Non-caseating granuloma in lungs.
2. Bilateral hilar and paratracheal lymphadenopathypotato nodes on chest X-ray.
3. Involvement of almost any organ in the body except
adrenals.
Diagnosis: Kveims test.
HYPERSENSITIVITY PNEUMONITIS/EXTRINSIC
ALLERGIC ALVEOLITIS
These are a group of disorders caused by hypersensitivity
to organic dusts. For deposition of the dust to occur
predominantly in the gas exchanging tissues, particle size
must be largely confined to the range 0.5 to 5 m.
This is a combination of type III and type IV
hypersensitivity reactions.
Examples of hypersensitivity pneumonitis
Disease
Antigen
Source of Antigen
Bagassosis
Thermophilic
actinomycetesa
Parakeet, pigeon,
chicken, turkey
Moldy bagasse
(sugar cane)
Avian droppings
or feathers
Bird fanciers,
breeders, or
Contd...
Respiratory System
185
Contd...
Disease
Antigen
b
handlers lung
Chemical
workers lungb
Farmers lungb
Source of Antigen
proteins
isocyanates
Polyurethane foam,
varnishes,lacquer
Thermophilic
Moldy hay, grain,
actinomycetesa
silage
Humidifier or
Aureobasidium pullulans Contaminated water
air-conditioner or other microorganisms in humidification or
lung (ventilation
forced-air airpneumonitis)
conditioning systems
Woodworkers
Wood dust, Alternaria
Oak, cedar, pine, and
lung
mahogany dusts
a
Thermophilic actinomycetes species include Micropolyspora faeni

Thermoactinomyces vulgaris, T. saccharrii, T. viridis, and T. candidus.
Most common causes of hypersensitivity pneumonitis in the United
States.
Farmers Lung
Hypersensitivity to mouldy hay containing thermophilic
actinomycetes, particularly Micropolyspora faeni (now
known as Saccharopolyspora rectivirgula) and
Thermoactinomyces vulgaris; also non-thermophilic
aspergillus species.
Bagassosis
Hypersensitivity to sugar cane dust.
Bagasse control - spraying bagasse dust with 2%
propionic acid.
Diagnosis
After acute exposure to antigen, neutrophilia and
lymphopenia are frequently present. Eosinophilia is
not a feature (cf. pulmonary infiltrates with
eosinophilia).
Elevations in erythrocyte sedimentation rate, C-reactive
protein, rheumatoid factor, and serum immunoglobulins.
Precipitin test - presence of serum precipitins against
suspected antigens.
186
PNEUMOCONIOSIS
Asbestosis
Asbestosis is pulmonary fibrosis caused by exposure to
fibres of asbestos.
Type of fibers: Chrysolite, amosite, anthophyllite, and
crocidolite (most common).
Epidemiology: The disease does not usually appear until
after 5-10 years of exposure. But once established, it is
progressive even after removal of the worker from contact.
Pathology:
The characteristic lung lesions are:
Macroscopic appearance - grey fibrosis more marked
peripherally and in the lower zones. In severe cases
the fibrosis appears like a honeycomb.
Parietal pleural plaques implies exposure and not
disease. These are often calcified.
Microscopically there is diffuse alveolar wall fibrosis;
larger asbestos fibers may be seen coated with a protein
complex (the asbestos or ferruginous bodies).
Benign pleural effusions may occur.
Clinical feature: Asbestosis produces a restrictive type of
lung defect.
Diagnosis:
Chests X-ray shows predominantly basal and peripheral
irregular linear shadowing progressing to honeycombing,
ground glass appearance in some cases.
Sputum may show the presence of asbestos bodies
(sheek kebab appearance).
Complication:
There is increased risk of developing malignancies like Lung cancer most commonly squamous cell
carcinoma and adenocarcinoma.
Mesothelioma of pleura and peritoneum.
Colonic carcinoma.
Laryngeal carcinoma.
Silicosis
Silicosis is a fibrotic disease of the lungs due to inhalation
of crystalline silicon dioxide, usually in the form of quartz.
Respiratory System
187
Pathology:
Progressive massive fibrosis of lung which is
characteristically apical and nodular.
Hilar lymphadenopathy and calcification of hilar nodes.
Epidemiology:
Most dangerous are the particles of size 0.5-3 m.
Classic disease appears after 15-20 years of exposure.
Chest X-ray:
In acute disease diffuse military infiltration or
consolidation.
In long-term disease rounded opacities in upper lobe
(snow-storm appearance).
Egg shell pattern of calcified hilar nodes.
Complication: There is increased chance of acquiring
tuberculosis infection.
Coal Workers Pneumoconiosis (Anthracosis)
This occurs due to exposure to coal dust, especially in
anthracite miners after more than 20 years of exposure.
Pathology:
Nodular fibrosis in early stages progressing to nodule
size > 1 cm involving the upper lobe or the whole
lung, known as progressive nodular fibrosis (less chance
than silicosis).
It is additive to cigarette smoking in developing COPD.
Caplans syndrome - seropositive rheumatoid arthritis
with characteristic PMF.
Berylliosis
It has some genetic predisposition.
Pathology: The disease is identical with that of sarcoidosis,
with non-caseating granulomas and varying amounts of
interstitial fibrosis; with bilateral hilar lymphadenopathy
being less common, It is Kveims test negative.
Clinical feature:
In acute phases it causes acute pneumonitis and
tracheobronchitis.
Chronic berylliosis is characterized by a restrictive lung
defect.
188
DIFFUSE ALVEOLAR HEMORRHAGE SYNDROME

Goodpastuers Syndrome
Pathology
Diffuse pulmonary hemorrhage and cresentic, rapidly
progressive glomerulonephritis with linear deposition of
antibody (90 per cent of which are directed against the
-3 chain of type IV collagen) along the glomerular
basement membrane.
Clinical feature:
1. Renal- hematuria, nephritic urinary sediment and
subnephrotic proteinuria (that of RPGN).
2. Pulmonary- hemoptysis which may be massive and
fatal. It precedes hematuria.
Diagnosis: Serological testing (for anti-GBM antibodies)
and kidney biopsy.
Treatment: Steroids, cyclophosphamide and plasmapheresis.
COLLAGEN VASCULAR DISEASE
Lung involvement in collagen vascular disease
Disease
Progressive systemic
sclerosis (PSS)
Polymyositis/dermatomyositis
Rheumatoid arthritis
Respiratory manifestations
Fibrosing alveolitis
Pulmonary vascular disease
Diffuse lung disease
Fibrosing alveolitis
Organizing pneumonia
Bronchiolitis obliterans
Bronchiectasis
Pulmonary rheumatoid nodules
(Caplans syndrome)
Pleurisy with or without effusion
Sjgrens syndrome
Systemic lupus erythematous Pleuritis with or without effusion
(SLE)
(most common)
Extrapulmonary restriction
(shrinking lung syndrome)
Diffuse alveolar hemorrhage
Pulmonary hypertension
Respiratory System
189
PULMONARY INFECTIONS
PNEUMONIA
Pneumonia is an acute or chronic infection involving the
pulmonary parenchyma.
Etiology
Microbial pathogens that cause pneumonia
Community-acquired
Hospital-acquired
Streptococcus
Enteric aerobic gram
pneumoniae (MC)
negative bacilli (MC)
Haemophilus influenzae
Pseudomonas
Mycoplasma pneumoniae aeruginosa
Chlamydia pneumoniae
S. aureus
Legionella pneumophilia Oral anaerobes
Oral anaerobes
Moraxella catarrhalis
Staphylococcus aureus
Nocardia spp.
Virusesa
Fungib
Mycobacterium tuberculosis
Hlarnydia psittaci
HIV infectionassociated
Pneumocystis
carinii
M. tuberculosis
S. pneumoniae
H. influenzae
Influenza virus, cytomegalovirus, respiratory syncytial virus, measles

virus, varicella-zoster virus, and hantavirus.
b
Histoplasma, Coccidioides, and Blastomyces spp.
Pathology
The pneumonic process may involve primarily the
interstitium or the alveoli. Involvement of an entire lobe
is called lobar pneumonia. When the process is restricted
to alveoli contiguous to bronchi, it is called bronchopneumonia. Cavities develop when necrotic lung tissue
is discharged into communicating airways, resulting in either
necrotizing pneumonia (multiple small cavities, each
<2 cm in diameter, In one or more bronchopulmonary
segments or lobes) or lung abscess (one or more cavities
>2 cm in diameter).
Classification of illness for infants aged 2 months to 5 years
1. Very severe disease- convulsions, stridor, malnutrition.
2. Severe pneumonia- chest indrawing, grunting, cyanosis.
190
3. Pneumonia- fast breathing (>50/mm for 2 month to

1 year and >40/mm for 1-5 years).
4. No pneumonia - only cough and cold.
Streptococcal Pneumonia
Streptococcus pneumoniae is the most common cause
of community-acquired pneumonia.
Pathology
Stages:
1. Congestion.
2. Red hepatization- alveolar spaces packed with
neutrophils, red cells and fibrin.
3. Gray hepatization- red cells get lysed but the fibrinous
exudate persists.
4. Resolution.
Clinical features:
Symptoms - sudden onset of cough productive of blood,
fever and chest pain.
Sign - tachypnea, tachycardia. Signs of pulmonary
consolidation (dullness, increased fremitus, egophony,
bronchial breath sounds, and rales) may be found.
Chest X-ray: CXR invariably shows an infiltrate, and lobar
consolidation specifically suggests this diagnosis. A pleural
effusion is present in about 25 percent of patients.
Treatment: Streptococcus pneumoniae shows escalating
rates of resistance to penicillin, other -lactams, macrolides,
cotrimoxazole (TMP-SMX), clindamycin, and tetracycline.
The only drug that is virtually always active is vancomycin.
Fluoroquinolones with enhanced activity against S.
pneumoniae include levofloxacin, trovafloxacin, and
gatifloxacin.
Atypical Pneumonia
Organisms:
Mycoplasma pneumoniae - most common.
Chlamydia pneumoniae.
Legionella pneumophila.
Pneumocystis carinii in HIV infected patients.
Certain viruses.
Respiratory System
191
Pathology: Interstitial inflammation; the inflammatory

reaction is largely confined within the walls of alveoli. They
are usually mononuclear cell infiltrates.
Clinical features: The atypical presentation is characterized
by a more gradual onset, a dry cough, shortness of breath,
a prominence of extrapulmonary symptoms (such as
headache, myalgias, fatigue, sore throat, nausea, vomiting,
and diarrhea), and abnormalities on chest radiographs
despite minimal signs of pulmonary involvement (other
than rales) on physical examination.
Chest X-ray:
Hilar lymphadenopathy occasionally seen in M.
pneumoniae infection.
Patchy of lobar consolidation
Diagnosis:
Sputum - often NAD.
Mycoplasma pneumoniae - Polymerase chain reaction
(PCR); cold agglutinins may be found in blood.
Treatment: The usual therapeutic agents are macrolides
(such as erythromycin, clarithromycin or azithromycin) or
doxycycline; fluoroquinolones are also active.
Staphylococcal Pneumonia
Pathology: Pneumatocele - pathognomonic of Staphylococcal pneumonia.
Clinical features: Grunting respiration.
Complication:
1. Empyema- in a child <2 years is almost always due
to staphylococcus.
2. Along with staph. endocarditis, it is a serious
complication of IV drug users.
Chest X-ray: Lung cavities often found (also in
pneumococcus type 3 infection).
Treatment: Antistaphylococcal penicillin (flucloxacillin,
oxacillin, or nafcillin) or a first-generation cephalosporin
(cefazolin), or vancomycin (for methicillin-resistant strains
and for patients with severe penicillin allergy).
192
Klebsiella pneumonia
The classic presentation of Friedlanders pneumonia was
a serious pneumonia in an alcoholic patient with a chest
radiograph that showed upper lobe involvement and the
bulging fissure sign (indicating abscess formation) and
sputum that resembled currant jelly.
Pneumocystis pneumonia
It is a fungus causing lung diseases in immunocompromised patients.
Risk factors:
1. In HIV-infected individuals, those at greatest risk have
CD4+ T lymphocyte counts less than 200 cells/l.
2. In non-HIV immunosuppressed individuals,
glucocorticoid administration is an independent risk
factor.
3. Children with primary immunodeficiency diseases.
Pathology:
Within the lung, P. carinii infection is characterized by
an eosinophilic, foamy intra-alveolar exudate,
associated with a mild plasma cell interstitial
pneumonitis. Morphologically, two forms of P. carinii
may be identified: thick-walled cysts (6-7 m diameter)
which lie freely within the alveolar exudate are
demonstrated by Grocotts methenamine silver,
toluidine blue O, or cresyl violet stains. The exudate
consists largely of thin-walled, irregularly shaped, singlenucleated trophozoites (2-5 m diameter) which are
shown by Geimsa stain but lack distinctive features.
Extrapulmonary dissemination is rare.
Most important risk factor is pentamidine prophylaxis.
The most common sites of extrapulmonary involvement
are the lymph nodes, spleen, liver, and bone marrow.
Clinical feature:
Symptom - dyspnea, fever, and nonproductive cough;
retrosternal pain.
Sign - tachypnea, tachycardia, and cyanosis, but lung
auscultation reveals few abnormalities.
Diagnosis:
Chest X-ray: the changes are non-specific.
Respiratory System
193
In early cases, CXR may be normal.

Classical finding - bilateral diffuse infiltrates beginning
in the perihilar regions; these may progress to diffuse
bilateral alveolar (air space) consolidation that mimics
pulmonary edema.
Atypical findings - intrapulmonary nodules, cavitary
lesions, lobar consolidation, pneumatoceles, or hilar/
mediastinal lymphadenopathy. Predominantly apical
change may be seen in patients who have received
prophylaxis with nebulized pentamidine.
Induced sputum may demonstrate cyst or trophozoite
with appropriate staining.
Bronchoscopy - Fibreoptic bronchoscopy with BAL has
a sensitivity of more than 90 percent for detection of
P. carinii. Immunofluorescence staining increases the
diagnostic yield compared to conventional
histochemical staining.
Molecular diagnostic tests - Detection of P. cariniispecific DNA by the polymerase chain reaction (PCR)
on BAL fluid and induced sputum has the greatest
sensitivity.
Transbronchial biopsy and open lung biopsy - rarely
used.
Oxygen desaturation with exercise is a relatively sensitive
and specific test.
Gallium-67 and indium-111 lung scans are highly
sensitive indicators of Pneumocystis carinii pneumonia.
Treatment: Co-trimoxazole is the drug of choice.
Alternative regimens:
For mild to moderate cases: TMP plus dapsone,
clindamycin plus primaquine, or atovaquone alone.
Moderate to severe forms of pneumocystosis:
pentamidine IV or trimetrexate plus folinic acid.
Prophylaxis:
Indications for primary prophylaxis - those who have
CD4+ cell counts of <200/L, unexplained fever
[>37.8C (100 F)] for 2 weeks, or a history of
oropharyngeal candidiasis.
Co-trimoxazole is again the drug of choice for primary
prophylaxis.
Alternative drugs are dapsone either alone or in
combination with pyrimethamine, pentamidine or
atovaquone.
194
PULMONARY INFILTRATES WITH EOSINOPHILIA

Pulmonary infiltrates with eosinophilia
Etiology known
Idiopathic
Allergic bronchopulmonary
mycoses
Parasitic infestations
Drug reactions
Eosinophilia-myalgia syndrome
Loefflers syndrome
Acute eosinophilic pneumonia
Chronic eosinophilic pneumonia
Allergic granulomatosis of Churg
and Strauss
Hypereosinophilic syndrome
Allergic Bronchopulmonary Mycosis

Etiology: A. fumigatus is the most common cause of ABPA
(allergic bronchopulmonary aspergillosis).
Pathology:
The disorder is caused by a combination of type I and
type II hypersensitivity reactions. The bronchial asthma
of ABPA likely involves an IgE-mediated
hypersensitivity, whereas the bronchiectasis associated
with this disorder is thought to result from a deposition
of immune complexes in proximal airways.
It may complicate existing cystic fibrosis.
Clinical features:
It is a fungal hypersensitivity developing in atopic
subjects with asthma, additional manifestations may
occur in the lung. These include eosinophilic
pneumonia, mucoid impaction, bronchiectasis and
pulmonary fibrosis.
Earliest feature is breathlessness. When bronchiectasis
develops productive cough, intermittent hemoptysis may
occur.
Investigation:
Chest X-ray - the classic radiographic feature is fleeting
pulmonary infiltrates.
High-resolution CT is a sensitive, noninvasive technique
for the recognition of proximal bronchiectasis,
Diagnosis:
Diagnostic features of allergic bronchopulmonary
aspergillosis (ABPA)
Main diagnostic criteria
Bronchial asthma
Respiratory System
195
Pulmonary infiltrates
Peripheral eosinophilia (>1000/mL)
Immediate wheal-and-flare response to A.
fumigatus
Serum precipitins to A. fumigatus
Elevated serum IgE
Central bronchiectasis
Other diagnostic features
History of brownish plugs in sputum
Culture of A. fumigatus from sputum
Elevated IgE (and IgG) class antibodies specific for
A. fumigatus
Treatment: Long-term use of systemic glucocorticoids.

Aspergilloma:
Fungus ball-occurs in preexisting pulmonary cavities.
Lofflers syndrome (acute eosinophilic
pneumonia, simple pulmonary eosinophilia)
It is characterized by transient, benign syndrome of
migratory pulmonary infiltrates and peripheral blood
eosinophilia.
Etiology:
Blood borne parasites migrating through the lung,
particularly larvae of Ascaris lumbricoides.
Drugs - p-amino salicylic acid, aspirin, sulphonamides
(including the antimalarial combination sulphadiazine
and pyrimethamine or Fansidar), penicillin, and
imipramine; also nitrofurantoin.
Chest X-ray: The pulmonary shadows reflect fan-shaped
areas of consolidation, often peripheral and sometimes
rather nodular.
Tropical Eosinophilia
This is caused by migrating larvae of the filarial worms
Wuchereria bancrofti and Brugia malayi.
Churg-Strauss syndrome (Allergic angiitis and
granulomatosis)
Pathology:
Vasculitis of small arteries and veins with necrotizing
extravascular granulomas.
196
It commonly involves lungs, gut, peripheral nerves, skin,

and kidneys.
Clinical feature:
It frequently develops in persons with asthma.
It is characterized typically by asthma, eosinophilic
pneumonia, and very high numbers of circulating
eosinophils (>5 10 9 /l) but the pulmonary
manifestations may additionally include localized
hemorrhage and hemoptysis.
Diagnosis: Biopsy tissue is needed to confirm the diagnosis.
Treatment:
Immunosuppressive therapy including steroids,
azathioprine and cyclophosphamide.
Hypereosinophilic syndrome
Pathology: The eosinophils appear mature, and infiltrate
a number of organs including the bone marrow (most
important), lungs, liver, spleen, skin, and nervous system.
Clincal features:
Eosinophilic pneumonia may be extensive and
associated with pleural effusion.
The heart may be involved with tricuspid valve
abnormalities or endomyocardial fibrosis and a
restrictive, biventricular cardiomyopathy.
Weight loss, muscle weakness, enlargement of spleen
and lymph nodes, gut and renal dysfunction, and
venous thromboembolism.
Treatment: Treatment consists of glucocorticoids and/or
hydroxyurea.
Lung Abscess
Etiology:
1. Aspiration of infected material- most common cause.
2. As a complication of necrotizing bacterial pneumonia,
particularly those caused by Staph. aureus.
3. In children- Staph. aureus (most common), Klebsiella,
E. histolytica.
4. Bronchiectasis.
5. Lung cancer.
Respiratory System
197
Site:
Posterior segment of right upper lobe - most common
site.
Apical segment of right lower lobe.
INFECTIONS OF THE LARYNX
Infectious Croup (Laryngitis and
laryngotracheobronchitis)
Etiology: Parainfluenza type I (most common), influenza
or respiratory syncytial virus, rhinovirus, adenovirus.
Pathology: It causes marked subglottic edema.
Clinical feature: It mainly affects 2- and 3-year-old children
and usually follows the onset of upper respiratory tract
infection by 1 to 2 days. Symptoms include fever,
hoarseness, a seals bark cough, and inspiratory stridor.
Treatment:
1. Humidified O2.
2. Adequate hydration -IV fluid.
3. Antibiotics - ampicillin.
4. Sedatives should not be used.
Epiglottitis
Etiology
H. influenzae type b was the most common pathogen
before the introduction of Hib vaccine. The disease is rare
now.
Clinical feature: The typical young child with epiglottitis
has a several-hour history of fever, irritability, dysphonia,
and dysphagia and presents sitting forward and drooling.
Diagnosis: Lateral neck films may show an enlarged
epiglottis (the thumb sign).
Treatment: Intravenous cefuroxime, ceftriaxone, ampicillin/
sulbactam, or trimethoprim-sulfamethoxazole.
VASCULAR DISORDERS
Pulmonary Thromboembolism
Source:
Deep vein thrombosis of leg (most common - 70 to 80%)
and pelvis (10-15%). Isolated calf vein thrombi are the
most common source of paradoxical embolism.
198
Pathophysiology:
Massive emboli become lodged in the proximal
pulmonary arteries and chambers of the right heart
patient develops right heart failure. They present
with systemic arterial hypotension.
Small and medium sized emboli become lodged in
segmental arteries causing pulmonary infarction.
Infarcts are typically hemorrhagic and adjacent to
pleura, often covered by fibrinous exudates. They have
normal right heart function and normal systemic arterial
pressure.
Precipitating factors:
Stressors that may precipitate pulmonary thromboembolism
Surgery, trauma
Obesity
Oral contraceptives, pregnancy, postpartum,
postmenopausal hormone replacement
Cancer (sometimes occult) or cancer chemotherapy
Immobilization (stroke or intensive care unit patients)
Indwelling central venous catheter
Factor V Leiden defect.
Clinical features:
Dyspnea is the most common symptom.
Tachypnea is the most common sign.
Massive emboli - Patients usually present several days after
a major operation with central chest pain, acute dyspnea
and apprehension. Others features are cyanosis, syncope,
hypotension due to right ventricular failure.
Small or medium sized emboli Pleuritic chest pain, cough
and hemoptysis.
Investigations:
1. Arterial blood gas analysis- shows hypoxemia.
2. Estimation of D-dimer - it has high negative predictive
value.
3. Chest X-ray- a normal or near normal CXR in a
dyspneic patient suggests PTE. Well- established
abnormalities include focal oligemia (Westermarks
sign), a peripheral wedged- shaped density above the
diaphragm (Hamptons hump), or an enlarged right
descending pulmonary artery (Pallas sign).
4. ECG - sinus tachycardia, right ventricular strain.
Respiratory System
199
5. Ventilation-perfusion scan - investigation of choice.

6. Pulmonary angiography - is most diagnostic; gold
standard investigation.
7. Spiral CT scan.
Treatment:
Primary therapy
Indication- right ventricular dysfunction as diagnosed by
echocardiography
Therapy
1. Thrombolysis with recombinant tissue plasminogen
activator.
2. Embolectomy.
Secondary therapy1. Anticoagulants (LMWH, warfarin) are mainstay of
treatment in recurrent PTE. They have no role in acute
attack.
2. Inferior vena caval filters- The Birds nest filter
infrarenally or, if necessary, a Greenfield filter
suprarenally are recommended to prevent recurrent
embolism in those with contraindication to
anticoagulant therapy.
Primary Pulmonary Hypertension (PPH)
By definition pulmonary hypertension is defined as a mean
pulmonary artery pressure in excess of 25 mmHg at rest.
More importantly, during exercise there is a rapid rise in
pulmonary artery pressure as the pulmonary blood flow
increases with cardiac output.
Clinical feature:
Typical patient is female aged 20-40 years.
Symptoms - unexplained breathlessness at the onset
followed by symptoms of right ventricular failure,
including syncope, angina-like chest pain, and
peripheral edema. General malaise and cachexia of
cardiac failure are end stage symptoms.
Sign - loud second heart sound.
Diagnosis:
The ECG shows right ventricular strain and RBBB
pattern.
Chest radiography shows large pulmonary arteries.
The screening test is transthoracic echocardiography
with Doppler estimation of the tricuspid valve regurgitant
flow velocity.
200
Ventilation and perfusion lung scintigraphy followed

by a diagnostic right heart catheter.
Treatment:
Anticoagulation therapy.
Vasodilators like nifedipine and diltiazem.
Prostacyclin.
DISORDERS OF PLEURA
PLEURAL EFFUSION
The normal volume of pleural fluid is 20-30 ml.
Differential diagnoses of pleural effusions
Features
Transudative
Exudative
Pleural fluid
protein
Pleural fluid
protein: Serum
protein
Pleural fluid
LDH: Serum LDH
Fluid LDH
concentration
< 30 gm/L
> 30 gm/I
<0.5
>0.5
<0.6
>0.6
<200 IU
>200 IU
Causes
1. Congestive heart
failure
2. Cirrhosis
3. Pulmonary embolization
4. Nephrotic syndrome
5. Peritoneal dialysis
6. Superior vena
cava obstruction
7. Myxedema
1. Neoplastic diseases
a. Metastatic disease
b. Mesothelioma
2. Infectious diseases
a. Bacterial infections
b. Tuberculosis
3. Gastrointestinal disease
a. Esophageal perforation
b. Pancreatic disease
4. Collagen-vascular
diseases
5. Others - Sarcoidosis,
Uremia, Meigs syndrome,
Drug-induced pleural
disease, Chylothorax
Pleural Fluid Examination

Macroscopic appearance:
Transudates are clear, straw-colored fluids that do not
clot on standing.
Exudates may be turbid due to presence of cells; bloodstained fluid is seen in malignancy (mesothelioma) and
acute pancreatitis.
Respiratory System
201
Biochemistry:
The glucose concentration in the pleural fluid is < 16
mmol/l in rheumatoid arthritis, tuberculosis, empyema,
malignancy, and lupus.
Increased pleural fluid amylase is seen in acute
pancreatitis, pancreatic pseudocyst, or esophageal
rupture.
Presence of cholesterol crystals in pleural fluid may
be seen in tuberculosis, rheumatoid arthritis and
myxedema.
In tubercular effusion there may be TB markers in the
pleural fluid (adenosine deaminase > 45 IU/L, gamma
interferon> 140 pg/mL).
Microscopic and cytological examination:
Most transudates have cell counts of less than
1000/mm 3 , with the cells being a mixture of
lymphocytes, polymorphs, and mesothelial cells;
exudates tend to have higher white cell counts.
A polymorphonuclear leucocytosis is indicative of a
bacterial infection, pulmonary infarction or pancreatitis.
Predominant lymphocytosis may be seen in
tuberculosis, malignancy including lymphoma and after
by-pass surgery.
Chest X-ray
At least 200 ml of fluid is required to produce a change
in CXR (blunting of the costophrenic angle).
Best CXR view for minimal pleural fluid to be visualized
is lateral decubitus view.
Best view for CXR to detect interlobular effusion is
reverse lordotic.
Drainage
In patients with a large pleural effusion or a
pneumothorax, the most usual site is in the axilla, in
a triangle bounded by the anterior axillary line, the lateral
margin of the pectoralis major, and a horizontal line at
the level of the nipple (usually through 7th IC space in
mid-axillary line). An alternative site for an apical
pneumothorax is in the second intercostal space in the
midclavicular line.
202
PNEUMOTHORAX
Pneumothorax is the presence of gas in the pleural
space.
A spontaneous pneumothorax is one that occurs without
antecedent trauma to the thorax.
A primary spontaneous pneumothorax occurs in
the absence of underlying lung disease, while a secondary spontaneous pneumothorax occurs in its
presence.
A traumatic pneumothorax results from penetrating
or nonpenetrating chest injuries.
A tension pneumothorax is a pneumothorax in which
the pressure in the pleural space is positive throughout
the respiratory cycle.
Primary Spontaneous Pneumothorax
Cause:
Rupture of apical pleural blebs. It occurs almost
exclusively in smokers.
Recurrence is common after treatment.
Clinical feature:
Symptom - sudden onset of chest pain and
breathlessness.
Sign reduced breath sounds.
Treatment:
i. Initial therapy - simple aspiration.
ii. Recurrent disease Pleurodesis by doxycycline or talc.
Pleuredectomy with stapling- definitive treatment.
Note: agents used for pleurodesis are tetracycline, talc,
c. parvum, mustine HCl.
Secondary Spontaneous Pneumothorax
Cause: COPD (open type).
Treatment:
Tube thoracostomy and the instillation of a sclerosing
agent such as doxycycline or talc.
Thoracoscopy with bleb resection and pleural
abrasion for patients with persistent air leak or
recurrent disease.
Respiratory System
203
Traumatic Pneumothorax
Cause: Penetrating or non-penetrating chest injuries; may
be iatrogenic.
Treatment: Tube thoracostomy (intercostal drainage)
through the 2nd intercostal space.
Tension Pneumothorax
Cause: It occurs during mechanical ventilation and
resuscitative efforts.
Feature: Pressure in the pleural space is positive throughout
the respiratory cycle resulting in decreased venous return
to heart.
Treatment:
It is a medical emergency; a large bore needle is inserted
through the 2nd intercostal space.
Definitive treatment is tube thoracostomy.
EMPYEMA
Etiology: Most common cause is postpneumonia (Staph.
aureus is the causative agent under 2 years of age).
Diagnosis: Fever persisting even after treatment of
pneumonia likely to be empyema.
Treatment: Acute- water seal drainage.
MEDIASTINAL DISORDERS
MEDIASTINAL MASSES
Mediastinum and its masses
Anterior
mediastinum
Contents Remnant of
the thymus
gland, Branches
of the internal
mammary artery,
veins, and
associated
lymph nodes.
Middle
mediastinum
Posterior
mediastinum
The pericardium,
Ascending aorta
and aortic arch,
The vena cavae,
The brachiocephalic vessels, and
the pulmonary
arteries and veins,
The trachea and
The descending
thoracic aorta,
Esophagus,
Azygos veins,
Thoracic duct,
lymph nodes,
and Autonomic
nerves.
Contd...
204
Contd...
Anterior
mediastinum
Masses
Middle
mediastinum
Posterior
mediastinum
major bronchi with

their associated
lymph nodes, The
phrenic nerves and
the vagus nerve.
Thymoma (most Vascular masses
Neurogenic
common),
(e.g. aortic
tumors
Lymphoma,
aneurysm) - most (neurilemmoma
Teratoma,
common,
most
Thyroid masses Meningoceles,
common,
Lymph node
neurofibroma),
enlargement,
Gastroenteric
Mediastinal cysts
cysts,
(pericardial and
Esophageal
bronchogenic cysts) diverticula.
Thymoma
Most common mediastinal mass.
Site: The superior portion of the anterior mediastinum.
Pathology: Composed of two types of cells i.e. epithelial
cells and variable infiltrate of lymphocytes
X-ray: The sail sign, the wave sign, the notch sign.
Associated with: Myasthenia gravis is the commonest
(incidence 5-15%), Graves disease, hypogammaglobulinemia (immunodeficiency), aplastic anemia, pure
red cell aplasia, thrombocytopenia, systemic lupus
erythematosus, and polymyositis.
Bronchogenic Cyst
Site: Most common site is the middle mediastinum behind
carina or mainstem bronchi; also occurs in lungs.
Feature: They are lined by respiratory epithelium and may
contain inspissated mucus. They are not premalignant.
Complication: Chance of recurrent infection.
Chest X-ray: CXR shows air-fluid level which differentiates
them with pericardial cysts.
Treatment: Surgical excision.
Respiratory System
205
MEDIASTINITIS
Causes
Acute:
1. Esophageal perforation - most common cause.
2. Medial sternotomy for cardiac surgery.
Chronic:
1. Granulomatous inflammation of lymph nodes - most
common cause is tuberculosis or histoplasma; other
causes are sarcoidosis, silicosis, and other fungal
diseases.
2. Fibrosing mediastinitis.
Note: Most common cause of mediastinal fibrosis is
histoplasma.
PNEUMOMEDIASTINUM
Cause:
1. Alveolar rupture,
2. Perforation or rupture of esophagus.
Clinical feature: Hammans sign - a crunching or clicking
noise synchronous with the heartbeat and best heard in
the left lateral decubitus position.
DIAPHRAGM
Diaphragmatic Paralysis
Diaphragmatic paralysis
Bilateral
Unilateral
Less common.
Commonly due to high
spinal nerve injury.
May produce hypercapnic respiratory failure
More common.
Most commonly due to nerve invasion
by bronchogenic carcinoma.
Diagnosis: Sniff test- when a patient is
observed with fluoroscopy while sniffing,
the paralyzed diaphragm moves
paradoxically upward (paradoxical
breathing).
206
Congenital Diaphragmatic Hernia

Openings:
1. Through the foramen of Morgagni - anteriorly
Cause - defect in the sternal origin of diaphragm.
2. Through the foramen of Bochdalek - posteriorly, behind
the lateral arcuate ligamentmost common type.
Cause - persistence of pleuroperitoneal canal.
Clinical features: It is seen more often on the left side.
Triad of
i. Respiratory distress (slow, gasping respiration),
ii. Apparent dextrocardia (due to mediastinal shift to the
right) and
iii. Scaphoid (flat) abdomen. .
Pathology: It may produce hypoplasia of the lung.
Diagnosis: Chest X-ray shows - multiple air-containing
lesions (intestine) in chest.
Treatment: Urgent nasogastric suction followed by surgery.
MISCELLANEOUS DISORDERS
Sleep Apnea Syndrome
It is defined as temporary pause in breathing during sleep
lasting at least 10 seconds.
Types:
1. Obstructive sleep apnea is due to occlusion of the upper
airway usually at the level of the oropharynx.
Cause In infants - pre-maturity.
In adults - alcohol, obesity.
2. Central sleep apnea is due to transient abolition of
central drive to the ventilatory muscles.
Clinical features:
Recurrent episodes of nocturnal asphyxia and arousal
from sleep.
Tachyarrhythmias.
Pulmonary hypertension, mild to moderate systemic
hypertension.
Diagnosis:
Polysomnography.
Respiratory System
207
Acute Respiratory Distress Syndrome

Also known as-shock lung or diffuse alveolar damage.
Etiology:
Conditions that may lead to the acute
respiratory distress syndrome
Direct injury to
alveolar epithelium
Indirect lung injury
Aspiration of gastric contents

Diffuse pulmonary infection
Near drowning
Pulmonary contusion
Toxic inhalation
Sepsis syndrome
Severe nonthoracic trauma
Hypertransfusion
Pancreatitis
Cardiopulmonary bypass
Pathophysiology: Increased vascular permeability to proteins

leading to transudation of albumin in alveoli and terminal
bronchioles.
Pathology:
Lungs are heavy, edematous, atelectic - stiff lung.
Formation of hyaline membrane composed of fibrin.
Clinical features:
Earliest sign - increase in respiratory frequency followed
shortly by dyspnea (acute onset),
Arterial blood gas - decreased PO2 and decreased PCO2
LV function is normal,
It is the most common cause of non-cardiogenic
pulmonary edema with normal PCWP.
Chest X-ray: Fields are either clear or show only minimal
and scattered interstitial infiltrates in early stage; diffuse
infiltrates in late stage.
Recommended criteria for acute lung injury (ALI) and
acute respiratory distress syndrome (ARDS)
Timing Oxygenation
Chest radiograph
Pulmonary arterial
occlusion pressure
l8 mmHg
when measured
or no clinical
evidence of left
atrial hypertension
Bilateral infiltrates l8 mmHg when
ALI
Criteria
Acute PaO2/FIO2
Bilateral infiltrates
onset 300 mmHg seen on frontal
(regardless of chest radiograph
PEEP level)
ARDS
Acute Pao2/FIO2
Contd...
208
Contd...
Timing Oxygenation
Criteria
onset
Chest radiograph
Pulmonary arterial
occlusion pressure
200 mmHg seen on frontal

(regardless
chest radiograph
of PEEP level)
measured or no
clinical evidence of
left atrial hypertension
NOTE: PaO2, arterial oxygen tension; FIO2, inspiratory O2 fraction; PEEP,

positive end expiratory pressure.
Treatment:
Once the X-ray shows diffuse, extensive, bilateral
interstitial and alveolar infiltrates, hypoxemia cannot
be corrected by increasing O2 concentration of inspired
gas and mechanical ventilation is needed.
O2 concentration used to treat is 50-100 mmHg
PEDIATRIC DISORDERS
Hyaline Membrane Disease: (Respiratory Distress
Syndrome)
It occurs most commonly in pre-mature infants.
Risk factors:
Maternal diabetes,
Asphyxia,
Acidosis,
Hypothermia,
Delivery by caesarean section,
Breech delivery.
Pathology: Deficiency of pulmonary surfactant.
Pathophysiology: Same as ARDS.
Pre-natal assessment of lung maturity:
Lecithin: Sphingomyelin ratio >2.0 indicates maturity
of lungs;
Presence of phosphatidyl glycerol;
Shake or Bubble test - +ve test indicates lung maturity.
Clinical feature: Respiratory distress which occurs within
6 hours of birth with respiratory rate> 60/min.
Chest X-ray:
Ground glass appearance (also seen in pneumonia,
obstructive TAPVC);
Respiratory System
209
Reticulonodular pattern in mild disease and white out

lungs in severe disease.
Treatment:
O2 therapy (usually 90%).
Transient Tachypnea of Newborn
It is seen in term infants due to delayed clearance of lung
fluid as in caesarean section.
Clinical feature: Tachypnea starts few hours after birth and
rarely lasts beyond 48 hours; no or minimum respiratory
distress.
Chest X-ray: CXR shows increased vascular markings.
Treatment: Treatment is symptomatic.
Prognosis: Prognosis is good.
Meconium Aspiration Syndrome
It is the most common cause of respiratory distress in
mature newborn. It is common in post-dated and smallfor-date babies.
Clinical feature: Respiratory distress within 24 hours of
birth.
Chest X-ray: CXR shows bilateral pneumonia; may cause
air-leak (pneumomediastinum).
Treatment: IV fluids, oxygen and IPPV, if needed.
Bronchopulmonary Dysplasia
It occurs in premature infants.
Diagnosis: Oxygen requirement beyond 36 weeks postconceptional age or beyond 28 days of life.
Cause: Barotraumas and oxygen toxicity.
Chest X-ray: Pulmonary edema due to capillary damage.
Treatment: Frusemide, salbutamol, steroids.
Hypoxemic-ischemic Encephalopathy
Etiology: Perinatal asphyxia.
210
Clinical features: Cerebral cortical damage hypertension

infants assume extensor posture.
Surfactant
Composition: A mixture of dipalmitoyl phophatidyl choline
(DPPC), other lipids and proteins.
Site: Lining the alveolar membrane.
Source: Secreted by type II alveolar epithelial cells.
Surfactant production starts at 20 weeks of intranatal life
and peaks at 35 weeks.
Action:
Lowers the surface tension and prevents alveolar collapse.
Control:
Maturation of surfactant in lungs is accelerated by
glucocorticoids.
Surfactant level is decreased in smoking.
MECHANICAL VENTILATION
Indications
a. Hypoxemic respiratory failure:
1. Severe pneumonia
2. Pulmonary edema
3. Respiratory distress syndrome causing V/Q mismatch
and shunt
b. Hypercarbic respiratory failure:
1. Asthma and COPD
2. Restrictive lung disease
3. Neuromuscular diseases
Ventilator Modes
Characteristics of different ventilatory modes
Ventilator
mode
Independent
variables
(Set by user)
Dependent
variables
(Monitored
by user)
Advantages
Disadvantages Initial
settings
ACMVa
FIO2
Tidal volume
Ventilator rate
Level of PEEP
Inspiratory flow
Peak airway Timer backup Not useful

pressure,
Patient-vent for weaning
PaO2, PaCO2 synchrony
Potential for
Mean airway Patient
dangerous
pressure
controls
respiratory
FIO2=1.0b
Vt = 10 -15
mL / Kga
f = 12 15
/min PEEP
Contd...
Respiratory System
211
Contd...
Ventilator
mode
Independent
variables
(Set by user)
Dependent
variables
(Monitored
by user)
pattern, Peak
I/E ratio
inspiratory flow
Pressure limit
SIMVa
CPAP
PCVa
PSV
Advantages
Disadvantages Initial
settings
minute
ventilation
alkalosis
= 0-5 cm
H2 O
Inspiratory
flow = 60
L/min
Same as for
Same as for Timer backup Potential
Same as
ACMV
ACMV
useful for
dysynchrony for
weaning
ACMVa
FIO2
Tidal volume Allows
No backup FIO2 = 0.5
Level of CPAP Rate, flow
assessment of
1.0b CPAP
pattern
spontaneous
= 5 15 cm
Airway
function
H2 O
pressure
Helps prevent
PaO2,
atelectasis
PaCO2,
I/E ratio
FIO2
Tidal volume System
Requires
FIO2 =1.0b
Inspiratory
Flow rate,
pressure
heavy
PC = 20 -40
pressure level pattern
regulated
sedation
cm H2O
Ventilator rate Minute
Useful for
Not useful
PEEP = 5Level of PEEP ventilation
barotraumas for weaning 10 cm H2O
pressure limit
PaO2,
treatment
f = 12 -15 /
I /E ratio
PaCO2
Timer backup
min I /E =
0.7 / 1 -4 / 1
FIO2
Same as for Assure
No timer
FIO2=0.5Inspiratory
PCV + I /E synchrony
backup
1.0b
pressure level ratio
Good for
PS = 10 PEEP pressure
weaning
30 cm H2O
limit
5 cm H2O
usually the
level used
PEEP =
0-5 cm
H2 O
open lung ventilation (OLV) involves the use of any of these specific
types of tidal volumes (or applied pressure) to achieve 5-6 ml/kg,
and positive end expiratory pressures achieve maximal alveolar
recruitment.
FIO2 is usually set to 1.0 initially, unless there is a specific indication
to minimize FIO2 such as history of chemotherapy with bleomycin.
Once adequate oxygenation is documented by blood gas analysis,
FIO2 should be decreased in decrements of 0.1-0.2 as tolerated,
until the lowest FIO2 required for an SaO2 > 90 percent is achieved.
Abbreviations - f, frequency; l/E, inspiration/expiration.

ACMV Assist control mode ventilation
SIMV Synchronized intermittent mandatory ventilation
CPAP Continuous positive airway pressure
PCV Pressure control ventilation
PSV Pressure support ventilation
CARDIOVASCULAR
SYSTEM
PULSE
Arterial Pulse
Special types of arterial pulse
Type
Seen in
Bounding pulse
Mitral regurgitation, ventricular

septal defect, arteriovenous
fistula
Aortic regurgitation, hypertrophic
cardiomyopathy
Aortic stenosis
Dilated cardiomyopathy
Left ventricular failure
Pulsus bisferiens
Anacrotic pulse
Dicrotic pulse
Pulsus alternans (varying pulse
pressure with normal rhythm)
Pulsus paradoxus (decreased
SBP in inspiration)
Pericardial tamponade, airway

obstruction, SVC obstruction
Note: Bisferiens and alternans pulses are more prominent in peripheral

artery (e.g. radial artery).
Jugular Venous Pulse
a
x
v
y
c
wave produced by right atrial contraction

descent produced by atrial relaxation
wave produced by ventricular systole
descent produced by ventricular filling
wave produced by bulging of TV during isovolemetric
contraction of RV
Cardiovascular System
213
Variants of jugular venous pulse

Variant
Seen in
Giant a wave
Tricuspid stenosis, pulmonary

hypertension, pulmonary stenosis
(all cause increased resistance to
atrial contraction)
Junctional rhythm, AV
dissociation (ventricular
tachycardia, complete heart block)
Atrial fibrillation
Constrictive pericarditis, cardiac
tamponade
Tricuspid regurgitation, constrictive
pericarditis
Severe TR, constrictive pericarditis
Right ventricular failure,
constrictive pericarditis
Cannon a wave
Absent a wave
Accentuated x descent
Prominent v wave
Deep y descent
Kussmauls sign (increase
in CVP during inspiration)
HEART SOUND
First Heart Sound (S1)
It is produced by closure of AV valves at ventricular
systole.
Louder S1 is seen in tachycardia, increased cardiac
output, mitral stenosis, short PR interval.
Soft S1 is seen in mitral regurgitation, rigidity and
calcification of mitral valve leaflets.
Reverse splitting of S1 is seen in left bundle brunch
block.
Second Heart Sound (S2)
It is produced by closure of aortic and pulmonary valves
at ventricular diastole.
Loud P2 is seen in pulmonary hypertension.
Fixed splitting is seen in ASD.
Variable splitting is seen in VSD.
Paradoxical splitting is seen in congenital aortic stenosis,
LBBB, hypertension, coarctation of aorta.
Wide splitting is seen in ASD, VSD.
Reverse splitting is seen in LBBB, right ventricular
ectopic beat, systolic hypertension, ischemic heart
disease.
214
Third Heart Sound (S3)

It is produced by termination of rapid filling after A2.
It is related to myocardial contraction.
Physiological S3 is seen in children and young adults,
athletes, pregnancy, fever.
Pathological S3 in persons over age 40 years indicates
impairment of ventricular function, AV valve
regurgitation, constrictive pericarditis (pericardial knock)
or heart failure.
Fourth Heart Sound (S4)
It is a presystolic sound produced during ventricular
filling. It is associated with an effective atrial contraction.
Pathology: decreased Ventricular compliance and
increased resistance to ventricular filling.
It is seen in systemic hypertension, aortic stenosis,
hypertrophic cardiomyopathy, mitral regurgitation,
acute myocardial infarction.
Abnormal Heart Sounds
Adventitious heart sounds

Type
Pitch
Time
Cause
Ejection click
High
Early systolic
Aortic stenosis,
pulmonary stenosis,
hypertension
Mitral stenosis,
tricuspid stenosis
Opening snap High
Pericardial
knock (S3)
Tumor plop
Non-ejection
click
High
Low
Early diastolic
(corresponds to
dicrotic notch
in carotid pulse)
Early diastolic
Early/mid diastolic
Systole
Constrictive
pericarditis
Atrial myxoma
Mitral valve prolapse
215
MURMUR
Systolic Murmur
Early Systolic
Acute severe mitral regurgitation (due to papillary
muscle/chordae tympani rupture).
Ventricular septal defect (small muscular).
Tricuspid regurgitation with normal pulmonary artery
pressure.
Mid/ejection Systolic
Semilunar valve stenosis (aortic, pulmonary).
Increased flow and hyperkinetic states (e.g. - Stills
murmur in children and young adults normal).
Hypertrophic cardiomyopathy.
Late Systolic
Mitral valve prolapse (non-ejection click).
Holo/pansystolic
AV valve regurgitation (mitral and tricuspid Carvallos
murmur).
Ventricular septal defect.
Diastolic Murmur
Early Diastolic
Semilunar valve incompetence (aortic and tricuspid
regurgitation Graham Steell murmur).
Mid Diastolic
AV valve stenosis (mitral and tricuspid).
Carey Coombs murmur in acute rheumatic fever.
Austin Flint murmur in severe/chronic aortic
regurgitation.
Left atrial myxoma.
Atrial septal defect.
216
Continuous Murmur
Patent ductus arteriosus.
Coronary arteriovenous fistula.
Atrial septal defect.
Ruptured aneurysm of sinus of Valsalva.
Coarctation of aorta.
Note: Regurgitation murmurs tend to be early where as
stenotic murmurs tend to be mid/ejection.
ECG
PR interval = 0.12 to 0.2 seconds.

QRS complex = 0.08 to 0.10 seconds.
QRS axis = - 30 to +100.
PR = Atrial depolarization + conduction through AV
valve.
QRS = Ventricular depolarization + atrial
repolarization.
QT = Ventricular depolarization + ventricular
repolarization.
ST = Ventricular repolarization.
Cardiac Hypertrophy
LVH = SV1+(RV5 or RV6) 35 mm.
Bundle Branch Block
LBBB - wide, predominantly negative QS complexes
in V1 and entirely positive R complexes in lead V6.
Myocardial Ischemia
Transmural- ST elevation, hyper acute T wave.
Subendocardial - ST depression (elevation in aVR).
Metabolic Changes
Hyperkalemia
K+ > 7 mEq/L = starts with tall T wave (Tenting
of T wave), prolong PR and QRS.
K+ > 8.5 mEq/L = absent P wave, broad QRS
complex, sine- wave pattern, ventricular fibrillation or
asystole.
217
Hypokalemia
K+ prolongs ventricular repolarization (QT prolongation)
with prominent U wave actually there is QU
prolongation.
Flattening or inversion of T wave, ST depression,
prolongation of PR, decreased voltage and widening
of QRS.
Causes of QT change
QT prolongation
QT shortening
1. Hypokalemia
1. Hypercalcemia
2. Intracranial bleeding
2. Digitalis toxicity
particularly subarachnoid
(scooping of the ST-T
hemorrhage
wave complex)
3. Hypothermia (Osborn wave)-J wave
4. Hypocalcemia (ST prolongation)
Causes of Electrical Alternans

Cardiac tamponade, often in pericardial effusion.
DISORDERS OF RHYTHM
Bradycardia = <60 beats/min; Tachycardia = >100 beats/
min.
Sinus Bradycardia
Causes
Hypothyroidism - myxedema
Advanced liver disease
Hypothermia
Typhoid fever
Brucellosis
Athletes
Treatment: Permanent pacemakers are the mainstay of

therapy for patients with symptomatic sinus node
dysfunction.
AV Conduction Disturbances
Etiology
Levs disease: Calcification and sclerosis of fibrous
cardiac skeleton.
218
Lenegres disease: Sclerosis of conducting system

without involvement of the myocardium or fibrous
skeleton.
Heart Block
First-degree block prolongation of AV conduction
(PR interval >0.25 seconds).
Mobitz second-degree block
Type I (Wenckebach phenomenon) progressive
PR interval prolongation prior to block of an atrial
impulse.
Type II disease of His-Perkinje system. QRS
prolongation (conduction fails without prior PR
changes).
Type III (third degree or complete block) may
produce syncope (Stokes - Adams syndrome). The
ventricle beats at a low rate independent of atria
known as idioventricular rhythm.
Idioventricular rate: In AV nodal block = 45 beats/min.
In infranodal block = 35 beats/min.
Treatment: Pacing.
Indication of permanent pacing:
1. AV block in adults- complete heart block.
2. After myocardial infarction - with partial or complete
AV block bundle brunch block.
3. Sinus node dysfunction - Sick sinus syndrome.
4. Hypertensive carotid sinus and neovascular syndromes.
TACHYARRHYTHMIAS
Atrial Premature Complexes
APCs can be found on 24-hour Holter monitoring in over
60 percent of normal adults.
Ventricular Premature Complexes
(Ventricular Ectopics)
They are followed by a compensatory pause and SA
node discharges normally.
APC and VPCs are not strong enough to produce a
pulse at the wrist.
219
Diagnosis: 24 hour Holter monitoring.

ECG: Wide (>0. 14s), bizarre QRS complexes not preceded
by P waves and a fully compensatory pause.
Treatment:
Indications More than 5 beats/minute, occurring in
pairs, R-on-T phenomenon in ECG.
-blockers are the drug of choice.
Atrial Fibrillation
Causes:
Normal individual
Acute alcohol intoxication
Rheumatic heart disease
Hypertension
Atrial septal defect
Constrictive pericarditis
Mitral valve diseases (e.g. MS)
Myocardial infarction
Clinical feature: Pulse 350-600 beats/min. ventricular rate
80-160/min.
ECG
Atrial activity - wavy irregular baseline with no discrete
P waves.
Ventricular activity - irregularly irregular (variable RR).
Treatment:
No severe cardiovascular
complication
Slowing of ventricular rate

by -blockers/CCBs/Digitalis
Successful
Severe cardiovascular
complication
DC cardioversion t/t
of choice
Fails in 24 hrs
Conversion to sinus rhythm

by quinidine/flecainide
Amiodarone is used in resistant AF and to prevent

recurrence. When presented late (>48 hrs) anticoagulants
(aspirin) should be started to prevent embolization.
220
Atrial Flutter
Clinical Feature:
Atrial rate 250-350 beats/min.
Ventricular rate 1/2 of that, i.e. about 150 beats/min.
ECG: Saw tooth like flutter waves with variable AV block.
Treatment:
DC cardioversion t/t of choice.
Atrial pacing - in patient with open heart surgery or
acute myocardial infarction.
Drugs to reduce ventricular rate (as above) and to
restore sinus rhythm. Digitalis is least effective and
occasionally converts atrial flutter to fibrillation.
Paroxymal Supraventricular Tachycardia (PSVT)
In PSVT impulses arise from SA node, atria and AV node.
AV nodal re-entry (circus movement)
Most common cause of paroxysmal arrhythmia.
Tachycardia @ 120-250 beats/min.
ECG: Tachycardia with narrow QRS.
Treatment:
No
Mild
hypertension
hypertension
Carotid sinus massage IV phenylephrine

Valsalva maneuver
Ocular pressure
If fails
Adenosine drug of choice
Atrial or ventricular pacing via a temporary
Severe ischemia
and/or hypertension
DC cardioversion
pacemaker.
-blockers and verapamil are second line drugs.

WPW syndrome (pre-excitation syndrome)
There is an additional muscular nodal tissue (Bundle
of Kent) between atria and ventricles.
ECG: Short PR interval (< 0.12s) and broad QRS (>
0.12s but < 0.14s) with a slurred upstroke of the QRS
complexes- delta wave.
Treatment: For symptomatic patients only:
Drugs to reduce conduction flecainide, amiodarone
(digitalis and verapamil should be used cautiously as
they may reduce ERP of the aberrant pathway).
221
With AF DC cardioversion or procainamide (drug

of choice)/lignocaine.
Permanent cure radiofrequency catheter ablation of
the aberrant tract treatment of choice.
Ventricular Tachycardia
Clinical feature: Intermittent cannon a wave and varying
S1 suggests AV dissociation and is diagnostic of VT. Pulse
rate 160-240 beats/mean.
ECG: Characteristic 12 lead ECG shows
i. AV dissociation
ii. Capture/fusion beats
iii. QRS > 0.14s
iv. Extreme left axis deviation
v. Concordance of QRS complexes in all precordial leads.
Treatment: For symptomatic patients only
With organic heart disease -blockers, verapamil,
procainamide, flecainide, amiodarone.
Without organic heart disease:
Presence of ischemia/CHF/CNS hypoperfusion
DC cardioversion.
Well tolerated IV lignocaine is the drug of choice.
Torsades de Pointes
ECG:VT characterized by polymorphic QRS complex with
QT prolongation.
i. Hypokalemia
ii. Amiodarone
iii. Chlorpromazine
iv. TCAs (Mnemonic - CATcH)
v. Quinidine.
Treatment: -blockers.
Prolonged QT Syndrome
Congenital (Romanoward syndrome).
Treatment: -blockers.
Acquired caused by drugs, hypokalemia.
Treatment: Atrial or ventricular overriding pacing and
magnesium.
222
Ventricular Fibrillation (Cardiac Arrest)

Cause: In patients with severe hypoxia or ischemia.
It is the most common cause of cardiac arrest and
sudden cardiac death.
Management:
Immediate defibrillation - asynchronous DC cardioversion
(use CPR before arrangements are ready)
fails
2 or more DC shock + CPR
fails
IV adrenaline
Defibrillation within 30-60 sec

fails
Other drugs like procainamide, lignocaine, bretyllium, mag
sulph, NaHCO3 can be tried.
HEART FAILURE
Etiology
In infants:
i. Congenital heart diseases.
Note: Most common cause in first week of life is
hypoplastic right/left ventricle.
Patent ductus arteriosus is the most common
congenital heart disease to produce CCF.
ii. Myocarditis
iii. PSVT
In children: Most common cause is rheumatic heart
disease.
Clinical Feature
Left heart failure - it is indicated by PCWP > 20 mmHg.
In infants manifested by tachypnea and tachycardia.
In adults manifested by pulmonary congestion (cough,
wheezing, rales).
Right heart failure:
In infants manifested as hepatomegaly, facial edema.
Pedal edema appears late.
In adults manifested as facial and pedal edema,
congestive hepatomegaly, systemic venous distension,
and oliguria.
223
Framingham criteria:
Major
1. Paroxysmal nocturnal dyspnea
2. Neck vein distension
3. Rales
4. Cardiomegaly
5. Acute pulmonary edema
6. S3 gallop
7. Positive hepatojugular reflex
Pathology
Heart failure cells: alveolar macrophages filled with
hemosiderin due to phagocytosis of RBCs.
Chest X-ray
Kerley B line (when left atrial pressure > 20 mmHg).

Pleural effusions with interlobular effusion.
Chamber enlargement.
Prominent pulmonary and apical veins (NOT lower
lobe veins).
Treatment
Diuretics are the most effective drugs for symptomatic
relief in cases of moderate to severe CHF.
Combination of diuretics and ACE inhibitors is used
for initial therapy.
Digitalis is not used in primary therapy. It is used in
persistently symptomatic patients and cases associated
with atrial fibrillation. Digitalis reduces morbidity due
to CHF but does not increase life expectancy.
Drugs that reverse the disease progression and improve
survival are - ACE inhibitors, AT1 antagonists, blockers - metoprolol, bisoprolol and carvedilol;
aldosterone antagonists spironolactone.
Digitalis
Mechanism of action: Inhibition of Na+-K+ ATPase.
Glycosides prolong the effective refractory period of
the AV node as a result of vagal effect. This explains the
slowing of ventricular rate produced by digitalis in AF or
Afl.
224
Use in HF:
Digitalis is particularly useful in patients with HF
accompanied by atrial flutter and atrial fibrillation and
a rapid ventricular rate.
Poor response in high output failure (anemia).
Digitalis Toxicity
Occurs when plasma concentration is>2.4 ng/ml.
Risk factors:
Old age,
Hypothermia,
Hypokalemia (most common cause),
Acute MI,
Hypoxemia,
Renal insufficiency,
Hypocalcemia.
Symptoms:
Anorexia, nausea, vomiting - earliest symptoms.
Headache,
Visual disturbance.
ECG:
Ventricular premature beats (most frequent finding).
VT, VF, AV block bradycardia.
Non-paroxysmal atrial tachycardia with variable AV
block is characteristic.
PR interval widening to 1/2 times the initial PR interval.
Treatment: withdrawal of the drug.
For tachyarrhythmias - infusion KCl.
For VF/VT Lignocaine.
For PSVT propanolol.
For AV block- atropine.
Fab fragments - digitalis antibodies.
Diuretics and hemodialysis are not very effective.
Acute Pulmonary Edema
Treatment:
Morphine
100 percent O2 in sitting position.
Positive pressure ventilation.
IV frusemide.
IV Na-nitroprusside.
225
Dopamine/Dobutamine.
Rotating tourniquets in extremities.
EXTRACARDIAC ASSOCIATIONS
Extracardiac associations
Syndrome
Cardiac
manifestation
Noonan
syndrome
Pulmonary stenosis, Antimongoloid slant,

cardiomyopathy
short stature, webbed
(usually hypertrophic) neck, pectus excavatum,
cryptorchidism
(mnemonic ASNEC)
AV fistula
Multiple telangiectasias
high output failure
Supravalvular aortic Elfin facies, idiopathic
stenosis
hypercalcemia, mental
retardation
Arterial dilatation
Hyperextensible joints,
and rupture,
hyperplastic and
mitral regurgitation
friable skin
Aortic dilatation,
Arachnodactyly with
aortic and mitral
hyperextensibility,
incompetence
lens subluxation
Intravascular
Lens subluxation,
thrombosis
osteoporosis
Ventricular septal
Moon face, broad chest,
defect
cat like cry,
microcephaly,
antimongoloid slant
Mental retardation
of endocardial
and other features
cushion type
Coarctation
Short stature, primary
of aorta
amenorrhea, shield
chest and other
anomalies
Patent ductus
Sensorineural deafness,
arteriosus, VSD,
cataract, glaucoma
pulmonary stenosis
and other features
Ebsteins anomaly
Hypothyroidism
Osler-RenduWeber syndrome
Williams syndrome
Ehlers-Danlos
syndrome
Marfans syndrome
Homocystinuria
Cri-du-chat
syndrome
Downs syndrome
Turners syndrome
Congenital rubella
Lithium
Extracardiac
manifestation
CONGENITAL HEART DISEASES

Classification
I. Acyanotic with left to right shunt:
1. Atrial septal defect
2. Ventricular septal defect
3. Patent ductus arteriosus
226
II. Acyanotic without shunt (obstructive)

1. Congenital aortic stenosis
2. Coarctation of aorta
3. Pulmonary stenosis
III. Cyanotic with right to left shunt:
A. With pulmonary stenosis (decreased pulmonary
blood flow):
1. Fallots tetralogy
2. Tricuspid atresia
3. Ebstein s anomaly
B. With pulmonary hypertension:
Eisenmenger syndrome
C. With increased pulmonary blood flow:
1. Complete transposition of great vessels
2. Total anomalous pulmonary venous connection
Causation
Multifactorial.
Strongest genetic influence is seen in Holt-Oram
syndrome.
Strongest environmental influence is high altitude increased chance of PDA and ASD.
ACYANOTIC WITH LEFT TO RIGHT SHUNT
Atrial Septal Defect
Ostium primum - lies immediately adjacent to the AV
valves, either of which can be deformed.
Ostium secundum most common type, defect
involving fossa ovalis.
Pathology:
Right atrial and ventricular hypertrophy with normal
left atrium.
Clinical features:
Most cases are asymptomatic. More common in
patients with Downs syndrome.
S2 - widely split and fixed.
Murmurs - no shunt murmur, only flow murmurs.
Delayed diastolic murmur (TV), ejection systolic
murmur (PV).
Parasternal impulse.
227
Chest X-ray:
Pulmonary plethora is characteristic because pulmonary
flow > systemic flow.
Associations of ASD
Lutembacher syndrome
Holt-Oram syndrome
Ellis Van Crevald syndrome
Osteum secondum defect

ASD with bony defect
ASD with single atrium
ECG:
Ostium primum - RBBB with left axis deviation beyond
30.
Ostium secundum - right axis deviation with right
ventricular hypertrophy.
Fluoroscopy: Hilar dance sign.
Complications: CCF and infective endocarditis are very
rare with ASD.
Treatment:
Operation between the ages of 2-5 years for all patients
with uncomplicated atrial septal defect.
Contraindication - small defect and trivial left to right
shunt, severe pulmonary vascular disease (pulmonary
hypertension with increased pulmonary vascular
resistance) without significant left to right shunt.
Ventricular Septal Defect
Most common congenital defect.
90 percent situated in the membranous part.
Maladie de Roger = small VSD.
Clinical feature:
Highest frequency in Downs patients.
Pansystolic murmur at left sternal border.
S2 widely split and variable.
Course:
70-80 percent cases undergo spontaneous closure.
Patient may develop pulmonary stenosis.
Complications:
VSD is the most common cause of infective
endocarditis, may also develop CCF.
228
Chest X-ray:
Increased cardiac silhouette of LV type, pulmonary
plethora.
Complications of CHD
Most common cause

Least common cause
Infective
endocarditis
Congestive
cardiac failure
Ventricular septal
defect
Patent ductus
arteriosus
Tetralogy of Fallot
Patent Ductus Arteriosus

Ductus arteriosus: Bifurcation of pulmonary artery to the
aorta just distal to left subclavian artery.
Closure - physiologically it closes soon after birth (by
bradykinin). Anatomically it closes in 1-3 months.
It forms ligamentum arteriosum.
It is kept patent by PGE2 and PGI2.
Pathology: Blood flows from aorta to pulmonary artery
(aorto-pulmonary window)
Clinical feature:
Continuous murmur.
Diffirential cyanosis - in reversal of shunt.
Complications:
Most common congenital disease to produce CCF, pure
LVF may occur.
Bacterial endocarditis.
Treatment:
Indomethacin may help in closure if treated within 2
weeks after birth.
It is kept patent by Alprostadil (PGE1) before surgery
is undertaken.
Surgery:
Complication - recurrent laryngeal nerve injury.
Contraindication - reversal of shunt.
ACYANOTIC WITHOUT SHUNT
Congenital Aortic Stenosis
Clinical feature: Paradoxically split S2.
May cause sudden death in children.
229
Coarctation of Aorta
Site: Most common distal to the origin of the left subclavian
artery.
Coarctation syndrome:
Coarctation of aorta is associated with other cardiac
anomalies, most commonly a bicuspid aortic valve.
Others are PDA, VSD, tubular hypoplasia of aortic
isthmus.
It is seen in patients with Turners syndrome.
Clinical feature:
Mostly asymptomatic.
Symptoms - intermittent claudication, dyspnea on
running, headache, epistaxis, cold extremities.
Sign- hypertension in the upper extremities.
Absence, marked diminution or delayed pulsation in
the femoral artery.
Enlarged and pulsatile collateral in intercostals spaces,
axillae and interscapular area may be palpated.
Supex and thorax may be more developed than infex.
X-ray: characteristic E sign or 3 sign.
Ribs - notching at the lower border due to erosion by
dilated collateral vessels. Typically involves 4th-8th ribs
bilaterally.
Double bulging.
Heart size remains normal but LVH may be present.
Causes of rib notching
Superior notching
Inferior notching
Marfans syndrome
Systemic lupus erythematous
Systemic sclerosis
Coarctation of aorta
Tetralogy of Fallot
Takayasus arteritis
Superior/inferior venacaval
obstruction
Arteriovenous fistula
Hyperparathyroidism
Atheroma
Neurofibromatosis
Complications: Rupture of aneurysm in circle of Willis,

rupture of aorta, left ventricular failure, infective
endocarditis.
Treatment: Surgical. Surgery may not cure hypertension.
230
Pulmonary Stenosis
Association with Noonans syndrome.
Site: Supravalvular (uncommon), valvular (most
common) and subvalvular.
Most common associated cardiac anomaly is atrial
septal defect.
CYANOTIC WITH RIGHT TO LEFT SHUNT
Tetralogy of Fallot
Most common congenital cyanotic heart disease.
Components:
1. Ventricular septal defect.
2. Pulmonary stenosis (outflow obstruction).
3. Overriding or dextroposed aorta.
4. Right ventricular hypertrophy (without enlargement).
Clinical feature:
Commonest symptoms are dyspnea on exertion,
syncope (most common congenital heart disease to
produce syncope).
Patient assumes squatting position.
Sign - central cyanosis with clubbing.
X-ray: Boot shaped heart (Coeur en sabot). But heart size
is normal.
ECG: Right axis deviation with right ventricular hypertrophy.
Complications: CCF never occurs. No chance of recurrent
respiratory tract infection.
Treatment: Shunts used in treatment of Fallots tetralogy
are
1. Ballock Taussig shunt - between subclavian and
pulmonary artery.
2. Potts shunt - between descending aorta and pulmonary
artery.
3. Waterson shunt - between ascending aorta and right
pulmonary artery.
Tricuspid Atresia
Pathology: Hypoplasia of right ventricle, patent foramen
ovale or ASD.
Clinical feature: Central cyanosis since birth.
231
X-ray: Lungs are oligemic.

ECG: Left axial deviation, left ventricular hypertrophy, right
atrial enlargement.
Ebsteins Anomaly
Pathology: Downward displacement of tricuspid valve into
the right ventricle. Due to anomalous attachment of
tricuspid leaflets called atrialization of ventricle.
Clinical feature: Progressive cyanosis.
X-ray: Marked cardiomegaly.
Diagnosis:
Intracardiac ECG with pressure recording.
Echocardiography.
Eisenmengers Syndrome
VSD with pulmonary hypertension - right to left shunt.
Mechanism: Left to right shunt RV hypertrophy
pulmonary hypertension right to left shunt.
Transposition of Great Vessels
Pathology:
Aorta arises from right ventricle and pulmonary artery
from left ventricle.
Mitral valve is continuous with pulmonary valve.
Pulmonary O2 saturation always > systemic arterial
saturation.
Clinical feature: Central cyanosis with systolic murmur.
Chest X-ray:
Cardiomegaly, plethoric lung fields and features of
pulmonary hypertension.
Egg-on-side appearance.
Treatment: Confirmation of diagnosis is done by cardiac
catheterization and angiocardiography.
Prostaglandin E
Balloon atrial septostomy (Rashkind)
Atrial switch procedure (Mustard) or Jantenes switch

procedure - treatment of choice.
232
Total Anomalous Pulmonary Venous Connection

Pathology: All the pulmonary veins join anomalously to
result in all the venous blood ultimately reaching the right
atrium.
Type: Infracardiac type is always obstructive.
Hemodynamics: The O2 saturation of blood in the
pulmonary artery that in aorta.
Chest X-ray:
Non-obstructive type-Snowman heart or figure of 8
heart
Obstructive type- ground glass appearance.
Anomalous Origin of Left Coronary
Artery from Pulmonary Artery
Clinical feature:
Presents with CCF within first few months of life.
Recurrent attacks of abdominal pain, restlessness,
irritability, diaphoresis on feeding.
Non-specific murmur.
X-ray: Cardiac enlargement.
Risk: Development of myocardial infarction and fibrosis.
RHEUMATIC HEART DISEASE
Etiopathogenesis
Causative organism - group A -hemolytic streptococcus
(Streptococcus pyogenes).
Preceding event - URTI (sore throat). Incidence 3
percent.
Time interval - 10 days to few weeks.
Pathology
Fibrosis is common in cardiac tissue in rheumatic fever.
Aschoff body: It is the hallmark of acute rheumatic carditis.
It may occur in any layer of heart but most common
in subendocardial region and myocardial interstitium.
It contains Fibrinoid material surrounded by histiocytes
Aschoff giant cells
Lymphocytes
233
Plasma cells
Fibroblasts
Collagen
Anitschkow cells.
Carditis:
It is characteristically pancarditis.
Pericardium- fibrinous pericarditis with serous or
serosanguinous pericardial effusion - bread and butter
pericarditis.
Endocardium- foci of fibrinoid necrosis. Mitral valve
is involved in 100 percent cases. Small wart like
vegetations at valve cusp margins. Least commonly
involved is pulmonary valve.
McCallums plaque: subendocardial lesion in left atrium.
It is the hallmark of chronic rheumatic carditis.
Clinical Feature
Major criteria:
1. Carditis:
Pancarditis, early manifestation (within 2 weeks of
onset of fever).
Myocarditis - Carey Coombs murmur (diastolic).
Endocarditis - pansystolic murmur of MR (most
common valvular abnormality).
Pericarditis - pericardial friction rub.
Others - sinus tachycardia, cardiomegaly (most
common cause of in children).
Note: Rheumatic carditis is aggravated by
pregnancy.
2. Migratory polyarthritis:
Risk increases with age, no residual damage.
3. Sydenham s chorea: Late manifestation (after 3
months of fever), self-limiting.
4. Erythema marginatum and
5. Subcutaneous nodules: Painless, over extensor surface
of joints; appear 4 weeks after onset of fever. Rarely
occurs unless active carditis is present.
Note: The last 2 features are more common in children.
Minor criteria:
Clinical- fever and arthralgia
Laboratory- increased acute phase reactants (increased
polymorphonuclear leucocytes, ESR and C-reactive
protein).
ECG - prolonged PR interval.
234
Diagnosis
Jones criteria:
2 major or 1 major and 2 minor criteria are required
plus essential criteria as below Evidence of recent streptococcal infection indicated
by increased ASO titer, positive throat culture, or
recent history of scarlet fever.
Chest X-ray: Cardiomegaly (most common cause in
children).
Complication
Mitral stenosis (fish mouth or button hole stenosis) with
or without AF - may lead to cerebral embolism.
Treatment
Aspirin.
Steroids - in severe carditis with CCF.
Chronic Rheumatic Carditis
Characterized by fibrosis.
Mitral stenosis is more common than mitral
regurgitation (c.f. acute carditis).
McCallums patch in left atrium due to chronic valvular
involvement is characteristic.
Vegetations
Rheumatic
fever
Non-bacterial
thrombotic
Small, firm,
warty, friable
Small, friable
Libman Sacks Infective

endocarditis
endocarditis
Medium size,
flat, verrucous,
irregular
Along the line Along the line
On surface,
of valve
of valve closure both sides of
closure
cusps; mainly
undersurface
Sterile
Sterile
Sterile
No destruction Non destructive Destructive
of underlying
structures
Rheumatic
Hypercoagulable SLE
fever
state
Large, bulky,
irregular
On upper
surface
Infected
Ulceration and
perforation
Infective
endocarditis
235
VALVULAR HEART DISEASE

Mitral Stenosis
Pathology:
Normal area of mitral orifice in adults = 4-6 cm2.
Left ventricular diastolic pressure is normal in isolated
MS. LVH is due to presence of MR, aortic valve disease
or systemic hypertension.
There is a gradient between PCWP (left atrial pressure)
and left ventricular diastolic pressure. Such gradient
is also seen in atrial myxoma (see later).
Clinical feature:
Symptom - hemoptysis.
On examination - Accentuated S1.
Opening snap- audible in expiration. OS corresponds
to dicrotic notch in carotid pulse.
Murmur - low-pitched, mid-diastolic, rumbling murmur
best heard at the apex and left lateral recumbent
position.
Graham Steell murmur of PR.
Severity of MS: It is assessed by A2-OS gap (inverse
relation) and the length of the diastolic murmur.
ECG: Right ventricular hypertrophy.
Chest X-ray:
Straightening of left heart border.
Prominence of main pulmonary arteries.
Dilatation of upper lobe pulmonary veins.
Kerley B line.
Echocardiography: most useful.
Differential diagnosis: Left atrial myxoma.
Mitral Regurgitation
Most common valvular defect in rheumatic carditis.
Clinical feature: systolic murmur that is most prominent
at the apex and radiates into the axilla.
Severity of MR: is assessed by presence of pulmonary
hypertension, wide split S2, diastolic murmur and S3 gallop.
236
Mitral Valve Prolapse

(Barlows syndrome/Floppy valve syndrome/Billowing mitral
valve)
Autosomal dominant trait.
Pathology: Myxomatous degeneration of the valve.
Clinical feature:
More common in females.
Symptoms- chest pain that is difficult to evaluate.
Arrhythmias- palpitation.
Auscultation- mid/late systolic click (non-ejection).
Late systolic crescendo-decrescendo murmur.
Factors regulating murmur: Increased by standing and
Valsalva maneuver. Decreased by squatting and exercise
(c.f. - HOCM).
ECG: Normal.
Echocardiography: Investigation of choice.
Complication:
Transient ischemic attacks
Mitral regurgitation
Sudden death
Infective endocarditis.
Aortic Stenosis
Etiology: May be due to degenerative calcification of the
valve.
Pathology: Aortic orifice <0.5 cm2/m2 of body surface
area is considered critical to maintain left ventricular
outflow. There develops gradient between aortic and left
ventricular systolic pressure (also occurs in hypertrophic
cardiomyopathy).
Clinical feature:
Exertional dyspnea, angina pectoris and syncope - 3
cardinal features. Sudden death is common.
Poorest symptom is dyspnea.
Ejection systolic murmur, sustained systolic thrust
(characteristic of severe AS).
ECG: LVH.
Severity of AS: is assessed by:
Symptomatic patients
Presence of S3, S4 or systolic thrill
237
Delayed peak of systolic murmur

Narrow pulse pressure
ST and T changes in ECG
Cardiac enlargement
Note: Exercise tolerance test is absolutely
contraindicated in aortic stenosis.
Aortic Regurgitation
Etiology:
1. Rheumatic fever- most common cause.
2. Infective endocarditis.
3. Syphilis and ankylosing spondylitis.
4. Marfans syndrome
Clinical feature:
Water hammer pulse.
Widening of aortic pulse pressure to 75-90 mmHg in
severe AR.
Corrigans pulse at the carotids.
Quinckes pulse - alternative flushing and paling of the
skin at the root of the nail while pressure is applied.
Traubes sign - pistol shot sound over femoral arteries.
Palpation- apex beat is heaving.
Auscultation - high pitch, blowing, decrescendo, early
diastolic murmur.
Austin Flints murmur mid diastolic (often mistaken
for MS).
ECG: LVH.
Tricuspid Regurgitation
Usually functional and most commonly due to dilatation
of right ventricle.
COR PULMONALE
Etiology:
Acute- most common cause is pulmonary embolism.
Chronic- most common cause is chronic obstructive
pulmonary disease (COPD).
Others- obesity, kyphoscoliosis.
Chest X-ray: Pulmonary trunk and hilar vessels are
enlarged, widening of the descending right pulmonary artery
shadow.
238
Complication: COPD leads to pulmonary hypertension due

to:
i. Pulmonary vasoconstriction.
ii. Increased cardiac output.
iii. Increased blood viscosity caused by polycythemia.
CARDIOMYOPATHY AND MYOCARDITIS
Dilated Cardiomyopathy
Most common type of cardiomyopathy in India.
Most common myocardial disease in children.
Secondary causes of DCM:
1. Infective myocarditis (all types by virus, bacteria,
protozoa, etc.).
2. Metabolic.
3. Connective tissue disorder.
4. Alcohol.
5. Peripartum heart disease.
Pathology: Progressive cardiac hypertrophy, dilatation and
contractile (systolic) dysfunction.
Treatment: Cardiac transplantation (most common
indication of cardiac transplantation in children).
Alcoholic cardiomyopathy:
Without heart failure- consists of recurrent ventricular
tachyarrhythmia and follows an episode of binge drinking
- Holiday heart syndrome.
Note: Most common alcoholic cardiotoxicity is atrial
fibrillation.
Hypertrophic Cardiomyopathy
Also called asymmetric septal hypertrophy or idiopathic
hypertrophic subaortic stenosis.
Characterized by:
1. Left ventricular hypertrophy with asymmetric septal
hypertrophy (ASH).
2. Dynamic left ventricular outflow obstruction due to
subaortic stenosis.
3. Abnormal diastolic filling.
4. Systolic anterior motion (SAM) of the mitral valve.
Pathology: Atrial dilatation occurs but ventricular dilatation
is uncommon.
239
Clinical feature:
Symptoms most common complaint is dyspnea.
Graying out spells- cyanosis
On examination- Double or triple apical precordial
impulse.
Late systolic murmur- best heard at the lower left sternal
border.
Factors regulating murmur of HOCM
Factors worsening obstruction
and increasing murmur
Factors decreasing obstruction

and murmur
Increased myocardial
contractility
i. Exercise
ii. Digitalis
iii. Isoprotenanol
Decreased ventricular volume
(preload)
i. Valsalva maneuver
ii. Standing
iii. Nitroglycerine
Increased arterial pressure

i. Phenylephrine
ii. Squatting
iii. Sustained hand grip
Increased venous return
i. Passive leg rising
ii. High blood volume
Treatment:
-blockers (propanolol), amiodarone, disopyramide,
verapamil and diltiazem.
Digitalis is avoided.
Restrictive Cardiomyopathy
Pathology:
Myocardial fibrosis.
Characterized by- defective diastolic filling decreased
cardiac output and increased filling pressure
symmetrical thickening of ventricular walls.
Secondary causes:
Beriberi
Amyloidosis
Hemochromatosis
Glycogen deposition (Pompes disease)
Fabrys disease
Sarcoidosis
Eosinophilia (eosinophilic endomyocardial fibrosis or
Loefflers endocarditis).
Friedreichs ataxia
240
Muscular dystrophy
Cystic fibrosis
Tapioca (endomyocardial fibrosis).
Myocarditis
Cause:
Most common cause is Coxsackie B virus infection.
Others- rubella, diphtheria, measles, trichinella.
Cardiac Hypertrophy
Concentric: Due to pressure overload - apex not shifted.
Caused by hypertension, aortic stenosis, coarctation
of aorta.
Eccentric: Due to volume overload - apex is shifted.
Caused by Aortic regurgitation.
Mitral regurgitation.
Anemia.
Thyrotoxicosis.
Ventricular septal defect.
Patent ductus arteriosus.
PERICARDIUM
Pericarditis
Etiology:
I. InfectiveViral- Coxsackie virus A and B.
Pyogenic (empyema).
Tuberculosis.
II. Non-infective- uremia.
Clinical feature: Friction rub is the most important sign
of acute pericarditis.
ECG:
Widespread (in all leads) elevation of the ST segment
in acute pericarditis except in aVR which shows ST
depression.
PR depression but T wave remains normal until late
in the disease (c.f. AMI).
241
Pericardial Effusion
Pericardial effusion is the most common presentation of
radiation carditis.
Clinical feature:
Heart sounds become faint.
Ewarts sign- a patch of dullness beneath the angle
of scapula.
Signs are obvious when fluid accumulates > 500 ml.
Chronic constrictive pericarditis may produce
proteinuria.
Diagnosis:
X-ray - Water bottle configuration.
ECG - Electrical alternans (pathognomonic).
Two-dimensional transthoracic echocardiography- most
sensitive method.
Causes of bloody effusion:
Tuberculosis.
Tumor.
Rheumatic fever.
Uremic pericarditis.
Cardiac Tamponade
Etiology:
1. Neoplastic diseases.
2. Idiopathic pericarditis.
3. Uremia.
4. Bleeding into pericardial sac following cardiac
operations and trauma (hemopericardium).
Clinical feature:
Hepatic engorgement.
Jugular venous hypertension.
Hypotension.
Narrow pulse pressure.
Pulsus paradoxus- hallmark of tamponade.
ECG: Electrical alternans.
Diagnosis: 2-D echocardiography - shows right atrial and
ventricular diastolic collapse.
Treatment: Emergency pericardiocentesis.
242

Differential diagnosis
Features
Cardiac
tamponade
Constrictive
pericarditis
Pulsus paradoxus
Prominent y descent
Kussmauls sign
Electrical alternans
Pericardial knock
Prominent x descent
+ ve
ve
ve
May be + ve
ve
+ ve
ve (only in 1/3rd cases)

+ ve
+ ve
ve
+ ve
Usually + ve
Chronic Constrictive Pericarditis

Etiology:
Tuberculosis - most common.
Pyogenic - empyema thoracis.
Uremia.
Clinical feature:
Kussmauls sign - venous pressure fails to decline during
inspiration.
Distended neck veins- Square root sign - in ventricular
pressure pulse.
Apical impulse- decreased in intensity.
Splenomegaly, hepatic engorgement.
Ascites.
Diagnosis:
ECG - low voltage QRS in all leads. No ST change.
Echocardiography.
CT scan and MRI - most sensitive to detect thickened
pericardium.
Causes of hemorrhagic pericarditis:
1. Tuberculosis.
2. Malignant involvement of pericardial sac.
3. Bleeding diasthesis.
4. Post-myocardial infarction.
5. Uremia.
6. Cardiac surgery.
7. Dissecting aortic aneurysm.
CARDIAC TUMORS
Metastatic tumors are more common than primary.
243
Metastatic Tumors
Source:
Carcinoma lung (most common) and breast.
Malignant melanoma (high incidence).
Lymphomas and leukemias.
Primary Tumors
Atrial Myxoma
Sporadic:
Most common primary tumor of heart.
Site: Left atrium (most common).
Pathology: Usually solitary.
Microscopy- composed of mucopolysaccharide rich
stroma.
Clinical feature:
More common in older age group (30-70 years) with
female preponderance.
May present with peripheral or pulmonary emboli.
Clubbing, rash.
Raynauds phenomenon.
Prolonged fever.
ESR increased.
Mid-diastolic low pitched sound - tumor plop (c.f. mitral
stenosis).
Diagnosis: 2-D echocardiography.
Treatment: Recurrence is uncommon.
Familial:
Occurs in younger are group.
Usually multiple.
Recurrence more common.
Associations:
NAME syndrome.
LAMB syndrome.
Rhabdomyoma
Most common cardiac tumor in infancy and childhood.
In 90 percent cases associated with tuberous sclerosis.
244
VASCULAR DISEASES
ATHEROSCLEROSIS
Pathology
The key processes in atherosclerosis are intimal thickening
and lipid accumulation in smooth muscles known as
atheroma.
Fatty streaks are lipid-filled foam cells. They are the
initial lesions in atherosclerosis and may evolve into
precursors of atheromatous plaque.
Histology: Parts of an atheroma are:
i. Fibrous cap - consisting of smooth muscle cells,
macrophages and dense collagen.
ii. Necrotic centre - consisting of cell debris, cholesterol
crystals and foam cells.
iii. Tunica media of vessel wall.
Risk factors:
Hypercholesterolemia.
High LDL level - atherogenic fatty acid and low HDL
level.
High lipoprotein A level.
Hyperhomocysteinemia.
Obesity, diabetes, hypertension.
Pathogenesis: The response to injury hypothesis - ATH is
a chronic inflammatory response of the arterial wall
initiated by injury to the endothelium.
Monckeberg medial calcific sclerosis: Characterized by
calcific deposits in muscular arteries.
ACUTE MYOCARDIAL INFARCTION
Pathology
Pathology of AMI
Artery involved
Site of heart involved
Left coronary artery (LCA)

anterior descending branch
Anterior and apical left

ventricle, anterior 2/3rd of
interventricular septum
Posterior wall of left ventricle,
posterior 2/3rd of
interventricular septum
Lateral wall of left ventricle
Right coronary artery
Left circumflex coronary artery
245
Sequence of changes: Earliest irreversible changes in

electron microscopy occurs after 1-2 hours.
Sequence of changes
Time interval Gross changes
4-12 hours
24-72 hours
4-7 days
7-8 days
10 days
7-8 weeks
Microscopic changes
None
Early coagulation necrosis
Pallor
Heavy neutrophilic infiltration
Central pallor with Macrophages appear
hyperemic border
Ingrowth of granulation tissue
Yellow shrunken
Phagocytes, organization of
granulation tissue
Gray
Fibrosis (healed)
Diagnosis
A. ECG:
Transmural - Q waves (may be ST elevationhallmark of MI).
Non-transmural - absence of Q waves, only ST
segment (ST depression) and T wave (T wave
inversion) changes.
B. Serum cardiac markers:
1. Creatine phosphokinase: Earliest enzyme to appear after
MI.
CKl or CK-BB - brain and lungs.
CK2 or CK-MB - myocardium.
CK3 or CK-MM - skeletal muscle and heart.
CK enzymes
Total CK
CK-MB
Appearance
Peak
Disappearance
2-4 hours
2-4 hours
24 hours
18 hours
48-72 hours
48 hours
CK-MB2 : CK-MB 1 ratio > 1.5 is highly sensitive.

However CK is not specific as it is elevated in other
conditions like
i. Muscular diseases- including muscular dystrophy,
myopathy and polymyositis.
ii. Skeletal muscle injury.
iii. Cardioversion.
iv. Clofibrate therapy.
2. Troponins:
Cardiac troponin T (cTnT) - heart.
Troponin I (cTnI) - skeletal muscle.
cTnT is more specific than CK-MB.
246
3.
4.
C.
Appearance
Disappearance
cTnT 2-4 hrs
10-14 days
Hence TnT is of little value in case of reinfarction.
Lactate dehydrogenase: appears last in MI (after 24
hours).
AST.
Imaging:
Two-dimensional echocardiography.
Myocardial perfusion scanning with thallium 201 or
Tc99m sestamibi - shows cold spots. With Tc99m
strontium pyrophosphate shows hot spots.
Management
1. Morphine- to relieve pain.
2. Aspirin, infusion of nitroglycerine, infusion of
unfractionated heparin or SC administration of lowmolecular weight heparin, -blockers.
3. Thrombolysis:
Indications: MI with ST elevation.
Agents: tissue plasminogen activator (tPA),
streptokinase, tenecteplase (TNK), and reteplase (rPA).
Time: within 1-3 hours (golden hours) of onset of pain
is most effective (should be started before 12 hours).
Contraindications:
i. H/O cerebrovascular hemorrhage at any time.
ii. H/O nonhemorrhagic stroke or other cerebrovascular event within past 1 year.
iii. Marked hypertension (> 180/110 mmHg).
iv. Aortic dissection/internal hemorrhage.
v. Relative contraindications recent (< 2 weeks)
surgery, current use of anticoagulants, prolonged
cardiopulmonary resuscitation, known bleeding
diasthesis, pregnancy, a hemorrhagic ophthalmic
condition (e. g. hemorrhagic diabetic retinopathy),
active peptic ulcer and a history of severe
hypertension that is recently adequately
controlled.
Complications: Hemorrhage- most common.
4. Antithrombotics:
i. Antiplatelet agents.
ii. Antithrombin .
5. Treatment of complications.
247
Complications
1. Cardiac arrhythmias: most common complication of
AMI
More with subendocardial infarct.
Ventricular fibrillation is most common and vast
majority of deaths due to ventricular fibrillation occur
within 24 hours (>50% occurs within 1 hour) of onset
of symptoms.
Treatment: Lignocaine is the drug of choice. For
ventricular ectopic after MI drug of choice is -blocker.
2. Left ventricular failure with pulmonary edema:
Treatment of choice - intra-aortic balloon pump.
3. Cardiogenic shock: Treatment- dopamine, intra-aortic
balloon pump.
4. Right ventricular infarction: Occurs in 1/3rd cases of
inferior wall MI.
Features: Increased JVP, Kussmauls sign, hepatomegaly, cardiomegaly and arrhythmia.
Treatment: IV fluid.
5. Mitral regurgitation: Occurs in 10-50 percent cases.
Most common valvular defect after MI. It is due to
papillary muscle rupture.
6. Dresslers syndrome (post-myocardial infarction
syndrome):
Characterized by- fever and pleuropericardial chest
pain.
Cause- autoimmune pericarditis
Time- develops from a few days to 6 weeks after
infarction.
Treatment- responds promptly to salicylates.
7. Thromboembolism: Arterial emboli occur most
commonly in anterior MI. Both arterial and pulmonary
embolisms occur in septal MI.
8. Ventricular aneurysm: ECG shows persistent ST
elevation.
9. Myocardial rupture: Occurs in first week.
Characterized by sudden loss of pulse and drop in BP;
electromechanical dissociation in ECG.
ISCHEMIC HEART DISEASE
Etiology:
Atherosclerosis most common cause.
Critical narrowing - >80 percent of the lumen of
coronary artery.
248
Angina Pectoris
Stable angina:
Clinical feature: Pain lasts for 1-5 minutes.
ECG: ST segment depression (plateau or square
wave).
Unstable angina:
i. Patients with new onset (<2 months) angina that
is severe and frequent (3 episodes/day).
ii. Patients with accelerating angina.
iii. Angina at rest.
Prinzmetals variant:
It represents transmural ischemia.
Ischemic pain occurring at rest, often in sleep.
ECG: Multilead ST-elevation during pain, normal
without pain.
Treatment:
Calcium antagonists (diltiazem - DOC).
-blockers are contraindicated in Prinzmetals variant.
Coronary Revascularization
Indications:
a. PTCA (Percutaneous transthoracic coronary
Angiography) indicated in
i. Angina pectoris- most common.
ii. To dilate stenosis in native coronary arteries and
in grafts following coronary artery bypass surgery.
PTCA is contraindicated in LCA stenosis.
b. Coronary artery bypass grafting (CABG) - is indicated
in multivessel disease (3 vessel CAD) and LCA (Left
Coronary Artery) stenosis.
Grafts used for CABG are Long saphenous vein,
internal mammary artery (best).
HYPERTENSIVE VASCULAR DISEASE
Morphology
Vascular changes in hypertension are most prominent in
kidneys. These include:
1. Hyaline arteriosclerosis - in benign hypertension.
2. Hyperplastic arteriosclerosis - in malignant hypertension. Characterized by onion-skin like concentric
249
thickening of vessel wall with fibrinoid necrosis

(nectrotizing arteriolitis).
Seen in - kidneys, small gut, gallbladder, peripancreatic
and periadrenal fat.
Heart- left ventricular hypertrophy (concentric type).
Diagnosis
a. Pheochromocytoma - measurement of catecholamine
or their metabolites in a 24 hour urine sample.
b. Cushings syndrome - 24 hour urine test for cortisol
or dexamethasone suppression test (a +ve test rules
out the diagnosis).
c. Renovascular (Gold Blatt hypertension) most
common cause is renal artery stenosis. Renal artery
stenosis causes increased renin activity.
Tests for renovascular hypertension:
ScreeningCaptropril enhanced radionuclide scan (best).
Duplex Doppler flow study.
Magnetic resonance imaging.
Spiral CT scan - most sensitive and specific.
Diagnostic Renal angiogram and renal vein renin determination.
Malignant Hypertension
BP >200/140 mmHg,
Papilledema,
Retinal hemorrhage and exudates,
Renal failure,
Microangiopathic hemolytic anemia.
Wagner-Barker Classification
of Hypertensive Retinopathy
Normal A:V (diameter of artery to vein) ratio= 3:4.
Grade I:
Mild arteriolar narrowing (A:V= 1:2)
Grade II:
A:V ratio 1:3.
Focal spasm 2:3 (area of spasm: proximal arteriole).
Arteriolar light reflex - Copper wire.
250
A V crossing defect - Nicking, depression or humping

of veins.
Grade III:
A:V ratio 1:4.
Focal spasm 1:3.
Hemorrhage +, Exudates +.
Cotton wool spots.
Arteriolar light reflex - Silver wire.
AV crossing defects - right angle deviation, tapering
and disappearance of vein under artery.
Grade IV:
Arteriole - Cord like. Obliteration of distal flow.
Hemorrhage/Exudates +.
Papilledema +.
ARTERIAL DISORDERS
Aortic Aneurysm
Arteries involved:
1. Abdominal aorta - most common site. Least common
site is the arch and root of aorta.
2. Splenic artery - next common site.
3. Peripheral aneurysm - most commonly involves the
popliteal artery.
4. Superficial temporal artery - involved in cirsoid
aneurysm.
Causes and sites of aneurysm
Cause
Site
Atherosclerosis
Cystic medial necrosis
Syphilis
Marfans syndrome
Takayasus arteritis
Abdominal aorta distal to renal artery

Proximal aorta and the sinus of Valsalva
Ascending and arch of aorta
Ascending aorta
Arch of aorta, subclavian artery
Abdominal Aortic Aneurysm

Abdominal aorta is the most common site of
atherosclerotic aneurysm, commonly involves below the
renal arteries.
Clinical feature:
Most cases are asymptomatic.
Sudden severe symptoms may appear when they
expand and rupture (e.g. severe back pain indicates
enlargement of sac).
251
Complications: Rupture- posterior rupture is most common;

produces retroperitoneal hematoma.
Diagnosis:
Plain X-ray - may reveal calcified outline of the
aneurysm.
USG.
CT scan and MRI - best (MRI is the investigation of
choice).
Differential diagnosis: With other pulsating tumors viz.:
1. Bone sarcoma.
2. Osteoclastoma.
3. Secondaries from hypernephroma.
Treatment:
For symptomatic patients - excision with replacement
with graft.
Asymptomatic - surgery is indicated if size > 6.5 cm.
Prognosis:
Depends on size.
Without surgery 80 percent of symptomatic patients
die within 1 year.
An elective surgery carries 2-5 percent mortality.
Popliteal Aneurysm
Most common peripheral aneurysm.
Often bilateral and associated with aortic aneurysm.
Iliac Aneurysm
Occurs in conjunction with aortic aneurysm.
Clinical feature: GI bleeding.
Diagnosis: P/R examination.
Cystic Medial Necrosis
Produces fusiform aneurysm of proximal aorta and
sinus of Valsalva.
Associated with: Marfans syndrome, Ehlers-Danlos
syndrome, pregnancy, hypertension.
Treatment: Long term -blocker therapy.
252
Syphilitic (Leutic) Aneurysm

Pathology:
It is an endarteritis obliterans in tertiary syphilis.
Site: Involves the vasa vesorum of arch of aorta medial
necrosis and scarring the proximal aorta and arch
become dilated aneurysm.
Abdominal aorta is not involved.
X-ray: Tree- barking like calcification.
Mycotic Aneurysm
Not caused by fungus, but by bacteria viz. Staphylococcus,
Streptococcus and Salmonella.
Pseudoaneurysm
Produces pulsating tumor.
Cause:
1. Atherosclerosis - most common cause.
2. Post MI rupture.
3. Leak at the junction of a vascular graft with a natural
artery.
Aortic Dissection
It is a transverse tear of the intima.
Cause:
Hypertension - most common.
Marfans syndrome.
Iatrogenic.
Cystic medial necrosis - produces spontaneous
dissection.
Site: Along the right lateral wall of ascending aorta.
Type:
Proximal: Involves the ascending aorta - more common
and more dangerous - peripheral pulses may be
abnormal.
Distal: Peripheral pulses normal.
Clinical feature:
Severe pain in chest which radiates downwards and
to back.
Pleural effusion may develop.
253
Complication: Rupture (most common cause of death).

Investigation:
Transesophageal echocardiography - initial
investigation of choice.
MRI-best.
DSA.
Treatment: Antihypertensive and surgery (definitive).
VASCULAR DISEASES OF EXTREMITIES
Atherosclerosis
Risk factors: Diabetes, hypercholesterolemia, smoking.
Clinical feature:
Intermittent claudication: Occurs during exercise and
relieved by rest.
Site- distal to the site of occlusion. Calf claudication
in femora-popliteal disease.
Symptoms may appear at night.
Lerich svndrome:
Buttock, hip and thigh discomfort in patients with
aortoiliac obstruction.
In bilateral obstruction there is male infertility.
Fibromuscular Dysplasia
Hyperplastic disorder of arteries.
Renal artery involvement may cause stenosis and
hypertension.
Angiography shows string of beads appearance.
Thromboangiitis Obliterans (Buergers Disease)
Pathology: Inflammation of small and medium sized
arteries and veins in the distal upper and lower extremities.
Most commonly involves the tibial artery.
Epidemiology: Does not occur in women and non-smokers.
Clinical feature: Triad of:
1. Claudication.
2. Raynauds phenomenon.
3. Migratory superficial vein thrombophlebitis.
Normal brachial and popliteal pulses but reduced or
absent radial, ulnar and/or tibial pulses.
254
Death occurs most commonly due to myocardial

infarction.
Diagnosis: Arteriography - may show corrugation of the
femoral arteries.
Treatment: Sympathectomy may relieve rest pain and
venous leg ulcers. But it is not much effective in pain of
claudication.
Raynauds Phenomenon
Characterized by: Sequential development of digital
blanching, dusky cyanosis and rubor of the fingers and
toes on exposure to cold and subsequent rewarming.
Types:
1. Idiopathic or Raynauds disease More common in
females.
Upper extremities commonly affected.
Peripheral pulses are normal.
2. Secondary Due to collagen vascular diseases particularly
scleroderma and SLE
Atherosclerosis of extremities.
Thromboangiitis obliterans.
Treatment:
Calcium channel blockers- nifedipine.
Adrenergic blockers- reserpine.
Sympathectomy.
VENOUS DISORDERS
Varicose Veins
Pathology:
Normal blood flow in extremities is from superficial to deep
veins. This is regulated by valves. In varicose vein, the
valves are defective and blood flows from deep to superficial
veins resulting in dilatation of superficial veins.
There are four valves in the leg, and one at the lower
thigh.
Site:
Long saphenous vein is the most commonly affected.
Most common site of reflux are - saphenofemoral
junction (SFJ) and saphenopopliteal junction (SPJ).
255
Cause: Incompetence of the valves.

Note: Pulsatile varicose vein is seen in AV fistula, KlippelTrenaunay syndrome.
Klippel Trenaunay syndrome:
Congenital AV fistula.
Cutaneous hemangiomas.
Varicose veins.
Hypertrophy of involved extremity.
Absence of deep venous system.
Test: Trendelenburgs test to detect perforator incompetence.
Complications: Venous ulcers - usually located just proximal
to the lateral or medial malleolus.
Management:
First management of ruptured varicose vein is
compression and elevation of limb.
Injection sclerotherapy using Ethanolamine oleate for
varicosity <3 mm.
Surgery:
Indication - varicosity >3 mm in size.
Contraindication - deep vein thrombosis.
Procedure Trendelenburgs procedure - ligation of SFJ and
SPJ and removal of varicose vein.
Cocket and Dodds procedure- subfascial ligation
Complications - bleeding and discomfort.
Recurrence rate after surgery 10 percent.
Deep Vein Thrombosis
Causes:
1. SurgeryOrthopedic operations on the lower limbs (hip
and knee replacement) are at increased risk. Also
abdominal operations.
2. Paraneoplastic syndromeAdenocarcinoma of
pancreas, stomach, colon or lung may produce
migratory thrombophlebitis - Trousseaus sign.
3. High estrogen therapy.
4. Thrombocytosis.
5. PNH.
6. Endocrinal - Nephrotic syndrome, Cushings syndrome.
7. Thrombophilia - congenital deficiency of antithrombin
III, protein C and S.
256
Risk factors:
Old age
Obesity
Pregnancy and puerperium
Immobilization (for >4 days)
Varicose vein
Lupus anticoagulant
Behcets syndrome
Homocystinemia
Site: Calf veins (popliteal and posterior tibial) most
common.
Clinical feature:
Swelling, pain, calf tenderness.
Dilated superficial veins.
Fever (low grade).
Pain in calf on dorsiflexion (Homans sign).
Complications: Pulmonary embolism (most common
source is from femoral veins).
Investigations:
Duplex ultrasound- method of choice.
Enhanced helical CT- for pulmonary embolism.
Treatment:
IV heparin + warfarin at the same time (for at least
5-7 days).
Heparin dose should be 2.5 to 3.5 times the normal
INR (international normalized ratio).
Phlegmasia alba dolens (milk leg): Ilio-femoral vein
thrombosis in pregnancy.
Superficial Vein Thrombosis
Cause: Most common cause is canulation of vein for IV
infusion.
Site: Most commonly involves great saphenous vein.
Treatment: Symptomatic with analgesic and antiinflammatory drugs.
Axillary Vein Thrombosis
Cause:
As a complication of thoracic outlet syndrome
associated occasionally with cervical rib.
May also occur following vigorous exercise.
257
Clinical feature: Swollen arm with dilated superficial veins.

Treatment:
Anticoagulants- early.
Fibrinolytics (streptokinase or tPA) - in severe cases.
Arteriovenous Fistula
Causes:
1. Congenital.
2. Traumatic - most common cause.
Effects:
a. Structural - veins become dilated, tortuous and thick
(arterialization of veins).
b. Physiological- increased venous return leads to
increased pulse rate and cardiac output.
Increased pulse pressure.
LVH and failure.
Local gigantism.
Clinical feature:
Pulsatile swelling, dilated veins, thrill and bruit.
Pressure on artery proximal to fistula causes decrease
in size of swelling, decrease in thrill and bruit, decrease
in pulse rate. Pulse pressure returns to normal. This
is known as Nicoladonis or Branhams sign.
Diagnosis: Arteriography (confirmatory).
Treatment:
Embolisation, excision.
Ligation of artery and vein both above and below the
lesion (quadruple ligation).
LYMPHATIC DISORDERS
Acute Lymphangitis
Organism: Streptococcus pyogenes or Staphylococcus
aureus.
Treatment: IV penicillin.
Lymphedema
Types:
Congenital - onset before 1 year of age.
i. Sporadic
ii. Familial - Milroys disease.
258
Precox - onset between 1-35 years of age.

i. Sporadic
ii. Familial - Meige s disease.
Tarda - onset after 35 years of age.
Causes:
PrimaryCongenital (Milroys disease)
SecondaryFilariasis (most common cause), lymphatic malignancy,
radiation.
Complication: Chronic lymphedema predisposes to 1. Lymphangiosarcoma.
2. Recurrent infections.
3. Thickening of skin.
Milroys Disease
Onset: At or within one year of birth (present at birth or
noticed shortly thereafter).
Clinical feature:
More common in males.
Often bilateral.
Involves the whole leg.
Lymphedema Precox
Occurs in post-menarche females with involvement of single
leg only.
Lymphangiogram shows:
Hypoplasia of the lymphatics (absent or reduced distal
superficial lymphatics).
Lymphangiosarcoma
Most common cause - post-mastectomy.
Occurs after several years of operation.
IMMUNE SYSTEM
ANTIGEN AND ANTIBODY
ANTIGEN
Antigens are substances which, when introduced
parenterally into the body, stimulate production of an
antibody with which it reacts specifically and in an
observable manner.
Smallest unit of antigenicity is antigen determinant or
epitope (the site on antigen which is recognized by antibody).
Isospecificity
Isoantigens are antigens found in some but not all members
of a species e.g. blood group antigens and histocompatibility antigens.
Haptens
Are substances which do not induce antibody production
but can react specifically with antibodies. They become
immunogenic on combining with a carrier.
ANTIBODY
The combining area of antibody corresponding to epitope
is paratope.
Character: On the basis of electrophoretic mobility, they
fall into the group of gamma-globulins.
All antibodies are immunoglobulins (Ig), but all
immunoglobulins are not antibodies because proteins in
multiple myeloma, cryoglobulinemia, etc. are also
immunoglobulins.
Structure:
An Ig is lysed by papain into:
i. An insoluble fraction called Fc (crystallizable) it is
composed of the carboxyterminal of the H chain.
260
ii. A soluble fragment called Fab (antigen binding)

composed of the aminoterminal of H chain and L
chains.
Igs are glycoproteins, each molecule consists of 2
pairs of polypeptides called light chain (molecular weight
25000) and heavy chain (molecular weight 50000).
The H chains are structurallty and antigenically
distinct for each class. The L chains are similar in all
classes of Igs, and are either kappa () or lambda ()
chains.
The aminoterminals act as antigen binding sites
(hypervariable region).
The carboxy terminals determine the biological
properties of Ig molecule like complement fixation,
placental transfer, etc.
Types
IgG
It is the most abundant Ig (80% of the total). IgG1
is the most abundant subtype.
It is the only maternal antibody to cross placenta.
It is a late antibody and appears after IgM.
Examples antiRA antibody, antiRh antibody.
It is more powerful than IgM in complement fixation.
IgA
It is present in colostrums, saliva and tears. It is secreted
by mucosal or glandular epithelial cells.
It has a dimeric structure with a J or joining piece.
It has a secretory piece which is responsible for its
presence in secretions.
It has important role in local immunity against
respiratory and intestinal pathogens.
It is the only Ig to fix complement via alternate pathway.
IgM
Molecular weight 1000000 millionaire molecule.
It is a pentamer.
Effective valency is 5 (due to steric hindrance).
It is the earliest Ig to appear in the fetus (at 20 weeks).
Presence of IgM in fetal or newborn blood indicates
intrauterine infection (e.g. syphilis, rubella, HIV,
toxoplasmosis).
It is short lived, so presence of IgM indicates recent
infection.
Immune System
261
It is responsible for the primary response.

It is more effective than IgG in opsonization.
IgM deficiency is often associated with septicemia.
Treatment with 0.12M 2-mercaptoethanol selectively
destroys IgM and is a method for differential estimation
of IgG and IgM.
IgE
It is the atopic reagin antibody responsible for type I
hypersensitivity.
It is heat labile.
Its levels are increased in asthma, hay fever, intestinal
parasitism.
It has the shortest half-life.
It has affinity for the surface of tissue cells (particularly
mast cells) of the same species (homocytotropism).
It mediates the Prausnitz-Kstner reaction.
Abnormal Igs
Bence Jones protein they are the light chains of Ig,
either or , but never both, found in multiple
myeloma.
It is detected in urine it agglutinates at 50oC but
redissolves at 70oC.
Cryoglobulins form a gel or precipitate on cooling
which redissolves on heating. They are IgG or IgM,
found in myelomas, macroglobulinemias, SLE, etc.
ANTIGEN-ANTIBODY REACTION
Forces:
Forces that act to bind antigen to antibody are:
i. Van der Waals forces
ii. Ionic bonds
iii. Hydrogen bonds.
Detection of Antibody and Antigens
Precipitation Test
i.
ii.
Occurs with soluble antigens.

Exhibits Zone phenomenon:
Prozone or antibody excess
Postzone or antigen excess
262
Mechanism lattice hypothesis.

Examples:
1. Ring test Lancefield grouping of streptococci and
Ascolis thermoprecipitation test.
2. Slide test VDRL test for syphilis.
3. Tube test Kahn test for syphilis.
4. Immunodiffusion (precipitation in gel) Erek gel
precipitation test for toxigenicity of diphtheria bacilli.
5. Electroimmunodiffusion counterimmunoelectrophoresis for fetoprotein in serum, specific antigens
of cryptococcus and meningococcus in CSF.
Agglutination Test
Occurs with particulate antigens.
More sensitive and convenient than precipitation test.
Examples:
1. Slide agglutination for blood grouping and crossmatching.
2. Tube agglutination Widal test for typhoid, Weil-Felix
reaction for typhus fever, Paul-Bunnel test for infectious
mononucleosis, cold agglutination test for atypical
pneumonia.
3. Coombs test for detection of incomplete antibodies.
a. Direct Coombs test sensitization of RBC occurs
in vivo, e.g. hemolytic disease in newborn due to
Rh incompatibility.
b. Indirect Coombs test sensitization occurs in vitro,
e.g. in brucellosis.
4. Passive agglutination test a precipitation test can be
converted to an agglutination test by attaching a
soluble antigen to the surface of a carrier particle (like
RBC, latex particles or bentonite). Examples include
Rose-Waller test for RA factor, latex agglutination is
used to detect hepatitis B, ASO, CRP, RA factor, hCG,
etc.
Complement Fixation Test
Reagents:
a. Complement system antigen, antibody (patients
serum) and complement.
Immune System
263
b. Hemolytic system sheep RBC, amboceptor (rabbit

antibody to sheep RBC).
Result
Lysis of sheep RBC negative CFT.
No lysis of sheep RBC positive CFT.
Example Wassermann test for syphilis.
Opsonization
This helps in phagocytosis.
IgM is more effective in opsonization than IgG.
Other opsonins are Fc portion of IgG, C3b and
collectins.
Immunofluorescence
Direct for detection of rabies antigens.
Indirect FTA test for syphilis.
Radioimmunoassay
Most sensitive method of antigen detection.
Hormones are assayed by this method.
ELISA
Enzyme Linked Immunosorbent Assay.
Example detection of rotavirus antigen in feces, detection
of anti-HIV antibody.
THE COMPLEMENT SYSTEM
Complement Activation
Two pathways:
1. Classical pathway in this pathway, C3 is activated
by C42 (classical C3 convertase).
First step in this pathway is binding of C1 to the antigenantibody complex (bound IgG or IgM).
At the end, all the component levels are decreased.
2. Alternative pathway (Properdin system)
Activator is zymosan. In vivo activators are bacterial
endotoxin, IgA and IgD, cobra venom and the nephritic
factor.
264
Alternate pathway C3 convertase is C3b,Bb. Properdin

stabilizes this enzyme.
C1,2,4 are not involved, hence their levels remain
normal at the end.
Functions
C3a and C5a (anaphylatoxin) cause increased
histamine release from mast cells leading to increased
vascular permeability and vasodilatation.
C5a chemotaxis.
C3b opsonization.
Dysfunction
1. Hereditary angioneurotic edema:
Cause: Deficiency of C1 inhibitor leads to autocatalytic
activation of C1 and unrestrained breakdown of C4
and C2. Consequently levels of C1 remain normal but
that of C4 and C2 are depleted.
Clinical feature: Episodic laryngeal edema with
respiratory distress.
2. Deficiency of C1,2,4 is associated with SLE and other
collagen vascular diseases.
3. Deficiency of C5 to C8 is associated with bacteremia,
mainly with gram-negative diplococci (e.g.
meningococci).
STRUCTURE AND FUNCTION
OF THE IMMUNE SYSTEM
Types
1. Humoral or antibody mediated immunity (AMI)
mediated by immunoglobulins.
2. Cell mediated immunity (CMI) mediated by sensitized
lymphocytes.
Cells
Lymphocytes
T cells (thymus derived) produce lymphokines and mediate
CMI. It constitutes 70-80 percent of normal peripheral
blood lymphocytes.
Immune System
265
B cells (bursa or bone marrow derived) produce plasma

cells which synthesize Igs and mediate AMI.
B cell precursors, pro B cells, develop in the fetal liver
during embryonic life and in the bone marrow afterwards.
Plasma cells are antibody secreting cells. They have
a cartwheel appearance.
Differentiation:
Differentiation of T and B cells
Property
T cells
B cells
Binding to sheep RBC
Forms rosettes
No
by CD2 antigen
EAC rosette (C3 receptor) No
Yes
Blast transformation with
phytohemagglutinin
Yes
No
Surface immunoglobulins Negative
Positive
Markers
CD1 to CD8
CD10, CD19
except CD6.
to CD23
CD1 Langerhans cells
CD2 Receptor cells
CD3 Pan T
cell marker
CD4 Helper T cells
CD8 Cytotoxic T cells
Null Cells
Also known as the large granular lymphocytes, they
lack the features of either T or B cells.
They constitute 5-10 percent of lymphocytes and are
present in peripheral blood.
Most important member of the group is the natural
killer (NK) cells.
IL-2 acts as a growth factor for NK cells (lymphokine
activated killer LAK cells).
Properties:
1. Their activity is natural or nonimmune.
2. Their cytotoxicity is not antibody dependant or MHC
restricted.
3. They cause direct cell lysis without prior sensitization.
Function: Immune surveillance and natural defence against
virus infected and malignant mutant cells.
Markers: CD16 (Fc portion of IgG), CD56.
266
Antigen Presenting Cells

1. Macrophages In blood they are called monocytes.
In tissues called histiocytes (e.g. alveolar
macrophages in lungs), Kupffer cells in liver, microglia
in the brain.
Activated macrophages secrete tumor necrosis
factor alpha (TNF ), colony stimulating factor (CSF),
IL-1 and IL-8.
Function MHC II positive and central APC to
CD4+ helper T cells.
Involved in CMI (delayed hypersensitivity).
They also give rise to multinucleated giant cells in
granulomatous inflammation.
Markers CD13 to CD15 and CD33.
2. Dendritic cells:
These are nonphagocytic cells that express high
levels of MHC class II. Also express CD83.
They are present in lymphoid tissue (interdigitating
dendritic cells) and in epidermis of skin (called the
Langerhans cells).
They are the most potent APCs to T cells.
Follicular dendritic cells are found in the germinal
centers of lymphoid follicles in spleen and lymph nodes.
They express Fc portion of IgG. They facilitate the
maintenance of immunological memory.
3. B lymphocytes.
MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)
MHC I proteins determine histocompatibility and the
acceptance or rejection of allografts.
MHC II proteins regulate the immune system
MHC III proteins some are components of
complement system; govern the susceptibility to
autoimmune diseases.
Human Leukocyte Antigen (HLA)
HLA gene is located on the short arm of chromosome
6. HLA system is highly polymorphic, i.e. multiallelic.
Immune System
267
Human leukocyte antigen

HLA I
Loci
HLA II
HLA III
3 loci A, B
and C
1 loci D with
3 sub faces
DR, DQ and DP
Location Present on all
Expressed on antigen
nucleated cells
presenting cells
and platelets
(macrophages,
dendritic cells
and B cells)
Function Presentation of Presentation of
Components of
antigen by APCs antigen to
complement
to CD8+ cells
CD4+ cells
system (C2 and
C4), properdin,
factor B, TNF
alpha and beta
HLA typing: Typing is done serologically by microcytotoxicity. Serological typing is not possible for HLAD and HLA-DP antigens, which are detected by the mixed
leukocytic reaction (MLR) and primed lymphocyte typing
(PLT), respectively.
This is used primarily for testing compatibility between
recipients and potential donors before tissue transplantation
(mainly HLA-D). It has application also in disputed
paternity.
Disease association:
HLA type and disease association
HLA B27 Ankylosing spondylitis HLA DR2 SLE
Reiters syndrome
Goodpastures
syndrome
Reactive arthritis
IgA nephropathy
Psoriatic arthritis
Multiple sclerosis
Juvenile rheumatoid arthritis
Narcolepsy almost
Acute anterior uveitis
100 percent
association
HLA DR3 SLE
HLA DR4 Type I diabetes
Gluten sensitive
enteropathy (DQ2)
Chronic active hepatitis
Type I diabetes
Myasthenia gravis
HLA B5
Ulcerative colitis
Behcets disease
HLA A3
Primary
hemochromatosis
268
IMMUNE RESPONSE
Primary Response
It is short, slow with long lag phase and low titre of
antibodies.
Predominant antibody is IgM.
Secondary Response
It is prompt, powerful and prolonged with short lag
phase and higher levels of antibodies.
Predominant antibody is IgG.
CYTOKINES
They are peptide in nature.
Cytokines
Types
Interleukins
IL-1
( and )
IL-2
IL-3
IL-4
IL-6
IL-7
IL-8
IL-12
Source
Effects
Macrophages and
other APCs,
somatic cells
Proliferation and differentiation of T, B and other cells;

endogenous pyrogen; induce
acute phase proteins
Proliferation of cytotoxic
T cells and NK cells
Induce hematopoiesis
B cell proliferation, IgE
expression and MHC II
expression
Acute phase proteins
Activated TH1 cells,

TC cells, NK cells
T cells
TH2 cells, mast cells
Activated TH2 cells,

APCs
Spleen and bone
marrow stromal cells
Activated
CXC () chemokine,
macrophages
chemotactic for neutrophils
Cell mediated immunity
Tumor necrosis factor

TNF
Activated
macrophages
TNF
Activated TH cells
(lymphotoxin)
Interferons
IFN
IFN
IFN
Leukocytes (B
lymphocytes),
macrophages
Fibroblasts
TH1 cells, NK cells
IL-1 like effects; vascular

thrombosis and tumor necrosis,
cachexia
Do
Antiviral activity
CMI, activation of
macrophages
Immune System
269
Note:
TH1 cells secrete IL-2 and IFN which help direct CMI
responses including macrophage and NK cell activation.
TH2 CD4+ cells secrete IL-4, IL-5 and IL-10 that
promote humoral immunity (B cell proliferation) and
type I hypersensitivity (synthesis of IgE).
CHEMOKINES
1. CXC or -chemokine IL-8 (chemotactic for
neutrophils).
2. CC/ chemokine monocytes, macrophage (MCP-1,
MIP1);
RANTES chemotactic for CD4+ T cells
Eotaxin chemotactic for eosinophils.
Note CXCR4 and CCR5 act as coreceptors for binding
of HIV to lymphocytes.
HYPERSENSITIVITY
Coombs and Gell Classification
a. Immediate (B cell or antibody mediated)
Type I Anaphylactic/atopic (IgE mediated)
Type II Cytolytic and cytotoxic
Type III immune complex disease Arthus reaction
and serum sickness.
b. Delayed (T cell mediated)
TYPE I REACTION: ANAPHYLAXIS
It is the immediate (most rapid) hypersensitivity reaction
to an antigen when introduced in a sensitized host.
The first dose is called the sensitizing dose and a second
dose is called the shocking dose (most effective with a
gap of 2-3 weeks).
Anaphylaxis has been extensively studied in guinea pig.
Mediators
a. Immunological IgE.
b. Chemical
i. Primary histamine (most important mediator),
serotonin, chemotactic factor (eosinophilic and
neutrophil), heparin.
270
ii. Secondary formed by the action of primary

mediators prostaglandins and leukotriens (also
called the slow reacting substance of anaphylaxis
or SRS-A).
iii. Anaphylatoxins C5a and C3a.
Mechanism: Allergen stimulates TH2 cells IL 4 and
IL 5 increased IgE from B cells.
Example:
Theobald Smith phenomenon
Casonis test for hydatid disease.
Atopy
This refers to naturally occurring familial
hypersensitivities in human beings.
Mediated by IgE (also called the reagin antibody).
Characteristics of IgE:
1. It cannot be demonstrated by conventional serological
methods such as the precipitation or complement
fixation tests. IgE is detected by ELISA, passive
agglutination and radioallergosorbent test (RAST).
2. It is homocytotropic, i.e. species specific. This is the
basis of Prausnitz-Kustner (PK) reaction for detection
of atopic antibody.
3. It is heat sensitive.
Example:
i. Asthma
ii. Hay fever
iii. Atopic dermatitis or eczema
iv. Urticaria.
Management: Specific desensitization
a. Serial small dose injection of the antigen causes
exhaustion of the intracellular store of histamine in
mast cells.
b. Depot therapy or injection of the allergen in an oil
adjuvant produces blocking (IgG) antibodies.
TYPE II REACTION: CYTOLYTIC AND CYTOTOXIC
Combination of IgG or IgM antibodies with the antigenic
determinants on the surface of cells produces cell lysis and
cell death.
Mediators complement, NK cells.
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271
Examples:
i. Autoimmune hemolytic anemia, thrombocytopenia
and agranulocytosis
ii. Blood transfusion reaction
iii. Transplant rejection (acute)
iv. Diabetes
v. Goodpastures disease
vi. Graves disease
vii. Myasthenia gravis
viii. Pernicious anemia
ix. Rheumatic fever
x. Pemphigus vulgaris
xi. Erythroblastosis fetalis
xii. Drug reactions e.g. penicillin induced hemolysis.
TYPE III REACTION: IMMUNE COMPLEX DISEASE
Antigen-antibody complex mediated.
Arthus Reaction
Localized manifestation of a generalized disease
Occurs with repeated doses of antigens.
Latent period of 4-12 hours after subsequent dose.
Serum Sickness
Systemic disease
Occurs with single massive dose of antigen.
Latent period of 7-12 days.
Examples:
i. PAN
ii. Post-streptococcal glomerulonephritis
iii. Rheumatoid arthritis
iv. Acute viral hepatitis
v. Penicillamine toxicity
vi. SLE.
TYPE IV REACTION: DELAYED HYPERSENSITIVITY
Occurs after several hours of introduction of an antigen
in a sensitized host.
Mediators:
Cellular T4 lymphocytes and macrophages
Chemical IL 2 and IL 12, interferon gamma (most
important) and tumor necrosis factor.
272
Example:
i. Tuberculosis (tuberculin test)
ii. Lepromin test
iii. Sarcoidosis
iv. Contact dermatitis
Note: Granulomatous inflammations are special type of
delayed hypersensitivity.
TYPE V REACTION:
It is also antibody mediated (like type II), but instead of
killing cells, antibodies stimulate their target. For example,
Graves disease mediated by LATS.
ORGAN TRANSPLANTATION
Types of Transplants
a. According to source
Between same species
Genetically identical (twin) isograft.
Genetically different allograft.
Between different species heterograft or xenograft
b. According to site
Orthotropic when placed in normal anatomical
position, e.g. skin graft.
Heterotropic when placed in anatomically abnormal
sites, e.g. thyroid placed in subcutaneous tissue, kidney
placed in iliac fossa.
c. According to purpose
Vital grafts those living grafts which function
physiologically, e.g. kidney or heart.
Static/structural graft nonliving, provide only a
scaffolding on which new tissues are laid, e.g. bone/
artery.
GRAFT REJECTION
Transplantation immunity is predominantly cell mediated
(T cell) but antibodies do play some role mainly in
hyperacute rejection.
Hyperacute Rejection
Occurs within minutes to hours.
Due to preformed antibodies against HLA class I
antigen of donor.
Immune System
273
Pathology intravascular thrombosis and fibrinoid

necrosis of arterial walls.
Such graft is called white graft.
Most commonly seen after renal transplantation.
It is avoidable by prior antibody detection and cross
matching.
Acute Rejection
Occurs within 6 months.

It is predominantly T cell mediated.
Pathology mononuclear cell infiltration.
It is reversible by immunosuppressant therapy.
Chronic Rejection
Occurs after 6 months.
Due to both cell mediated and antibody mediated
effector mechanisms.
Risk factor most important risk factor for chronic
rejection is acute rejection.
Pathology vascular changes in the form of arterial
myointimal proliferation resulting in ischemia and
fibrosis.
It is non-reversible.
Note: Liver is remarkably resistant to all types of graft
rejection.
Pretransplant Testing
1. Blood grouping (only ABO) and cross matching. Rh
groups need not to be tested.
2. HLA typing and matching most important factor
of allograft survival is HLA compatibility.
HLA typing is done by microcytotoxicity test.
HLA groups important in transplant immunology are
HLA-DR > HLA-B > HLA-A.
HLA matching is not necessary before liver
transplantation.
Organ Donation
Most of the organs used for transplantation are obtained
from brainstem dead, heart-beating cadaveric donors.
Commonly used preservatives are university of
Wisconsin solution and Eurocollins solution.
274
Kidney Transplantation
Please see Renal System.
Pancreas Transplantation
For treatment of diabetes mellitus, isolated pancreatic islets
are transplanted into recipient liver by injection into portal
vein.
Liver Transplantation
First attempted by Starzl in 1963.
Indications
i. Chronic cirrhosis or chronic liver failure most
common.
ii. Acute fulminant liver failure
iii. Metabolic liver diseases
iv. Primary hepatic malignancy.
Heart Transplantation
First performed by Christian Barnard in 1967.
First heart-lung transplantation was performed by Bruce
Reitz in 1981.
Indication NYHA class III or IV disease in patients
< 65 years of age.
Contraindication carboxyhemoglobin level > 20
percent, prior myocardial infarction and prolonged cardiac
arrest.
GRAFT-VERSUS-HOST DISEASE (GVHD)
It is the opposite of graft rejection. In GVHD, graft mounts
an immune reaction against the host antigens.
This occurs when immunologically competent cells are
introduced into recipients who are immunocompromised.
Occurs most commonly in allogenic bone marrow
transplantation.
Pathology:
Acute GVHD causes epithelial cell necrosis in three
primary target organs liver, skin and gut.
Runt disease is an example of GVHD.
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275
PRIMARY IMMUNODEFICIENCIES
DISORDERS OF SPECIFIC IMMUNITY
Classification
A. Humoral immunodeficiencies (B cell defects)
1. X linked agammaglobulinemia
2. Common variable immunodeficiency
3. Hyper IgM syndrome
B. Cellular immunodeficiency
1. Thymic hypoplasia (DiGeorges syndrome)
2. Chronic mucocutaneous candidiasis
C. Combined immunodeficiencies (B and T cell defects)
1. Nezelof syndrome
2. Ataxia telangiectasia
3. Wiskott-Aldrich syndrome
4. Severe combined immunodeficiency
5. Immunodeficiency with thymoma.
X-Linked Agammaglobulinemia (Bruton Disease)
Cause: Mutation in tyrosine kinase.
Inheritance: X-linked recessive.
Clinical feature: Recurrent bacterial infection in childhood,
chronic giardiasis.
Diagnosis: Absent or decreased B cells, absent plasma
cells, decreased Ig in serum.
Treatment: IV gammaglobulin.
Common Variable Immunodeficiency
Defective humoral immunity due to lack of differentiation
of B cells.
Clinical feature: Same as Bruton disease, onset is late,
chronic giardiasis.
Diagnosis: Normal B cells but absent plasma cells.
Others: Increased chance of autoimmune diseases
(hemolytic anemia, pernicious anemia) and lymphoid
tumors.
276
Isolated IgA Deficiency

Most common of all the primary immunodeficiencies.
Clinical feature: Usually asymptomatic, chronic
sinopulmonary infection and diarrhea.
Hyper-IgM Syndrome
Cause: Mutations in CD40L or CD40, resulting in defective
isotype switching.
Inheritance: Usually X-linked.
Diagnosis: Normal or increased IgM but lack of IgG, IgA
or IgE isotypes.
Severe Combined Immunodeficiency
Defects in both humoral and cell-mediated immunity.
Cause: X-linked cytokine (IL-7) receptor mutation
Autosomal recessive adenosine deaminase
deficiencythe most common enzyme deficiency.
Clinical feature: Recurrent infection.
Treatment: Bone marrow transplantation.
Wiskott-Aldrich Syndrome
There is loss of cellular as well as humoral immunity.
Clinical feature: Characterized by thrombocytopenia,
eczema and recurrent infection.
Inheritance: X-linked.
Diagnosis:
Decreased T cell and defective cellular immunity,
Defective antibody formation to polysaccharide
(encapsulated organisms),
Decreased IgM but IgG, IgA are normal or increased,
IgE is also increased,
Decreased ratio of CD4:CD8 cells,
Small platelets in peripheral smear.
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277
Thymic Hypoplasia (DiGeorges Syndrome)

Cause: Deletion of chromosome 22q11.
Clinical feature: Thymic hypoplasia leads to deficient T
cell maturation increased viral, fungal and protozoal
infection.
Parathyroid hypoplasia hypocalcemic tetany.
It is associated with Fallots tetralogy and other
congenital anomalies and a characteristic facial
appearance.
Nezelof Syndrome
Depressed cell mediated immunity is associated with
selectively elevated, decreased or normal levels of
immunoglobulin.
Immunodeficiency with Thymoma
Spindle cell thymoma is associated with hypogammaglobulinemia, impaired cell mediated immunity and
aplastic anemia.
INHERITED DISORDERS
OF PHAGOCYTIC FUNCTION
Classification
a. Defective adhesion leukocyte adhesion deficiency
b. Defective chemotaxis Jobs syndrome, Lazy leukocyte
syndrome, Shwachmans disease.
c. Defective microbicidal activity myeloperoxidase
deficiency, Chediac-Higashi syndrome, chronic
granulomatous disease.
Leukocyte Adhesion Deficiency
Defect:
Type 1 defective synthesis of CD18 -subunit of
leukocyte integrins LFA-1 and Mac-1.
Type 2 absence of Sialyl-Lewis X (selectin receptor
on endothelium).
Clinical feature:
Type 1 delayed separation of umbilical cord, recurrent
infection.
278
Type 2 severe mental retardation, short stature,

Bombay blood group, recurrent infection.
Hyper IgE-recurrent Infection (HIE)
or Jobs Syndrome
Clinical feature: Eczema, cold abscess, recurrent
staphylococcal pneumonia, coarse facies, bony
abnormalities, serum IgE > 2000 IU/ml.
Myeloperoxidase Deficiency
Most common neutrophil defect.
Chediac-Higashi Syndrome
Defect: Reduced chemotaxis and phagolysosome fusion.
Clinical feature: Recurrent pyogenic infections specially with
Staphylococcus aureus.
Oculocutaneous albinism, nystagmus, peripheral
neuropathy, mental retardation.
Diagnosis: Giant primary granules in neutrophils.
Chronic Granulomatous Disease
60 percent X-linked, 40 percent autosomal recessive.
Defect: Lack of one of four NADPH oxidase subunit
absent respiratory burst decreased production of H2O2.
Clinical feature: Recurrent infection with catalase positive
pyogenic organisms like Staphylococcus aureus.
Lymph node suppuration, granuloma formation which
may obstruct GI tract or genitourinary tract.
Diagnosis:
NBT test (screening test)
Absent superoxide and H2O2 production by neutrophils.
Shwachmans Disease
Decreased neutrophil mobility, pancreatic malfunction,
bone abnormalities.
Immune System
279
HIV AND ACQUIRED

IMMUNODEFICIENCY
HIV VIRUS
Formerly known as the HTLV III.
Two subtypes:
HIV 1 is the prevalent form worldwide; and
HIV 2 was isolated from West Africa. HIV 2 differs
in envelope glycoprotein. Infection with HIV 2 is mostly
asymptomatic.
Structure: Spherical enveloped virus.
Genome contains diploid DNA. In association with
the viral RNA is the enzyme reverse transcriptase (RT) or
RNA directed DNA polymerase. RT allows formation of
a dsDNA form a ssRNA. DNA in turn forms mRNA as
otherwise.
Genome contains three structural genes gag, pol and
env.
The gag gene determines the core. The major core
antigen is p24 which is the earliest to appear in HIV
infection.
Env gene shows greatest variability.
Pathogenesis
HIV virus attacks CD4+ cells such as the TH cells,
monocytes and the macrophages and also the B
lymphocytes. Macrophages act as reservoir for the virus.
Immunological abnormalities after HIV infection
i. Reduction in number of T4 (CD 4) cells (normal 950/
l.
ii. Inversion of T4:T8 ratio (normally CD4 is expressed
in 60% T cells and CD8 in 30% T cells, so that normal
CD4:CD8 ratio is 2:1).
iii. Decreased delayed hypersensitivity.
iv. Hypergammaglobulinemia: Predominantly IgG and
IgA.
Chemokine receptors: CCR5 and CXCR4 are important
for HIV import. Persons with CCR5 deletions are less likely
to be infected with HIV.
280
Transmission
1. Sexual most common in homosexual males (receptive
anal intercourse). But in developing countries,
maximum transmission occurs in heterosexuals.
2. Blood transfusion least common mode (1 in 1
million).
Products that transmit HIV are whole blood,
packed red cell, platelets, leukocytes and plasma.
Products that do not transmit HIV are hyperimmune
gammaglobulin, hepatitis B immunoglobulin, plasmaderived hepatitis B vaccine, Rh immunoglobulin.
3. Vertical transmission maximum transmission in the
perinatal period. Prophylaxis with antiretroviral drugs
reduce the chance of transmission (see below).
Postnatal transmission through colostrum and
breast milk.
4. IV drug abusers chance of transmission is 1.5
percent.
5. Needle prick in occupational set up chance of
transmission is 0.3 percent (c.f. similar chance of
hepatitis B transmission is 6-30%).
Clinical Feature
1. Acute HIV infection after 3-6 weeks of primary
infection.
Symptoms low grade fever, malaise, headache,
spontaneous resolution occurs.
Diagnosis detection of p24 antigen.
2. Asymptomatic stage HIV replication continues even
during clinical latency period.
3. Persistent generalized lymphadenopathy.
4. Early symptomatic disease:
i. Generalized lymphadenopathy
ii. Oral thrush
iii. Reactivation of herpes zoster
iv. Thrombocytopenia.
Neurological diseases
i. Aseptic meningitis
ii. AIDS dementia complex or HIV encephalopathy.
most common CNS manifestation of AIDS.
iii. Lymphoma
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281
iv. Seizures most commonly due to toxoplasmosis; next

is due to cryptococcal meningitis.
v. GB syndrome
vi. Progressive multifocal leukoencephalopathy (PML)
due to JC virus; occurs years after infection. MRI scan
shows multiple white matter lesions in T2.
AIDS
Definition:
1. Infections or malignancies that rarely occur in absence
of immunodeficiency (e.g. P. carinii, CNS lymphoma
etc.).
2. Positive HIV serology with some infection/malignancies
that are more common in HIV patients (e.g. pulmonary
TB, invasive cervical Ca).
3. Positive HIV serology with nonspecific conditions, e.g.
dementia and wasting.
4. CD4 count < 200//l.
Findings that are specific for and indicative of HIV:
1. Hairy leucoplakia of tongue
2. Disseminated Kaposis sarcoma
3. Cutaneous bacillary angiomatosis.
Mean time interval to develop AIDS is 10 years from
the initial infection.
Opportunistic Infection
Protozoa
1. Pneumocystis carinii most common opportunistic
infection worldwide.
Clinical feature:
Fever, dyspnea, non-productive cough, tachypnea,
tachycardia, cyanosis.
Recurrent pneumonia due to P. carinii is the most
common manifestation of childhood AIDS.
Diagnosis: Chest X-ray shows bilateral pulmonary
infiltrates (diffuse or perihilar).
Upper lobe cavitary lesion in patients with pentamidine
prophylaxis.
Lobar infiltration, pleural effusion.
282
Demonstration of trophozoite or cyst in samples

obtained by induced sputum, BAL or transthoracic biopsy.
Stain used is silver nitrate.
Wright-Giemsa stain of induced sputum if negative,
go for BAL.
Treatment
Co-trimoxazole is the drug of choice.
Prophylaxis with aerolized pentamidine or systemic
therapy with co-trimoxazole (best).
Note: Extrapulmonary (most commonly to lymph nodes)
involvement may occur. Pentamidine prophylaxis is a risk
factor for that.
2. Toxoplasmosis It is the most common cause of secondary CNS
infection.
It is the most common cause of mass lesion in CNS.
It is the most common cause of seizure in AIDS
patients.
3. Cryptosporidiosis
4. Systemic strongyloidosis
Bacteria
1. Tuberculosis most common opportunistic infection
in India.
It is one of the totally curable conditions in HIV infected
persons.
Organism in developing countries M. tuberculosis.
In developed countries atypical mycobacteria (M.
avium intracellulare).
Mycobacterium avium complex infection in AIDS
It occurs in patients with CD4 count < 100 l (late
complication)
Often the patient has < 10/ l CD4 count at the time
of presentation.
Clinical feature
Fever, weight loss and night sweats, diarrhea,
lymphadenopathy, liver involvement is common
with increase in alkaline phosphatase level.
Chest X-ray shows bilateral lower lobe infiltrates.
Diagnosis demonstration of AFB in biopsy from
bone marrow/lymph node or liver and stool
specimen.
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283
Treatment clarithromycin (or azithromycin) +

ethambutol rifabutin.
2. Others salmonella, campylobacter, nocardia,
legionella.
Fungal
1. Candidiasis most common fungal infection.
2. Cryptococcus neoformans most common cause of
meningitis in AIDS.
Treatment - amphotericin B.
3. Histoplasmosis
4. Aspergillosis
5. Coccidioidomycosis
Viral
1. CMV most common viral infection.
2. Herpes simplex
3. E-B virus oral hairy leucoplakia.
Infections according to CD4 count
CD4 count
Infection
< 500/l
M. tuberculosis, candida, herpes zoster
< 200/l
P. carinii, histoplasma, Cryptococcus,
toxoplasma
< 50/l
M. avium intracellulare (now 10/l at the
time of presentation), CMV
Note: CD4 count provides information about the
immunological status of the patient.
Neoplasms
1. Kaposis sarcoma It is the most common malignancy in AIDS.
It is not specific of AIDS as it is also seen after renal
transplantation. It is not seen in childhood AIDS.
More common in homosexual males and in women
with bisexual partners.
Origin
Endothelial cells.
They are multicentric, consisting of multiple vascular
nodules appearing in the skin, mucous membrane and
viscera (GI tract and lungs), lymph nodes.
284
They are either indolent or aggressive but rarely invasive.

Commonly seen in the lower limbs.
Cause
Herpes virus KSHV or HHV 8.
Skin manifestation
Nodular, reddish-purple.
Site
Sun-exposed skin most commonly on the tip of the
nose. Propensity to occur on areas of trauma Koebner
phenomenon.
May be disabling when involves the lower extremities.
Diagnosis Biopsy.
Lymph node involvement occurs early and is of little
significance.
Treatment
Localized irradiation
Interferon and chemotherapy in disseminated disease.
2. Lymphoma 1. Grade III or IV immunoblastic lymphoma.
2. Burkitts lymphoma (B cell non-Hodgkins
lymphoma)
3. Primary CNS lymphoma (non-Hodgkins ) second
most common cause of SOL in brain in AIDS.
3. Intraepithelial dysplasia and neoplasia of the cervix
or anus Malignancies common in childhood AIDS are nonHodgkins lymphoma, leiomyosarcoma.
Others
Gynecological: Vaginal candidiasis, PID, CIN.
Ophthalmic manifestation:
1. Cotton wool spots most common fundoscopic finding
due to ischemia of nerve fiber layer (cystoid bodies)
2. CMV retinitis most common opportunistic infection
of eye in AIDS.
Clinical feature - permanent painless, progressive loss
of vision.
Fundoscopy perivascular hemorrhage and exudates.
Treatment - IV ganciclovir, foscarnet, cidofovir.
Immune System
285
CNC
Perivascular giant cells (macrophages) are seen in
frontal and temporal lobes, may produce
infarction.
Diffuse and focal spongiform changes.
Microglial nodules most characteristic.
Vacuolar myelopathy.
Kidney: Focal segmental glomerulosclerosis (collapsing
glomerulopathy) most common.
Skin: Ichthyosis, seborrheic dermatosis.
Immunology: Drug allergies, anaphylaxis is extremely rare.
Diagnosis
1. Antigen detection: p24 (marker of active replication).
Earliest test to be positive (after 2 weeks).
2. Antibody detection:
IgG antibodies appear 4-8 weeks after infection
(seroconversion). The time period between primary
infection and detection of antibodies is called window
period.
a. ELISA test sensitivity > 99.5 percent. It is more
sensitive but less specific than Western blot test.
It is 50 percent positive after 22 days and 95
percent positive in 6 weeks.
False positive ELISA is seen in recurrent
influenza vaccination, connective tissue disorders.
b. Karpas test
c. Western blot test confirmatory and most specific.
Specificity when combined with ELISA is
>99.99 percent.
3. HIV RNA detection:
It is the best predictor of disease progression, i.e.
prognostic indicator.
PCR is useful for at-risk infants gold standard
investigation.
Indication positive or intermediate ELISA and
intermediate Western blot test results.
Note: Antibody detection is unreliable in neonatal HIV
(hence ELISA and Western blot). DNA-PCR is the preferred
method in neonates.
286
Treatment
Antiretroviral therapy: Classification of antiretroviral drugs:
a. Nucleoside reverse transcriptase inhibitors - purine
(thymidine) analogue
Zidovudine, lamivudine, stavudine, didanosine and
zalcitabine.
b. Nonnucleoside reverse transcriptase inhibitors Nevirapine, efavirenz and delavirdine.
c. Protease inhibitors Ritonavir, indinavir, saquinavir, nelfinavir.
Mechanism of action they act at a late stage; inhibit
aspartate protease.
Side effects
1. Zidovudine anemia and neutropenia (most common);
headache and myalgia.
2. Peripheral neuropathy occurs with stavudine, zalcitabine
and didanosine.
3. Pancreatitis didanosine (most common), zalcitabine.
4. Lamivudine relatively safe.
5. Protease inhibitors cause gastric intolerance, crystaluria
by indinavir.
Drug interactions
Rifampicin induces metabolism of NNRTI and PIs.
(rifabutin should be given in place of rifampicin).
Ritonavir is contraindicated with both.
Indication for therapy
1. All cases of symptomatic HIV disease.
2. Asymptomatic with CD 4 count <500/l.
3. Asymptomatic with CD 4 count > 200/l. with
i. CD 4 count declines at the rate of 100 cell/l. or
ii. HIV-RNA > 20000 copies/ml.
Regimens
Initial case 2NRTI + 1 PI/ 2NRTI + 1 NNRTI/ 3
NRTI.
Late case NRTI + NNRTI + PI/ Boosted PI (PI
+ low dose ritonavir) + 1 NNRTI.
Antiretroviral therapy in pregnancy
1. Short-term/truncated regimen Zidovudine to mother during last few weeks of
pregnancy or during labour and delivery and to infant
for a week reduces the chance of transmission by
50 percent.
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287
2. Perinatal regimen Beginning in the second trimester plus during labour

and delivery plus to infant for 6 weeks reduces the
chance of transmission by 67-68 percent.
Post-exposure prophylaxis: Combination of zidovudine,
lamivudine and indinavir started as soon as possible after
the injury for at least 4 weeks.
AMYLOIDOSIS
Amyloid is an amorphous, eosinophilic, hyaline,
extracellular deposition.
Structure
95 percent of any amyloid deposition consists of fibril
protein. Remaining 5 percent consists of P component or
other glycoproteins.
Fibril proteins:
In X-ray crystallography and infrared spectroscopy have pleated sheet structure.
Light microscopy amorphous, eosinophilic,
extracellular hyaline.
Electron microscopy non-branching fibril of 7.5-10
nm width.
Types with Etiology
1. AL amyloid protein in primary amyloidosis:
i. They are immunoglobulins (light chains) derived
from plasma cells.
ii. Classically seen in multiple myeloma.
iii. Macroglossia is a characteristic feature.
2. AA amyloid protein in secondary or reactive
amyloidosis:
i. They are non-immunoglobulin proteins derived from
liver from serum amyloid associated protein.
ii. Found in tuberculosis, leprosy, Hodgkins
lymphoma, chronic osteomyelitis, bronchiectasis,
rheumatoid arthritis (most common), ankylosing
spondylitis, inflammatory bowel diseases and renal
cell carcinoma.
288
3. A amyloid protein: Found in cerebral lesions in

Alzheimers disease and is derived from amyloid
precursor protein.
4. 2 microglobulin: Deposited in the carpal ligaments
of wrist joint (causing carpal tunnel syndrome) and
in knee joints in patients on chronic hemodialysis.
5. AE proteins: Found in medullary carcinoma of thyroid.
6. Heredofamilial amyloidosis:
i. Familial Mediterranean fever AA protein.
ii. Familial amyloidotic neuropathies ATTR (mutant
transthyretin) protein.
7. Amyloidosis of aging: Normal transthyretin is deposited
in the heart.
Clinical Presentation
1. Kidney: It is the most common and most serious
involvement.
It causes severe proteinuria (nephrotic syndrome),
azotemia but no hypertension (only in 20-25% cases
hypertension is seen).
Grossly, the kidneys may appear normal.
Renal failure is the most common cause of death
in secondary amyloidosis.
2. Nervous system: Peripheral neuropathy especially in
heredofamilial amyloidosis.
3. GI tract: Macroglossia is a characteristic feature in
primary amyloidosis.
4. Spleen: When involves the splenic follicles (focal
involvement) sago spleen.
When involves the sinusoids in red pulp (diffuse
involvement) lardoceous spleen.
5. Heart: Gray-pink dewdrop like subendocardial
elevations are seen.
Heart is most commonly involved in senile amyloidosis.
Restrictive cardiomyopathy is the most common cause
of death in primary amyloidosis.
Diagnosis
Biopsy
Site rectum, gingival or intestine.
Dye Congo red
Shows bright pink under light microscopy and green
birefringence under polarizing light.
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289
Note:
Most common organ involvement in primary
amyloidosis is heart.
Most common organ involvement in secondary
amyloidosis is kidney.
Most common organ involvement in localized (nodular/
tumor forming) amyloidosis is lung.
IMMUNOLOGICALLY
MEDIATED SKIN DISEASE
Please see the chapter of Dermatology.
SYSTEMIC LUPUS ERYTHEMATOSUS
This is an autoimmune disorder probably mediated by CD
4+ helper T cells, more common in females (in the child
bearing age) and blacks.
Pathogenesis
Genes involved are MHC class II and complement
system.
T cell involved are the CD 4+ T cells.
There is production of IgG autoantibodies.
LE bodies or hematoxylin bodies are seen.
Criteria
1. Malar rash erythematous maculopapular (butterfly
rash).
2. Discoid rash
3. Photosensitivity
4. Oral ulcers
5. Arthritis nonerosive polyarthritis involving peripheral
joints.
6. Serositis pleuritis and pericarditis.
7. Renal disorders: proteinuria > 0.5 gm/dL or > 3+
or cellular cast.
8. Neurologic disorders.
9. Hematologic disorders.
290
10. Immunological disorders

11. Positive antinuclear antibody (ANA).
Any 4 of the above 11 criteria are required for the
diagnosis.
Renal Disorder
Class I Normal
Class II Mesangial lupus glomerulonephritis mildest
form.
Class III Focal glomerulonephritis
Class IV Diffuse proliferative glomerulonephritis
most common and most serious renal lesion. When
extensive, they produce wire loop appearance on light
microscopy. Should be treated with aggressive
immunosuppressant.
Class V Membranous glomerulonephritis.
Renal lesion in SLE is due to immune-complex disease.
Features proteinuria, hematuria and RBC cast.
Spleen
Onion skin lesion.
Neurological Disorders
Seizures, psychosis and pseudotumor cerebri.
Investigation EEG is abnormal in 70 percent cases.
CSF shows elevated protein in 50 percent cases.
Neurological symptoms improve with immunosuppressants.
Hematological Disorders
This is present in 100 percent patients with SLE.
Anemia, usually normocytic normochromic but
occasionally hemolytic.
Leucopenia or lymphopenia
Thrombocytopenia should be treated with
glucosteroids.
Immunologic Disorders
Anti dsDNA antibody specific and diagnostic.
Anti Sm antibody specific and diagnostic.
Anti-phospholipid antibodies
Immune System
291
Antinuclear Antibody (ANA)

Very sensitive but not specific best screening test.
Cardiac Lesions
Pericarditis, myocarditis,
Libman-Sacks endocarditis non-infective verrucous
endocarditis involving both sides of valve leaflets.
Valvular incompetence.
Other Features
1.
2.
3.
4.
Thrombosis
Hair loss non-scarring (lupus hair)
Hypocomplementenemia
LE cells are neutrophils or macrophages.
Antiphospholipid Antibodies
Lupus anticoagulant (LA) and anti-cardiolipin (aCL) in blood
produce
Thrombocytopenia,
Recurrent venous/arterial clotting
Pulmonary embolism, hypertension
Recurrent fetal loss
Hypoprothrombinemia leading to bleeding
False positive VDRL test.
Effect on pregnancy
Pregnancy induced hypertension, IUGR and abruptio
placentae.
Spontaneous abortion and stillbirths are frequent.
In children
Heart block is seen in babies born to SLE mothers
due to anti Ro antibody.
Arthritits and skin rash are common presenting
symptoms in children. CNS and renal involvement are
more common than adults.
Treatment
Indications of steroids in SLE
i. Neuropsychiatric lupus
ii. Nephrotic syndrome
iii. Pericarditis, myocarditis (but not endocarditis)
iv. Thrombocytopenia, hemolytic anemia
292
Drug Induced SLE

Drugs causing SLE are hydralazine, isoniazid,
phenytoin and procainamide.
Renal and CNS diseases are rare.
Anti dsDNA antibody is absent.
Anti-histone antibody is characteristic.
RHEUMATOID ARTHRITIS
Pathology
Initially, the synovium becomes swollen or edematous.
Microvascular injury and increase in the number of
synovial lining cells appear to be the earliest lesion in
RA.
Pannus formation.
May lead to fibrosis and calcification with permanent
ankylosis.
Note: Possible causative agents Mycoplasma, EBV,
CMV.
Pathogenesis
Association with HLA DR 4 and/or HLA DR 1.
Stages
1. Soft tissue proliferation
2. Early cartilage erosion. On X-ray there is reduction in
joint space.
3. Bony changes
X-ray shows para-articular erosion, subchondral
cyst, juxta-articular rarefaction.
Clinical Feature
Age of onset 20-50 years.
Sex women are affected three times more commonly
than men.
Note: Autoimmune disorders are more common in
females.
Articular
1. Morning stiffness
2. Bilateral symmetrical polyarthritis involving large and
small joints.
Immune System
293
Joints involved are metacarpo-phalangeal and proximal

interphalangeal joints (MP and PIP) of fingers (but not
the distal interphalangeal joint).
Axial involvement only the cervical spine.
Deformities Swan-neck deformity, Z deformity.
3. Pain and swelling behind the knee due to extension
of inflamed synovium into popliteal space (Bakers
cyst).
Extra-articular manifestations
1. Rheumatoid nodule
Non-tender, up to 2 cm in size.
Sites olecrenon bursa (most common), dorsal surface
of forearm, tendo-Achilles.
2. Rheumatoid vasculitis
Raynauds phenomenon, chronic leg ulcers.
Peripheral neuritis (mononeuritis multiplex, treated by
steroids).
3. Pleuropulmonary manifestations
Pulmonary nodule, when associated with
pneumoconiosis in diffuse nodular fibrosis, it is called
Caplans syndrome.
4. Cardiac manifestation
Asymptomatic pericarditis (serofibrinous) is found in
50 percent cases at autopsy.
5. Eye uveoparotitis (also seen in sarcoidosis).
6. Others
i. Normocytic normochromic anemia
ii. Feltys syndrome rheumatoid arthritis +
splenomegaly + neutropenia and occasionally
anemia and thrombocytopenia.
iii. Anserine bursitis
iv. Splenic infarcts.
Laboratory Findings
1. Blood decreased Hb level and increased ESR (c.f.
in osteoarthritis, these are not seen).
2. Rheumatoid factor is present in 80 percent of cases.
It is an autoantibody (IgM type) reactive with the Fc
portion of IgG.
This is not specific for RA because RF is also found
in tuberculosis, infectious mononucleosis and syphilis.
It is associated with a bad prognosis.
294
Tests for RF latex fixation test (most sensitive)

and Rose-Waaler test.
Treatment
a. Disease modifying antirheumatic drugs gold,
d-penicillamine, chloroquine and sulfasalazine.
b. Surgery
Preventive synovectomy
Reconstructive
c. Physiotherapy muscle-building exercise to gain
strength.
JUVENILE RHEUMATOID ARTHRITIS
Onset before 16 years of age.
Pauciarticular
Involves 4 joints.
1. Iridocyclitis is observed in 25 percent cases. Other eye
signs are complicated cataract, band shaped
keratopathy.
2. Large joints of lower extremities usually the hip girdle
is commonly affected.
3. A family history of ankylosing spondylitis may be
present.
4. Associated with HLA B27.
5. X-ray shows epiphyseal enlargement.
6. Positive ANA, negative RF.
Systemic (Previously Called the Stills Disease)
Common in boys.
Clinical features
i. Intermittent fever
ii. Evanescent maculopapular rash with central clearing
most characteristic of Stills disease.
iii. Hepatosplenomegaly
iv. Lymphadenopathy
v. Leukocytosis.
vi. ANA may be present my RF is absent.
Treatment naproxen, ibuprofen, pyroxicam (note
aspirin was the previous drug of choice; but it is not
used now because of the risk of Reyes syndrome).
Immune System
295
Polyarticular
Involves 5 joints.
ANA positive, may be RF positive.
Uveitis may be present.
SYSTEMIC SCLEROSIS/SCLERODERMA
It is a multisystem disease of unknown etiology
characterized by fibrosis of skin (most common, hence
the name scleroderma), blood vessels and visceral organs
(GI tract, lungs, heart and kidneys).
Pathologic hallmark: Fibroblast activation and excessive
fibrosis.
Types
1. Diffuse: Characterized by rapid development of
symmetric skin thickening of proximal and distal
extremities, face and trunk. Greater chance of organ
involvement.
2. Limited: Skin thickening limited to distal extremities
and face. It is also known as the CREST syndrome
for calcinosis, Raynauds phenomenon, esophageal
dysmotility, sclerodactyly and telangiectasia.
Clinical Feature
1.
2.
3.
4.
Raynauds phenomenon
Skin thickening, subcutaneous calcification.
Arthritis
GI tract esophageal dysmotility (rubber-hose like),
dysphagia, pneumatosis intestinalis, malabsorption.
5. Pulmonary pulmonary fibrosis, pulmonary
hypertension and aspiration pneumonia.
6. Congestive cardiac failure due to myocardial fibrosis.
7. Renal failure malignant hypertension.
Diagnosis
Autoantibodies
Antitropoisomerase 1 specific for diffuse scleroderma.
Anticentromere specific for limited scleroderma.
ANA may be positive.
296
Radiology: Diffuse periosteal reaction, esophageal

dysmotility, erosion of the tip of the phalanges.
Prognosis
Patients with diffuse disease develop renal and other visceral
disease early and have a worse prognosis.
POLYMYOSITIS AND DERMATOMYOSITIS
Clinical Feature
1. Gradual onset, symmetrical involvement
2. Weakness of the proximal limb muscles, especially the
hip and thigh (Inability to rise from squatting position,
climbing stairs, combing, etc.).
3. Patient may present with weakness of the large muscles
of trunk, neck (flexion) and limbs (deltoid).
4. Ocular muscles are not involved.
5. May cause dysphagia, respiratory impairment.
6. In dermatomyositis erythematous maculopapular
rash (Lilac colored or heliotrope rash) on eyelids.
Laboratory Findings
Elevated levels of enzymes creatine kinase, aldolase
and lactate dehydrogenase.
Anti-Jo antibodies (against tRNA synthetase) are
common in polymyositis.
Diagnosis
Typical clinical picture, typical EEG, elevation of serum
CK.
Muscle biopsy diagnostic. Perivascular inflammatory
cell infiltration is the hallmark of polymyositis.
SJGRENS SYNDROME
Primary form is idiopathic and is known as Sicca syndrome.
Secondary form is associated with
i. Rheumatoid arthritis (most commonly)
ii. SLE
iii. Polymyositis
iv. Scleroderma
v. Chronic active hepatitis
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297
vi. Sarcoidosis
vii. Thyroiditis.
Clinical Feature
Dry mouth (xerostomia), dry eye (keratoconjunctivitis
sicca) and bilateral enlargement of parotids.
Other features synovitis, pulmonary fibrosis,
peripheral neuropathy, increased risk of MALT
lymphomas (pseudolymphoma).
Bilateral parotid gland enlargement
1. Mumps, EBV, influenza
2. Sarcoidosis
3. Sjgren syndrome
4. Diabetes mellitus
5. Chronic pancreatitis.
6. Amyloidosis
7. Cirrhosis
8. Acromegaly
Diagnosis
ANA and RF may be present.
Anti RNP antibodies [SS-A (Ro) and SS-B (La)].
ANKYLOSING SPONDYLITIS
Pathology
Sacroiliac joint is the first joint to be involved. Earliest
lesion is subchondral granulation tissue.
Least affected is the elbow joint.
Clinical Feature
Common in males during early adulthood (15-30 years).
Earliest symptom is low back pain.
Peripheral involvement asymmetric polyarthritis.
Others
Acute anterior uveitis (most common extra-articular
manifestation).
Aortic insufficiency, cardiomegaly, pericarditis,
conduction defect.
298
Examination
Schober test for measuring flexion of the lumbar
vertebrae.
Gaenlsens test for sacroiliac joint involvement.
Fleches test for cervical spine involvement.
Chest expansion < 5 cm.
Investigation
1. X-ray lumbar spine shows
i. Squaring of the vertebrae.
ii. Loss of lumbar lordosis
iii. Bamboo-spine appearance.
Others
Haziness of the sacroiliac joint is the first change
on X-ray.
Subchondral erosion.
Enthesopathy calcification of tendons, ligaments
and muscle attachments.
Bony ankylosis.
2. Genetic marker HLA B 27 is present in > 85 percent cases.
3. Mild anemia.
REACTIVE ARTHRITIS
Acute non-purulent arthritis complicating an infection
elsewhere in the body.
Reiters Syndrome
Triad of
i. Arthritis
ii. Urethritis
iii. Conjunctivitis
With additional mucocutaneous lesions.
Etiology:
Most commonly associated with Shigella flexneri
infection (diarrhea) and chlamydia.
Associated with HLA B27.
Others Yersina, Campylobacter, Salmonella, ureaplasma urealyticum and Mycoplasma genitalium.
Immune System
299
Skin lesion:
Characteristic skin lesion is called keratoderma
blenorrhagica. On glans penis produce circinate
balanitis.
Treatment:
Indomethacin is the drug of choice.
BEHETS SYNDROME
It is a multisystem disorder presenting with recurrent oral
and genital ulceration with ocular involvement.
Epidemiology
Worldwide distribution.
Affects mainly young adults.
Males having more serious disease than females.
Associated with HLA B5.
Clinical Feature
Recurrent apthous ulceration sine-qua-non for
diagnosis.
Eye hypopyon uveitis.
Arthritis, superficial and deep vein thrombosis,
Pulmonary emboli.
Diagnosis
Pathergy test a non-specific skin inflammatory reactivity
to any scratches or intradermal saline injection.
Treatment
Symptomatic; steroids.
VASCULITIS SYNDROMES
POLYARTERITIS NODOSA (PAN)
This is a necrotizing vasculitis of small to medium size
arteries of any organ except the lungs.
Pathology
Characterized by segmental transmural necrotizing
inflammation of medium to small size arteries.
300
Acute stage polymorphonuclear cell infiltration with

fibrinoid necrosis.
Chronic stage fibrous thickening may produce
nodules.
Segmental erosion with weakening of arterial wall may
cause aneurysmal dilatation and rupture.
Clinical Feature
PAN is often preceded by a history of bronchial asthma.
Kidney renal involvement is most common with
hypertension but no glomerulonephritis.
GI tract abdominal pain and melena.
Muscular pain.
Peripheral neuritis (motor).
Skin palpable purpura, livedo reticularis, cutaneous
infarcts (digital gangrene).
Diagnosis
1. Renal biopsy
2. p-ANCA positive in < 20 percent cases. Classical
PAN is ANCA negative.
3. Hepatitis B antigenemia.
Treatment
Cyclophosphamide, steroids.
CHURG-STRAUSS DISEASE
Allergic angitis and granulomatosis characterized by
granulomatous vasculitis of multiple organ systems,
particularly the lungs (c.f. PAN, where lungs are not
involved).
Vasculitis may involve vessels of any size or type (vein
or arteries).
Association with asthma or peripheral eosinophilia.
WEGENERS GRANULOMATOSIS
Pathology
Necrotizing vasculitis of small arteries and veins together
with granuloma formation typically involving the respiratory
tract.
Immune System
301
Lung involvement multiple bilateral nodular cavitary

lesions.
Clinical Feature
Persistent pneumonitis is the most common
presentation.
Typically presents with paranasal sinus pain and purulent
or bloody nasal discharge.
Serous otitis media conductive deafness.
Renal involvement proteinuria, hematuria (cresenteric
glomerulonephritis).
Lower respiratory tract infection cough, hemoptysis,
dyspnea.
Skin palpable purpura.
Investigation
c-ANCA positive, increased ESR, increased IgA level,
may be RF positive.
But complement levels remain normal.
Treatment
Treatment of choice is cyclophosphamide.
MICROSCOPIC POLYANGIITIS
Necrotizing vasculitis affecting arteries, capillaries and
venules.
More commonly involves the lungs (causing hemoptysis)
and kidneys (90%) causing glomerulonephritis.
p-ANCA is positive in over 80 percent cases.
Vasculitis causing
necrotizing inflammation
Vasculitis causing
granuloma
1. Polyarteritis nodosa
2. Churg-Strauss disease
3. Microscopic polyangiitis
1.
2.
3.
4.
Giant cell arteritis

Takayasus arteritis
Wegners granulomatosis
Churg-Strauss disease
MONONEURITIS MULTIPLEX
Causes:
1. PAN the most common cause.
2. Hypersensitivity vasculitis.
302
3. Leprosy most common cause in India.

4. Rheumatoid arthritis.
Treatment: Steroids.
TEMPORAL ARTERITIS
(GIANT CELL ARTERITIS)
It is a granulomatous inflammation characteristically
involving one or more branches of the carotid artery,
particularly the temporal artery. Vertebral and ophthalmic
arteries are also involved.
Clinical Feature
Age of onset about 70 years, female preponderance.
Symptoms: Headache is predominant symptom (most
commonly temporal headache). It is unilateral but may
be bilateral, dull and boring with episodic lancinating pain,
worse at night and aggravated by exposure to cold.
May cause ischemic optic neuritis which leads to sudden
blindness.
Claudication of tongue, jaw, scalp pain.
Sign
Tender thickened or nodular artery, which may be
pulsatile.
Polymyalgia rheumatica stiffness and pain in muscles
of neck, back and thigh.
Fever, anemia and weight loss.
Diagnosis
Increased ESR.
Liver function increased alkaline phosphatase.
Temporal artery biopsy is confirmatory.
Treatment
NSAIDs, glucosteroids.
TAKAYASUS ARTERITIS
It is characterized by fibrous thickening of aorta and its
branches (most commonly the subclavian artery).
Immune System
303
Pathology
Intimal proliferation and fibrosis
Vascularization of the media
Degeneration of the elastic lamina.
Clinical Feature
Common in younger females (< 40 years).

Ocular symptoms blindness.
Absent pulses in the upper extremities (pulseless disease).
Asymmetric radial pulse.
Renal artery stenosis may cause hypertension.
KAWASAKIS DISEASE
Also known as mucocutaneous lymph node syndrome.
Characterized by
1.
2.
3.
4.
Nonspecific cervical lymphadenopathy.

Congested conjunctiva (conjunctivitis).
Erythema of the oral cavity, lips and palms.
Desquamation of the skin of the fingertips.
Others
Occurs in children with prolonged fever (for > 5 days)
that is unresponsive to antibiotics.
Associated with coronary artery aneurysm, myocarditis
and even myocardial infarction.
Blood thrombocytosis and increased ESR.
Treatment
High dose IV gamma globulin.
Note: Best result occurs with IV gammaglobulin in
Kawasakis disease.
SARCOIDOSIS
Pathology
It is characterized by non-caseating epitheloid granuloma.
Granulomas contain Langerhans or foreign body type
of giant cells. These cells contain 3 types of inclusion
304
bodiesSchaumann body, asteroid body and residual

body.
Clinical Feature
Lungs
Involved in 90 percent cases.
It is an interstitial lung disease.
Pleural effusion (unilateral) is seen in 1-5 percent cases.
Lymphadenopathy Bilateral hilar lymphadenopathy
Paratracheal nodes.
Skin: Erythema nodosum, lupus pernio.
Eye Most common involvement after the lungs.
Anterior uveitis (causing blurred vision) and
keratoconjunctivitis sicca.
Kidney: Rarely involved. May cause hypercalciuria with
or without hypercalcemia. Renal stones, if chronic.
Nervous system: Unilateral facial paralysis.
Endocrine: Diabetes insipidus, Addisons syndrome.
Exocrine: Bilateral parotid gland enlargement.
Note: Uveoparotitis is seen in rheumatoid arthritis and
sarcoidosis.
Laboratory Findings
Chest X-ray
Bilateral hilar lymphadenopathy is the hallmark of
sarcoidosis.
Other features eggshell calcification, military shadow.
Cavitation is rare.
Blood: False positive RF and ANA. Increased ACE level
(60% cases).
Skin: Kveim-Siltzbach skin test.
Biopsy
Most commonly from the lungs shows non-caseating
granuloma.
Immune System
305
Bronchoalveolar lavage shows

Increased lymphocytes, increased CD4:CD8 ratio.
Gallium 67 lung scan, CECT chest.
Treatment
Prednisolone.
50 percent cases resolve spontaneously.
Prognosis
Most common cause of death is due to respiratory failure
due to interstitial lung disease.
DISEASES OF JOINTS
OSTEOARTHRITIS
This is a degenerative condition.
1.
2.
3.
4.
5.
6.
Congenital malformation of a joint.

Irregularity of the joint surface from previous trauma.
Damaged articular surface.
Internal derangement of the knee such as a loose body.
Mal-alignment (bow legs).
Obesity and excessive weight.
Osteoarthritis occurs at an early age in Ehler-Danlos
syndrome.
Pathology
First change is an increase in water content and depletion
of the proteoglycans from the cartilage matrix.
Fibrillation, osteophyte formation.
Clinical Feature
Knee is the most common involvement.
Hand
DIP and PIP joint are the most commonly involved
with sparing the wrist and MCP and CMC joints except
at the base of thumb.
DIP Heberdens node,
PIP Bouchards node.
306
Radiology
1.
2.
3.
4.
5.
Narrowing of joint space

Subchondral sclerosis
Osteophyte formation
Loose bodies in joint
Subchondral cyst.
Treatment:
Glucosamine and chondroitin sulphate.
Total joint replacement.
PSEUDOGOUT
Deposition of CPPD (calcium pyrophosphate dehydrate)
crystals in articular cartilage, synovium, periarticular
ligaments and tendons.
Clinical Feature
Knee is most commonly involved.
Meniscal calcification (chondrocalcinosis).
Investigation:
Polarizing microscopy rhomboid crystals with weak
positive birefringence in the extracellular fluid and in
neutrophils.
Treatment
Joint aspiration, NSAIDs and intra-articular glucocorticoid
injection.
INFECTIVE ARTHRITIS
Organism
Staphylococcus aureus is the most common cause of nongonococcal arthritis.
Pathology
Exudation of fluid within the joint space.
It is the most common cause of ankylosis.
Clinical Feature
Monoarticular arthritis.
Knee is the most commonly involved joint.
Note: Most common cause of infective polyarticular
arthritis is gonococcus.
Diagnosis
Joint aspiration best method.
Immune System
307
PSORIATIC ARTHRITIS
Asymmetric polyarthritis involving the distal joints of hand
and foot.
PIP and DIP are the most commonly involved with
sausage-shaped digits (dactylitis).
Onychodystrophy onycholysis, ridging and pitting of
nails. This helps it to be distinguished from rheumatoid
arthritis.
Sacroilitis.
X-ray
Pencil-in-cup appearance, opera glass deformity.
Laboratory Findings
RF may be positive.
Uric acid levels may be increased.
ARTHRITIS IN INFLAMMATORY
BOWEL DISEASES
Symmetric, migratory polyarthritis affecting mainly the large
joints of the lower extremities most commonly the knee joint.
Joint involvement in arthritis
Rheumatoid
arthritis
Osteoarthritis
Psoriatic
arthropathy
MP and PIP joints of hand

Spares the DIP
PIP and DIP of hand but spares the MCP and
CMC (wrist) joints except at the base of the thumb
i.e. the first CMC joint is also involved.
PIP, DIP, MCP with or without the wrist joint.
SERONEGATIVE ARTHRITIS
Causes
1.
2.
3.
4.
5.
Ankylosing spondylitis
Reiters arthritis
Psoriatic arthritis
Enteropathic arthritis (IBD)
Reactive arthritis
Clinical Feature
Involvement of the sacroiliac joint.
Absence of rheumatoid factor (hence called
seronegative).
Association with HLA B 27.
308
ARTHRITIDES
Neuropathic Joint Disease (Charcots Joint)
Causes
1. Diabetes mellitus affects the tarsal and
tarsometatarsal joints of foot.
2. Tabes dorsalis knees, hips and ankles are most
commonly involved.
3. Syringomyelia shoulder, elbow.
4. Amyloidosis
5. Leprosy.
Clinical feature: Progressive, painless swelling of joints with
articular destruction.
Tietzes Syndrome
Painful swelling of costochondral joint, most commonly
the second and third costochondral joints.
HEMOPHILIC ARTHROPATHY
Hemophilia is the most common cause of acute or
chronic hemarthrosis.
Most commonly involved joints are the knees.
X-ray feature
i. Juxta-articular osteopenia, marginal sclerosis and
subchondral cyst.
ii. Osteoporosis.
iii. Widening of the femoral intercondylar notch.
iv. Enlargement of the proximal radius.
v. Squaring of the distal end of patella.
Note: Bleeding may occur into the joint space. Blood
remains liquid because of the absence of intrinsic
clotting factors.
Most common muscle into which bleeding may
occur is iliopsoas.
ALKAPTONURIC ARTHRITIS
Seen in alkaptonuria (a defect of metabolism of
phenylalanine).
Spine and shoulders are most commonly involved.
X-ray shows characteristic disc space calcification
(ocronosis).
RENAL SYSTEM
PHYSIOLOGY
Nephrons
Types:
1. Cortical nephron- 85 percent.
2. Juxtamedullary nephron-15 percent. They have long
loops.
Renal tubule:
1. Proximal convoluted tubule- 15 mm long, lined by
columnar epithelium.
2. Descending loop of Henle- lined by flattened epithelium.
3. Ascending loop of Henle- lined by cubical epithelium.
4. Distal convoluted tubule- 5 mm long, lined by cuboidal
epithelium.
Note: Urothelium or Transitional cell lining is present in
bladder, ureter and urethra.
Juxtaglomerular apparatus:
Formed by juxtaglomerular of JG cells (which secret
renin), the macula densa and the lacis cells.
JG cells are smooth muscular cells (epitheloid cells)
in the afferent arterioles of glomerulus.
Renal medulla: Is made up of loop of Henle, vasa rectae
and renal pyramids.
Renal cortex: Is made up of superficial and juxtamedullary
glomerulus, arcuate artery and vein, interlobular artery and
capillary bed.
Renal Blood Flow
Measurement: By infusing p-aminohippuric acid (PAH)
and measuring its concentration in urine and plasma.
Value: The value obtained by above method is called
Effective Renal Plasma Flow (ERPF). In humans, ERPF=
625 ml/min.
310
Renal blood flow accounts for 20 percent of cardiac

output.
Regulation of renal blood flow:
1. Norepinephrine- constricts renal vessels (afferent).
2. Dopamine- dilates renal vessels.
3. Angiotensin II constricts efferent vessels.
4. Acetylcholine- dilates renal vessels.
Regional blood flow and O2 consumption: Arteriovenous
O2 difference for whole kidney is 14 ml/L of blood.
1.
2.
3.
Cortex
Outer medulla
Inner medulla
Blood flow
(ml/gm/min)
O2 consumption
(ml/gm/min)
5
2.5
0.6
7
3.5
0.084
Glomerular Filtration Rate

Measurement: Substances used are
1. Creatine clearance- good measure (normal plasma
creatinine= 0.6-1.2 mg/dl)
2. Inulin best.
3. 51Cr-EDTA
4. Tc99DTPA
Value: 125 ml/min
Filtration fraction: The ratio of GFR and the renal plasma
flow.
Filtration barrier: It is made up of
1. Podocytes,
2. Basement membrane,
3. Capillary endothelium.
Tubular Function
Na+ - excreted amount 150 mEq/24hr.
Na+ Absorbed from PCT (maximum), DCT, CD except
thin portion of loop of Henle.
Glucose, amino acids and HCO3 - absorbed along
with Na+ in the early portion of PCT.
PAH - secretion is a linear function of plasma level
(hence, PAH is used to measure ERPF).
Urea clearance - 88 ml/min.
K+ - reabsorbed only in PCT and secreted in DCT.
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311
Water Clearance
Water loss as sweat - 600-800 ml/day.
60-70 percent of filtered water (GFR) is reabsorbed
in PCT.
Water is reabsorbed from PCT, DCT, descending loop
of Henle, CD.
Acidification of Urine
HCO3 reabsorption is associated with H+ secretion
and occurs maximally in PCT.
H+ secreted by renal tubular cells reacts with NH3 (also
secreted) to produce NH4+ which is responsible for
acidification of urine.
Minimum pH that can be attained in urine is 4.8.
Bladder Function
Emptying of bladder: The first urge to void is felt at bladder
volume of 150 ml. Marked sense of fullness at about 400
ml.
Regulation of Renin Secretion
Stimulatory:
1. Increased sympathetic activity.
2. Increased circulatory catecholamines.
3. PGs.
Inhibitory:
1. Increased Na+ and Cl reabsorption across macula
densa (at DCT).
2. Increased afferent arteriolar pressure.
3. Angiotensin II.
4. Vasopressin.
ACUTE RENAL FAILURE
Definition: ARF is a syndrome characterized by rapid decline
in GFR (hours to weeks), retention of nitrogenous waste
products (azotemia) and disturbance in ECF volume and
acid-base homeostasis.
Oliguria (<400 ml urine in 24 hours) is the major
symptom of ARF.
312
Types with etiology:

I. Pre-renal azotemia: diseases that cause renal
hypoperfusion.
Causes1. Hypovolemia.
2. Low cardiac output.
3. Altered renal-systemic vascular resistance ratio.
Note: Most common cause of post-operative renal failure
is decreased renal perfusion due to hypovolemia.
II. Renal azotemia:
Causes1. Acute tubular necrosis (ATN)- most common cause
of ARF (hence the terms ARF and ATN are often
used synonymously).
2. Glomerular disease.
3. Interstitial nephritis.
III. Post-renal azotemia: Due to urinary tract obstruction.
Pre-renal Azotemia
Hepatorenal syndrome- reversible.
Urine-NAD.
Renal Azotemia
Causes1. Ischemic ARF
2. Nephrotoxic ARF
Ischemic ARF
Etiology:
1. Hypovolemia and shock.
2. Trauma.
3. Acute pancreatitis.
4. Septicemia.
5. Hemolytic crisis.
Pathology: 3 phases
1. Initiation phase- GFR declines rapidly.
2. Maintenance phase- GFR stabilizes at its nadir (typically
5-10 ml/min), urine output is lowest and uremic
complications arise.
3. Recovery or diuretic phase- gradual improvement of
GFR marked diuresis.
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313
Nephrotoxic ARF
Etiology:
1. Heavy metals- mercury, Pb, As (produce PCT necrosis).
2. Organic solvents- carbon tetrachloride.
3. Radiographic contrast agents.
4. Aminoglycoside toxicity- non-oliguric renal failure.
5. Rhabdomyolysis and hemolysis.
6. Multiple myeloma- Tamm-Horsfall protein.
Renal Failure Indices
Helps in distinguishing prerenal and renal azotemia.
1. Fractional excretion of sodium (FeNa)- most useful
2. Urine Na+ concentration (UNa)
3. Urine creatinine to plasma creatinine ratio
4. Urine specific gravity (SG)
5. Urine osmolality (UO)
Index
1.
2.
3.
4.
5.
FeNa (%)
UNa (mmol/L)
UCr : P Cr
Specific gravity
Urine osmolality
(mosmol/kg H2O)
6. Serum urea: Creatinine
7. Renal failure index
Pre-renal azotemia Renal azotemia

<1
<10
>40
>1.018
> 500
>1
>20
>20
<1.015
<300
>20
< 1
<10
> 1
Complications of ARF
General:
1. Intravascular volume overload.
2. Electrolyte disturbance- hyponatremia, hypocalcaemia,
hyperkalemia, hyperphosphatemia, and hypermagnesemia (decreased Na+ and Ca++; increased K+, PO4,
Mg++).
3. Metabolic acidosis with increased anion gap.
4. Anemia.
Rhabdomyolysis: Hyperkalemia, hyperphosphatemia,
hypercalcemia and increased serum uric acid and increased
CK (Creatine kinase).
Recovery phase: Vigorous diuresis leads to intravascular
volume depletion, hypernatremia and decreased K+, Mg++,
PO4, Ca++.
314
CHRONIC RENAL FAILURE

Definition: Progressive and irreversible destruction of
nephron mass.
Etiology:
1. Diabetes mellitus
2. Hypertension
3. Glomerulonephritis
Stages:
GFR 35-50 percent of normal- no symptoms.
GFR 20-35 percent of normal- azotemia appears.
GFR 20 percent or less of normal- overt renal failure.
Effects of Uremia
1. Fluid and electrolytes:
Hyper/hyponatremia
Hyper/hypokalemia
Hypocalcaemia
Hyperphosphatemia
Metabolic acidosis
2. Endocrine-metabolic:
Secondary hyperparathyroidism
Aluminium induced osteomalacia- due to dialysis
Vitamin D-deficient osteomalacia
Hyperuricemia
Infertility and sexual dysfunction
3. Neuromuscular:
Peripheral neuropathy, myelopathy
Dialysis dementia- Al+3 may be the cause
4. Cardiovascular:
Congestive heart failure and/or pulmonary edema
Pericarditis
Uremic lung
5. Dermatology:
Pruritus
6. Hematological:
Normocytic normochromic anemia
Note: All the complications are improved by dialysis except
sexual dysfunction and pruritus.
Renal Osteodystrophy
Radiological examination of uremic patients before dialysis
reveals 3 types of lesions:
Renal System
315
1. Renal rickets
2. Osteitis fibrosa cystica- due to secondary
hyperparathyroidism; characterized by osteoclastic
bone resorption and subperiosteal erosion, especially
in terminal phalanges.
3. Osteosclerosis- enhanced bone density in the upper
and lower margins of vertebrae, producing so-called
rugger jersey spine.
(Note: Difference with osteomalacia- in osteomalacia,
serum Ca++ decreased and PO43 decreased. In renal
osteodystrophy Ca++ decreased but PO43 either
normal or increased).
DIALYSIS
Principle: Diffusion across a semipermiable membrane.
Indications:
1. Plasma urea>30 mmol/L and creatinine >600
mol/L
2. Hyperkalemia
3. Fluid overload
4. Uremic pericarditis
5. Convulsion
6. Metabolic acidosis (pH < 7.2)
7. Encephalopathy
8. Coagulopathy.
Note: Dialysis should be started when GFR = 10 ml/
min or serum creatinine is 8 mg/dl.
Hemodialysis
Types:
1. Conventional hemodialysis
2. Slow continuous ultrafiltration
3. Continuous arteriovenous hemodialysis (CAVHD)
4. Continuous venovenous hemodialysis (CVVHD)
Complications:
1. Infection- most common organism is Staph. aureus
2. Hypotension
3. Dementia- long-term
4. Microcytic anemia secondary to5. Aluminium toxicity
6. Mechanical- blood leak
316
7. Cardiovascular disease
8. Malnutrition
Peritoneal Dialysis
Types:
1. Intermittent peritoneal dialysis (PID)
2. Continuous ambulatory peritoneal dialysis (CAPD)
3. Continuous cyclic peritoneal dialysis (CCPD).
Advantage:
1. Avoidance of heparization and vascular surgery
2. Slower clearance (helpful in cardiovascular patients)
3. Self-amenable.
Disadvantage/complications:
1. Peritonitis- most common
2. Protein loss- malnutrition
3. Hypercholesterolemia and hypertriglyceridemia- obesity
Contraindications:
1. Pulmonary disease
2. Extensive abdominal adhesion
3. Scleroderma, vasculitis
4. Malignant hypertension.
RENAL TRANSPLANT
Indications: Advanced CRF.
The transplant: Usually the left kidney of a cadaver is
selected because it has a longer artery than right side.
Immunosuppression: Drugs used are
1. Azathioprine- most commonly used
2. Mycophenolate mofetic
3. Cyclosporin
4. Tacrolimus
5. Sirolimus
6. Glucocorticoids.
Complications:
1. Pulmonary infection- most commonly by Pneumocystis
carinii
Treatment- cotrimoxazole
2. Malignancy- most common is cancer of the skin and
lips.
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317
Transplant Rejection
a. Hyperacute rejection:
Occurring immediately- most common type.
Cause- preformed antibodies against HLA class I
antigens expressed by the donor.
Pathology due to intravascular thrombosis.
The graft in hyperacute rejection is called the white
graft.
It is avoidable by prior immunosuppression.
b. Acute rejection:
Mediated by T-lymphocytes, occurring within 6
months.
Pathology characterized by mononuclear cell
infiltration.
It can be reversed by immuno suppressive therapy.
c. Chronic rejection:
It is due to antibody and cell mediated effector
mechanism.
Most important risk factor for chronic rejection is
acute rejection.
Diagnosis:
Most sensitive and specific indicator of rejection is
creatinine clearance.
Best investigation to detect early graft rejection is
Doppler ultrasound. Radionuclid study is also used.
Prognosis:
Recovery of renal function after renal transplant takes
about 1 month.
Diseases that can recur after renal transplantation are
diabetes mellitus, membrano-proliferative GN, and focal
segmental glomerulosclerosis.
Disease that never recur after renal transplantation is
Alports syndrome.
GLOMERULOPATHIES
Acute Nephritic Syndrome
Onset: very acute (over days to weeks).
Characterized by1. Acute renal failure and oliguria
318
2. Macroscopic hematuria- with dysmorphic red cells and

RBC cast in urine.
3. Extracellular fluid retention, edema and hypertension.
Pathology with Types
There are 3 basic pathologies involved in acute nephritic
syndromeI. Immune-complex glomerulonephritis: (>70%)
Characterized by Hypocomplementemia
Normal ANCA and anti-GBM antibody
Granular deposition of Ig along GBM.
Types:
1. Idiopathic Proliferative GN
Crescentic GN
Mesangioproliferative GN
2. Post-streptococcal GN- Most important
3. Systemic diseases Lupus nephritis
H-S purpura
Cryoglobulinemia
Bacterial endocarditis
Basic pathology: Proliferation- due to infiltration of
glomerular tuft by neutrophils and monocytes and
subsequently to proliferation of resident endothelial and
mesangial cells (endocapillary proliferation).
II. Anti-GBM disease: (Very rare <1%) - mainly
crescentic.
Characterized by Anti-GBM antibody in blood
No ANCA and normal C3
Linear deposition of Ig along GBM
Types:
1. Idiopathic
2. Goodpastures syndrome
III. Pauci-Immune GN: (<30%) - Mainly crescentic.
Characterized by ANCA in blood
No anti-GBM antibody and normal C3
Renal System
319
Types:
1. Wegeners granulomatosis
2. Microscopic PAN
3. Idiopathic
ANCA positive glomerulonephritis
pANCA
cANCA
Microscopic polyangiitis
Goodpastures disease
Churg Strauss disease
Cresentic glomerulonephritis
Wegeners granulomatosis
Active glomerulonephritis
Note: PAN does not cause glomerulonephritis.
Rapidly Progressive/Crescentic GN (RPGN)

Onset- weeks to months.
Features: Nephritic urinary cast (RBC cast, dysmorphic
RBC) and subnephrotic proteinuria (<3.5 gm/24 hours).
Oliguria, hypertension, edema and hypervolemia are
variable features.
Pathology: Whatever may be the cause, RPGN in
characterized by presence of crescents in most of the
glomeruli.
Crescents are made up by proliferation of parietal cells
and migration of monocytes with multinucleated giant cells.
Etiology:
1. Type I CrGN (Anti-GBM)-very rare <10 percent
i. Idiopathic
ii. Goodpastures syndrome
2. Type II CrGN (Immune complex) - 45 percent
i. SLE
ii. Postinfections
iii. H-S purpura
3. Type III CrGN (Pauci-immune) - 45 percent.
Treatment of RPGN:
1. IV pulse methylprednisolone
2. Plasmapheresis
3. Combination of prednisolone, cyclophosphamide and
anticoagulants.
Prognosis: Depends upon the number of crescents.
320
Diagnosis of ANS and RPGN:

1. Renal biopsy- gold standard
2. Immunofluorescence microscopy
3. Serology- for C3, anti-GBM antibody and ANCA
(antinuclear cytoplasmic antibody).
Post-streptococcal GN
It is the prototype of acute proliferative immune-complex
disease.
Epidemiology: Age- 2-6 years.
Cause: Streptococcal infection (group A -hemolytic).
Predisposing illness:
i. Sore-throat (pharyngitis) - by strain 4 and 12, develops
after 10 days; common in winter, may cause
epidemic.
ii. Skin (impetigo) - by strain 49; common in summer.
Note: Early treatment of throat/skin infection does
not eliminate the risk of glomerulonephritis.
Clinical features:
Puffiness around eyes and edema of the feet
Hypertension.
Complications:
1. Convulsions- due to hypertensive encephalopathy
2. LVF
3. ARF (CRF is very rare in PSGN).
Diagnosis:
1. Urine: Smoky due to gross hematuria, RBC cast,
dysmorphic RBC.
2. Serology: Increased ASO, increased anti-DNAse B,
antistreptokinase, antihyaluronidase- indicates recent
streptococcal infection.
Decreased C3 and Ig.
3. Immunofluorescence: Deposition of IgG and C3 along
GBM- Starry sky appearance.
4. Renal biopsy: Mostly proliferative (subepithelial
humps) changes. May show crescents.
Goodpastures Disease
It is the prototype of Anti-GBM disease.
Etiology: Autoantibody directed against type IV collagen.
Renal System
321
Clinical features:
1. Renal- hematuria, nephritic urinary sediment and
subnephrotic proteinuria (that of RPGN).
2. Pulmonary- hemoptysis-precedes hematuria
Hypertension is unusual.
Pathology: Anti-GBM disease mainly presents as crescentic
GN (RPGN).
Diagnosis: Renal biopsy.
Treatment:
As in RPGN
Plasmapheresis is the treatment of choice.
Pauci-immune GN
Mainly presents as RPGN.
There is overlapping between proliferative and crescentic
GN.
Treatment steroids with or without cyclophosphamide/
azathioprine.
NEPHROTIC SYNDROME
Features:
1. Massive proteinuria (>3.5 gm/24 hours)
2. Hypoalbuminemia (<3 gm/dl)
3. Edema- most obvious sign.
4. Hyperlipidemia and lipiduria
5. Hypercoagulability:
Pathology:
1. Proteinuria: Altered permeability of the glomerular
filtration barrier to protein.
2. Hypoalbuminemia: Due to
i. Proteinuria
ii. Increased renal catabolism
iii. Inadequate hepatic production.
3. Edema:
Underfilling hypothesis
Hypoalbuminemia decreased plasma oncotic
pressure leakage of ECF from blood to interstitium
activation of renin-angiotensin-aldosteron system
and release of ADH with suppression of ANP salt
and water retention more leakage of fluid into the
interstitium.
322
4. Hyperlipidemia- increased hepatic production of

lipoprotein.
5. Hypercoagulability:
Increased fibrinogen
Decreased antithrombin III, protein C and S.
Classification:
a. In children most cases are idiopathic.
Minimal change disease is the most common type.
Significant lesions include mesangial proliferative
(most commonly), FSGS, MPGN (in children over
8 years).
b. In adults
Idiopathic membranous GN is the most common
type.
Secondary due to various causes.
Complications:
1. Protein malnutrition
2. Microcytic hypochromic anemia
3. Hypocalcemia and secondary hyperparathyroidism
4. Infections- due to low IgG.
5. Pulmonary embolism, DVT
6. ARF.
Minimal Change Disease
(Nil Disease or Lipoid Nephrosis)
This is the most common cause of nephrotic syndrome
in children between 3-8 years of age.
Pathology:
On light microscopy no change is seen.
Only pathological change on EM is- loss of foot
processes of the podocytes of visceral epithelial cells.
Glomerular function is lost due to loss of poly charge
on both sides of glomerular foot process.
Pathogenesis:
Mutations in the nephrin gene give rise to congenital
nephrotic syndrome (Finnish type) with minimal change
morphology.
Nephrin (NPHS1) is located on chromosome 19q13.
Podocin (NPHS2) is associated with an autosomal
recessive form of FSGS.
Renal System
323
Clinical features: Selective proteinuria.

Diagnosis:
Hyaline or granular cast in urine
Renal biopsy- not required.
Treatment: Prednisolone most effective among the
nephrotic lesions.
Prognosis: Excellent. May progress to FSGS.
Focal and Segmental Glomerulosclerosis
with Hyalinosis (FSCG)
Characterized by sclerosis with hyalinosis involving portions
(segmental) of <50 percent (focal) glomeruli.
Variants:
i. Collapsing worst prognosis. Characterized by proliferation and hypertrophy of glomerular visceral epithelial
cells.
ii. Cellular tip lesion best prognosis.
Etiology:
i. HIV infection Collapsing FSG.
ii. Reflux nephropathy
iii. SLE
iv. Heroin use.
Clinical feature: Presents as nephrotic (in 2/3rd cases) or
nephritic (in 1/3rd cases) syndrome.
Membranous Glomerulopathy
Most common cause of idiopathic nephrotic syndrome in
adults.
Pathology:
Diffuse thickening of GBM, most apparent on staining
with PAS.
It is the Most common cause of renal vein thrombosis.
Subepithelial deposits (spike and dome pattern) are
seen.
Etiology:
1. Infection- Hepatitis B and C, malaria, syphilis, leprosy,
filariasis, schistosomiasis.
2. SLE
324
3. Ca breast and lung

4. Drugs- gold and penicillamine
5. Miscellaneous- Fanconis syndrome
Membrano (Mesangio) Proliferative GN (MPGN)
Pathology:
Thickening of GBM, and proliferative changes on LM.
This is caused by Splitting of the GBM.
Type I MPGN (2/3)- subepithelial or mesangial deposits
of IgG or IgM and C3.
Type II MPGN (1/3)- dense deposit disease.
Deposition of only C3 in the GBM and mesangium.
(presence of autoantibody C3 nephritic factor); tram
track appearance.
Treatment: These patients are not responsive to steroid
therapy.
Isolated Hematuria - IgA Nephropathy
(Buergers Disease)
Pathology:
Immune-complex disease with normal C3 level in
blood.
Deposition of IgA in the mesangium (hence, a type
of MPGN) proceeds from diffuse proliferative to focal
and segmental involvement.
IgA complex contains IgA, C3, properdin and IgG or
IgM (in 50% cases).
Clinical features:
Age- commonly affects children and young adults.
Patients present with gross hematuria often 24-48 hours
after a pharyngeal or gastrointestinal infection. (c.f.
HS purpura presents 10-12 days after infection).
May present with microscopic hematuria at routine
examination with or without proteinuria.
Hypertension is unusual presentation.
Etiology:
1. H-S purpura
2. Idiopathic interstitial pneumonitis
3. Crohns disease
4. Leprosy
5. Ankylosing spondylitis
6. Sjgrens syndrome
Renal System
325
Treatment: Corticosteroids.
Note:
Subepithelial deposits are seen in PSGN,
membranous GN and RPGN.
Subendothelial deposits are seen in MPGN and SLE.
GLOMERULOPATHIES IN SYSTEMIC DISEASES
Diabetic Nephropathy
Changes in kidneys associated with diabetes are:
Gross: Kidneys are normal or increased in size.
Microscopic:
1. Capillary basement membrane thickening.
2. Diffuse glomerulosclerosis - most common lesion.
3. Nodular glomerulosclerosis - also called KimmelstielWilson lesion most characteristic.
4. Renal atherosclerosis and arteriosclerosis.
5. Pyelonephritis - including necrotizing papillitis.
Clinical feature: Microalbuminuria (30-300 mg/dl).
Wegeners Granulomatosis
Type III CrGN (pauci-immune)
Treatment: Glucocorticoids and cyclophosphamide.
Hemolytic-Uremic Syndrome
Pathology: Hyaline thrombi only in the afferent arterioles
and glomerular capillaries in kidney.
Pathogen:
In India, Shigella dysenteriae type 1
Others - E. coli (EHEC O157:H7)
Toxin - verotoxin
Clinical features:
Microangiopathic hemolytic anemia- pallor (Coombs
ve)
Thrombocytopenia- purpura
Acute renal failure- oliguria
Fever
Onset is preceded by an acute diarrheal or dysenteric
illness
326
Hyperkalemia, hyponatremia, hypoglycemia,

hypertension
CNS involvement seizures, altered sensorium
Diagnosis:
Blood- broken and distorted RBC (schistocytes)
Increased urea and creatinine
Hypofibrinogenemia
Feces - verotoxin
Urine - hematuria, cylinduria
Prognosis: Has improved than past.
Diarrhea negative HUS: Microangiopathic lesions affect
interlobular arteries and result in severe hypertension and
progressive renal insufficiency.
Amyloidosis
Most common involvement is kidney.
Features:
Massive proteinuria
Acute/chronic renal failure- azotemia
No hypertension
Kidney size - usually normal.
HEREDITARY DISEASES
Alports Syndrome
Usually X-linked dominant.
Clinical features:
Males are commonly affected
Renal- microscopic hematuria
Extra-renal- sensorineural deafness
Bilateral anterior lenticonus.
Pathogenesis:
Mutation of the gene coding for collagen type IV
Morphology foam cells, basket weave appearance.
Diagnosis: Renal biopsy and EM examination
characteristic.
Treatment:
Many patients progress to ESRD (End stage renal
Disease) and are suitable candidates for dialysis and
transplantation.
This does not recur after renal transplantation.
Renal System
327
Systemic Lupus Erythematosus (SLE)

Pathology:
Diffuse proliferative glomerulonephritis- most common
renal lesion
Focal segmental glomerulosclerosis
When extensive, Wire loop appearance on LM.
Clinical features:
Persistent proteinuria
Cellular cast- RBC cast
Treatment: Should be treated with aggressive immunosuppressants.
Lipodystrophy
MPGN II (dense deposit disease) is the most common
glomerular lesion.
Denys-Drash Syndrome
Nephrotic syndrome in the first 3 months of life
Male pseudohermaphroditism
Increased risk of Wilms tumor.
TUBULOINTERSTITIAL DISEASE
Inflammatory conditions that primarily involve
interstitium and tubules.
Often involves the renal pelvis- hence called
pyelonephritis (infections).
Interstitial nephritis- is the term reserved for noninfectious causes of TIN such as drugs.
Etiology:
1. Bacterial: Most common - acute and chronic
pyelonephritis
2. Interstitial nephritis:
a. Toxinsi. Drugs- methicillin
ii. Analgesic nephropathy
iii. Lead nephropathy
b. Metabolici. Gouty nephropathy
ii. Hypercalcemic nephropathy
iii. Hypokalemic nephropathy
c. Radiation injury
328
Pathology:
PCT dysfunction leads to selective reabsorption defecthypokalemia, aminoaciduria, glycosuria, phosphaturia,
uricosuria or bicarbonaturia (proximal or type II RTA)Fanconi syndrome.
DCT- impaired absorption of Na + (Salt wasting
nephropathy).
Hyperchloremic acidosis- due to reduced capacity to
generate and excrete NH4+.
Papillary Necrosis
Necrosis of renal pelvis.
Causes:
1. Diabetes
2. Sickle cell disease
3. Analgesic nephropathy
4. Chronic alcoholism
5. Chronic interstitial nephritis
6. Renal vascular thrombosis.
Diagnosis: Ring shadow on pyelography.
Acute Pyelonephritis
Organism: E. coli is the most common organism.
Pathology: Necrotising papillitis or papillary necrosis.
Diagnosis: Urine- may show pyuria, bacteriuria and pus
cell cast.
Chronic Pyelonephritis
Salt-wasting nephropathy.
Morphology:
Gross - kidneys are unevenly contracted
Microscopic - periglomerular fibrosis
Thyroidisation- colloid casts in dilated renal
tubules.
Xanthogranulomatous Pyelonephritis
Occurs in middle aged poorly functioning kidneys (as
in diabetics).
Renal System
329
Features:
More common in females
Diffuse disease is more common
Lipid laden foam cell (fat density lesion on USG)
Renal stones.
Hypercalcemic Nephropathy
Pathology: Inability to concentrate urine maximally resulting
in polyuria and nocturia.
Radiation Nephritis
Clinical features: Rapidly progressive azotemia, moderate
to malignant hypertension, anemia and proteinuria.
INFECTIONS OF KIDNEY
Pyonephrosis
Etiology:
1. Renal calculi- most common cause
2. Infection of a hydronephrosis
3. Acute pyelonephritis.
Clinical features:
Usually unilateral
Triad of symptoms- anemia, fever and a swelling in
the loin.
Treatment: It is a surgical emergency.
Procedure1. Percutaneous nephrostomy- to aspirate the pus
2. Subcapsular nephrectomy- in long standing cases.
Renal Tuberculosis
Route: Hematogenous infection from a distant focus.
Clinical features:
1. Urinary frequency- earliest symptom.
2. Acidic, Sterile pyuria- most consistent finding.
3. Painless hematuria- most common cause of hematuria.
Diagnosis:
X-ray - shows areas of calcification (pseudocalculi).
330
Tuberculous granulomas may be visible in the bladder

wall.
IVU - earliest investigation needed and also the best.
Cystoscopy golf hole ureteric orifice.
Urine culture of 3 morning specimens.
Schistosomiasis
Caused by schistosoma hematobium.
Features:
Calcified granulomas (sandy patches) on bladder wall
fetal head appearance on X-ray.
Bladder contracted, risk of developing squamous cell
carcinoma.
VASCULAR INJURY TO THE KIDNEY
Renal Artery Stenosis
Etiology:
1. In middle-aged and elderly- atheromatous plaque.
2. In young women- fibromuscular dysplasia (in western
countries); aorto-aortitis (in India).
Clinical features:
Age >50 or <30 years
Hypertension
Epigastric bruit
Diagnosis: DSA.
Fibromuscular Dysplasia
Non-atherosclerotic and non-inflammatory irregularity
of medium and small arteries.
Usually affects women in 3050 years.
Vessels involved are renal (most common), carotid and
common iliac.
Clinical feature: Renovascular hypertension, renal
insufficiency, TIA, claudicaiton, intracranial aneurysms are
present in 50 percent patients with carotid artery
involvement.
Diagnosis: Angiography shows string of beads pattern.
Renal System
331
Renal Vein Thrombosis

Associated with
Nephrotic syndrome
Renal cell Ca
OCP use
In children, dehydration.
Clinical feature: Proteinuria, hematuria, lumbar tenderness
with enlarged kidney, hypovolemic shock.
Benign Nephrosclerosis
It is the renal change in benign hypertension.
Morphology:
Gross- symmetrically bilateral contracted kidney (c.f.chronic pyelonephritis).
Microscopic- hyaline arteriosclerosis, interstitial fibrosis,
fibrinous thickening of media (vessels).
Malignant Nephrosclerosis
Occurs in malignant hypertension.
Morphology:
Gross flea-beaten appearance.
Microscopic fibrinoid necrosis, necrotizing arteriolitis,
hyperplastic arteriolitis (onion-skin lesion).
Bilateral contracted kidney
Symmetrical
Benign nephrosclerosis
Chronic glomerulonephritis
Flea beaten kidney

Assymetrical
Chronic
Pyelonephritis
Malignant hypertension
Infective endocarditis
Polyarteritis nodosa
HEREDITARY TUBULAR DISORDERS

Polycystic Kidney (Adult)
Inheritance:
Autosomal dominant.
Gene- PKD1 (90%)- on short arm of chromosome 16
which codes for polycystin 1.
PKD2 (10%)- on chromosome 4 which codes for pol. 2.
Pathology:
Often associated with cysts of liver (5070%), pancreas,
spleen, ovaries and lungs; Berry aneurysm of circle of
Willis.
332
Other associations- colonic diverticula, MVP.

Morphology cylindrical dilatation of renal tubule.
Clinical features:
Onset - 3rd/4th decade.
Almost always bilateral.
Features
1. Massive renal swelling
2. Flank pain most common symptom.
3. Hypertension
4. Urinary infection
5. Intermittent hematuria
6. Intracranial/subarachnoid hemorrhage
7. End-stage renal disease (ESRD)
Diagnosis:
Excretory urography - Spider leg appearance.
USG investigation of choice.
Treatment: Surgery
Uncap the cyst (Rovsings operation).
Surgery does not restore normal renal function.
Ultimate treatment of choice is renal transplantation
when renal failure develops.
Autosomal Recessive Polycystic Kidney
Clinical feature:
Age of onset first year of life.
Bilateral abdominal mass.
Complication:
Hypertension, renal insufficiency and end stage renal
disease.
Death is due to pulmonary hypoplasia.
Diagnosis: by USG.
Screening: By perinatal USG in at risk females.
Medullary Sponge Kidney (MSK)
Clinical features:
Age of onset 3rd or 4th decade.
UTI.
Recurrent hematuria.
Hypercalciuria- renal stone formation.
Investigation: IVU.
Renal System
333
Juvenile Nephronophthisis
Pathology:
Cysts throughout renal medulla, cortex and pelvis.
Clinical feature:
Age of onset childhood.
Polyuria, anemia, renal failure, growth retardation.
Diagnosis:
USG/CT scan shows bilateral small kidneys, loss of
corticomedullary differentiation and renal cyst.
Biopsy is confirmatory.
Medullary Cystic Disease
All are same as juvenile nephronophthisis except:
i. Autosomal dominant.
ii. Age of onset in 3rd or 4th decade.
iii. No growth retardation.
iv. Hypertension may be seen.
von Hippel-Lindau Syndrome
Renal cysts + angioma of retina + hemangioma of
cerebellum.
Bartters Syndrome
1.
2.
3.
4.
Hypokalemia - polyuria, polydypsia and weakness,

Metabolic alkalosis,
Normal to low BP,
Growth retardation.
RENAL TUBULAR ACIDOSIS

Characterized by: Hyperchloremic metabolic acidosis with
normal anion gap.
Pathology:
i. Defective bicarbonate reabsorption in the PCT.
ii. Suppressed renal amoniagenesis.
iii. Inadequate distal tubule proton (H+) secretion.
All these abnormalities lead to acidosis.
334
Types
Type 1 (Distal) RTA
Pathology:
i. Excessive back-diffusion of H+ from lumen to
blood
ii. Inadequate transport of H+ alkaline urine.
a. Chronic acidosis decreased Ca++ reabsorption
renal hypercalciuria and secondary
hyperparathyroidism.
b. Decreased urinary concentration and decreased K+
conservation polyuria and hypokalemia.
c. Decreased citrate reabsorption.
All these lead to mobilization of Ca++ from bones
(rickets and osteomalacia) calcium phosphate stones
and nephrocalcinosis.
Diagnosis:
Oral NH4Cl loading test- no fall in urinary pH
Metabolic acidosis with alkaline urine (pH >5.5)
Rickets, osteomalacia, calcium phosphate stones or
nephrocalcinosis support diagnosis
Differential diagnosis: GI bicarbonate loss where urine anion
gap is ve.
Type 2 (Proximal) RTA
Pathology:
HCO3 reabsorption in the PCT is defective leading
to bicarbonaturia.
Absorption of glucose, amino acid, phosphate are also
decreased- Fanconis syndrome.
Diagnosis:
Hyperchloremic acidosis with bicarbonaturia.
Urinary pH <5.5.
Ca-stones are unusual.
Type 4 RTA (Hyperkalemic Distal RTA)
Pathology: Distal tubule secretion of both K+ and H+ are
abnormal- hyperchloremic acidosis with hyperkalemia.
Renal System
335
RTA at a glance
Findings
RTA 1
1. Minimum urinary pH >5.5

2. Serum K+
Low
(hypokalemia)
3. Fanconis syndrome
Ve
4. Renal stone
+Ve
RTA 2 RTA 4
<5.5
Low
+Ve
Ve
<5.5
High
(hyperkalemia)
Ve
Ve
Fanconis Syndrome
Idiopathic variety is inherited as autosomal dominant/
recessive or X-linked recessive.
Features: Generalised defect in PCT transport involving
amino acids (amino aciduria), glucose (glycosuria), uric
acid (hypouricemia), Na+, K+ (hypokalemia), PO42
(hypophosphatemia) and also polyuria.
NEPHROLITHIASIS
Kidney Stones
Etiology:
1. Idiopathic hypercalciuria
2. Hyperuricosuria
3. Primary hyperparathyroidism
4. Distal RTA
5. Interstitial hyperoxaluria
6. Hereditary hyperoxaluria
7. Gout
8. Medullary sponge kidney
9. Randalls plaque and Carrs microlith.
Types of Stone
1. Calcium stones: Calcium oxalate or calcium phosphatemost common.
Causesi. Primary hyperparathyroidism,
ii. Distal RTA (type I).
Clinical features: Oxalate stones are most painful.
Diagnosis: X-ray.
2. Uric acid stones:
Radiolucent - so not visible on X-ray.
336
3. Cystine stones:
Appears in acid urine- so UTI (E. coli) favours
cystine stones.
Radioopaque.
4. Struvite (MgNH4PO4) stones: Common in females.
i. Bladder catheterization,
ii. UTI with urea-splitting organism Proteus that produces
alkaline urine.
Pathology: These stones tend to grow in size and fill the
whole renal collecting system- Stag horn calculus.
Diagnosis:
1. X-ray KUB region:
90 percent stones are radiopaque (except urate
stones)
Bowels must be evacuated before taking X-ray.
Features of renal stones on X-ray i. Keeps a constant position relative to urinary tract
during respiration,
ii. Uniform opacity (Gallstones are usually ring
shaped with a radiolucent center).
iii. Lateral X-ray- renal stones superimpose on the
bodies of vertebrae. So if the opacity is in front
of the vertebrae it is probably a calcified mesenteric
node or opacity within the alimentary canal.
D/D of renal stone opacity:
i. Calcified mesenteric lymph node
ii. Gallstone
iii. Phleboliths
iv. Calcified tip of the 12th rib
v. Foreign body
2. IVU - most diagnostic.
3. CT scan investigation of choice.
Treatment:
1. Conservative: Stones smaller than 0.5 cm are likely
to pass spontaneously unless they are impacted.
2. Surgery - Percutaneous nephrolithotomy
3. ESWL- Contraindications are
i. Uncontrolled bleeding disorder
ii. Pregnancy
iii. Ureteric stricture
iv. UTI
v. Cardiac pacemaker
Renal System
337
Ureteric Stones
Ureteric stones almost always arise in kidney and passes
down to the ureter.
Usually small and single.
Clinical features:
Ureteric colic passes from loin to groin and not
associated with fever. Colic is caused by hyperperistalsis
of ureter and spasm of smooth muscle to overcome
the obstruction.
Location of pain depends on the site of stone in the
ureter.
Stone at
Pain referred to
Pelvi-ureteric jn.
(upper ureter)
Mid-ureter
Testicles
Pelvic brim
Intramural ureter
McBurneys point on right side and iliac fossa

on left side
Inner side of thigh via genitofemoral nerve
Tip of penis (strangury)
Management:
i. Proximal stone:
<2.5 cm ESWL.
>2.5 cm Percutaneous nephrolithotomy.
ii. Distal stone (lower third of ureter):
Small stone Dormia busket.
Ureteroscopic removal.
iii. Midureteric stone: Can be pushed back to renal pelvis
by flushing through cartheter (Push bang) and then
removed.
Urinary Bladder Stone
a. Primary stone:
Develops in sterile urine often in the kidneys and
drops down to bladder.
Rare in western countries especially among children.
E.g. oxalate stone (Jack stone), uric acid stone.
b. Secondary stone: Develops in the bladder in presence
of urea splitting organism proteus, e.g. triple phosphate
stone.
c. Mixed stone: Most common.
Incidence:
Common in Indian children.
Secondary stones are more common than primary.
338
Clinical features:
More common in males.
Frequency is the earliest symptom.
Pain (strangury) maximum with speculated oxalate
stones. Occurs at the end of micturition and referred
to the tip of penis.
Terminal hematuria (at the end of micturition).
Interruption of urinary stream.
Investigation:
Most stones are visible on X-ray.
IVU radiolucent stones appear as filling defect.
Cystoscopy confirmatory.
Treatment:
Transurethral litholapaxy for large and hard stones.
Endoscopic lithotripsy.
Contraindications to litholapaxyi. Very large stone,
ii. Contracted bladder,
iii. Urethral stricture,
iv. Patients age < 10 years.
Nephrocalcinosis
1. Herditary distal RTA.
2. Medullary sponge kidney.
3. Hypercalcemic states, hyperparathyroidism, vitamin D
toxicity.
X-ray: Shows multiple papillary calcifications.
Development of Kidney
From two sources:
1. The excretory tubules (nephrons) from metanephros.
2. The collecting part from ureteric bud.
Note:
Full number of nephrons is present by 36 weeks of
gestation.
GFR begins between 9 and 12 weeks initiating urine
formation.
Adult concentrating ability is achieved at 1 year of
age.
Renal System
339
Renal Ectopia
Incidence: 1 in 1000 people.
Site: near the pelvic brim usually on left side.
Ectopic Ureter
Always opens above the external sphincter.
Most commn site of opening is prostatic urethra.
May produce continuous incontinence (paradoxical
incontinence).
Renal Agenesis
Unilateral increased chance in single umbilical artery.
Bilateral Potters disease.
Non-ascent of Kidney
This is due to fault in the peritoneal fold containing umbilical
arteries.
Horseshoe Kidney
Complications: Urinary stasis leading to infection and
nephrolithiasis.
Diagnosis: Usually radiological, usually calyces of lower
poles are directed towards midline. Rarely all the calyces
are reversed.
On IVU - Ureters have flower vase like curves.
Aberrant Renal Vessels
Most commonly on the left side
Aberrant vessels probably do not cause hydronephrosis,
although a hydronephrotic renal pelvis may bulge
between renal vessels.
Duplication of Renal Pelvis
Most common congenital abnormality of upper renal tract.
Ureterocele
Cause: Cystic dilatation of the intramural part of ureter
due to congenital atresia of the ureteric orifice.
340
Clinical features:
Present from childhood.
Common in women.
May cause hydronephrosis or pyonephrosis.
Diagnosis:
Excretory urography- Adder head appearance.
Cystoscopy- diagnostic.
Treatment: Endoscopic diathermy incision.
Congenital PUJ Obstruction
May be bilateral.
Associated with renal agenesis, most often results from
intrinsic disease.
Often asymptomatic.
Prenatal diagnosis with USG.
Diagnosis - Whittaker test.
Treatment - dismembered pyeloplasty or endoscopic
pyelotomy.
Vesicoureteric Reflux
Risk factors for:
Urinary tract infection most common cause in
neonates.
Acute pyelonephritis.
Reflux nephropathy.
Renal dysplasia.
Incidence:
Most common in newborn females.
3035 percent cases are familial.
Diagnosis:
Radiocontrast MCU most commonly used method.
Isotope radionuclide cystography more sensitive, used
for screening.
Grading:
I to V depending on anatomical change of kidneys
and ureters.
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341
Management:
a. Medical: Continuous antibiotic prophylaxis with
cotrimoxazole (drug of choice) to prevent UTI.
b. Surgery:
Indications
Bilateral III/IV grade reflux in 610 years of age
group.
Bilateral grade V reflux in children over 1 year of
age.
Otherwise antibiotic prophylaxis is indicated.
Reflux Nephropathy
Characterized by renal cortical scarring (in the poles).
Results in hypertension, ESRD in children.
NEOPLASMS OF KIDNEY
Wilms Tumor
Site: Usually unilateral (in one or other pole of one kidney).
Multicentric in origin.
Associated features: Malformations associated with Wilms
tumor are:
1. Aniridia
2. Hemihypertrophy
3. Genitourinary
i. Cryptorchidism
ii. Hypospadias
iii. Gonadal dysgenesis
iv. Pseudohermaphroditism
v. Horseshoe kidney
4. Beckwith-Wiedeman syndrome
5. Drash syndrome gonadal dysgenesis, renal anomalies.
6. WAGR syndrome
Wilms tumor
Aniridia
Ambiguous genitalia
Mental retardation
Chromosomal anomaly:
WT2 gene on 11p15 is associated with BeckwithWiedeman syndrome.
342
Deletion of WT1 gene on 11p13 is associated with

Drashs syndrome and WAGR syndrome.
Clinical features:
Age of onset- during first 4 years of life.
Symptoms- triad of
Painless abdominal mass (earliest symptom).
Fever
Hematuria often with pain not always present.
Denotes extension to renal pelvis and poor prognosis.
Diagnosis:
USG- hypoechoic shadow.
Biopsy nephrogenic rests are precursor of Wilms
tumor. Patients with these may have Wilms tumor
in contralateral kidney.
Metastasis:
Via bloodstream to lungs (most common).
Sarcoma type metastasizes to bones.
Rhabdoid type metastasizes to brain.
Treatment:
Nephrectomy- as early as possibly followed by
radiotherapy with or without chemotherapy.
Chemotherapeutic agent actinomycin D and
vincristine.
Prognosis:
Related to age.
Age <1-year carries 80 percent survival rate.
Neuroblastoma
Note: D/D of abdominal mass
Neonatal period an asymptomatic abdominal mass
is due to multicystic renal dysplasia.
1-3 years Wilms tumor, HUS, RTA.
3-6 years minimal change disease, acute PSGN.
6-14 years acute PSGN, non-minimal nephrotic
syndrome.
Renal Cell Carcinoma (Hypernephroma)
Type: Adenocarcinoma.
Renal System
343
Origin: From renal tubular cells.

Pre-existing adenomas may be present.
1. Smoking
2. Obesity
3. Polycystic kidney (acquired) following chronic dialysis
4. Tuberous sclerosis
5. von-Hipple-Lindau syndrome
6. Exposure to cadmium.
Pathology: Site- usually upper pole of the kidney.
Grossly Cut section is yellowish or dull white with areas
of hemorrhage and necrosis.
Microscopici. Clear cell Ca (most common) defect in chromosome
3 (loss of VHL gene).
Solid areas of polyhedral or cubical clear cells with
deeply stained small rounded nuclei and abundant
cytoplasm and scanty stroma.
ii. Papillary Ca characteristically invades the renal vein.
Associated with trisomy 7 (gain of MET gene).
iii. Chromophobe Ca - Tumor cells are large tan-brown
with prominent nuclei surrounded by halo.
Metastasis:
1. To IVC via renal vein (most common)- pulsatile
metastasis, then to lungs.
2. To bones.
3. To para-aortic lymph nodes.
Clinical features: Sex- male: female= 2:1
Symptoms Painless hematuria (most common)
Rapidly developing varicocele
PUO
Hypertension
Paraneoplastic syndrome
Polycythemia
Hypercalcemia
Other hormones like renin and calcitonin are also
produced.
344
Diagnosis:
MRI is the most sensitive in detecting IVC invasion.
Next sensitive is Doppler ultrasound.
CXR- cannon ball shadow.
Treatment:
Nephrectomy with a transabdominal approach.
Renal collar is put around renal vein to prevent
metastasis.
Adenocarcinoma of kidney does not respond well to
radio/chemotherapy.
Prognosis: Poor prognosis depends on
1. Macroscopic involvement of renal vein,
2. Tumor invasion beyond the capsule,
3. Lymph node involvement,
4. Sarcomatoid type worst type,
5. Pulmonary secondaries worst prognosis.
Tumors of Renal Pelvis
Transitional cell Ca most common type.
Squamous cell (epidermoid) Ca associated with renal
stones.
Benign Tumors of Kidney
Angiomyolipoma associated with tuberous sclerosis.
RENAL INJURIES
Injury to Kidney
Clinical feature:
1. Hematuria the cardnal sign.
2. Meteorism abdominal distension 24-48 hours after
injury due to retroperitoneal hematoma.
Investigation: After initial resuscitation an urgent IVU should
be obtained to assess the damage.
Management:
1. Conservative - > 90 percent cases with fluid
resuscitation, analgesics, antibiotics and daily urine
examination.
2. Surgery indicated in < 10 percent cases with massive
hemorrhage.
Renal System
345
Nephrectomy is done if the kidney is completely

avulsed.
Route of operation transperitoneal.
Complications:
i. Bladder outflow obstruction by clot,
ii. Pararenal pseudohydronephrosis,
iii. Hypertension,
iv. Renal artery aneurysm and subsequent rupture least
chance (occurrence < 1%).
Injury to Bladder and Urethra
Rupture of urethra:
a. Bulbar urethra most common; due to fall astride
on object (like manhole injury).
b. Membranous urethra due to violent injury like pelvic
fracture (road traffic accidents).
Rupture of bladder:
a. Intraperitoneal duet to fall on a full bladder.
b. Extraperitoneal most common; due to pelvic fracture.
Extravasation of urine:
a. Bulbar rupture superficial extravasation. Urine collects
in the scrotum and penis and beneath the deep layer
of superficial fascia (of Scarpa) in the abdominal wall.
b. Membranous urethra and extraperitoneal bladder
rupture deep extravasation. Urine extravasates in the
layers of the pelvic fascia and retroperitoneal tissue.
Note: Membranous urethra is a content of deep perineal
space bounded above and below by superior and inferior
fascia of urogenital diaphragm, respectively.
c. Intraperitoneal bladder rupture urine extravasates into
the peritoneal cavity may cause peritonitis.
Clinical feature:
Triad of signs in rupture of bulbar urethra
Retention of urine, perineal hematoma and bleeding
from urinary meatus.
Investigation:
For intraperitoneal bladder rupture retrograde
cystrography most reliable.
Intravenous urography.
346
Management:
a. Bulbar rupture Analgesics and antibiotics.
If the bladder is full percutaneous suprapubic
catheterization.
Patient should be discouraged to pass urine.
b. Membranous rupture and extraperitoneal bladder
rupture usually associated with serious pelvis fracture.
So initial attention should be given towards that.
A suprapubic catheter may be inserted for shortterm.
c. Intraperitoneal bladder rupture urgent laparotomy
with repair of bladder.
Complication:
i. Urethral stricture most common complication of
urethral rupture.
ii. Peritonitis in intraperitoneal bladder rupture.
MISCELLANEOUS
Radiological Appearance
Rim/crescent sign hydronephrosis.

Flower vase pattern horse shoe kidney.
Cobra (adder) head ureterocele.
Thimble bladder TB bladder.
Spider leg appearance polycystic kidney.
Soap bubble appearance hydronephrosis.
NEUROLOGICAL
DISORDERS
NEUROIMAGING
CT scan:
CT scan is helpful in imaging osseous structures of
the spine, skull base and temporal bones.
CT is more sensitive and specific than MRI in detecting
acute parenchymal and subarachnoid hemorrhage.
MRI:
This utilizes hydrogen ions (protons).
Contrast material most commonly used is gadolinium.
CSF (and other watery media like edema fluid) appears
low (hypointense) on T1 and high (hyperintense) on
T2 weighted MRI.
Contraindications: Pacemaker, metallic foreign body,
hemostatic clips in CNS, clostrophobia, cochlear
implants, prosthetic valves, insulin pump.
Myelography:
Contrast material iodinated compound myodil.
Complication
i. Headache, nausea and vomiting most common.
ii. Postural headache due to CSF leak. This is aggravated
on standing and relieved on lying down.
iii. Allergic reaction most serious complication.
iv. Puncture of the spinal cord.
Angiography: Route through the femoral artery.
Lumbar puncture: Contraindication
i. Increased ICT due to chance of cerebellar or tentorial
herniation.
ii. Brain abscess.
iii. Mass lesion in brain.
CSF albumino-cytological dissociation is seen in
infective polyneuritis (G-B syndrome) and spinal cord
tumors.
Normal CSF pressure in sitting posture is 2-12 mmHg.
348
CONGENITAL ANOMALIES OF CNS

Classification
a. Neural tube defects
1. Anencephaly most common CNS malformation.
2. Encephalocele
3. Spinal anomalies
i. Spina bifida or spinal dysraphism
ii. Meningocele
iii. Meningomyelocele.
iv. Tethered cord
v. Syringomyelia
vi. Diastematomyelia.
b. Disorders of neural migration forebrain abnormalities
1. Lissencephaly
2. Schizencephaly
3. Porencephaly
4. Holoporencephaly
5. Corpus callosum agenesis.
c. Posterior fossa abnormalities
1. Arnold Chiari malformation (Chiari type II).
2. Dandy-Walker malformation.
Anencephaly
This is the most common and most severe CNS
malformation.
Risk
i.
ii.
iii.
factors:
Low socioeconomic status.
Maternal age over 40 years.
Dietary folate deficiency during pregnancy.
Associations:
i. Polyhydramnios.
ii. Increased gestational age.
Complications in pregnancy:
i. Malpresentation face (most common), breech.
ii. Postmaturity.
iii. Shoulder dystocia.
Clinical feature:
Baby dies in utero or soon after birth.
Diminution of size of adrenal glands.
349
Antenatal diagnosis:
i. Amniocentesis at 10-12 weeks, shows increased
alpha fetoprotein and ACE levels in amniotic fluid.
ii. USG at 14-16 weeks, investigation of choice.
Management of pregnancy:
Before 20 weeks termination of pregnancy.
Late presentation induction of labour with PGE2
vaginal gel.
Shoulder dystocia cleidotomy.
Prevention: Folic acid supplementation beginning 1 month
before conception to about 12 weeks of pregnancy.
Spina Bifida
Spina bifida occulta:
Most common type.
Mildest form.
Site most common in lumbosacral spine (S1).
Clinical feature asymptomatic, telltale sign in the
form of a dimple in skin, lipoma, dermal sinus or a
tuft of hair.
Investigation MRI.
Spinal bifida aperta:
Most common site dorso-lumbar spine.
Types myelocele (most common), meningocele,
meningomyelocele, syringomyelocele.
Note: Lacunar skull is associated with meningocele.
Hydrocephalus
CSF production:
Amount 50 ml in infant, 150 ml in adults.
Rate 500 ml/day or 20 ml/hour.
Source choroid plexus mainly in the lateral ventricle
(also third and fourth ventricles).
Pathways
Lateral ventricle
foramina of Monro
Third ventricle
aqueduct of Sylvius
Fourth ventricle
foramina of Luschka and Magendie
Basal cisterns (subarachnoid space)
Absorbed in subarachnoid villi.
350
Hydrocephalus resulting from obstruction in ventricular

system is called obstructive or non-communicating and
from obliteration of subarachnoid cisterns or malformation
of arachnoid villi is called non-obstructive or
communicating hydrocephalus.
Note: CSF pressure is mainly regulated by rate of
absorption.
Etiology:
a. Obstructive Aqueductal stenosis (most common),
Chiari malformation (type II), Dandy-Walker syndrome,
b. Non-obstructive Subarachnoid hemorrhage (most
common) usually as a result of intraventricular
hemorrhage in premature infant.
Meningitis Pneumococcal and tuberculous.
Clinical features:
In infants Head is enlarged most prominent sign,
anterior fontanel wide open and bulging. In late cases
Spasticity, brisk tendon reflexes, Babinski sign.
In older children (whose sutures have closed)
symptoms of increase ICT like headache, vomiting,
etc.
Signs Sunset sign in eyes, cracked-pot or Macewen
sign.
Investigation:
Xray skull beatensilver appearance,
CT scan/MRI and USG.
Treatment:
Conservative Acetazolamide, Furosemide.
Most cases require Ventriculoperitoneal shunt.
Hydrocephalus ex vacuo: Compensatory enlargement of
ventricles and increase in CSF volume secondary to loss
of brain parenchyma. Seen in Alzheimers disease, Picks
disease.
Chiari Malformation
Chiari Type I
Presents during adolescence or adult life and usually not
associated with hydrocephalus. There is protrusion of
cerebellar tonsils through the foramen magnum into the
cervical canal. Most common associated finding is
syringomyelia.
351
Chiari Type II: Arnold Chiari Malformation

Characterized by hydrocephalus and myelomeningocele.
Pathology:
Small posterior fossa, malformed midline cerebellum,
extension of vermis through foramen magnum.
Other changes caudal displacement of brainstem,
tectal beaking, aqueductal stenosis, hydromyelia.
Clinical feature:
Hydrocephalus may develop at anytime in life, with
foreshortened occiput. May present with ataxia,
spasticity, incoordination.
Dandy-Walker Malformation
Consists of cystic dilatation of 4th ventricle and posterior
fossa expansion. (Due to obstruction of foramen of
Lushcka and Magendie).
There may be hypoplasia or aplasia of cerebellar
vermis and corpus callosum.
Clinical feature: Hydrocephalus with prominent occiput
(Bendas sign), cerebellar ataxia.
Syringomyelia
It is a cyst like cavity within the spinal cord (in the central
canal) with progressive destruction of gray and white matter.
It may communicate with CSF pathways (associated with
Chiari type I) or may remain localized and noncommunicating.
Clinical feature:
Most common site involved is cervical spine.
Disruption of lateral spinothalamic tract produces
dissociated sensory loss (loss of pain and temperature
sensation in supex with preservation of touch).
Corticospinal tract and anterior horn cell involvement
leads to muscle wasting of hands, absent deep tendon
reflexes in supex, UMN paralysis of infex.
Investigation:
MRI is the study of choice.
352
Diastematomyelia
It is division of spinal cord into two halves by a
fibrocartilaginous or bony septum. It is a disorder of neural
tube fusion.
Most commonly involves lumbar vertebrae (L1 L3).
There may be associated bony deformities like
hemivertebra, kyphoscoliosis, etc.
Clinical feature: Cutaneous hemangioma (tell tale sign)
over midline skin. Unilateral foot abnormalities TEV,
claw toes, atrophy of gastrocnemius, loss of pain and
temperature.
Forebrain Abnormalities
Lissencephaly or agyria: Decrease in number of gyri
to total absence, leaving a smoothsurfaced brain.
Schizencephaly: Presence of uni / bilateral clefts within
cerebral hemisphere.
Porencephaly: Presence of cysts or cavities within the
brain. It is seen in vascular malformation. Leads to
cerebral infarction.
Holoporencephaly: Incomplete separation of cerebral
hemisphere across the midline.
Agenesis of corpus callosum: Radiology shows
misshapen lateral ventricles (bat-wing deformity).
Cranio-facial Malformations
Treacher-Collins Syndrome
Autosomal dominant.
Features:
Hypoplasia of malar bones.
Anti-mongoloid (downward) slant of palpebral fissure.
Colobomas in outer third of lower eyelid.
Blind fistula between angle of mouth and ear.
Deafness.
Dental malocclusion, high arched / cleft palate.
Craniosynostosis
Premature closure of cranial sutures.
Normally, metopic suture (between two frontal bones)
closes before 2 years of age and coronal, sagittal and
lambdoid sutures close after age 13 years.
353
Name
Premature closure of
Scaphocephaly (most common)

or dolicocephaly (long head)
Brachycephaly
Trigonocephaly
Sagittal suture
Coronal suture
Metopic suture
Associations
Crouzon syndrome: AD. Brachycephaly, ocular proptosis,
hypoplasia of maxilla and orbital hypertelorism.
Apert syndrome: Above plus syndactyly and high arched
palate.
Carpentar syndrome: AR. Kleeblattschadel skull deformity,
soft-tissue syndactyly of hand and feet, mental retardation.
HEADACHE
Migraine
Clinical feature: Headache is characterized by pulsating
headache usually restricted to one hemisphere
(frontotemporal), lasts for 4-48 hours and often associated
with nausea (most commonly), vomiting, visual
disturbances (scintillating scotoma, photopsia, fortification
spectrum, visual hallucinations), paresthesia, seizures,
vertigo, etc.
Headache starts after awakening, and quelled by sleep.
Incidence:
Occurs in all ages, but more common in children and
young adults.
Types:
Migraine with aura classical type. Symptoms are
better with increasing age.
Migraine without aura common type.
Theories:
Vascular theory headache is due to extracranial
vasodilatation.
Neurogenic theory.
Treatment:
Severe migraine ergot alkaloids/sumatriptan (drug of
choice) + antiemetics. Early treatment aborts an attack.
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Prophylaxis propanolol, amitriptyline, flunarizine,

methysergide/cyproheptadine.
Note: Triptans are selective serotonin activators and act
on serotonin receptor 5HT IB/ID.
Ophthalmoplegic Migraine
Headache followed by partial paralysis of the III cranial
nerve on the same side (most common nerve involvement
in migraine).
Cluster Headache
Clinical feature:
Peak age 30-50 years, with male preponderance.
Headache periodic, nocturnal, periorbital or temporal
in location, strictly unilateral.
Headache is provoked by alcohol ingestion.
Associated with ipsilateral lacrimation, reddening of
the eyes, nasal stuffiness and nausea.
Treatment For chronic disorder lithium (drug of choice
for prevention).
EPILEPSY
Neonatal Seizure
Etiology:
1. Perinatal anoxia most common cause.
2. Intracranial birth injuries.
3. Intraventricular and subarachnoid hemorrhage.
4. Metabolic hypoglycemia, hypocalcemia.
5. Others homocystinuria, phenylketonuria.
Type: Subtle seizures are most common.
Prognosis:
Poor prognosis birth injury and anoxia.
Best prognosis hypocalcemic seizure.
Treatment:
IV phenobarbitone is the drug of choice.
Preventive in intraventricular hemorrhage
phenobarbitone, vitamin K.
Febrile Convulsion
Most common cause of seizure in early childhood (6
months to 5 years).
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Characteristics:
Convulsions occur during fever (within 24 hours of onset
of fever).
This is not related to the height of temperature, but
usually seen when temperature rises above 38oC.
Frequently seen if temperature rises abruptly.
Recurrent in nature in 30-40 percent cases.
Does not last for > 10 minutes.
Generalized convulsion.
No post-ictal neurological deficit.
EEG done a few days after the seizure is normal.
Family history among siblings may be present.
Treatment:
Acute attack antipyretics (aspirin not given), IV
diazepam/phenobarbitone.
Intermittent prophylaxis antipyretics and diazepam.
Continuous prophylaxis sodium valproate/
phenobarbitone.
Prognosis:
Prognosis is good. Only 1-5 percent cases progress to
epilepsy.
Breath Holding Spells
This occurs between 6 months and 5 years of age.
Clinical feature: Breath is held in expiration for few seconds.
Child becomes cyanosed and limp. If persists for 10-15
seconds, convulsions may occur.
Treatment:
The attack could be aborted by strong stimulus like
pinch at the beginning of the spell.
Iron supplementation.
Atropine sometimes used.
Antiepileptics are not used.
Kindness and understanding attitude towards the infant.
Overanxiety of the parents is harmful.
GENERALIZED SEIZURES
Generalized Tonic-clonic Seizure
Most common type. GTC seizures tend not to occur in
the first month of life.
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Phases:
1. Aura
2. Tonic phase
3. Clonic phase
4. Postictal phase.
Investigation: EEG when abnormal, it is diagnostic of
epilepsy.
Treatment:
First year of life phenobarbitone is the drug of choice.
Beyond first year phenytoin or valproic acid.
Status Epilepticus
Treatment:
IV lorazepam (drug of choice)/diazepam,
Phenobarbitone/phenytoin/paraldehyde.
Generalized Absence Seizure (Petit-mal)
Characteristic:
Common between ages 4-5 years.
Abrupt onset of unawareness or loss of consciousness
usually for short duration.
No aura, no post-ictal confusion.
No loss of motor functions hence called absence
seizure.
Hyperventilation often precipitates an attack.
EEG: Shows characteristic 3 per second spike and slowwave pattern.
Treatment:
Ethosuximide drug of choice.
Others valproate, clonazepam.
Myoclonic Seizure
Sudden shock-like momentary contraction of muscles of
a limb or the whole body.
Juvenile Myoclonic Seizures (Janz Syndrome)
Clinical feature:
Myoclonic jerks on awakening in the morning. Some
patients can present with GTC seizures. About onethird patients present with absence seizures.
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Salaam seizures sudden flexion of body at waist.

EEG: 4-6 Hz irregular spike.
Treatment: Valproate for whole life.
Infantile Spasms (West Syndrome)
EEG: Hypsarrhythmic pattern.
Treatment:
Corticosteroids or ACTH given for 8-12 weeks in
gradually decreasing doses drug of choice.
Sodium valproate, clonazepam.
PARTIAL SEIZURES
Simple Partial Seizure
Convulsion limited to localized group of muscles, without
loss of consciousness.
Complex Partial Seizure (Temporal Lobe
Epilepsy)
Bizarre or confused behavior and purposeless movements,
emotional changes lasting for 1-2 minutes along with
impairment of consciousness. An aura often precedes. The
seizure focus is located in the temporal lobe.
Treatment: Carbamazepine is the drug of choice.
Mesial Temporal Lobe Epilepsy
Positive family history.

Aura common.
Temporal spikes on EEG.
Small hippocampus with increased signal on T2
weighted MRI.
Surgery extremely helpful.
Note: Drugs of choice in epilepsy
GTC valproate/phenytoin.
Partial seizure carbamazepine.
Absence seizure ethosuximide.
Atonic seizure valproate.
Myoclonic seizure valproate.
Status epilepticus IV lorazepam.
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CEREBROVASCULAR DISEASES
Classification
a. Cerebral ischemia-infarction:
i. Atherosclerosis with thromboembolism most
common cause.
ii. Embolic obstruction (cardiogenic) most commonly
non-rheumatic atrial fibrillation.
b. Intracranial hemorrhage:
i. Intracerebral hemorrhage most common type.
Hypertension is the most common cause.
ii. Subarachnoid hemorrhage most common cause
is trauma, next is rupture of sacular aneurysm.
iii. Subdural and epidural hemorrhage traumatic.
Cerebral Ischemia Infarction
Major cause of cerebral ischemia infarction is atherosclerosis
which commonly affects the origin of the internal carotid
artery in the neck and the origins of the major and minor
arterial branches inside the head.
Clinical feature:
Transient ischemic attack (TIA) is a feature of ischemic
stroke. So, history of TIA excludes the possibility of
hemorrhage.
Clinical feature depends upon the level of obstruction
by the atherosclerotic plaque.
Levels and symptoms of obstruction
Internal carotid artery
Hemiplegia with decreased vision in

contralateral side.
Middle cerebral artery

Entire MCA
Contralateral hemiplegia, hemianaesthesia, homonymous hemianopia, global
aphasia (if involves the dominant
hemisphere).
Superior division of MCA Sensory weakness, motor weakness,
motor aphasia (dominant hemisphere)
Inferior division of MCA Wernickes aphasia.
Anterior cerebral artery
Proximal ACA (A1)
No symptoms due to rich collaterals.
Post-communal (A2)
Contralateral motor and sensory loss
branch
over foot and leg, abulia, bilateral
pyramidal signs with paresis, urinary
incontinence if both A2 branches are
blocked.
(Contd...)
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(Contd...)
Penetrating branch
(Heubners artery)
Frontal ataxia (contralateral),

apraxia, ideomotor dyspraxia.
Posterior cerebral artery

Peripheral territory
Bilateral homonymous hemianopia with
cortical blindness (with macular sparing
due to collaterals from MCA); memory
defect due to hippocampal lesion
Central territory
Thalamic syndrome sensory loss,
spontaneous pain (hyperpathia).
Webers syndrome lesion in mid-brain
produces third nerve palsy with
contralateral hemiplegia.
Antero-inferior cereContralateral spinothalamic tract is
bellar artery
affected causing loss of pain and
temperature sensation over the opposite
half of the body.
Vertebro-basilar artery Midbrain Webers syndrome (see
above)
Claudes syndrome crossed cerebellar
ataxia.
Pons Millard Gublar syndrome
ipsilateral VII nerve palsy with
contralateral hemiplegia.
Medullary Syndromes
Medial Medullary Syndrome
Etiology: Occlusion of vertebral or lower basilar artery.
Features: Ipsilateral 12th nerve involvement paralysis
and atrophy of half of the tongue.
Contralateral
Pyramidal tract involvement paralysis of arm and
leg sparing the face.
Medial lemniscus involvement impaired tactile and
propioceptive senses.
Lateral Medullary Syndrome
(Wallenbergs Syndrome)
Etiology: Block of vertebral, postero-inferior cerebellar artery
and superior, middle or inferior branches of medullary
arteries.
Features: Ipsilateral
5th nerve involvement pain, numbness and sensory
loss over half of the face.
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Vestibular nucleus involvement nystagmus, diplopia.

Sympathetic tract involvement Horners syndrome.
9th and 10th nerves involvement dysphagia,
hoarseness of voice, palatal paralysis.
Cerebellar tracts ataxia.
Contralateral Spinothalamic tract involvement loss of
pain and temperature sensation.
Intracerebral Hemorrhage
This is the most common type of intracranial
hemorrhage.
Most common cause is hypertension. This is most
commonly due to rupture of lenticulostriate branch of
MCA.
Most common sites are putamen of basal ganglia,
thalamus.
Clinical feature:
Putamen eyes deviated to healthy side.
Thalamus eyes deviated downwards with pupil 23 mm dilated and minimally reactive.
Pons pin-point pupil (1 mm) reactive to light, loss
of consciousness, hyperpyrexia.
Cerebellum eyes deviated laterally.
Investigation:
CT scan can detect hemorrhage 1 cm in diameter.
MRI more sensitive for posterior fossa lesions.
Lumbar puncture contraindicated.
Management:
Surgical drainage for hematomas more than 3 cm in
size.
Mannitol to decrease ICT.
Prognosis:
Depends on the size and location of hemorrhage.
Subarachnoid Hemorrhage
Subarachnoid space: Ends at S2 and contains CSF.
Etiology:
Most common cause of subarachnoid hemorrhage is
trauma.
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Most common cause of spontaneous hemorrhage is

the rupture of sacular aneurysm.
Site:
i. Junction of the anterior communicating and anterior
cerebral arteries most common site.
ii. Junction of the posterior communicating and internal
carotid artery.
iii. Bifurcation of the MCA.
iv. Vertebral artery least common site.
Clinical feature:
Sudden, severe headache in the absence of focal
neurological symptoms.
3rd and 6th nerve palsies (intracranial aneurysms most
commonly compress the 3rd nerve).
Delayed neurological deficits
Cause rerupture, hydrocephalus, vasospasm (most
common cause), hyponatremia.
Diagnosis:
Lumbar puncture: Hallmark of aneurysmal rupture is blood
in the CSF.
CT scan: Investigation of choice. If done within 72 hours,
sensitivity is 80 percent.
Cerebral angiography: Best to determine the cause of
hemorrhage.
AV Malformation
They are hamartomas most common vascular
malformation of nervous system.
Presentation intracerebral (subarachnoid) hemorrhage
with headache.
Investigation: MRI.
Treatment:
Surgery (stereotactic radiosurgery).
Embolotherapy using heat contrast.
PRIMARY DEMENTIAS
Alzheimers Disease
Most common cause of dementia in people over 65 years
of age.
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Risk
i.
ii.
iii.
iv.
v.
vi.
factors:
Age over 65 years
Female sex
Head trauma
Lower educational attainment
Downs syndrome
Family history of dementia.
Pathology: Pathological hallmarks in Alzheimers disease

are
i. Neurofibrillary tangles.
ii. Senile plaques.
iii. A amyloid deposition.
iv. Biondi ring tangles in choroid plexus (also seen in
elderly).
Most common sites for pathological changes are
hippocampus (degeneration), temporal lobes and nucleus
basalis of Meynert.
Clinical feature:
Progressive dementia without neurological sign.
Released reflexes in dementia due to frontal lobe
pathology. They are grasp reflex, palmo-mental reflex
and glabellar tap reflex.
Biochemistry:
There is decrease in acetylcholine concentration in brain.
Choline acetyltransferase (CAT) and nicotinic
cholinergic receptors are also reduced.
CT scan of brain:
Shows diffuse atrophy of cerebral cortex with
enlargement of ventricles.
Treatment:
Anticholinesterases tacrine, rivastigmine, donepezil
and galantamine.
Normal Pressure Hydrocephalus
This
i.
ii.
iii.
is characterized by the triad of:

Dementia,
Abnormal gait (ataxia or apraxia),
Urinary incontinence.
Investigation
MRI shows enlarged lateral ventricles (hydrocephalus)
with little or no cortical atrophy.
CSF pressure high normal.
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Huntingtons Disease
Genetics: Autosomal dominant. Disorder of trinucleotide
repeat sequence.
Clinical feature:
Chorea, behavioral abnormalities and dementia.
Memory is frequently not impaired until late in the
disease.
Adult HD onset in 4th/5th decade. Duration is
typically 15 years.
Juvenile HD onset before 20 years of age. Associated
with rigidity, ataxia and cognitive decline. More rapid
disease progression.
Pathology:
Most commonly affects the striatum.
There is atrophy of the caudate nucleus.
Biochemically, there is loss of intrastriatal GABA-ergic
and cholinergic pathways.
Progressive Supranuclear Palsy (SteeleRichardson-Olszewski Syndrome)
This is characterized by
Vertical supranuclear gaze palsy (difficulty with down
gaze),
Axial rigidity frequent falls,
Subcortical dementia,
Convulsions.
Picks Disease
Reveals characteristic inclusions known as Picks bodies
composed of Tau protein.
Note: Lewy bodies contain synuclein.
EXTRAPYRAMIDAL DISORDERS
Parkinsons Disease
Pathology:
Degeneration of the nigrostriatal dopeminergic system.
Eosinophilic intranuclear inclusion granules called the
Lewy bodies are present in the basal ganglia.
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Clinical feature:
Tremor at rest 4-6 Hz in frequency, decrease on
movement.
Rigidity (lead pipe or cog wheel).
Bradykinesia or akinesia.
Mask like facies.
Festinant gait.
Others micrographia, flexed attitude of the body,
slurred speech, normal intelligence.
Plantar response flexion.
Shy-Drager Syndrome
Parkinsonism, impaired autonomic function (postural
hypotension, sweating, abnormal bowel and bladder
control, impotence and gastroparesis) and widespread
neurological involvement (pyramidal, cerebellar or lower
motor neuron).
Treatment:
1. Anticholinergics trihexyphenidyl (Benzhexol),
benztropine, procyclidine and orphenadrine.
2. Dopamine facilitator amantadine.
3. Dopamine precursor levodopa.
4. Dopamine agonist bromocriptine.
5. Neuroprotective to prevent neuronal degeneration,
MAO-B inhibitor selegiline and vitamin E (tocopherol).
Drug Induced Parkinsonism
Cause:
1. Antipsychotics phenothiazines (maximum with
trifluoperazine and haloperidol, least with thioridazone).
2. Metoclopramide.
3. Reserpine.
Rabbit syndrome or perioral tremors late onset (years
after) drug induced EPS.
Treatment:
i. Discontinution of the offending drug.
ii. Anticholinergics trihexyphenidyl.
iii. Levodopa is not used.
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ATAXIAS
Classification:
Autosomal dominant spinocerebellar ataxia.
Autosomal recessive Friedriechs ataxia,
telangiectasia, Cockayne syndrome, xeroderma
pigmentosa.
Infective chickenpox.
Friedreichs Ataxia
Cause:
Inherited disorder (autosomal recessive).
Associated with vitamin E deficiency.
Pathology: This involves the pyramidal tract, dorsal column
and spinocerebellar tracts.
Clinical feature: Symptoms
Progressive staggering gait (lower limbs are commonly
affected), frequent falling, dysarthria, sensory loss.
Signs
Extensor plantar response with absent deep tendon
reflexes.
Cardiomegaly
Increased incidence of diabetes, skeletal abnormalities,
optic atrophy.
MOTOR NEURON DISEASES
Classification:
UMN primary lateral sclerosis.
LMN progressive muscular atrophy or progressive
bulbar palsy.
UMN + LMN amyotrophic lateral sclerosis.
Amyotrophic Lateral Sclerosis
(Lou Gehrig Disease)
It is a degenerative disorder involving the upper motor
neurons (UMN) and lower motor neurons (LMN).
Note: UMN includes the anterior horn cells in spinal cord
and LMN includes the corticospinal tract.
Feature:
Progressive muscle weakness, atrophy (amyotrophy)
and spasticity. Earlier asymmetric weakness, gradually
progresses to symmetrical involvement.
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Sensory, bowel and bladder and cognitive functions

are preserved.
Extraocular muscles are not involved.
Reflexes hyperactive (UMN) or hypoactive (LMN).
Fasciculation is characteristic of MND.
Spinal Mascular Atrophy
Genetically linked.
Infantile SMA most rapidly fatal.
CRANIAL NERVES
Trigeminal (5th Nerve) Palsy
Features:
i. Loss of corneal reflexes.
ii. Loss of sensation of face.
iii. Deviation of jaw on opening of mouth to the affected
side.
iv. Bilateral UMN lesion above pons causes exaggerated
jaw jerk.
Trigeminal Neuralgia (Tic Doulourux)
Characterized by excruciating paroxysms of pain in
the lips, gums, cheek or chin.
Initiation of pain by stimulation of certain areas of
face (trigger zone).
Treatment: Carbamazepine is the drug of choice.
Facial Nerve Palsy
Important causes of facial nerve palsy
a. Central pontine gliomas, polio, multiple sclerosis.
b. Intracranial (CP angle) acoustic neuroma,
meningioma.
c. Intratemporal
i. Idiopathic Bells palsy (most common cause),
Melkerssons syndrome.
ii. Infections
iii. Trauma
Note: Facial nerve palsy in temporal bone fracture is most
common with transverse fractures.
iv. Mastoidectomy
v. Malignancy glomus jugulare tumor
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d. Extracranial parotid gland surgery.

e. Systemic causes diabetes, hypothyroidism, uremia,
PAN, Wegeners granulomatosis, sarcoidosis.
Features:
UMN palsy produces contralateral involvement of lower
face (upper face escapes because of bilateral
innervation).
LMN palsy produces ipsilateral involvement of both
upper and lower face.
Complete paralysis causes:
1. Deviation of corners of mouth to the opposite side.
2. Loss of wrinkling on forehead.
3. Eyelids are difficult to close on forced closure of the
lids, the eye on the paralyzed side is seen to roll upwards
(Bells phenomenon).
4. Drooling of saliva from the angle of mouth.
In case of incomplete recovery: Attempts to move one
group of facial muscles result in contraction of all the muscle
groups synkinesis or associated movement.
Anomalous regeneration causes:
Tearing while eating food (crocodile tear).
Jaw opening causes closure of the eyelids on the side
of palsy (jaw-winking).
Other effects of facial nerve palsy:
At the lateral geniculate body loss of lacrimation.
At sternomastoid canal loss of ipsilateral corneal
reflex.
Bells Palsy
It is idiopathic LMN type of facial nerve palsy.
Ramsay Hunt Syndrome
Unilateral facial nerve palsy.
Bilateral Facial Nerve Palsy
G-B syndrome or infective polyneuritis.
Heerfordt syndrome a variant of sarcoidosis. Also
known as uveoparotid fever.
Melkersson-Rosenthal syndrome
Characterized by the triad of recurrent facial nerve palsy,
facial (particularly labial) edema, plication of the
tongue.
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Oculomotor (3rd Nerve) Palsy

Features:
i. Severe ptosis
ii. Dilated pupil
iii. Divergent squint
iv. Crossed diplopia
Note:
3rd nerve palsy with crossed hemiplegia Webers
syndrome.
Isolated 3rd nerve palsy occurs in diabetes.
SPINAL CORD
Hemisection (Brown-Sequard Syndrome)
Characterized by:
Ipsilateral weakness (pyramidal tract involvement), loss
of joint position and vibration senses (lemniscal system
involvement).
Contralateral loss of pain and deep temperature senses
(spinothalamic tract involvement).
Complete Transection (Spinal Shock)
Stages:
1. Stage of spinal shock all reflexes are decreased, lasts
for a minimum of two weeks.
2. Return of reflexes with hyperactivity first reflex to
return is a slight contraction of the leg flexors and
adductors in response to noxious stimulus.
Complication:
i. Negative nitrogen balance.
ii. Decubitus ulcer.
iii. Hypercalcemia and hypercalciuria predispose to
renal stone formation.
iv. UTI most common complication.
Treatment:
i. Acute administration of high dose of glucocorticoids
as early as possible.
ii. Neurotrophins.
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Spinal Cord Compression

Epidural Masses
1. Metastasis from the breast (most common), lungs,
prostate, kidneys, lymphoma and plasma cell dyscrasias
(multiple myeloma).
2. Thoracic cord is most commonly involved.
3. Prostate and ovarian carcinomas involve the sacral
and lumbar vertebrae due to spread through Bartons
plexus of veins in the epidural space.
4. Investigation of choice MRI.
Epidural Abscess
Causative organism: Most commonly due to
Clinical feature: Triad of pain, fever and rapidly progressive
weakness.
Risk factors:
i. Impaired immune status (diabetes mellitus, renal
failure, alcoholism, malignancy).
ii. IV drug abuse.
iii. Infections of the skin and other tissues
hematogenous spread (most common route).
Intradural Masses
1. Meningioma.
2. Neurofibromas most common.
Intramedullary Masses
Ependymoma.
Spinal Cord Trauma
Causes:
1. Atlantoaxial dislocation is seen in
i. Rheumatoid arthritis
ii. Hydrocephalus
iii. Retropharyngeal abscess
iv. Downs syndrome
2. Jeffersons fracture is a ring fracture of atlas.
370
3. Hangmans fracture is a fracture through the pedicle

of C2.
4. Teardrop fracture is crushing of vertebral body.
Diagnosis: Investigation of choice for traumatic paralysis
is MRI.
Spinal Cord Infarction
Blockade of anterior spinal artery causes paraplegia or
quadriplegia and dissociated sensory loss affecting pain
and temperature sensations but sparing vibration and
position senses.
Transverse Myelitis
Initial symptom is focal neck or back pain.
Most commonly involves the thoracic and lumbar
vertebrae.
Often begins during recovery from a viral infection.
Clinical feature: Paresthesia, sensory loss, motor weakness,
sphincter disturbance.
Treatment:
Steroids.
CHRONIC MYELOPATHIES
Syringomyelia
Clinical feature:
Dissociated sensory loss loss of only pain and
temperature sensations with sparing of vibration and
position senses.
Areflexic weakness in the upper limbs.
Balaclava helmet type of sensory loss over face.
Chiari Malformations and
Dandy-Walker Syndrome
Please see the chapter of Congenital CNS Anomalies.
Subacute Combined Degeneration
Etiology: Vitamin B12 deficiency.
Pathology: Involvement of the pyramidal tract and the
posterior and lateral tracts.
371
Clinical feature:
Paresthesia in the hands and feet.
Early loss of vibration and position senses.
Progressive spastic and ataxic weakness.
Corticospinal tract involvement causes increased
tendon reflexes, clonus, extensor plantar response.
Note: Neurological symptoms may occur in the absence
of anemia.
Diagnosis: Schilling test.
Treatment: Vitamin B 12 for life. Folate may cause
deterioration of symptoms.
Tabes Dorsalis
Pathology
Involvement of dorsal column loss of position and
vibration senses.
Dorsal root ganglia and nerve roots.
Clinical feature:
Fleeting and repetitive, lancinating pain, occur mostly
in the legs.
Bladder disturbance.
Cardinal signs impaired position and vibration senses,
loss of reflexes in the legs, Rombergs sign, bilateral
Argyll Robertson pupil, ataxia (due to loss of position
sense), ptosis, miosis, flexor plantar response.
Note: Frenkels exercise is done in tabes dorsalis.
TRAUMATIC INJURY
Acute Subdural Hemorrhage
This is hemorrhage beneath the dura (between dura
and arachnoid matter).
Subdural hemorrhage is the most common type of
traumatic hemorrhage in brain.
Cause:
Contusions of head most common cause.
Acceleration forces such as whiplash injury.
Most commonly due to disruption of the bridging veins.
Clinical feature:
Most patients are comatosed from the onset (though
a lucid interval is found in 1/3 cases).
Unilateral headache.
Dilated pupil on the side of injury.
372
Diagnosis: CT scan shows crescentic (concavo-convex)

hyperdense lesion located mainly in the frontotemporal
region.
Management: In acutely deteriorating patients with impaired
alertness and pupillary dilatation burr holes or emergency
craniotomy may be performed even before obtaining a
CT scan.
Acute Epidural (Extradural) Hemorrhage
This is hemorrhage between the dura and the skull.
Etiology:
Most commonly associated with fracture of the
squamous portion of the temporal bone.
Most commonly due to middle meningeal artery
rupture.
Clinical feature:
Characterized by a lucid interval before the onset of
coma.
Pupils dilated.
CT scan: Shows lenticular (biconvex) hyperdense lesion.
Treatment: Require urgent evacuation by burr hole.
Chronic Subdural Hemorrhage
Clinical feature:
Symptoms appear after a period of weeks, or even
months, following a trivial injury.
Symptoms headache which is fluctuating and often
positional; confusion, personality changes, seizures.
CT scan shows hypodense lesion.
Note: Acute bleeding appears hyperdense in CT scan,
whereas old bleeding appears hypodense.
Most common type of hemorrhage in boxers ear bleed.
Glasgow Coma Scale
Eye opening
Motor response
Verbal response
Spontaneous4
To loud voice3
To pain2
Nil1
Obeys command6
Localizes pain5
Withdraws limbs4
Abnormal flexion3
Extension2
Nil1
Oriented5
Confused4
Inappropriate word3
Incomprehensible
sounds2
Nil-1
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Note:
Maximum Glasgow score = 15 and minimum score
= 3.
Score of 3-4 85 percent chance of dying.
Score > 11 85 percent chance of surviving.
BRAIN TUMORS
Primary Brain Tumors
Most common solid tumor in children.
In children mostly infratentorial.
In adults mostly supratentorial.
Gliomas
Astrocytoma: Tumors arising from astrocytes are the most
common intracranial neoplasm.
Classification:
a. High grade (infiltrating) fibrillary astrocytoma
Grade I includes juvenile pilocytic astrocytoma
excellent prognosis after surgical excision.
Grade II astrocytoma (well differentiated).
Grade III anaplastic astrocytoma (moderately
differentiated).
Grade IV glioblastoma multiforme most aggressive,
worst prognosis.
b. Low grade astrocytoma.
Low-grade astrocytoma
More common in children, benign in nature.
Pilocytic astrocytoma
Arises from the cerebellum.
Shows characteristic spindle-shaped cells.
Management :
1. Surgical excision in symptomatic children.
2. Radiotherapy usually reserved for tumor recurrence.
3. In undissectable tumor partial excision or biopsy with
external beam irradiation.
Prognosis: Excellent (best prognosis in children).
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High-grade astrocytoma
Features of aggressiveness:
i. Hypercellularity
ii. Miotic activity correlation with clinical course.
iii. Cellular atypia
iv. Endothelial
Most common predictors of
proliferation
aggressiveness
v. Necrosis
Common in adults, supratentorial.
Metastasis via CSF to spine.
Management:
Steroids, surgery, post-op radiation, chemotherapy
(nitrosoureas).
Prognosis usually fatal.
Oligodendrogliomas
Benign, supratentorial, occurs in adults.
Pathology:
Usually show a mixture of astrocytes and
oligodendrocytes.
70-90% are calcified. Some show satellitosis.
Management: Surgery.
Prognosis: Good.
Ependymomas
Site:
In children, they occur within the ventricles, most
commonly the 4th ventricle causing increased ICT and
hydrocephalus.
In adults, they are located mainly in spinal canal,
usually the lumbosacral region.
Metastasis: Via CSF (brain tumor metastases that spread
to the spinal cord by this means are called drop
metastases).
Management: Total surgical excision.
Prognosis: Excellent.
Medulloblastoma
This is the most common malignant brain tumor in children.
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Origin: From the primitive neuroepithelial cells (others such

tumors are neuroblastoma, Ewings sarcoma).
Site: Most common in the midline posterior fossa
(cerebellum).
Pathology: Homer Wright rosettes.
Metastasis: It is the most common tumor to metastasize
through CSF. Metastasis outside the CNS occurs.
Clinical feature: Obstruction of fourth ventricle may produce
hydrocephalus, gait abnormalities.
Treatment:
Surgical excision.
Radiation in children less than 3 years.
Primary CNS Lymphoma
They are most common in immunocompromised patients.
But incidences among immunocompetent and
immunocompromised patients are equally increasing.
Nature:
B-cell origin (like non-Hodgkins lymphoma).
Intermediate to high grade.
Multicentric in origin.
Characteristically shows angiocentric growth.
Etiology: Most commonly associated with E-B virus.
Treatment: Radiotherapy is the mainstay of treatment.
Prognosis: Poor.
Meningiomas
They are derived from the cells of arachnoid
granulations (arachnoid cap cells).
They are associated with the loss of NF2 tumor
suppressor gene due to deletion of chromosome 22.
Histology: Psammoma bodies (also seen in ovarian
cystadenoma and papillary ca of thyroid).
Nature: Benign.
Management: Surgery.
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Schwannomas
Origin:
They arise from the schwann cells of nerve roots most
commonly the 8th cranial nerve (acoustic
schwannoma).
May arise from any cranial nerve except olfactory and
optic nerves.
Association: Neurofibromatosis type II strongly predisposes
to acoustic neuroma.
Treatment: Surgery.
Craniopharyngioma
Origin: From the remnants of Rathkes pouch.
Site: Supra-sellar.
Clinical feature:
1. Growth failure in children.
2. Endocrine abnormalities such as diabetes insipidus and
delayed puberty in adults.
3. Bitemporal homonymous hemianopia in either age
groups; sea-saw nystagmus.
4. Increased ICT headache, vomiting, papilledema
most common in young adults.
X-ray: 80 percent tumors show suprasellar calcification.
Treatment: Trans-sphenoidal resection + postoperative
radiotherapy.
BRAIN TUMORS AT A GLANCE
1. Astrocytomas are the most common brain tumors.
2. Medulloblastomas are the most common malignant
brain tumors in children.
3. Astrocytomas (gliomas) are the most common
4. Medulloblastomas are the most common midline
cerebellar tumors.
5. CSF metastases are seen in high-grade astrocytoma,
ependymoma, medulloblastoma (most common).
6. All tumors are treated by surgery except primary CNS
lymphoma where radiotherapy is the treatment of
choice (also unresectable low-grade astrocytoma).
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7. Medulloblastomas are the most radiosensitive tumors.

8. Intracranial calcification is seen in craniopharyngioma (most common), oligodendrogliomas.
9. Investigation for brain tumors:
Contrast enhanced CT scan.
MRI scan with gadolinium contrast.
Lumbar puncture is contraindicated as it may
produce brain herniation in patients with mass
lesions.
10. Most common supratentorial tumor in children is
craniopharyngioma.
11. Most tumors in children are infratentorial.
Metastatic Tumors of Brain
Route: Hematogenous.
Source:
i. Leukemias and lymphomas most common source.
ii. Lungs most common solid tumor.
iii. Breast
iv. Melanoma
v. GI tract.
Clinical feature: Focal neurological deficits most common
sign.
NEUROCUTANEOUS SYNDROMES
Neurofibromatosis Type 1 (von Recklinghausens Disease)
This is characterized by:
1. Neurofibromas (2 or more) these are benign tumors
of peripheral nerve or 1 plexiform neurofibroma
pathognomonic for NF1.
2. Caf au lait spots at least 6 spots measuring > 1.5
cm in diameter.
3. Lisch nodules (2 or more) hamartomas of the iris,
causes no clinical problem.
Others: Hydrocephalus, pseudoarthrosis, dysplasia of the
greater sphenoid wing, scoliosis, and limb hypertrophy
(elephant man).
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Genetics:
Autosomal dominant.
Mutation of NF1 tumor suppressor gene on
chromosome 17 that codes for neurofibromin.
Prognosis:
Increase risk of developing nervous system neoplasms
including plexiform neurofibromas, optic gliomas (most
common), pheochromocytoma, ependymoma,
meningiomas and astrocytomas.
May undergo sarcomatous changes in 5-10 percent
cases (fibrosarcoma).
Note: Plexiform neurofibromatosis (elephant man) involves
most commonly the orbital division of the 5th cranial nerve.
Neurofibromatosis Type 2
Characterized by bilateral acoustic schwannomas and
increased risk of meningiomas, ependymomas and
schwannomas of other cranial and spinal nerves.
Genetics:
Autosomal dominant.
Deletion of chromosome 22q is noted in 90 percent
cases. It encodes for merlin.
Difference between neurofibromas and schwannomas
Origin
Capsule
Cleavage plane
Neurofibroma
Schwannoma
Schwann cells and

fibroblasts
Not encapsulated
None nerve always
removed with tumor
Schwann cells
Encapsulated
Cleavage plane between
tumor and nervetumor
can be excised without
involving the nerve.
Tuberous Sclerosis (Bourneville Disease)

Autosomal dominant and spontaneous mutation of
chromosome 9, 11.
Characterized by:
1. Cutaneous lesions including
i. Adenoma sebaceum (facial angiofibromas),
ii. Ash-leaf shaped hypopigmented spots (best seen under
UV light with Woods lamp),
iii. Shagreen patches,
iv. Depigmented nevi.
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2. Seizures.
3. Mental retardation.
Note: Also called EPILOIA for epilepsy, low IQ and
adenoma sebaceum.
Others: Intracranial hamartomas (cortical tubers and
subependymal nodules, subependymal astrocytoma most
commonly at foramen of munro, rhabdomyomas of
myocardium, angiomyolipomas of kidney.
von Hippel-Lindau Syndrome
1. Retinal angiomas (hemangioblastoma).
2. Cerebellar hemangioblastomas may produce
increased erythropoietin leading to polycythemia.
3. Others renal cell carcinoma, pheochromocytoma and
cysts of the kidneys, pancreas, epididymis and liver.
INTRACRANIAL INFECTIONS
Acute Bacterial Meningitis
Etiology:
a. First 2 months of life
i. Group B and D streptococci (streptococcus agalactiae
most common cause).
ii. E. coli
iii. Listeria monocytogenes
b. 2 months to 12 years
i. Streptococcus pneumoniae most common cause
ii. N. meningitides
iii. H. influenzae type b
c. 12 years to 20 years N. meningitides
d. Above 20 years Streptococcus pneumoniae.
Others
Fungal Cryptococcus, candida, coccidioides, sporothrix
Note: Cause of recurrent meningitis CSOM.
Complications:
i. SIADH hyponatremia
ii. Mental retardation
iii. Hydrocephalus
iv. Brain abscess.
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H. Influenzae Meningitis
Complication:
i. Subdural effusion
ii. Residual auditory deficit auditory evaluation (BERA)
should be done before discharge.
Treatment:
Ampicillin is the drug of choice for susceptible isolates.
Third generation cephalosporins for beta lactamase
producing strains.
CSF study: See below.
Tubercular Meningitis
Involves the basal brain (basal exudates), subarachnoid
space (subarachnoiditis), leptomeninges (pia and arachnoid
matters, dura is spared).
Complication: Arachnoid fibrosis which may lead to
communicating hydrocephalus and endarteritis obliterans.
May also cause arterial end occlusion and cerebral
infarction.
Aseptic Meningitis
Etiology:
i. Enteroviruses (polio, coxsackie A) most common
cause
ii. Arbovirus
iii. HIV
iv. HSV-2
v. Others mumps.
CSF study at a glance
Protein
Glucose
Chloride ion Cell count
(20-50 md/dl) (40-70 mg/dl) (116-122 mEq) (< 5/microlit)
Bacterial
meningitis
TB
meningitis
Aseptic
meningitis
Markedly
increased
(> 220)
Increased
(> 50)
Decreased
(< 34)
Decreased
Increased
neutrophils
Decreased
(<40)
Decreased
Increased
Normal
Normal
Increased
lymphocytes
and
neutrophils
Increased
lymphocytes
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Brain Abscess
Etiology:
Mixed infections are most common.
Most common organisms are streptococcus,
Staphylococcus aureus, gram-negative bacilli (E.coli)
etc.
Most common anaerobic organisms are bacteroides.
Source: Most common source is from otitis media.
Site: Most common sites are frontal lobes temporal lobes.
Clinical feature:
Headache is the most common symptom.
Triad of fever, headache and focal neurological deficits.
Investigation:
CT scan most useful.
MRI.
LP is contraindicated.
Treatment:
Antibiotics PnG is the drug of choice +
chloramphenicol/cefotaxime/metronidazole.
Total excision of the abscess.
Steroids.
Subdural Empyema
Causative organism: Streptococcus most common.
Pathogenesis:
Infection spreads from the paranasal sinuses (most
commonly the frontal sinus).
Osteomyelitis of the skull.
CSOM most common cause.
Clinical feature:
Headache, fever, stiff neck.
Increased ICT vomiting.
Focal deficits hemiparesis and hemiplegia.
Meningismus.
Diagnosis:
CECT and MRI.
LP is contraindicated.
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Treatment:
Emergency surgery.
Viral Encephalitis
Etiology:
i. Arbovirus (Japanese B encephalitis) most common
cause of epidemic viral encephalitis.
ii. Enteroviruses.
iii. HSV-1 most common cause of sporadic viral
encephalitis.
iv. Mumps virus.
v. Less common CMV, EBV, HIV, measles, nipah
virus (paramyxovirus).
Investigation:
1. PCR amplification of viral nucleic acid diagnostic
for many types.
2. Serology.
3. Brain biopsy.
4. MRI hyperintense areas in brain are seen in HSV
encephalitis.
Morphology:
i. Perivascular mononuclear cell infiltration.
ii. Microglial nodules.
iii. Inclusion bodies, e.g. rabies and CMV.
iv. Neuronophagia.
Clinical feature:
Features of meningitis and altered consciousness.
General fever, altered sensorium, headache.
Focal neurological signs especially in HSV encephalitis.
Treatment:
Acyclovir for HSV encephalitis.
Progressive Multifocal Leukoencephalopathy
Etiology:
JC virus.
Almost all patients have immunosuppressive disorder.
Clinical feature:
Visual defects homonymous hemianopia.
Mental impairment.
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Diagnosis:
MRI periventricular lesion,
PCR amplification of JC virus from CSF is diagnostic.
Subacute Sclerosing Panencephalitis (SSPE)
Etiology: Measles virus.
Clinical feature:
Age 5-15 years.
Progressive intellectual deterioration, seizures,
myoclonus, ataxia, visual disturbance.
EEG periodic patterns.
Prion Diseases
These are degenerative disorders of the CNS caused by
infectious proteins called the prions.
Features of prion diseases:
Long incubation periods.
Amyloid plaques in brain.
No inflammation.
Always fatal.
Etiology: Prion proteins are formed due to misfolding of
proteins.
Note: Secondary structure of prion proteins is -sheets.
Types:
i. Kuru
ii. Creutzfeldt-Jakob disease
iii. GSS syndrome
iv. Fatal familial insomnia
v. Scrapie in sheep.
Creutzfeldt-Jacob Disease
Pathology:
Spongiform degeneration of the brain mostly in the
cortex and basal ganglia.
This is equivalent to mad cow disease in cattle.
Diagnosis:
Brain biopsy is specific.
Clinical feature:
Rapidly progressive dementia.
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Prominent associated myoclonus (in 90% cases).

EEG is characteristic.
Gerstmann (GSS) Syndrome
Spinocerebellar degeneration.
NUTRITIONAL AND METABOLIC
DISEASES OF CNS
Anoxic-ischemic Encephalopathy
Pathology: Diffuse cortical necrosis almost invariably
involving the hippocampus.
MITOCHONDRIAL DISORDERS
Kearns-Sayre Syndrome
Triad of retinitis pigmentosa, external ophthalmoplegia
and heart block.
Others sensorineural deafness, dementia, diabetes,
hypothyroidism.
Lebers Optic Atrophy
Due to inherited point mutation in mitochondrial DNA.
Clinical feature:
Bilateral, subacute, painless loss of vision with central
scotomas and abnormal color vision.
MERRF Syndrome
Myoclonic epilepsy and ragged red fibers due to mtDNA
point mutation.
PERIPHERAL NEUROPATHY
Clinical feature:
1. Sensory loss - glove and stocking pattern.
2. Areflexia.
3. Motor weakness more in extensor muscles than the
flexor groups.
4. Muscle atrophy.
Diagnosis:
Nerve conduction study decreased velocity is most
important finding.
Nerve biopsy from the sural nerve.
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Etiology:
a. Pure motor neuropathy
i. Amyotrophic lateral sclerosis
ii. Poliomyelitis
iii. Lead poisoning chronic
iv. Porphyria - acute
v. Diphtheria - acute
vi. Others dapsone, L-E syndrome, M. gravis, tick
paralysis.
b. Pure sensory neuropathy
i. Diabetes mellitus chronic
ii. Beriberi
iii. Leprosy
iv. Alcohol
v. Vitamin B12 deficiency
c. Mixed neuropathy
i. G-B syndrome
ii. Uremia
iii. Nitrofurantoin
iv. Arsenic poisoning
POLYNEUROPATHY
Guillain-Barr Syndrome (Acute
Demyelinating Polyneuropathy)
Features:
Areflexia.
Muscle paralysis ascending, legs are more commonly
affected, may lead to respiratory failure.
Sensory loss
Facial nerve is involved in 50 percent cases. Lower
cranial nerves are also involved.
Deep tendon reflexes disappear within a few days of
onset.
Bladder function is spared.
CSF study acellular rise of total protein.
Treatment:
IV immunoglobulin.
Plasmapheresis.
Steroids have no role.
Ventilatory assistance may be needed in case of
respiratory failure.
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Prognosis:
Good. About 85 percent of patients make a complete
recovery.
Chronic Relapsing Polyneuropathy
Causes:
Diabetes, Djerine Sotta syndrome.
NEUROMUSCULAR JUNCTION
Myasthenia Gravis
Pathology:
Decrease in available ACh receptors at the N-M
junctions due to an antibody mediated immune attck.
Associated with HLA-B8, DR3.
Other associations thymoma (most common
association), hyperthyroidism.
Clinical feature:
Women are most commonly affected.
Diplopia and ptosis most common initial symptoms.
Difficulty in swallowing.
Limb weakness often proximal and asymmetric.
Deep tendon reflexes preserved.
Muscle weakness worsens by exercise.
Diagnosis:
Edrophonium chloride (tensilon) injection highly
probable diagnosis if unequivocally positive.
Repeated nerve stimulation detrimental response.
Treatment:
1. Anticholinesterases oral pyridostigmine.
2. Immunosuppressants.
3. Thymectomy should be carried out in all patients
with generalized myasthenia gravis between the ages
of puberty and at least 55 years.
4. Plasmapheresis.
5. IV immunoglobulin.
Prognosis:
Spontaneous remission may occur.
Stage with best prognosis is stage 1, active.
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Lambert-Eaton (L-E) Syndrome

It is a presynaptic disorder of the N-M junction due
to antibody against calcium channels.
Association small cell carcinoma of lungs.
Clinical feature:
Proximal muscles of lower limbs are most commonly
affected.
Diplopia and ptosis may be present.
Reflexes decreased or absent.
Autonomic changes such as dry mouth and
impotency.
Diagnosis:
Repeated nerve stimulation causes an incremental
response (c.f. myasthenia gravis).
Treatment:
Guanidine and pyridostigmine.
Plasmapheresis.
IV immunoglobulin.
DISEASES OF MUSCLE
Hereditary Myopathies
Duchenne Muscular Dystrophy
(Pseudohypertrophic Muscular Dystrophy)
Features:
Onset before 5 year of age.
Progressive muscle weakness Gowers sign. Usually
involves the proximal and neck flexors.
(Pseudo)hypertrophy of calf muscles.
CVS cardiomegaly, RVF.
Mental retardation.
Scoliosis impaired pulmonary function.
Pathology:
Defect in the gene that codes for the sarcolemmal
protein dystrophin.
There is marked variation in size of muscle fibers as
well as small groups of necrotic and regenerative fibers
(heterogenicity).
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Diagnosis:
Serum CK level increased this is positive before clinical
features are evident.
Muscle biopsy diagnostic, shows heterogenicity.
EMG.
Prognosis:
Death is due to respiratory failure in second or third
decade.
Becker Dystrophy
Onset in childhood (5-25 years).

Death in the fourth decade.
No mental retardation.
Rest same as Duchenne dystrophy.
Myotonic Dystrophy
This is the most common muscular dystrophy in adults.
Genetics: Autosomal dominant, involves the gene at
chromosome 19q13.3.
Features:
Onset in the second decade of life.
Involves the distal muscles (whereas all other
myopathies involve proximal muscles).
Hatched-faced appearance.
Congenital variety is characterized by neonatal
respiratory insufficiency appearing before the age of
5 years.
Others cardiac defects, mental retardation, cataract,
gonadal atrophy.
Diagnosis: Muscle biopsy shows selective atrophy of type I
muscle fibers.
Congenital Myopathies
Types:
i. Central core disease
ii. Nemaline myopathy
iii. Centronuclear (myotubular) myopathy.
Serum normal CK level.
Notes:
Most common dystrophy in old age (5th-6th decade)
is oculopharyngeal dystrophy.
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Heart is not involved in facioscapulohumeral and

oculopharyngeal dystrophies.
Floppy Baby Syndrome
Causes:
i. Downs syndrome
ii. Werding Hoffman spinal muscular dystrophy
iii. Central core disease
iv. Mitochondrial myopathies
v. E-D syndrome
vi. Infant botulism
Clinical feature: Hypotonia, frog-like posture, delay in motor
milestones.
Spinal Muscular Atrophy
Normal IQ.
Tongue fasciculation.
Plus above mentioned features.
Toxic Myopathies
Most common cause is injection of narcotic analgesics
(pentazocine), meperidine and heroin.
Periodic Paralysis
Etiology:
i. Hypokalemic periodic paralysis due to calcium
channel defect.
ii. Hyperkalemic periodic paralysis due to sodium
channel defect.
iii. Paramyotonia congenita.
iv. Thyrotoxic periodic paralysis.
v. Hypophosphatemia.
Note:
High carbohydrate diet can provoke hypokalemic
paralysis.
Drug of choice for an acute attack of familial periodic
paralysis is KCl.
Neurological Channelopathies
Calcium channelopathies:
i. Episodic ataxia type 2
ii. Spinocerebellar ataxia type 6
iii. Familial hemiplegic migraine
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iv. Malignant hyperthermia

v. Hypokalemic periodic paralysis
Sodium channelopathies:
i. Paramyotonia congenitax
ii. Hyperkalemic periodic paralysis
iii. Normokalemic periodic paralysis
Chloride channelopathies:
i. Generalized myotonia
ii. Myotonia congenitax
Potassium channelopathy:
i. Episodic ataxia type 1
Note: All are autosomal dominant, except myotonia
congenita which is autosomal recessive plus dominant.
MULTIPLE SCLEROSIS
It is characterized by chronic inflammation, demyelination
and gliosis (scarring).
Clinical feature:
Relapsing and remitting course.
Symptoms
Weakness of limbs pyramidal involvement.
Optic neuritis.
Sensory disturbance paresthesia, hypesthesia.
Diplopia.
Ataxia duet to cerebellar involvement.
Impotency.
Extrapyramidal symptoms are not seen.
Diagnosis:
CSF mononuclear cell pleocytosis, elevation of total
Ig, presence of oligoclonal Ig.
Others visual evoked response test slowing.
MRI diagnostic, shows white matter involvement.
ERG is normal.
Treatment:
Interferon 1.
AUTONOMIC NERVOUS SYSTEM
Postural Hypotension
Defined as a postural fall from supine to standing position
of at least 20 mmHg in SBP or 10 mmHg in DBP
sustained for at least 3 minutes.
391
Etiology:
i. Diabetes
ii. Tabes dorsalis
iii. Antihypertensive drugs
iv. Posterior fossa tumors
v. Syringomyelia
vi. G-B syndrome
vii. Amyloidosis
Test: Valsalva response.
Symptoms of autonomic dysfunction: Impotence, bladder
dysfunction, constipation (sometimes diarrhea), anhidrosis,
orthostatic hypotension, hypertension, resting tachycardia,
silent MI.
Mononeuropathy Multiplex
Pathology:
Involvement of multiple noncontiguous nerves
simultaneously.
It is a vasculitis affecting the vasa nervosum.
Cause:
Polyarteritis nodosa most common cause.
Hypersensitivity vasculitis.
Rheumatoid arthritis.
SLE.
Leprosy, sarcoidosis, amyloidosis.
MONONEUROPATHY
Carpal Tunnel Syndrome
Pathology: Compression of the median nerve as it passes
below the flexor retinaculum.
Etiology:
i. Idiopathic most common cause.
ii. Pregnancy.
iii. Tenosynovitis with arthritis involving the wrist.
iv. Hormonal acromegaly, hypothyroidism, diabetes.
v. Rheumatoid arthritis.
vi. Metabolic gout, amyloidosis.
vii. Trauma Colles fracture.
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Clinical feature:
Affects middle aged female.
Tingling and numbness of the thumb, index and middle
fingers which is worse at night.
Diagnosis:
Phallens test is positive.
Nerve conduction velocity along the median nerve is
slowed.
Treatment:
Surgical decompression.
Tarsal Tunnel Syndrome
Due to involvement of the posterior tibial nerve.
ENDOCRINOLOGY
AND METABOLISM
PHYSIOLOGY
Respiratory Quotient
It is the ratio of volume of CO2 produced and the volume
of O2 consumed per unit time in steady state equilibrium.
RQ values:
Carbohydrate 1.00
Fat 0.70
Protein 0.82
Basal Metabolic Rate
It is the minimum energy required at rest in a room at
a comfortable temperature in the thermoneutral zone 1214 hours after the last meal.
BMR falls by about 10 percent during sleep and up
to 40 percent during starvation.
It best correlates with body surface area.
Determinants:
1. Age BMR is high in children.
2. Sex BMR is high in males.
3. Mental state anxiety and tension increase the BMR.
4. Hormones BMR is increased by catecholamine and
thyroid hormones.
PITUITARY GLAND
Hormones from the Anterior Lobe of Pituitary
The pituitary hormones
Hormones
Nature
Secreted by cell type
ACTH
Prolactin
Growth hormone
TSH
LH and FSH
Polypeptide
Polypeptide
Polypeptide
Glycoprotein
Glycoprotein
Basophilic
Acidophilic
Acidophilic
Basophilic
Basophilic
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Hormones from the Posterior Pituitary

Vasopressin and oxytocin are secreted from the cell
bodies of the magnocellular neurons in supraoptic and
paraventricular nuclei of hypothalamus.
Vasopressin mainly from the suproptic nucleus and
oxytocin mainly from the paraventricular nucleus.
Oxytocin
Action:
i. It increases the force and frequency of uterine
contractions (uterine stimulant or oxytocic).
ii. Oxytocin contracts the myoepithelium of mammary
alveoli and causes milk ejection reflex.
T1/2 of oxytocin is 6 minutes.
Vasopressin or ADH
ADH circulates in free form in plasma.
Receptors:
V1 receptors all vasopressin receptors except those
on renal CD cells and some blood vessels.
V2 receptors located primarily on the collecting duct
cells in the kidney regulate their water permeability
through cAMP production.
Actions:
Kidney ADH acts on the collecting duct cells to
increase their water permeability. They promote
exocytosis of aquaporin-2 water channel through the
apical membrane of the principal cells.
GROWTH HORMONE
Actions:
1. Increased gluconeogenesis
2. Increased ketogenesis
3. Increased protein synthesis (anabolic)
4. Increased phosphate in blood
5. Decreased blood urea and nitrogen.
GH is diabetogenic because it increases hepatic glucose
output and exerts its anti-insulin effect in muscle. It
is also ketogenic.
Endocrinology and Metabolism
395
DISORDERS OF GH SECRETION
GH Excess (Acromegaly and Gigantism)
Cause:
Pituitary adenomas, 70 percent being macroadenomas.
Associated with mutation in GNAS1 gene on
chromosome 20q13.
TRH (thyroxin releasing hormone) increases secretion
of GH in acromegaly. Prolactin secretion is also
increased.
Clinical feature:
Tall stature (hands and feet are large acral means
parts).
Coarse facial features, protrusion of the jaw
(prognathism).
Thick skin and subcutaneous tissue.
Increased body hair.
CVS hypertension and cardiomegaly.
Gynecological amenorrhea, galactorrhea and
hirsutism.
1. Insulin resistance is seen in 80 percent of cases, although
abnormal glucose tolerance and clinical diabetes are
less common.
2. Increased serum phosphate, hypercalciuria.
Diagnosis:
1. Measurement of glucose-suppressed GH secretion.
2. Measurement of IGF-1 concentration (somatomedin C).
3. Increased TRH in 80 percent cases.
4. X-ray shows
Enlargement of the paranasal sinuses.
Increased heel pad thickness.
Arrow headed finger.
Treatment:
Surgery transsphenoidal surgery.
Radiation.
Drugs bromocriptine, octreotide.
Growth Hormone Deficiency (Hypopituitarism)
Most commonly due to chromophobe adenomas of
the pituitary.
396
Infants with GH deficiency are born normal. They

develop features of growth impairment within a few
months after birth. But a clinical diagnosis is made
at 1-2 years of age.
Clinical feature:
Short stature (dwarfism) with normal body proportions.
Premature fusion of epiphysis the height is less than
skeletal age (bone age is less than chronological age
by 2 years).
The development of teeth is delayed.
Macroglossia.
Normal mental state.
Associated hormone deficiencies:
ACTH hypoglycemia and convulsions in neonates.
Gonadotrophins delay in sexual development.
Diagnosis:
Insulin provocative test.
Note:
Bone age < chronological age in hypopituitarism,
hypothyroidism, constitutional delay and malnutrition.
Bone age > chronological age in Downs syndrome,
Turners syndrome and intrauterine infections.
PROLACTIN
Prolactin is under the control of TRH which also controls
TSH.
Action:
Prolactin causes proliferation of ductal and acinar cells
in the breast and induces synthesis of milk proteins and
lactose.
Regulation:
Prolactin synthesis is decreased by prolactin inhibitory
hormone (PRIH) from hypothalamus. PRIH is dopamine
which acts on pituitary lactotrope D2 receptors.
Prolactin synthesis is decreased by dopaminergic
agonists like bromocriptine, apomorphine.
Prolactin secretion is increased by dopaminergic
antagonists like chlorpromazine, haloperidol,
metoclopramide and dopamine depleters like reserpine
and methyldopa may cause hyperprolactinemia.
397
Hyperprolactinemia
Etiology:
i. Pituitary adenomas, mainly microadenomas
(prolactinomas) most common cause.
ii. Drugs mentioned above.
iii. Pituitary stalk lesion due to loss of normal inhibitory
influence of hypothalamus.
Clinical feature:
In females galactorrhea, amenorrhea and infertility.
In males gynecomastia, impotence and infertility.
Visual defects most common pressure symptom and
most distressing symptom of prolactinomas.
Diagnosis:
1. TRH response test no rise in prolactin level
(paradoxical effect see the normal effect).
2. MRI for detection of prolactinomas.
3. Serum prolactin level > 300 g/liter (normal 15-20
g/liter).
Note: Non-functioning pituitary adenomas may present
with features of hyperprolactinemia due to stalk
compression and mass effect but prolactin level is only
slightly increased.
Treatment: Bromocriptine a dopamine agonist.
CRANIOPHARYNGIOMA
Origin: From the remnants of Rathkes pouch.
Site: Most of these are suprasellar tumors.
Histology: Cysts lined by stratified squamous epithelium.
Clinical feature:
Features of increased intracranial pressure due to
hydrocephalus headache, vomiting and papilledema.
Visual abnormalities loss of vision and field of vision.
Diagnosis: X-ray shows suprasellar calcification. It is the
most common calcifying tumor of brain in children.
Empty Sella Syndrome
Clinical feature:
Middle aged obese female presents with headache and
hypertension.
398
CT scan the sella is symmetrically ballooned without

bony erosion. Pituitary volume is normal.
Cause: Cavernous venous thrombosis.
ANTIDIURETIC HORMONE
Physiology: See above.
Diabetes Insipidus
Cause: Deficiency of ADH.
a. Primary or idiopathic autosomal dominant.
b. Secondary due to head injury, pituitary tumors,
infections, metastasis, histiocytosis, pregnancy,
Sheenans syndrome and SLE.
Clinical feature: Polyuria, excessive thirst and polydipsia.
Diagnosis:
Urinary concentration < 300 mmol/kg and specific
gravity < 1.010.
Plasma osmolality not changed or slightly increased.
Mild hypernatremia.
Water deprivation test there is very little increase in
urine osmolality with increase in plasma osmolality.
Hickey-Hare test.
Treatment:
i. Desmopressin is the drug of choice.
ii. Chlorpropamide.
iii. Hydrochlorothiazide.
a. Psychogenic polydipsia both urine and plasma are
hypo-osmolar.
b. Dilutional hyponatremia (e.g. Adrenal insufficiency)
orthostatic hypotension, tachycardia and increased
BUN.
c. Pseudohyponatremia due to increased glucose/
protein/triglycerides in blood.
d. Sick-cell syndrome low set hypothalamic
osmoreceptors.
Note: Nephrogenic diabetes insipidus
Is due to inability of the kidneys to respond to
vasopressin.
399
Congenital - due to congenital defects in the V2

receptors (X-linked).
Drugs lithium, amphotericin B, aminoglycosides,
cisplatin.
Amyloidosis, pregnancy.
Treatment:
Thiazide effective both in central and in nephrogenic
diabetes insipidus.
Amiloride drug of choice in lithium induced
nephrogenic DI.
Syndrome of Inappropriate
ADH Secretion (SIADH)
Etiology:
1. Small cell carcinoma of lungs
2. Lung abscess, COPD
3. Skull fracture
4. Acute encephalitis
5. Drugs vincristine, vinblastine, cyclophosphamide
6. Hypothyroidism
7. Acute intermittent porphyria.
Pathology:
There is water retention and sodium excretion.
Excretion of concentrated urine (osmolality > 300
mmol/kg) despite a subnormal plasma osmolality
(< 280 mmol/kg) and low serum sodium concentration
hyponatremia and increased total body water, but
edema and hypertension do not develop.
Hypouricemia.
Urinary sodium > 20 mEq/lit.
Diagnosis:Water load test- normal values.
Treatment:
1. Fluid restriction to 800-1000 ml daily.
2. IV infusion of 3-5 percent (hypertonic) NaCl solution.
3. IV frusemide.
4. Treatment of the underlying cause.
5. In chronic SIADH, demeclocycline or fludrocortisone.
400
THYROID GLAND
ANATOMY
Position:
The thyroid gland lies against C5-T1 vertebrae.
Isthmus is situated on the 2nd and 3rd rings of trachea.
Capsule:
True capsule
False capsule it is derived from the pretracheal layer
of the deep cervical fascia.
Apex of the gland:
Apex is limited superiorly by the attachment of the
sternothyroid muscle which prevents upward
enlargement of the gland.
Arterial supply:
1. Superior thyroid artery branch of external carotid
artery.
2. Inferior thyroid artery branch of thyrocervical trunk.
3. Arteria thyroidea ima branch of brachiocephalic
trunk.
4. Accessory thyroid arteries.
Development:
From the thyroglossal duct.
Parafollicular cells are derived from the caudal
pharyngeal complex or the ultimo-branchial body.
PHYSIOLOGY
Thyroid hormones
a. Follicular cells secrete thyroxine (T4) and
triiodothyronine (T3).
b. Parafollicular C cells secrete calcitonin.
Synthesis:
Tyrosine 2 molecules condense to form thyroxine
iodination produce T3 and T4.
Steps:
1. Iodine uptake.
2. Oxidation and iodination
3. Coupling
4. Storage as thyroxine
5. Peripheral conversion of T4 to T3.
401
Transport: T4 is the main transport form. It binds to 3

plasma proteins thyroxine binding globulin (TBG),
prealbumin (transthyretin) and albumin.
TBG level:
Increased in pregnancy, estrogen therapy.
Decreased by glucocorticoids, L-asparaginase,
androgens.
Note:
Thyroglobulin is the storage form.
T4 is the transport form.
T3 is the active hormone.
Daily secretion
T4 80 g
T3-4 g
ECTOPIC THYROID AND ANOMALIES OF
THYROGLOSSAL TRACT
Lateral Aberrant Thyroid
Due to metastasis in a cervical lymph node from an occult
thyroid carcinoma, almost invariably papillary Ca.
Thyroglossal Cyst
Site: In the midline, below the hyoid bone (most common).
Clinical feature:
The swelling moves upwards on protrusion of the tongue
as well as swallowing.
Thyroglossal Fistula
Cause: Never congenital; it is due to infection or inadequate
removal of a thyroglossal cyst.
Histology: Lined by columnar epithelium, discharges
mucus.
Treatment: Sistrunks operation.
HYPOTHYROIDISM
Etiology
1. Endemic cretinism often goitrous and due to iodine
deficiency.
402
2. Autoimmune thyroiditis (chronic lymphocytic

thyroiditis).
Non-goitrous primary myxedema.
Goitrous Hashimotos disease.
3. Iatrogenic after thyroidectomy, after radioiodine
therapy.
Drug therapy antithyroid drugs, amiodarone, lithium,
PAS and iodides.
4. Dyshormonogenetic goiter congenital biosynthetic
defect.
5. Goitrogens cabbage.
6. Secondary to pituitary or hypothalamic diseases.
Cretinism (Congenital Hypothyroidism)
Most common cause of cretinism is thyroid dysgenesis.
Features: Not present at birth.
Infants:
Delayed closure of fontanelles earliest sign. It is also
seen in Downs syndrome, osteogenesis imperfecta.
Persistent physiological jaundice, absent social smile.
Dwarfism short stature, head size is normal but the
extremities aer short (disproportionate body
proportions).
Bone dentition and skeletal maturity are delayed
(bone age to height age ratio is deceased).
Mental retardation.
Others coarse features, large protruding tongue,
umbilical hernia, hypothermia, loss of eyebrows.
Note: In neonatal screening programme for detection of
congenital hypothyroidism, blood is collected from cord
on first day or from the heel pad on the fourth day.
Adult Hypothyroidism
Features:
Lethargy, constipation, cold intolerance.
Carpal tunnel syndrome.
Menorrhagia and galactorrhea.
Dementia.
Decreased appetite, weight gain.
Hair is dry and fall-out. Skin is dry.
Hoarseness of voice.
403
Myxedema:
This is due to accumulation of mucopolysaccharides
in the ground substance of dermis.
Dull expressionless face.
Periorbital edema.
Malar flush and yellow tinge of skin.
Pericardial effusion.
Increased plasma cholesterol may lead to
atherosclerosis.
Skin cool, dry with doughy consistency.
Hung-up reflex the relaxation phase of the deep
tendon reflexes is characteristically prolonged.
Mild diastolic hypertension. (Note: BP is increased in
both hypo and hyperthyroidism).
Laboratory diagnosis:
i. Increased serum TSH most useful (but not in case
due to pituitary dysfunction).
ii. Decreased serum T4 and T3.
iii. ECG bradycardia.
X-ray:
Bone punctate epiphyseal dysgenesis.
Skull wormian bones.
Chest cardiomegaly (water bottle configuration).
Treatment:
Levothyroxin (l-troxin) dose 0.1 to 0.2 mg/day.
Dose is best determined by clinical criteria and
measurement of TSH by an ultrasensitive assay.
In myxedema coma supplemented by IV liothyronine
(T3).
Others IV fluids, hydrocortisone, gradual warming.
GOITER
It is a generalized swelling of the thyroid gland.
Classification
1. Simple goiter (euthyroid)
i. Diffuse hyperplastic
ii. Multinodular
2. Toxic
i. Graves disease
ii. Toxic adenoma
iii. Neoplasms (benign and malignant)
404
3. Inflammatory
i. Autoimmune chronic lymphocytic thyroiditis,
Hashimotos thyroiditis.
ii. Granulomatous sub-acute thyroiditis.
iii. Fibrosing Riedels thyroiditis.
Simple Goiter
Etiology:
Iodine deficiency endemic cretinism.
Characterized by deaf-mutism, squint, mental
retardation and rigidity (spastic diplegia).
Stature normal (c.f. congenital cretinism).
Investigation:
Euthyroid normal serum T4 and T3 levels.
Radioactive iodine uptake studies usually normal but
may be increased in the presence of iodine deficiency
(endemic goiter).
Epidemiology:
Endemic goiter is said to be present when the
prevalence of goiter in a defined population is > 10
percent.
Treatment:
Levothyroxin which often causes the goiter to shrink.
Pendreds Syndrome
Goiter with congenital deafness.
Diffuse Hyperplastic Goiter
The goiter appears in childhood in endemic areas. In
sporadic cases, it occurs at puberty, so called the puberty
goiter.
Retrosternal Goiter
It arises from the lower pole of a nodular goiter.
Clinical feature: Dyspnea, dysphagia, engorgement of neck
veins.
Treatment: Resection from the neck.
405
Graves Disease
Characterized by hyperthyroidism with diffuse goiter,
ophthalmopathy and dermopathy.
It causes primary hyperthyroidism characterized by
goiter appearing at the same time as hyperthyroidism.
Cause:
Abnormal thyroid stimulating antibodies.
Strongly associated with HLA DR3.
Eye signs of primary hyperthyroidism:
Most commonly involved ocular muscle is the inferior
rectus muscle.
Lid retraction Dalrymples sign.
Lid lag Von Grafes sign.
Infrequent blinking Stellwags sign.
Poor forehead wrinkling Joffroys sign.
Weakness of convergence Mobius sign.
Proptosis or exophthalmos (may be unilateral).
Treatment:
For lid retraction guanethidine eye drop.
For malignant exophthalmos lateral tarsorrhaphy,
orbital decompression, sleeping propped-up.
CVS:
Hyperkinetic circulatory state characterized by
Tachycardia which is present at sleep.
Wide pulse pressure, atrial fibrillation (irregularly
irregular pulse).
Ejection systolic murmur.
Pericardial friction rub (Means-Lerman scratch).
Apex beat hyperdynamic but in normal position.
Skin: Localized or pretibial myxedema.
Thyrotoxicosis
Anxiety, tremor, increased sweating, heat intolerance,
weight loss, dancing carotid, diarrhea, amenorrhea.
Warm and moist hands differentiate with anxiety
state.
Proximal myopathy.
Note: Proptosis, ophthalmoplegia and pretibial myxedema
are not due to thyrotoxicosis per se and occurs only in
primary hyperthyroidism.
406
Diagnosis: Undetectable TSH, increased T4 and T3 levels,

increased RAIU values.
Treatment:
Propanolol alleviates sweating, tremor and
tachycardia.
Age < 45 years surgery for large goiter (subtotal
thyroidectomy), antithyroid drugs for small goiter.
Age > 45 years radioiodine (complication thyroid
insufficiency).
Toxic Nodular Goiter
Causes secondary thyrotoxicosis characterized by absent
eye signs.
It is a consequence of long-standing simple goiter. So
it occurs in elderly. Features of hyperthyroidism present
long after the appearance of goiter. It may present
with cardiac failure or atrial fibrillation.
Treatment:
Surgery or radioactive iodine (131I).
Surgery for Thyrotoxicosis
Subtotal thyroidectomy.
Pre-operative preparation:
Carbimazole is the drug of choice.
Iodides given with carbimazole and not alone.
Propanolol continued for 7 days after surgery.
Postoperative complications:
1. Hemorrhage: Management of postoperative
hemorrhage opening of the wound to remove tension
by removing the sutures.
2. Respiratory distress due to laryngeal edema which
is most commonly due to tension hematoma.
3. Hypocalcaemia manifests 2-5 days after surgery with
tetany.
Management IV calcium gluconate or oral calcium.
4. Thyrotoxic crisis (storm)
Clinical feature extreme irritability, delirium or coma,
fever, tachycardia, hypotension, vomiting and diarrhea.
Cause inadequate control of thyroid status before
operation (most common), stressful illness, radioiodine
therapy for thyrotoxicosis.
407
Management IV hydrocortisone, carbimazole, Lugols

iodine, propanolol.
5. Recurrent laryngeal nerve palsy.
Note: Hypocalcemia is not a complication of
hemithyroidectomy.
NEOPLASM
Benign
Adenomas
Follicular adenomas present as solitary thyroid nodules.
Scintiscan:
Follicular adenomas take up the dye and are called
hot nodules.
Eighty percent of solitary thyroid nodules are cold
nodules, but only 15 percent of them are malignant.
Diagnosis: FNAC is the investigation of choice for solitary
nodules.
Indication of surgery: Malignancy, pressure symptoms,
cosmetic.
Surgery for solitary nodule: Hemithyroidectomy.
Choice of treatment
Graves diasease
Toxic nodular goiter
Toxic nodules
Age < 45 years 131I

Age > 45 years subtotal thyroidectomy
Subtotal thyroidectomy
Age < 45 years hemithyroidectomy
Age > 45 years 131I.
Malignant
Usually euthyroid and appear as cold nodules on thyroid
scan.
Papillary Carcinoma
The most common type, also least malignant type.
Etiology: Papillary Ca develops often due to exposure to
radiation in childhood (latent period about 30 years).
Features: Bimodal frequency, unencapsulated and
multicentric.
Spread:
Through the thyroid capsule to structures surrounding
the neck, especially the regional lymph nodes may
408
present as occult primary with cervical lymphadenopathy.

Blood-borne metastasis is rare.
Pathology: Papillary Ca shows psammoma bodies and
orphan-Annie eyed cells.
Treatment:
Surgery near total thyroidectomy for tumors > 2
cm in size.
Regional lymph nodes should be explored and removed
if there is evidence of involvement, but radical neck
dissection is not justified.
For tumors < 2 cm in size lobectomy and
isthmusectomy (hemithyroidectomy).
131I for residual cancer or neck glands detected after
surgery.
Prognosis: Good.
Follicular Carcinoma
Etiology: They arise in long standing cases of goiter.
Features: Encapsulated, capsular and/or vascular invasion
is common.
Spread: Hematogenous spread to lungs, bone (osteolytic
secondaries) and brain.
Hurthle-cell tumor:
It is a variant of follicular Ca.
It metastasizes frequently to bones.
Diagnosis: FNAC is often unhelpful as it fails to demonstrate
capsular and/or vascular invasion which differentiates it
from follicular adenoma.
Prognosis: Worse.
Medullary Carcinoma
Origin: From the parafollicular C cells of the thyroid.
Features:
High levels of calcitonin are produced may lead to
hypocalcemia.
Diarrhea most common symptom.
It is associated with adrenal pheochromocytoma and
hyperparathyroidism (MEN IIa).
Associated with stimulation of RET proto-oncogene.
409
Metastasis: Involvement of cervical lymph nodes (most

common) occurs early. Blood borne metastasis is also
early.
Pathology:
Medullary Ca shows amyloid deposition.
Serum calcitonin screening measurement of serum
calcitonin is useful when the diagnosis of medullary
ca is suspected.
Treatment: Surgery total thyroidectomy and resection
of involved lymph nodes with either a radical or modified
neck dissection.
Other Carcinomas
Anaplastic Ca: Worst prognosis. Treatment is radiotherapy.
Lymphoma: Treatment by radiotherapy plus chemotherapy.
THYROIDITIS
Riedels Thyroiditis
Chronic fibrosing thyroiditis,
It is always hypothyroid and never hyperthyroid
(compare the later two).
Subacute Thyroiditis
Also called the de Quervains thyroiditis or
granulomatous thyroiditis.
Cause Viral infection.
Clinical feature:
Onset often follows an upper respiratory tract infection.
Pain in neck, fever, enlargement of thyroid.
Investigation:
Increased ESR, leukocytosis.
Decreased RAIU.
Early, serum T3 and T4 levels are high and TSH level
is low (hyperthyroidism).
Later, serum T3 and T4 levels are low and TSH level
is high (hypothyroidism).
Course:
Subsides spontaneously and return to normal in few
months.
410
Chronic Lymphocytic Thyroiditis

(Hashimotos Thyroiditis)
It is the most common type of thyroiditis.
Characterized by increased titer of thyroid antibody,
lymphocyte infiltration of the gland (Hurthle cells).
Cause:
Antithyroid peroxidase antibody.
Most commonly against thyroid receptors.
Clinical feature:
Hypothyroidism, transient hyperthyroidism occurs early.
Occurs in women at menopause.
Treatment:
Thyroxin.
ADRENALS
ANATOMY
Anterior relations of adrenal glands:
Right gland liver, inferior venal cava and right
suprarenal vein.
Left gland spleen, stomach, splenic artery, pancreas
and left suprarenal vein.
Medial border related to inferior phrenic artery.
Arterial supply:
1. Superior suprarenal artery branch of the inferior
phrenic artery.
2. Middle suprarenal artery branch of the abdominal
aorta.
3. Inferior suprarenal artery branch of the renal artery.
Venous drainage:
The right suprarenal vein drains into the inferior vena
cava.
The left suprarenal vein drains into the left renal vein.
Note: During fetal life the human adrenals are large.
411
ADRENAL CORTICAL HORMONES

PHYSIOLOGY
Source:
Zona glomerulosa aldosterone.
Zona fasciculata cortisol.
Zona reticularis androgens (dehydroepiandrosterone
and androstenedione).
Structure:
All contain a CPP ring in their structures.
Aldosterone and cortisol are C 21 steroids.
Androgens are C 19 steroids they contain a keto
group at position 17, hence called the 17 ketosteroids.
Adrenals are the major source of 17 ketosteroids in
urine.
Glucocorticoids
Action:
1. Metabolic effects
i. Carbohydrate decreased insulin synthesis and
decreased peripheral uptake of glucose lead to
increased hepatic glycogenesis and gluconeogenesis
hyperglycemia. Also increases the activity of glucose6-phophatase.
ii. Protein increased protein catabolism.
iii. Fat increased lipogenesis and ketosis in diabetics.
iv. Calcium decreased intestinal absorption and
increased renal excretion leads to hypocalcemia and
decreased formation and increased resorption of
osteoid.
2. Permissive actions
i. For glucagon and catecholamine to exert their
calorigenic action.
ii. For catecholamine to exert their lipolytic action.
iii. For catecholamine to produce pressor response and
bronchodilatation.
3. Inflammation
Glucocorticoids reduce inflammation by reduction
of capillary permeability, limitation of recruitment
of inflammatory cells at the site and inhibition of
phospholipase A leading to decreased production
of PG, LT and PAF.
412
Test for glucocorticoids reserve:

Within minutes after administration of ACTH, cortisol
level increases in venous blood.
Mineralocorticoid
Aldosterone increases sodium reabsorption from urine,
sweat, saliva, gastric contents and expands the CSF.
Increased loss of K+ and H+ in urine and increased
urinary acidity.
In kidneys, they act on the principal (P) cells of the
collecting duct.
Regulation:
Aldosterone secretion is increased by high K+ intake
and hemorrhage.
HYPERFUNCTION OF ADRENAL CORTEX
Cushings Syndrome
Due to increased production of cortisol from the adrenals.
Etiology:
1. Bilateral adrenal hyperplasia most common
endogenous cause.
This may be due to
i. Secondary to pituitary ACTH over production due
to pituitary ACTH-producing adenomas (usually
microadenomas) Cushings disease or due to
pituitary-hypothalamus dysfunction.
ii. Ectopic ACTH or CRH production by small cell
Ca of lungs, carcinoid of thymus, medullary Ca of
thyroid and pancreatic Ca.
2. Adrenal neoplasia
3. Iatrogenic exogenous steroid administration is the
most common cause of Cushings syndrome.
Pathology and features:
1. Mobilization of peripheral supportive tissue causes
muscle weakness, fatiguability, osteoporosis, cutaneous
striae and easy bruisability.
2. Increased gluconeogenesis and insulin resistance cause
impaired glucose tolerane (hyperglycemia).
3. Redistribution of body fat in the face (moon face),
the interscapular area (buffalo hump) and the
mesenteric bed (truncal obesity).
413
4. Hypertension (both systolic and diastolic BP are

increased).
5. Emotional changes to frank psychosis.
6. Due to increased androgen production acne, hirsutism,
amenorrhea in women.
Occasionally, hypokalemia, hypocalcemia and
metabolic alkalosis particularly common in ectopic
ACTH producing tumors (differentiate ectopic ACTH
production from Cushings disease).
7. Others weight gain, poor wound healing,
polycythemia, impotence and atrophy of testis in men,
pathological fracture.
Diagnosis:
Loss of circadian rhythm (plasma cortisol level does not fall
at midnight) earliest manifestation.
24 hour urinary free cortisol (> 275 nmol/day)

Low dose (1 mg) dexamethasone suppression test
High dose (2 mg) dexamethasone suppression test
Suppression
No suppression
- Adrenal hyperplasia
Adrenal hyperplasia due
secondary to pituitary
to ectopic ACTH production
ACTH overproduction
or adrenal neoplasia
Increased ACTH
Decreased ACTH
(Adrenal hyperplasia)
(Adrenal neoplasia)
Pituitary imaging
Abdominal CT, urinary 17 keto
Petrosal sinus sampling
Steroids or DHEA sulphate level
for ACTH
Pituitary adenoma or
Abdominal
No mass
ectopic tumor
mass
17 KS/DHEA
Normal
Adrenal Ca.
Adrenal adenoma
Treatment:
1. Adrenal neoplasm adrenal exploration and excision
of the tumor.
2. Adrenal hyperplasia
i. Surgery for pituitary microadenoma.
ii. Radiation.
iii. Bilateral adrenalectomy
iv. Medical adrenalectomy by aminoglutathimide,
metyrapone which decreases 11 beta hydroxylase.
414
Nelsons Syndrome
Pituitary adenomas that secrete ACTH in patients after
surgical removal of adrenal glands for the treatment of
Cushings syndrome.
Clinical feature:
Mass effect (e.g. visual disturbance), hyperpigmentation
due to increased MSH (melanocyte secreting hormone).
Aldosteronism
Etiology:
Primary due to aldosterone secreting adrenal adenoma
(Conns syndrome). May also be due to bilateral
cortical nodular hyperplasia.
Adrenal adenomas:
They are usually 1-2 cm in size and most are found
incidentally (incidentallomas).
Size > 4-6 cm suggests carcinoma.
Clinical feature:
1. Due to Na+ retention diastolic hypertension without
edema.
2. Due to K+ depletion hypokalemia (muscle weakness)
and metabolic alkalosis.
3. Polyuria and polydipsia.
Diagnosis:
1. Plasma renin activity
In primary aldosteronism, plasma renin is decreased.
In secondary aldosteronism due to renin producing
tumors it is increased with accelerated hypertension.
2. Failure of suppression of aldosterone secretion by
dexamethasone.
3. Adrenal carcinoma abdominal CT scan.
4. Postural decrease in plasma aldosterone and increased
plasma 18-hydroxycorticosterone levels differentiate
from bilateral adrenal hyperplasia.
Management:
Adenoma surgical removal of the tumor.
Bilateral hyperplasia bilateral adrenalectomy.
Drugs spironolactone, glucosteroids.
415
Liddles Syndrome
It mimics hyperaldosteronism with hypokalemia and
hypertension.
Androgen Excess
Please see later.
HYPOFUNCTION OF ADRENAL CORTEX
Addisons Disease
Etiology:
Destruction of more than 90 percent gland due to
1. Idiopathic autoimmune, most common cause.
2. Infection tuberculosis (most common cause in India).
3. Secondary to exogenous glucocorticoids administration.
Clinical feature:
1. Pigmentation of skin and mucous membrane.
2. Weight loss.
3. Hypotension.
4. Asthenia.
5. Hypoglycemia.
Laboratory finding:
Decreased levels of Na+, Cl- and HCO3- in blood.
Increased levels of K+ and Ca++.
Diagnosis:
ACTH stimulation test in primary case, fails to
increase aldosterone.
Low or absent 24 hour urine cortisol.
Polyglandular Syndrome
Associated with
Autoimmune adrenalitis
Hashimotos thyroiditis
Pernicious anemia
Type I diabetes mellitus
Idiopathic hypoparathyroidism.
Type I autosomal recessive; associated with AIRE gene
on chromosome 21q.
Type II associated with HLA B8, HLA DR3 and HLA
DQ5.
416
ADRENAL MEDULLA
Catecholamines
They are norepinephrine, epinephrine and dopamine.
Synthesis:
Phenylalanine
Phenylalanine hydroxylase
Tyrosine
Tyrosine hydroxylase
DOPA
DOPA decarboxylase
Dopamine
Beta hydroxylase
Norepinephrine
PNMT
Epinephrine
Tyrosine hydroxylase is the rate limiting enzyme.

Metabolism:
Most of the circulating catecholamines are sulfate
conjugates and inactive.
They are methoxylated and then oxidized to
vanillylmandelic acid (VMA).
50 percent of secreted catecholamines appear in urine
as free or conjugated metanephrine and
normetanephrine (major excreted products); and 35
percent are excreted as VMA.
Regulation:
1. Level of NE is increased by 50-100 percent on standing.
2. Level of E (also NE) are decreased during sleep.
3. Catecholamine levels are increased by sympathetic
discharge.
4. Hypoglycemia is a potent stimulus for catecholamine
secretion.
5. Adrenalectomy plasma NE remains normal, but free
E level falls to essentially zero.
Pheochromocytoma
They are composed of chromaffin cells and arise from
the adrenal medulla.
Extra-adrenal sites:
1. Organ of Zuckerkandl at the aortic bifurcation most
common extra-adrenal site.
417
2. Chromaffin cells in or about sympathetic ganglia

(paragangliomas).
3. Chemodectomas derived from carotid body.
4. Ganglioneuromas derived from postganglionic
sympathetic neurons.
5. Others urinary bladder, chest and neck.
Note: Extra-adrenal tumors are more malignant.
Rule of 10
1. 10 percent of pheochromocytomas arise in association
with one of the several familial syndromes MEN2A
and 2B, Type I neurofibromatosis (von Recklinghausen
disease), von Hippel-Lindau syndrome and SturgeWeber syndrome autosomal dominant trait.
2. 10 percent are extra-adrenal in origin.
3. 10 percent are bilateral.
4. 10 percent are malignant.
Pathology:
They secrete NE and E. The percentage of NE is greater
than in the normal adrenal.
Microscopically, characteristic nests of cells (zeuballen)
are seen.
Both capsular and vascular invasion are seen in benign
tumors. The diagnosis of malignancy is therefore based
exclusively on the presence of metastasis.
Malignant tumors produce increased amounts of
dopamine and homovanillic acid which is uncommon
in benign tumors.
Clinical feature:
1. Hypertension most common sign.
2. Headache most common symptom.
3. Profuse sweating and/or palpitation.
4. Mild to moderate weight loss.
5. Orthostatic hypotension.
6. Carbohydrate intolerance hyperglycemia.
7. Hypercalcemia.
8. Increased hematocrit values.
9. Ventricular arrhythmia sudden cardiac death may
occur.
Diagnosis:
1. Urine increased free catecholamines or their
metabolites mainly metanephrine, normetanephrine
(marker of choice) and VMA.
418
2. Pharmacological test
i. Phentolamine test reduction of BP of at least
35/25 mmHg that peaks after 2 minutes and
persists for 10-15 minutes.
ii. Glucagon provocative test.
Investigation:
CT scan and MRI for adrenal tumors.
Radionuclide scanning with radiopharmaceutical 131I
metaiodobenzylguanidine (MIBG) for extra-adrenal
sites.
Treatment:
a. Surgery
Preoperative management
i. -blocker phenoxybenzamine.
ii. Nitroprusside, calcium channel blockers and ACE
inhibitors to reduce BP. This should be continued till
the day of operation.
b. For non-operable cases
Metyrosine inhibits tyrosine hydroxylase.
PANCREAS
PHYSIOLOGY
Cells of pancreas:
cells secrete glucagon.
cells insulin is secreted from the cells of the islets
of Langerhans in the pancreas. In human, there are
1-2 million islets in the pancreas.
cells secrete somatostatin.
F cells secrete pancreatic polypeptide.
Insulin
Insulin is a polypeptide containing 51 amino acids.

It is formed from a precursor protein called proinsulin.
T1/2 of human insulin in plasma is 5-9 minutes.
Pig insulin contains alanine in its B chain 30 position
(human insulin contains threonine).
Regulation:
Glucose is the main regulator of insulin secretion. Glucose
increases insulin secretion by increasing ATP/ADP ratio
419
inhibition of ATP-sensitive K+ efflux channels

depolarization of B cells and activation of voltage-gated
Ca++ channels the calcium influx results in insulin
secretion.
Catecholamines decrease insulin secretion by 2 action
(predominant) and increase secretion by 2 action. Overall
action is decrease in insulin secretion.
Insulin secretion is also decreased by somatostatin,
diazoxide and aloxan.
Note: In animals, diabetes can be produced by
administration of aloxan.
Action:
Insulin acts primarily on liver, muscle and adipose tissue.
1. Increased glucose entry in muscle and adipose tissue
(direct action).
2. Increased hepatic glycolysis (by augmenting the actions
of glucokinase, phosphofructokinase and pyruvate
kinase). In diabetes, glucokinase is deficient.
3. Increased lipogenesis (by providing the glycerol involved
in TG synthesis). Mechanism increases acetyl-CoA
carboxylase activity, activates pyruvate dehydrogenase
and decreases intracellular cAMP level.
4. Increased protein synthesis.
5. Increased glycogen synthesis.
6. Increased uptake of amino acids, ketones and K+.
Glucose transporters
Glucose transporters
Transporters
Location
Function
Facilitated diffusion
GLUT 1
GLUT 2
GLUT 3
GLUT 4
GLUT 5
Brain, kidney, colon,

placenta, erythrocyte
Liver, pancreatic B cells,
small intestine, kidney
Brain, kidney, placenta
Heart and skeletal
muscle, adipose tissue
Small intestine
Uptake of glucose
Uptake and release
of glucose
Uptake of glucose
Insulin-stimulated uptake
of glucose
Absorption of glucose
Sodium dependant transporter

SGLT 1
Small intestine and

kidney
Active uptake of glucose from

intestine and reabsorption of
glucose in PCT of kidney
against a concentration
gradient
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Note:
Direct entry of glucose by insulin occurs in muscle and
adipose tissue (by GLUT 4).
Indirect entry of glucose occurs in liver by inducing
glucokinase.
Insulin receptor:
It is a tetramer (22 glycoprotein). The beta subunit
has tyrosine kinase activity.
The number of insulin receptor per cell is increased
in starvation and decreased in obesity and acromegaly.
DIABETES MELLITUS
Glucose Tolerance
Impaired glucose tolerance in diabetes is in part due
to decreased peripheral utilization of glucose.
Oral glucose tolerance test:
1. Fasting (overnight) venous plasma glucose 140 mg/
dl on at least 2 separate occasions.
2. Following ingestion of 75 gm of glucose, venous plasma
glucose 200 mg/dl at 2 hour and on at least one other
occasion during the 2 hour period.
HbA1c:
It gives an estimate of glucose level in plasma in the
preceding 3 months.
For good control, it should be < 7 percent.
Classification with cause
Primary:
1. Autoimmune (type 1) DM insulin dependant DM
(IDDM) or juvenile onset DM.
95 percent cases express HLA DR3 or HLA DR4.
It causes degeneration of B cells. Destruction of at
least 80 percent of B cells produce hyperglycemia.
Association of IDDM:
SLE, Addisons disease, Hashimotos thyroiditis.
2. Non-autoimmune (type 2) DM non-insulin dependant
DM (NIDDM) or maturity onset DM. This is due to
insulin resistance.
Secondary:
1. Chronic pancreatitis in alcoholics.
421
2. Hormonal pheochromocytoma, acromegaly,

Cushings syndrome.
3. Genetic myotonic dystrophy, ataxia telangiectasia.
4. Total pancreatectomy.
Epidemiology:
Prevalence of diabetes in India is 2-5 percent (3.8%).
Features
Features of diabetes
Characteristic
IDDM
Genetic locus
Chromosome 6;
association with
HLA DR3 or
HLA DR4
Age of onset
< 40 years
Body
Normal to wasted
Plasma insulin
Decreased or absent
Plasma glucagon
Increased, suppressible
Plasma triglyceride Normal
Acute complication Ketoacidosis
Insulin therapy
Responsive
Oral hypoglycemics Unresponsive
NIDDM
Unknown more
common familial,
autosomal dominant
trait
> 40 years
Obese
Normal or increased
Increased, resistant
Increased
Hyperosmolar coma
Responsive to resistant
Responsive
ACUTE COMPLICATIONS OF DIABETES

Hypoglycemia
More common with IDDM.
Somogyi phenomenon: Rebound hyperglycemia following
an episode of hypoglycemia due to counter regulatory
hormone release.
Dawn phenomenon: Early morning hyperglycemia requiring
increased amount of insulin to maintain normal glucose
level.
Diabetic Ketoacidosis
Occurs in IDDM.
Cause:
Insulin deficiency with a relative or absolute increase
in glucagon concentration.
It is precipitated by cessation of insulin intake, stress
either physical (infection, surgery) or emotional.
422
Pathogenesis:
The hormonal changes have two critical effects
1. Induce gluconeogenesis and impair peripheral utilization
of glucose causing severe hyperglycemia induce
an osmotic diuresis that leads to the volume depletion
that characterizes ketoacidotic state.
2. Increased ketogenesis and metabolic acidosis (mostly
beta hydroxybutyrate).
Clinical feature:
Symptoms
i. Anorexia, nausea, vomiting.
ii. Polyuria and abdominal pain.
iii. Coma.
Sign
i. Kussmaul respiration or air hunger rapid, deep
respiration with a low volume rapid pulse.
ii. Dehydration.
iii. Body temperature normal or decreased. Fever
indicates infection.
iv. Leukocytosis is a feature of diabetic ketoacidosis and
may not indicate infection.
v. Electrolytes- metabolic acidosis with high anion gap,
decreased K+ and Na+, hypertriglyceridemia.
Diagnosis: Urine for glucose and ketone bodies.
Treatment:
1. Insulin therapy 25-50 U initial dose IV followed by
an infusion of 15-25 U an hour until ketoacidosis is
reversed.
2. IV fluid total fluid loss in ketoacidosis is about 35 liters.
1-2 liters of normal saline or Ringers lactate solution
rapid IV.
When plasma glucose falls to 300 mg/dl, 5 percent
dextrose should be added to provide free water and
prevent later cerebral edema.
3. K+ supplementation.
4. Bicarbonate therapy in severe acidosis.
Prognosis: Acidosis is the most common cause of early
death in clinical diabetes.
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Hyperosmolar Non-ketotic Coma (HONC)

Occurs in NIDDM.
Cause:
Sustained diuresis under conditions when patient is
unable to drink enough water.
Phenytoin therapy precipitates HONC.
Clinical feature:
Severe hyperglycemia (plasma glucose level > 1000
mg/dl or 55 mmol/liter).
Profound dehydration (fluid loss 10-11 liters).
Hyperosmolarity of urine.
CNS clouded consciousness to coma.
Complications:
Infection particularly gram negative pneumonia and
sepsis indicates grave prognosis.
Treatment:
HONC can be corrected by large amount of fluid alone.
Protocol as described in diabetic ketoacidosis.
Insulin, K+ and HCO3- are also given.
LATE COMPLICATIONS
Diabetic Retinopathy
It is more common in IDDM.
Maculopathy is more common in NIDDM.
Predictor: The best predictor of diabetic retinopathy is the
duration of diabetes.
Pathogenesis: Increased vascular permeability as evidenced
by leakage of dye into vitreous after fluorescein injection.
Stages:
1. Background diabetic retinopathy
Features:
i. Microaneurysms.
ii. Dot and blot shaped hemorrhages.
iii. Superficial flame-shaped hemorrhage.
iv. Hard exudates.
2. Diabetic maculopathy
Most common cause of visual impairment in diabetic
retinopathy.
424
Feature: Macular edema.

3. Pre-proliferative diabetic retinopathy
Features:
i. Cotton wool spots (soft exudates).
ii. Intraretinal microvascular abnormalities (IRMA).
4. Proliferative diabetic retinopathy
Features:
i. Neovascularization most characteristic.
ii. Vitreous hemorrhage.
iii. Retinal detachment.
Treatment: Argon laser photocoagulation.
Diabetic Nephropathy
Occurs both in IDDM and NIDDM.
a. Glomerulus
Diffuse glomerulosclerosis (most common renal
lesion).
Nodular glomerulosclerosis (Kimmelstiel-Wilson
lesion).
b. Renal vasculature hyaline arteriosclerosis.
c. Pyelonephritis with necrotizing papillitis.
Clinical feature:
Stages
i. Asymptomatic for 10-15 years.
ii. Microalbuminuria excretion of 30-300 mg/day of
albumin.
iii. Macroproteinuria excretion of > 500 mg/day of
albumin.
Treatment: ACE inhibitors prevent progression of
nephropathy, hence they are the drug of choice in
hypertension with diabetes.
Diabetic Neuropathy
Peripheral polyneuropathy most common
manifestation.
Charcot joints, particularly in the feet (tarsal joints).
Treatment:
Topical application of capsaicin for burning pain and
hyperesthesia.
Others tricyclics (amitriptyline), phenytoin.
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Diabetic Foot Ulcer

This is secondary to diabetic neuropathy.
Others
1.
2.
3.
4.
Hypertriglyceridemia.
Skin lesions necrobiosis lipoidica.
Hyperviscosity.
Infections
Malignant otitis externa due to Pseudomonas
aeruginosa.
Rhinocerebral mucormycosis.
Emphysematous cholecystitis/pyelonephritis in
diabetic men.
Reversibility of Changes
Meticulous control of diabetes with insulin infusion pumps
has been reported to
1. Decrease microalbuminuria.
2. Improve motor nerve conduction velocity.
3. Decrease plasma lipoproteins.
4. Decrease capillary leakage of fluorescein in the retina.
HYPOGLYCEMIA
Recognizable symptoms occur when blood glucose falls
below 45 mg/dl.
Causes of Hypoglycemia
1. Hormonal hypopituitarism, Addisons disease,
catecholamine and glucagon deficiency.
2. Enzyme G-6-PD deficiency.
3. Liver disease hepatic congestion, severe hepatitis,
cirrhosis of liver.
4. Others hypothermia.
5. Tumors causing hypoglycemia insulinoma, soft tissue
sarcoma, heptocellular carcinoma.
Neonatal Hypoglycemia
Plasma glucose level < 40 mg/dl or blood glucose < 35
mg/dl.
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Hypoglycemic Unawareness
This occurs in meticulously controlled DM due to lower
symptomatic threshold. Patient shows neuroglycopenic
symptoms before autonomic symptoms are initiated.
TESTIS
ANATOMY
Coverings of testis:
From outside inwards skin, dartos muscle, external
spermatic fascia, cremasteric muscle and fascia,
internal spermatic fascia, tunica vaginalis (parietal layer).
Mnemonic: Some Decent English Call It Testis.
Venous drainage: Pampiniform plexus 15-20 in number
at the origin; 4 in the inguinal canal.
Testicular veins:
Right vein drains into the IVC.
Left vein drains into the left renal vein.
Lymphatic drainage: Lymphatics from the testis drain into
pre-aortic and para-aortic lymph nodes.
Development
Primordial germ cells are developed in the wall of the
yolk sac.
Descent of testis:
Testis passes through inguinal canal at 7th month of
intrauterine life.
Normally reaches the scrotum by 8th month.
Appendix of testis: It is a remnant of the paramesonephric
duct.
Appendix of epididymis: It represents the cranial end of
mesonephric duct.
PHYSIOLOGY
Sertoli Cells
They have FSH receptors on them.
Spermatogenesis occurs in them.
427
They are glycogen containing cells and have a cartwheel appearance.

Function:
1. They secrete.
i. Androgen binding protein.
ii. Inhibin inhibits FSH secretion.
iii. MIS causes regression of Mllerian ducts in males
during fetal life.
2. The tight junctions between the Sertoli cells form the
blood-testis barrier.
3. They provide nutrition to the germ cells.
4. They contain aromatase which converts androgens to
estrogen.
Leydig Cells
They are acted upon by LH.
They secrete gonadal androgens.
Spermatogenesis
Stages:
Spermatogonia (primitive germ cells)
Primary spermatocytes
Secondary spermatocytes
Spermatids (contain 23 chromosomes)
Spermatozoa
Pathway: Seminiferous tubules straight tubules rete

testes efferent tubule epididymis.
Spermatozoa acquire motility during their passage
through the epididymis.
Note:
Viability of sperms in female genital tract 48 hours.
Total period of spermatogenesis 61 days.
Time for capacitation 2-6 hours.
Length of spermatozoa 50 micron.
Spermatogenesis occurs at a temperature lower than
core body temperature (at about 32C).
428
Semen
Contents:
Sperm normally about 100 million/ml; at least 20
million/ml.
Secretions from the seminal vesicles, prostate and
Cowpers gland.
Prostaglandins are high in semen and comes from the
seminal vesicles.
Fructose is produced by the seminal vesicles and is
the main nutritional supply for the spermatozoa.
Note:
Human sperms move at a rate of 3 mm/min.
Volume of ejaculate 2-6 ml.
60 percent of the sperms should be motile and of
normal morphology.
Secretions from Testis
1. Androgens:
Synthesis:
Cholesterol pregnenolone androstenedione
testosterone dihydrotestosterone.
Dihydrotestosterone is the most potent androgen.
Testosterone to dihydrotestosterone conversion occurs
by the enzyme 5- reductase.
Action:
Increased protein synthesis and decreased protein
breakdown (anabolic action), electrolyte (e.g. calcium)
retention.
2. Estrogen: 80 percent of estradiol and 95 percent of
estrone in plasma of adult male is formed by
aromatization of circulating testosterone and
dihydrotestosterone. The rest comes from the testes.
3. Inhibin.
Note:
Androgen receptor is coded in long arm of X
chromosome.
Half of men who have been vasectomized develop
antibody against spermatozoa.
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Sexual Precocity
1. Virilizing syndrome (hypothalamopituitary activity is
normal for age).
Causes: Leydig cell tumors, adrenal tumors, congenital
adrenal hyperplasia (mainly 21-hydroxylase and 11
beta hydroxylase deficiency).
Diagnosis: Increased 17 ketosteroids in blood and urine.
2. Premature activation of hypothalamopituitary system
idiopathic or due to CNS abnormality.
Treatment:
For Leydig cell hyperplasia MDPA.
For idiopathic and inoperable CNS lesions LHRH
analogue.
OVARIES AND FEMALE

GENITAL TRACT
ANATOMY
Ovarian fossa:
It is bounded
i. Anteriorly, by the obliterated umbilical artery.
ii. Posteriorly, by the ureter and the internal iliac artery.
The ovaries are connected to the posterior layer of the
broad ligament by a short fold of peritoneum called the
meso-ovarium.
The suspensory ligament of ovary: It extends from the
infundibulum of the uterine tube to the external iliac vessels
(infundibulopelvic ligament). It contains the ovarian vessels
and nerves.
Ovarian artery: Arises from the abdominal aorta.
Ovarian vein:
Right vein drain into the IVC.
Left vein drains into the left renal vein.
Lymphatic drainage: Lymphatics from the ovaries drain
into the pre-aortic and para-aortic lymph nodes.
Fallopian tubes: They are lined by ciliated columnar
epithelium.
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PHYSIOLOGY
Ovarian Hormones
Five steroidal hormones are secreted from the ovaries
namely
i. Estrogen.
ii. Progesteron.
iii. Androgens.
iv. Inhibin secreted from the granulosa cells of ovarian
follicles. They inhibit FSH secretion.
v. Relaxin secreted from the preovulatory follicle and
corpus luteum.
Estrogen
Estrogen is a C18 steroid, i.e. they lack angular methyl
group at C10 position.
Synthesis :
Sites
Granulosa cells (most common site),
Theca cells and ovarian stroma,
Corpus luteum,
The placenta.
Pathways
Metabolism:
Three types of estrogen are secreted estradiol (most
potent) estrone and estriol.
In the liver, they are converted to glucuronide sulfate
conjugates. All these compounds along with their
metabolites are excreted in urine.
In postmenopausal women, estradiol is metabolized
to estrone (see later).
431
Actions:
Mechanism by binding to nuclear receptor.
1. Uterus increases vascularity and hyperplasia.
Withdrawal of estrogen causes bleeding (withdrawal
bleeding) and menstruation.
2. Secondary sex character feminizing, except axillary
and pubic hairs which are under the control of adrenal
androgens.
3. Metabolic decreases LDL cholesterol and increases
HDL cholesterol and TG. It has a cardioprotective
effect. It increases blood glucose.
4. Hormonal it decreases FSH secretion and increases
LH secretion.
5. Skeletal maturation and epiphyseal closure in both
sexes.
6. Others increases blood coagulability due to increased
synthesis of clotting factors, increases lithogenicity of
bile.
Progesterone
Secretion:
Sites
i. Theca cells and granulosa cells of corpus luteum
during the luteal phase main source.
ii. Both the cells of follicles and ovarian stroma.
iii. Placenta.
Pathway: Cholesterol pregnenolone progesterone.
Metabolism: It is metabolized in the liver to sodiumpregnanediol glucoronide and excreted in urine.
Actions: See below.
MENSTRUAL CYCLE
Normal age of menarche is around 13 years.
Normal Cycle
Interval 28 days.
Duration 5 days.
Amount 20-80 ml (mean 50 ml).
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Oogenesis
A mature ovum (oocyte) is the largest cell in the body
and measures 130 microns in diameter.
Oocytes are developed from the primitive germ cells
which are developed from the yolk sac in fetal life.
Germ cells (yolk sac)
mitosis
Oogonia
(Reaches maximum number at 20th week
of intrauterine life, about 7 million)
Some enter the prophase of first meiotic division and

are called the primary oocytes (46 XX) and
do not complete the meiotic division until puberty
Completes the first meiotic division and forms secondary

oocytes (23 X) and first polar body (23 X). Ovulation
occurs soon after the formation of secondary oocyte.
Secondary oocyte completes the second meiotic division

only after fertilization by the sperm in the fallopian tube (if
not fertilized, it undergoes degeneration within 24 hours).
Hormonal Changes
Gonadotrophins (LH and FSH) are glycoproteins secreted
by basophilic cells of the anterior pituitary under the control
of LHRH (which control both) of hypothalamus.
FSH (in association with minimal LH) causes
maturation of primary follicles which secrete 17-beta
estradiol from the granulosa cells of ovary.
Estradiol causes three changes
i. Produces proliferative changes in the endometrium.
ii. Decreases FSH secretion from anterior pituitary and
iii. Increases LH secretion from anterior pituitary.
LH in turn causes final maturation of graffian follicles
and rupture of follicles at ovulation and to form a corpus
luteum.
Note: Peak estrogen level occurs 48 hours before ovulation
whereas peak LH (LH surge) level occurs 24-36 hours
before ovulation.
Corpus luteum secretes progesterone which causes
a. Uterus
i. Myohyperplasia.
ii. Decreased frequency of uterine contraction.
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iii. Increased tone of circular muscles of uterus.

iv. Secretory changes in the endometrium.
v. Thick and viscid cervical mucosa and
vi. Sodium and water retention.
b. Raises basal body temperature by 0.5oF just after the
ovulation.
In the absence of pregnancy, both estrogen and
progesterone levels decline gradually and brings about the
menstruation.
Note: Pulsatile release of GnRH is under control of
glutamate (excitatory) and GABA (inhibitory). Before
puberty levels of glutamate are low and that of GABA
are high.
Points to be noted:
Selection of dominant follicle: The one with highest antral
estrogen concentration and lowest androgen:estrogen ratio
and whose granulosa cell contain the maximum receptors
for FSH, becomes the dominant follicle.
Cause of rupture of follicle: Necrobiosis of the overlying
tissue due to passive stretching.
Anovular menstruation:
Menstruation is unrelated to ovulation and anovular
menstruation occurs in adolescence, following
childbirth and in women approaching menopause.
Endometrium remains either in proliferative or
hyperplastic state and menstruation occurs due to
irregular shedding of endometrium (dysfunctional uterine
bleeding).
Endometrial Changes
Endometrium has two zones
i. Basal zone not under hormonal control and
regeneration after menstruation occurs from this zone.
ii. Functional zone under the influence of ovarian
hormones estrogen and progesterone and produces
the cyclical change seen in menstrual cycle.
Stages:
1. Regeneration from basal zone, complete in 2-3 days.
2. Proliferative stage is due to ovarian estrogen and
lasts up to ovulation. Ovulation occurs at the end of
this stage.
434
3. Secretory stage is due to progesterone secreted from

corpus luteum after ovulation.
The duration of secretory phase is constant and is 14
days. So ovulation occurs 14 days prior to the next
menstruation (and not 14 days after menstruation).
Changes earliest change (earliest evidence of
ovulation) is subnuclear vaculation containing glycogen.
4. Menstruation occurs due to degeneration of
endometrium as a result of vasospasm and ischemia.
Note: The stages of regeneration and proliferation are
collectively called the ovulatory phase, whereas secretory
phase is also called the luteal phase.
Changes in the Cervix
Estrogen makes it thinner and more alkaline.
Progesterone makes it thick, tenacious and cellular.
Estrogen causes fer n-like pattern of mucosa of the
cervix which is lost after ovulation.
Elasticity or spinnbarkeit is increased by estrogen
loss of elasticity occurs by progesterone after ovulation.
Tests for Ovulation
Tests for ovulation
Method
Day of cycle
Observation
BBT
Endometrial
biopsy
Cervical mucus
study
Throughout cycle
21-23
Biphasic pattern
Secretory endometrium
(best evidence)
Mucosa turns to thick and
viscid
Elasticity is lost, fer n-pattern
is lost after ovulation
12-14 and 21-23
Corpus Luteum
It is the ruptured graafian follicle after ovulation.
Life cycle:
1. Stage of proliferation
2. Stage of vascularization
3. Stage of maturation
Maximum secretory activity is seen 7-8 days after
ovulation (days 22-23 of menstrual cycle).
4. Regression transformed into corpus luteum.
435
Function:
It secretes progesterone and brings about the secretory
changes in endometrium.
Corpus luteum of pregnancy:
If fertilization occurs, there is a surge of hyperplasia
between 23-28 days due to HCG. The growth reaches
peak at about 8 weeks.
The corpus luteum of pregnancy is active up to
10-12 weeks of pregnancy.
DISORDERS OF MENSTRUATION
Definition
Menorrhagia: Bleeding more than 80 ml or/and duration
more than 5 days.
Poly(epi)menorrhea: Menstrual cycle 21 days apart.
Oligomenorrhea: Menstrual cycle > 35 days apart.
Metrorrhagia: Acyclical and irregular bleeding superimposed
on normal menstruation.
Dysmenorrhea: Painful menstruation.
Precarious menstruation: Menarche before the age of 13
years.
Hypomenorrhea: Scanty bleeding lasting less than 2 days.
Menorrhagia
Causes:
1. Dysfunctional uterine bleeding.
2. Fibroid uterus/uterine polyp.
3. Adenomyosis.
4. Chronic tubo-ovarian mass.
5. Granulosa cell tumor of ovary.
6. General hypothyroidism, generalized TB.
Metrorrhagia
Causes:
1. DUB.
2. Submucous fibroid.
3. Uterine polyps.
4. Carcinoma cervix and endometrium.
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Poly(epi)menorrhea
It usually occurs in adolescent girls and premenopausal
women.
Treatment: Cyclic hormone therapy (OCP for 3 cycles).
Dysmenorrhea
Types:
1. Primary or spasmodic most common type.
No identifiable pelvic pathology. May be associated
with submucous fibroid.
Seen in affluent girls 2-3 years after menarche.
Clinical feature: Pain starts few hours before or just after
onset of menstruation and radiates to the back and thigh.
Pain lasts for few hours. Systemic features like vomiting,
headache, syncope may be present.
Treatment: Often symptomatic.
i. Prostaglandin synthetase inhibitors like mefenamic
acid.
ii. OCP.
iii. Surgery dilatation of cervical canal, paracervical
block, presacral neurectomy.
2. Secondary or congestive: Due to some underlying pelvic
pathology like fibroids, adenomyosis, PID, endometriosis.
Clinical feature: Pain starts 3-5 days before menstruation
and relieves with the onset of bleeding. Pain does not
radiate. Pain is not associated with systemic features.
Unilateral dysmenorrhea: Causes
1. Ovarian dysmenorrhea
2. Bicornuate uterus
3. Unilateral pelvic endometriosis
4. Small fibroid near the cornu.
Mittelschmerzs Syndrome
Also called ovular pain.
Pain appears in midmenstrual period (around ovulation)
and is located in hypogastrium or one iliac fossa. Pain
lasts for less than 12 hours.
Treatment: Assurance and analgesics.
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Dysfunctional Uterine Bleeding

It is abnormal bleeding without any clinically detectable
pelvic pathology.
Classification:
Primary a. Anovular bleeding (80%) most common type.
i. Puberty menorrhagia,
ii. Metropathia hemorrhagica,
iii. Premenstrual menorrhagia.
b. Ovular bleeding
i. Epimenorrhea,
ii. Oligomenorrhea,
iii. Functional menorrhagia due to irregular shedding of
endometrium or irregular ripening of endometrium.
Secondary
Hematological disorders, e.g. ITP.
Hypothyroidism.
Iatrogenic IUCD or OCP.
Pathology:
The etiology is purely hormonal. There is increase titer
of estrogen with absent progesterone.
Endometrium becomes hyperplastic in 30 percent cases,
remain normal in 60 percent cases.
Puberty Menorrhagia
Treatment: Progesterone and OCP.
Premenopausal Menorrhagia
Endometrial carcinoma must be excluded by fractional
curettage.
Metropathia Hemorrhagica or Cystic Glandular
Hyperplasia (Schroeders Disease)
Clinical feature:
Most common in premenopausal women.
Presents with heavy vaginal bleeding.
Uterus symmetrically enlarged to size of about 810 weeks of pregnancy.
Endometrium proliferative (no secretory change).
Endometrium shows cystic glandular hyperplasia or
Swiss cheese pattern.
Treatment progesterone.
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Management of DUB
a. General blood transfusion for severe anemia.
b. Hormonal therapy method of choice.
Drugs used are
i. Norethisterone acetate.
ii. Medroxyprogesterone acetate.
iii. Estrogen.
iv. OCP.
v. Danazole.
vi. Gestrinone.
vii. Clomiphene citrate.
viii.GnRH analogue.
Note: Progesterone is most effective in anovular bleeding.
Clomiphene citrate is the drug of choice in anovular
DUB with infertility wanting pregnancy.
c. Anti-fibrinolytic agents
Tranexamic acid or EACA.
Use in IUCD induced menorrhagia.
d. Surgery
i. Premenopausal dilatation and curettage.
ii. Postmenopausal fractional curettage. Treatment
of choice is hysterectomy.
e. Recent methods
i. Radiofrequency induced thermal endometrial
ablation (RITEA) done soon after menses.
ii. Balloon therapy the depth of endometrial
destruction is 8 mm.
MENOPAUSE
It is the cessation of menstruation for more than
consecutive 6 months.
Premature menopause before the age of 40 years.
Hormonal Changes
In premenopausal period, estrogen output from ovary
begins to decline.
FSH level begins to increase before menses stop.
Eventually, both FSH and LH increase by 10-20 folds
(sustained elevation of FSH and LH is conclusive
evidence of ovarian failure).
439
Decreased serum androstenedione by 50 percent

(majority being produced by adrenals).
Increased testosterone from ovary.
Estrone becomes the main estrogen and is derived from
peripheral conversion of androstenedione in adipose
tissue.
Estradiol is produced by peripheral conversion of
testosterone.
DECREASED MENSTRUATION
Cryptomenorrhea
Causes:
a. Congenital:
i. Imperforate hymen most common cause.
ii. Transverse vaginal septum.
iii. Atresia of upper third of vaginal and cervix.
b. Acquired: Stenosis of the cervix following amputation,
deep cauterization and conisation.
AMENORRHEA
Types
Primary: Menarche does not occur till 16 years of age.
Causes:
1. Gonadal dysgenesis most common cause.
2. Mllerian agenesis.
3. Testicular feminization syndrome.
4. Hypogonadotrophic hypogonadism (Kallmann
syndrome).
5. Dysfunction of adrenal and thyroid glands.
6. Infections TB.
7. Unresponsive endometrium.
Secondary:
Causes:
1. Polycystic ovarian disease (PCOD) most common
cause worldwide.
2. Tubercular endometritis most common cause in India.
3. Premature ovarian failure.
4. Resistant ovary syndrome.
5. Uterine synechiae (Ashermans syndrome).
6. Pituitary prolactinomas, Sheehans syndrome.
7. Stress.
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8. Hypothyroidism.
Remember most common cause of secondary
amenorrhea is pregnancy.
ANATOMIC FACTORS
Mllerian Agenesis: (Mayer-Rokitansky-KusterHauser syndrome)
Karyotype 46 XX, phenotype female.
Feature: Primary amenorrhea, absent vagina, absent or
rudimentary uterus.
Diagnosis:
Biphasic BBT curve characteristic of ovulation.
Elevated levels of progesterone during luteal phase.
Treatment: Surgery for vaginal agenesis is done prior to
or soon after marriage vaginoplasty (McIndoe Williams).
Androgen Insensitivity/Testicular
Feminization Syndrome
Features:
Phenotype female.
Patient tends to be tall.
Breasts normal (grade IV thelarche).
Axillary and pubic hairs scanty (grade II puberche).
External genitalia normal.
Vagina short and blind. The upper third of vagina,
uterus and tubes are absent.
Gonads testes, are placed in labia or inguinal canal
or intra-abdominal.
Gonads secrete MIF (Mullerian inhibiting factor) by
sertoli cells.
Diagnosis:
Patient presents with primary amenorrhea or infertility.
Karyotype 46 XX (male).
Confirmation by gonadal biopsy.
Treatment: Pre-pubertal castration.
Testicular Agenesis
Karyotype 46 XY, phenotype female.
Features : Sexual infantilism, absent uterus.
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Ashermans Syndrome
Cause: Formation of adhesions following uterine curettage.
Feature: Seconday amenorrhea.
Treatment : Adhesiolysis with a uterine probe with IUCD
insertion.
OVARIAN FAILURE
Gonadal Dysgenesis
Causes hypergonadotropic (FSH > 40 MIU/ml)
hypogonadism.
This is the most common cause of primary
amenorrhea.
Turners Syndrome
Karyotype 45 XO, phenotype female.
Morphogenesis: Homebox gene defect (which is involved
in vertical growth).
Features:
i. Primary amenorrhea.
ii. Short stature with webbed neck and low hairline.
iii. Shield chest with widely spaced nipples.
iv. Short 4th metacarpals and metatarsals.
v. Edema of hand and feet.
vi. Cubitus vulgus deformity.
vii. Associations coarctation of aorta, bicuspid aortic
valves, horseshoe shaped kidney.
viii. No mental retardation.
Diagnosis:
Gonads are streaks.
Increased FSH and LH, decreased estrogen.
Treatment:
Gonadectomy.
Noonan Syndrome
Mental retardation.
Pectus excavatum.
Normal 4th metacarpals.
Pulmonary stenosis.
Others like Turners syndrome.
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Chromosomal Mosaicism
Karyotype 45 XX/45 XO.
Gonads streaks with few or absent follicles.
There is increased chance of malignancy in mosaicism
involving Y chromosome. Streak gonads are removed
prophylactically if Y chromosome is present on
karyotyping.
Premature Ovarian Failure
Menopause before the age of 40 years.
Cause: Ovarian autoantibodies.
Feature:
May be associated with adrenal insufficiency,
hypothyroidism and other autoimmune disorders.
Increased FSH with ovarian failure.
Resistant Ovary Syndrome
Cause: Resistance to the action of FSH in the ovary.
Chronic Anovulation with Estrogen Present
Diagnosis: Withdrawal bleeding present after progesterone
administration.
Polycystic Ovarian Disease (PCOD)
(Stein-Leventhal Syndrome)
Features: Secondary amenorrhea, hirsutism, obesity and
infertility.
Hormone status: Excess production of androgens
(androstenedione) leads to excess extragonadal production
of estrogen (mainly estrone) positive feedback on LH
secretion (increased LH secretion) and negative feedback
on FSH secretion (decreased FSH secretion).
i. Increased LH and decreased FSH and LH:FSH ratio
> 2.
ii. Decreased estrogen and increased estrone.
iii. Mild increase in testosterone level and DHEA-S level.
iv. There may also be increased prolactin level.
Diagnosis: USG shows necklace appearance of ovary.
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Treatment:
i. Clomiphene citrate drug of choice to induce
ovulation.
ii. HMG, LHRH analogues, purified FSH to induce
ovulation.
iii. OCP in patients not wanting pregnancy.
iv. Surgery.
Risk: Increased chance of endometrial carcinoma.
Chronic Anovulation with Estrogen Absent
Diagnosis no withdrawal bleeding after progesterone
challenge test.
Isolated Hypogonadotropic Hypogonadism
Kallmann syndrome:
Feature:
Amenorrhea with defects of smell (anosmia), sexual
infantilism, normal stature.
Prolactinomas
See above.
Panhypopituitarism
Cause:
i. Surgery for prolactinomas.
ii. Radiation.
iii. Postpartum hemorrhage in the pituitary Sheehans
syndrome.
Sheehans syndrome:
Pathology: Anterior pituitary necrosis due to postpartum
hemorrhage into the pituitary.
Feature: Failure to lactate or ovulate, loss of pubic and
axillary hair, hypothyroidism, adrenal insufficiency,
secondary amenorrhea, atrophy of breasts and genitalia.
Treatment: Cortisone.
DISORDERS OF SEXUAL DIFFERENTIATION
Disorders of Chromosomal Sex
Klinefelter Syndrome
Karyotype 47 XXY, phenotype male.
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Features:
Small, firm testes (testicular atrophy).
Azoospermia and infertility.
Gynecomastia.
Decreased body hair.
Tall stature with long legs, slim and underweight.
Increased plasma gonadotrophins, decreased
testosterone.
Diagnosis: Barr bodies are seen in cells.
Risk: Increased chance of breast malignancy in males.
DISORDERS OF PHENOTYPIC SEX
Female Pseudohermaphroditism
Congenital Adrenal Hyperplasia
Inheritance: Autosomal recessive trait.
Pathways:
Cholesterol
Pregnenolone
17 hydroxylase
Androgen
Progesterone
17 hydroxylase
21 hydroxylase
Deoxycorticosterone
11 hydroxylase
Corticosterone
21-hydroxylase Deficiency
It is the most common type and most common cause
of ambiguous genitalia in newborn.
Characterized by decreased aldosterone and increased
androgens.
Features:
Virilization in females and precocious masculinization
in males.
Female child is born with enlarged clitoris and fusion
of labia (pseudohermaphroditism).
Salt-losing form decreased sodium, increased
potassium and dehydration.
11- Hydroxylase Deficiency
Normal deoxycorticosterone, increased androgen.
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Hypertensive form.
Virilization in females and precocious puberty in males,
hypertension.
17- Hydroxylase Deficiency
Characterized by decreased androgen and increased
aldosterone.
Feature:
In girls sexual infantilism (amenorrhea).
In boys male pseudohermaphroditism.
In both hypokalemia, hypertension.
Note: Causes of male pseudohermaphroditism
i. Gonadal dysgenesis.
ii. Testicular feminization.
iii. Testicular agenesis.
MULTIPLE ENDOCRINE
NEOPLASIA (MEN)
MEN1 (Wermers Syndrome)
Associated with MEN1 tumor suppressor gene located on
chromosome 11q13.
Characterized by 3 Ps.
1. Parathyroid hyperplasia causing hyperparathyroidism.
2. Pancreas islets cell hyperplasia, endocrinal tumors,
most commonly gastrinomas (Z-E syndrome).
3. Pituitary hyperplasia or adenoma (most commonly
prolactin secreting microadenoma).
Clinical feature: Peptic ulceration (due to pancreatic
endocrine tumor) and renal stone (due to
hyperparathyroidism).
MEN2A (Sipple Syndrome)
Associated with mutation of RET proto-oncogene on
chromosome 10q11.2.
1. Thyroid medullary carcinoma of thyroid.
2. Adrenal medulla pheochromocytoma.
3. Parathyroid hyperplasia.
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MEN2B (Williams Syndrome)

Same as MEN2A except:
i. No hyperparathyroidism.
ii. Mucosal and gastrointestinal neuromas.
iii. Marfanoid features.
HEMOCHROMATOSIS
It is deposition of iron in parenchymal cells of the liver,
pancreas, heart and pituitary (but not in testes).
Cause: Increased absorption of iron from the intestine.
Inheritance:
Associated with HLA-A3.
Most common genetic defect is mutation of HFE gene
on chromosome 6.
Clinical feature:
1. Liver most common involvement. Causes
hepatomegaly, cirrhosis, hepatocellular Ca.
2. Skin pigmentation (bronze color).
4. Congestive cardiac failure.
5. Arthropathy most commonly involving the small joints
of hand.
6. Hypogonadism due to hypopituitarism.
Laboratory findings
Increased values of serum iron, increased ferritin and
increased transferrin saturation.
Liver biopsy confirmatory.
Treatment:
1. Phlebotomy weekly venesection for 2-3 years.
2. Deferoxamine when anemia or hypoproteinemia is
severe enough to preclude phlebotomy.
PORPHYRIAS
Porphyrins are synthesized in the liver and bone marrow.
Acute Intermittent Porphyria
Autosomal dominant.
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Cause: Deficiency of the enzyme HMB synthase

(uroporphyrinogen I synthase).
Pathology: Increased activity of ALA synthase and increased
gamma ALA level and increased urinary excretion of
porphobilinogen.
i. Endogenous and exogenous gonadal steroids.
ii. Drugs barbiturates (phenobarbitone).
iii. Alcohol ingestion.
Note: Bromides are safe in AIP and were used to control
seizures.
Clinical feature:
Seen in childhood.
Abdominal pain most common symptom.
Peripheral neuropathy due to axonal degeneration.
Mental symptoms are characteristic.
Fever and leukocytosis are usually absent or mild.
No photosensitivity.
Diagnosis: Watson-Swartz test to differentiate between
porphobilinogen and urobilinogen. It detects
porphobilinogen (also Hoesch test).
Porphyria Cutanea Tarda
Most common type of porphyria.
Cause: Deficiency of urobilinogen decarboxylase.
Clinical feature:
Photosensitivity characterized by increased fragility of
sun-exposed skin.
Vesicles and bullae that rupture and heal slowly with
crusting and purplish discoloration.
Hypertrichosis.
Hyperpigmentation.
Increased chance of hepatocellular Ca.
Treatment:
Phlebotomy
Low dose chloroquine.
Note: Preservative used for urine to detect porphyrin is
HCl.
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Congenital Erythropoietic Porphyria

(Gunthers Disease)
Cause: URO synthase III deficiency.
Genetics: It is autosomal recessive while all other porphyrias
are autosomal dominant.
Clinical feature:
Photosensitivity increased fragility of sun-exposed skin.
Hemolytic anemia.
HYPERURICEMIA AND GOUT

Blood Level
Mean blood level of uric acid is 6.8 mg/dl.
Hyperuricemia means > 7 mg/dl of urate in serum.
Causes
1. Urate overproduction
Myeloproliferative diseases
Polycythemia vera
Psoriasis
Pagets disease
Lesch-Nyhan syndrome
Lymphoma
2. Decreased urate excretion
Hyperparathyroidism
Renal failure
Diuretic therapy
3. Combined mechanism
Glucose-6-phosphatase deficiency (von-Gierkes
disease) hyperuricemia from infancy and gout
develops early in life.
Lesch-Nyhan Syndrome
It is due to complete deficiency of hypoxanthineguanine phosphoribosyl transferase (HGPRT) enzyme.
Inherited as X-linked trait.
Feature: Self-mutilation, choreoathetosis with gout, renal
calculi.
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Kelly-Seegmiller Syndrome
This is due to partial deficiency of HGPRT.
Feature: Patient develops only gout and renal calculi.
Clinical Feature
Gouty Arthritis
Acute monoarticular arthritis.
Most common site is the metatarso-phalangeal joint
of great toe.
Pathology:
There is deposition of sodium biurate crystals in soft
tissues, viz. cartilage, tendon and bursa.
Tophi deposition of monosodium urate monohydrate
crystals in the skin, muscle and articular cartilage.
Renal Disease
Uric acid stones are seen in 30-40 percent cases.
Diagnosis
Biochemical marker urate crystals aspirated from
joint fluid is confirmatory.
Note: Transport media for stones in gout is alcohol.
Treatment
a. Acute gout colchicines, NSAIDs (most effective),
intra-articular glucocorticoids.
b. Chronic gout allopurinol, probenecid.
DISORDERS OF
LIPOPROTEIN METABOLISM
LIPID TRANSPORT
Lipids are insoluble in water. To make them water
soluble, lipoproteins are formed.
Structure of lipoproteins
Central core contains hydrophobic non-polar lipids
triglycerides and cholesterol esters.
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Surface contains amphipathic phospholipids and free

(unesterified) cholesterol.
Apolipoproteins present on the surface.
Types of Lipoproteins
1. Chylomicrons transport lipid from intestine to tissues.
Contains maximum TG.
2. VLDL transports lipid from liver to tissues. Mainly
contains TG.
3. IDL also called VLDL-remnants, produced by
metabolism of VLDL.
4. LDL contains maximum cholesterol.
5. HDL transports cholesterol from tissues to the liver
(reverse cholesterol transport). Contains maximum
phospholipids and least TG.
Apolipoprotein
The protein part of a lipoprotein is called apolipoprotein.
VLDL contains Apo B100, Apo E and Apo C.
IDL contains Apo B100 and Apo E.
LDL contains Apo B100.
HDL contains Apo A, Apo E and Apo C.
Chylomicrons contain Apo B48, Apo A, Apo E and
Apo C.
Functions
Apo A-1 helps in reverse cholesterol transport (by
HDL). It activates LCAT (Lecithine:cholesterol
acyltransferase).
Apo B100 secretion of VLDL from the liver, ligand
for LDL receptor.
Apo B48 chylomicron secretion from intestine.
Note: Apo B100 and Apo B48 are synthesized by the
same gene and mRNA. It is an RNA-editing mechanism
in intestine that forms Apo B48.
Apo CII activation of lipoprotein lipase.
Apo E mediates LDL uptake in liver (also of
chylomicron remnants).
Lipoprotein Lipase
It is synthesized in adipose tissues and muscles and is
present on the endothelial surface of capillary beds.
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Action: It hydrolyses TG of chylomicrons and VLDL to

produce fatty acid and glycerol.
Regulation:
Insulin inhibits whereas epinephrine and norepinephrine
stimulate it.
Defective LPL is associated with hypertriglyceridemia.
LDL (Apo B100, E) Receptor
This is present on all cells (maximum in adrenals).
Action: Uptake of cholesterol rich LDL by live as well as
extrahepatic tissues.
Regulation:
Cholesterol delivered to cytoplasm by LDL receptor
decreases the rate of cholesterol synthesis in the liver and
also decreases the number of LDL-receptors in cell surface.
Note: Increased LDL and Apo B100 in blood increase
the risk of atherosclerosis (through a separate scavenger
receptor pathway where LDL undergoes peroxidation).
Probucol an antioxidant, inhibits LDL oxidation and
lowers the risk of CHD.
HYPERLIPOPROTEINEMIAS
Hyperlipoproteinemias
Type Disease
Defect
LPL
Normal
Increased
deficiency
LDL
Increased Normal
receptor
defect
Unknown Increased Increased
IIa
IIb
III
IV
V
Familial LPL
deficiency
Familial hypercholesterolemia
Familial mixed
lipoproteinemia
Familial
Apo E
dysbetalipoproteinemia
Familial
triglyceridemia
Familial
combined
hyperlipidemia
Serum
Serum
cholesterol TG
Increased Increased
Unknown Normal
Increased
Apo C
Increased
Normal
Elevated
lipoprotein
Chylomicron
LDL
LDL and
VLDL
VLDL
remnants
and
chylomicron
remnants
VLDL
VLDL and
chylomicrons
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Type I: Familial Lipoprotein Lipase Deficiency

Characterized by hyperchylomicronemia.
Clinical feature: Starts at infancy with pancreatitis, eruptive
xanthomas, hepatosplenomegaly, foam cell infiltration of
bone marrow, lipemia retinalis.
Diagnosis: A layer of cream (chylomicrons) at the top of
plasma.
Treatment: Diet containing less fat and more complex
carbohydrates.
Type II: Familial Hypercholesterolemia
Autosomal dominant.
Clinical feature:
Tendon xanthomas (most common in Achilles tendon).
Tuberous xanthomas, xanthelasmas (corporis =
deposition around eyelids).
Increased risk of CHD.
Note: All increase the risk of CHD except type I and type V.
Wolmans Disease
Cholesteryl ester storage disease due to deficiency of
cholesteryl ester hydrolase with increased LDL.
Secondary Causes of Hyperlipoproteinemias
Hypercholesterolemia
Nephrotic syndrome
Primary biliary cirrhosis
Hypertriglyceridemia diabetes mellitus.
Others myxedema, chronic alcoholism, drugs (OCP,
beta blockers, corticosteroids).
Treatment
a. In increased LDL-Chl. (Type II and V):
1. Bile acid sequestrants (resins)
Mechanism of action increase excretion of bile
and cholesterol in stool increase hepatic
cholesterol synthesis and increase LDL receptor (due
to increased HMG-CoA activity).
Action decrease LDL-Chl. All others are normal.
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2. HMG-CoA reductase inhibitors (statins) first

choice drug.
Mechanism of action decrease cholesterol
synthesis decrease LDL and VLDL compensatory increase in LDL receptors.
b. In increased TG (Type III, IV, V):
1. Nicotinic acid highly effective.
2. Fibric acid derivatives (gemfibrozil is the drug of
choice, clofibrate).
They both increase HDL.
HYPOLIPOPROTEINEMIA
Abetalipoproteinemia
Cause: Absent microsomal triglyceride transfer protein
(MTP).
Feature: Low cholesterol and no VLDL, IDL, LDL or
chylomicron.
Clinical feature: Malabsorption of fat, soluble vitamins A
and E. acantholytic RBC, ataxia and retinitis pigmentosa,
steatorrhea.
Treatment: Vitamin E supplementation.
Fish Eye Disease
LCAT deficiency.
Others
Hematological malignancies, Gauchers disease, NiemannPick disease.
LYSOSOMAL STORAGE DISEASES

THE MUCOPOLYSACCHARIDOSIS (MPS)
All are autosomal recessive except Hunters disease which
is X-linked recessive.
Cause: Defective metabolism of glycosaminoglycans (GAG)
due to specific deficiencies of lysosomal hydrolases.
Note: GAGs are heteropolysaccharides containing amino
sugars (d-glucosamine or d-galactosamine) and uronic acid
(d-glucuronate or d-iduronate).
454
MPS I (Hurlers Disease) or Gargoylism

Cause: -L-iduronidase deficiency.
Features:
Short stature, organomegaly (hepatosplenomegaly),
corneal clouding, coarse features, mental retardation,
joint stiffness, large tongue.
CVS Valvular heart disease, no ECG changes (c.f.
Pompes disease).
Others kyphosis, umbilical hernia, hydrocephalus,
profuse nasal discharge due to respiratory infection.
Urinary metabolites dermatan sulfate, heparan
sulfate, increased uronic acid in urine.
MPS II (Hunters Disease)
Cause: Iduronate sulfatase deficiency.
Absence of corneal clouding and mild or absent mental
retardation.
LIPID AND GLYCOGEN

STORAGE DISEASES
All are autosomal recessive except Fabrys disease which
is X-linked.
Storage Diseases
Disease
Gauchers
disease
Fabrys
disease
NiemannPick disease
Deficient enzyme
Features
Lipid storage disease

-glucocerebrosidase Type I: Hepatosplenoresults in accumulation megaly, cholestasis and
of cerebrosides in cells. mental retardation in
neonates; bone erosion,
pancytopenia.
No symptoms in adults.
Type II: CNS symptoms,
lethal.
Biopsy wrinkle paper
appearance of cells
Treatment enzyme
replacement therapy.
-galactosidase
Multiple angiokeratomas.
Sphingomyelinase
Foam cells in blood,

childhood cholelithiasis.
(Contd...)
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(Contd...)
Disease
Tay-Sachs
disease
Sandroffs
disease
Krabbes
disease
Wolmans
disease
1. VonGierkes
disease
2. Pompes
disease
Deficient enzyme
Features
GM2 Gangliosidosis
Hexosaminidase A
Cherry red spot in eye.
Hexosaminidase
A and B
Cherry red spot in eye.
Leukodystrophies
-galactosidase
Deep white matter lesion
with bilateral deep bright
thalamus
Adrenal calcification
Glycogen Storage Diseases
Glucose-6Hepatomegaly,
phosphatase
hypoglycemia, lactic
acidosis, hyperuricemia,
hyperlipidemia.
1,4 and 1,6
Hepatosplenomegaly, CVSglucosidase (acid
high voltage QRS complex
maltase) causes
and a short PR interval,
accumulation of
cardiomegaly, HOCM,
glycogen in lysosomes. CHF, hypotonia,
macroglossia, coarse
features.
Debranching enzyme
3. Forbes
disease
4. Andersons Branching enzyme
disease
5. McArdles Muscle phosphorylase
disease
6. Hers
Liver phosphorylase
disease
Note: Type 2, 3 and 5 of glycogen storage diseases involve muscles,

hence muscle biopsy is helpful in their diagnosis.
INHERITED DISORDERS OF
CONNECTIVE TISSUE
Osteogenesis Imperfecta
Inheritance:
Autosomal dominant in type 1 (most common type).
Autosomal recessive in type 2 (lethal).
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Pathology:
Abnormal development of type 1 collagen which is
present in bones, skin, joints and sclerae.
Features:
Type 1 mildest form, characterized by
Pathological fracture of bones (brittle bones) but
fractures heal normally.
Blue sclerae.
Dental abnormalities (dentinogenesis imperfecta).
Hearing loss due to otosclerosis.
Joint laxity and permanent dislocations.
Type 2 lethal in utero or shortly after birth.
Ehler-Danlos Syndrome
Inheritance:
Autosomal dominant/recessive/X-linked.
Characterized by:
Hyperelasticity of the skin and hypermobility of joints.
Complication:
Rupture of colon and arteries (type IV) due to
deficiency of collagen type III.
Ocular rupture (type VI).
Diaphragmatic hernia (type I).
Achondroplasia
Inheritance: Autosomal dominant. But a positive family
history is present in only 20 percent cases. Remaining 80
percent cases arise from a fresh gene mutation.
Pathology: Failure of normal ossification of bone leading
to dwarfism.
Clinical feature:
Dwarfism, characterized by disproportionate shortening
of proximal extremities.
Bowing of legs, increased lumbar lordosis, short and
stubby fingers (trident hand).
Intelligence and sexual characters are normal.
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Marfans Syndrome
Inheritance:
Autosomal dominant.
Associated with increased age of father.
Pathology:
Abnormality of fibrillin 1 which is a major component
of microfibrils found in extracellular matrix.
Fibrillin is coded by FBN1 gene on chromosome 15.
Features:
Stature tall, slender with long extremities.
Fingers tall and have a spider-like appearance
(arachnodactyly).
Eyes dislocation or subluxation of lens (bilateral)
ectopia lentis.
Chest pectus excavatum (depression) or pectus
carinatum (protrusion).
Spine kyphoscoliosis.
Joint mobility is normal but may be hypermobile.
CVS aortic aneurysm involving the ascending aorta
and aortic dissection, mitral valve prolapse and mitral
regurgitation, floppy valve syndrome; death is due to
aortic rupture.
Others high arched palate and high pedal arches,
spontaneous pneumothorax, inguinal and visceral
hernias, cutis laxa (premature aged appearance).
Alports Syndrome
Inheritance: Most common type is X-linked dominant.
Features: Hematuria, sensorineural deafness, lenticonus.
INHERITED DISORDERS
OF AMINO ACID METABOLISM
AND STORAGE
Phenylketonuria
Cause:
Deficiency of phenylalanine hydroxylase enzyme which
converts phenylalanine to tyrosine.
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Alternative pathways convert phenylalanine to

phenylpyruvate which undergoes incomplete oxidation
to produce phenyketoacids (phenylacetate,
phenyllactate) that are excreted in urine.
Phenylketonuria type II is due to deficiency of
dihydropteridine reductase.
Clinical feature:
Mental retardation, hyperactivity, seizures.
Skin hypopigmentation and eczema, vulnerable to
minor inflammatory lesions.
Mousy odor of skin, hair and urine due to phenylacetate.
Microcephaly at birth.
Maternal phenylketonuria causes
Microcephaly, mental retardation, growth retardation
and congenital heart disease in their babies.
Diagnosis:
Increased plasma phenylalanine (usually after feeding
provocative protein meal test).
Increased urinary levels of phenylpyruvate,
Normal plasma tyrosine.
Screening tests:
Guthrie bacterial inhibition assay.
FeCl3 turns green in presence of phenylalanine in urine.
2-4 dinitrophenol hydrazine yellow precipitate.
Treatment:
Tyrosine becomes an essential amino acid in PKU. So
treatment consists of diet low in phenylalanine and
rich in tyrosine (but phenylalanine should not be
completely eliminated from food).
Diet should be started soon after birth and continued
up to 6 years of age.
Prevention:
Neonatal screening test for PKU.
Homocystinurias
Pathogenesis:
Defects in metabolism of methionine.
Most common type is due to deficiency of cystathione
-synthase that converts methionine to cystine.
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Result is increased concentration of sulfur-containing

amino acids homocystine in blood and urine.
Methionine Homocystine Cystine
cystathione -synthase
Clinical feature:
Metal retardation, glaucoma, osteoporosis, ectopia
lentis, mousy odor in urine, thrombosis.
Diagnosis:
Cyanide nitroprusside test for detection of sulfur
containing compounds in urine.
Treatment:
Methionine-restricted, cystine-supplemented diet.
Some types respond to vitamin B6.
Tyrosinemia
Type I: Tyrosinosis
This causes hepatorenal symptoms cirrhosis,
hepatocellular carcinoma.
Others cabbage-like odor, respiratory tract infections,
neuropathy.
Without treatment death from liver failure occurs in
6-8 months.
Diagnosis: Millons test.
Type II: Tyrosine Transaminase Deficiency
Oculo-cutaneous manifestations (but no cataract).
Alkaptonuria
Cause: Defect in tyrosine metabolism due to deficiency
of the enzyme homogentisate oxidase.
Clinical feature:
Generalized pigmentation of connective tissues
(ochronosis). Sites involved are ears, sclerae, articular
cartilage, heart valves, larynx, skin and tympanic
membrane (not nose).
Arthritis, prostatic calculi.
Diagnosis: Darkening of urine on exposure to air.
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Maple Syrup Urine Disease

Cause: Deficiency of -keto acid decarboxylase enzyme.
Pathology: Branched-chain amino acids leucine, isoleucine
and valine and their alpha ketoacids are increased in plasma
and urine.
Clinical feature:
Infants are difficult to feed.
Vomiting, lethargy.
Characteristic odor of maple syrup or burnt sugar in
urine.
Ataxia, convulsions, spasticity.
Skin pigmentation.
Metabolic acidosis and ketosis.
Diagnosis:
Guthries test.
FeCl3 blue color.
Isovaleric Acidemia
Sweaty feet odor.
DEFECTS OF MEMBRANE TRANSFER
Cystinuria
Characterized by impaired tubular reabsorption and
excessive urinary exretion of cystine, ornithine, arginine
and lysine (COLA). There is malaborption of the amino
acids from intestine, too.
Clinical feature: Recurrent urinary calculi.
Hartnups Disease
Cause: Defects in the intestinal and renal transport of
neutral amino acids, including tryptophan (which is the
precursor of niacin in body).
Clinical feature:
Pellagra-like features (due to niacin deficiency).
Increased fecal excretion of indole derivatives.
Cystinosis
Due to defective carrier mediated transport of cystine.
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Clinical feature:
Photophobia, blindness, delayed puberty, fancony
syndrome, end-stage renal disease.
Diagnosis: Cystine level in leukocytes and fibroblasts.
Cystine crystals in cornea and conjunctiva.
DEFECTS IN CARBOHYDRATE
METABOLISM
Galactosemia
Cause:
Most commonly due to deficiency of galactose-1phosphate uridyl transferase.
Other enzymes involved are galactokinase, epimerase.
Clinical feature:
Symptoms start within few days after birth with onset
of breastfeeding. Physiological jaundice is prolonged.
Cataract, mental retardation, cirrhosis and liver failure.
Diagnosis: Presence of non-glucose reducing sugar in urine.
Management: Patient should avoid milk. Dietary
management should be continued life-long.
Hereditary Fructose Intolerance
Cause: Deficiency of aldolase B present in liver.
Feature:
Fructose induced hypoglycemia, e.g. after ingestion of
sugar cane juice.
Prolonged intake leads to hepatomegaly, jaundice, PCT
dysfunction and intellectual impairment.
Treatment: Complete elimination of sucrose, fructose and
sorbitol from diet.
CALCIUM, PHOSPHORUS AND

BONE METABOLISM
VITAMIN D
Vitamin D is a steroid prohormone.
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Synthesis and Metabolism

7-dehydrocholesterol cholecalciferol (vitamin D3)
(In sun exposed skin)
Vitamin D3
| Liver 25-hydroxylase (rate
limiting)
25-hydroxycholecalciferol (25-hydroxy vitamin D3)
| Renal, bone or placental 1- hydroxylase
1,25-Dihydroxycholecalciferol [1,25 (OH)2D] or Calcitriol
25-hydroxy vitamin D3 is the major form in circulation

and major storage form in liver.
Calcitriol is the most potent form.
Action calcitriol stimulates intestinal absorption of
calcium and phosphate.
It acts on nuclear receptors.
Effects of vitamin deficiency:
Calcium decreased absorption from intestine
feedback increase of PTH (secondary hyperparathyroidism) increased bone resorption
liberation of calcium in blood calcium level remains
normal in blood.
Phosphate increased release of PTH causes decreased
urinary reabsorption of phosphate hypophosphatemia.
PARATHYROID HORMONE
Source: Chief cells of parathyroid glands.
Actions:
1. It increases calcium concentration in blood by
i. Decreasing renal clearance of calcium (increases
calcium reabsorption from the DCT).
ii. Increased bone resorption.
iii. Increased calcium absorption from intestine by
promoting the synthesis of calcitriol.
2. Decreases phosphate concentration due to decreased
renal reabsorption of phosphate.
Note: Calcium is excreted by kidney and intestine.
Calcitonin
Source: Parafollicular C cells of thyroid.
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Action: It is a hypocalcemic hormone. It inhibits bone

resorption by direct action on osteoclasts.
Use: Pagets disease of bone, hypercalcemic states,
osteoporosis.
HYPERCALCEMIA
Etiology
a. Parathyroid related
1. Primary hyperparathyroidism
2. Lithium therapy
3. Familial hypocalciuric hypercalcemia
asymptomatic, occurs in the first decade of life.
b. Malignancy related
1. Solid tumors of breast
2. Squamous cell Ca of lung
3. Hematological multiple myeloma, lymphoma.
c. Vitamin D related
1. Vitamin D intoxication
2. Increased calcitriol sarcoidosis.
d. High bone turnover
1. Hyperthyroidism
2. Immobilization
3. Thiazide diuretics
4. Vitamin A intoxication.
e. Renal failure
1. Secondary hyperparathyroidism
2. Aluminum toxicity
3. Milk-alkali syndrome due to excessive ingestion
of calcium and absorbable antacids such as milk
or calcium carbonate. Characterized by
hypercalcemia, alkalosis and renal failure.
Primary Hyperparathyroidism
Cause:
Solitary adenoma of the parathyroids most common
cause. Most commonly involves the inferior parathyroid
glands.
MEN1 and MEN2A syndromes.
Hyperplasia of all the four parathyroid glands.
Result hypercalcemia and hypophosphatemia.
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Clinical feature:
Half or more of patients are asymptomatic.
Anorexia, nausea, vomiting.
Constipation, depression, polyuria.
Ectopic calcification.
(painful bones, renal stones, abdominal groans and
psychic moans).
Renal stones.
Bone osteitis fibrosa cystica.
Subperiosteal resorption of phalanges most
characteristic.
Tiny punched-out lesions may cause the so called
salt-and-pepper appearance of the skull.
Loss of lamina dura of teeth.
Giant multinucleated osteoclasts Brown tumor.
Subcutaneous calcification.
Triradiate pelvis.
Others increased level of alkaline phosphatase,
increased calcium and cAMP level in urine.
Secondary Hyperparathyroidism
Cause:
i. Renal failure most common cause.
ii. Osteomalacia.
iii. Pseudohypoparathyroidism (deficient response of
PTH at the level of receptors).
Characterized by: Increased PTH, normal or decreased
calcium and increased phosphate in blood.
Clinical feature: Characteristic bone lesion in renal failure
is called renal osteodystrophy.
Tertiary Hyperparathyroidism
Conversion of the parathyroids from a state of reversible
hyperplasia to an irreversible growth defect and state of
PTH hypersecretion no longer responsive to medical therapy.
Management of Hypercalcemia
1. Hydration with saline.
2. Forced diuresis.
3. Oral/IV phosphate.
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4. Hypocalcemic agents bisphosphonates (etidronate,

pamidronate), steroids, gallium nitrate, plicamycin,
mithramycin, calcitonin.
5. Dialysis.
Investigation for Localizing Parathyroid Adenoma:
Thallium-Tc substraction scan.
Treatment:
Treatment of parathyroid adenoma removal of
adenoma.
Treatment of parathyroid hyperplasia removal of 31/
2 glands.
Autoimplantation:
Indication tertiary hyperparathyroidism in patients
on chronic renal dialysis, recurrent hyperparathyroidism.
Site into the arm.
Recurrent hyperparathyroidism can also be treated by
USG guided alcohol injection into the mass.
Role of steroids:
Steroids increase urinary calcium excretion and decrease
intestinal calcium absorption.
In normal individuals and in primary hyperparathyroidism, steroids neither increase nor decrease
calcium level in blood.
In certain osteolytic tumors like multiple myeloma,
leukemia, lymphoma, breast Cathey are helpful.
They are also effective in vitamin D intoxication and
sarcoidosis.
HYPOCALCEMIA
Etiology
1.
2.
3.
4.
5.
6.
Chronic renal failure

Hereditary and acquired hypoparathyroidism
Vitamin D deficiency malabsorption
Pseudohypoparathyroidism
Hypomagnesemia
Surgical removal of parathyroid glands most common
cause in clinical practice.
7. Hyperventilation
8. Tumor lysis syndrome
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Clinical Feature
Signs of hypocalcemia starts to appear when serum
calcium level falls below 4 mg/dl.
Muscle spasm carpopedal spasm, laryngospasm,
circumoral tingling, hyperactive tendon reflexes.
CNS increased ICT with papilledema, psychosis.
ECG QT prolongation.
Chvosteks or Trousseaus sign, Erbs sign.
Electrolytes decreased calcium and increased
phosphate levels.
HEREDITARY/IDIOPATHIC
HYPOPARATHYROIDISM
DiGeorge Syndrome
Defective development of both thymus and parathyroid
glands due to deletion of chromosome 22q11.
Autoimmune Polyglandular Deficiency
Failure of adrenal, ovaries and parathyroids associated
with recurrent mucocutaneous candidiasis, alopecia,
vitiligo and pernicious anemia.
PSEUDOHYPOPARATHYROIDISM
Features:
Usually affect females.
Short stature, short metacarpals and metatarsals, flat
nose, round face and multiple exostosis.
Signs of hypoparathyroidism.
Mechanism:
Deficient end organ response to PTH hyperplasia
of parathyroids increased PTH level.
Albrights Hereditary Osteodystrophy
Short stature, round face, brachydactyly and
heterotopic calcification.
Electrolytes increased PTH, decreased calcium and
increased phosphate.
Resistance to PTH action defective urinary cAMP
response to PTH administration.
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METABOLIC BONE DISEASES

OSTEOPOROSIS
It is the reduction of bone mass per unit volume of bone
due to bone resorption more than bone formation.
Etiology:
a. Endocrinal
i. Hyperparathyroidism
ii. Hyperthyroidism
iii. Cushings disease
b. Others
i. Chronic glucocorticoid administration
ii. Rheumatoid arthritis
iii. Alcoholism
iv. Smoking
v. Old age
vi. Chronic heparin therapy
vii. Cytotoxic drugs, e.g. methotrexate.
Clinical feature:
Pathological fracture most common site is the dorsolumbar spine.
Pain in the back and deformity of the spine are the
most common symptoms.
Diagnosis:
Normal levels of calcium, phosphate and alkaline
phosphatase.
X-ray shows decreased mineral density in bones.
Cod-fish appearance of vertebra.
Dual energy X-ray absorptiometry (DEXA) gold
standard investigation for detection of bone density.
Treatment:
Estrogen to postmenopausal women.
Drug of choice etidronate.
RICKETS AND OSTEOMALACIA
Rickets
Defective mineralization of the organic matrix of the
skeleton predominantly at growth plates (epiphysis).
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Etiology:
Type I
1. Deficiency of vitamin D dietary deficiency.
2. Defective hepatic and renal metabolism.
Type II
1. Defective resorption of phosphates through renal tubules
familial hypophosphatemic vitamin D resistant rickets
X-linked dominant.
2. Fanconis syndrome
3. Renal tubular acidosis type I.
Clinical feature:
Age later half of first year or in second year (unusual
before 3 months of age).
Craniotabes earliest manifestation (it is also seen
in hydrocephalus, congenital osteodystrophy).
Bossing of the skull.
Broadening of the ends of long bones.
Delayed teeth eruption, growth retardation.
Harrisons sulcus along the lower part of the chest.
Pigeon chest elevation of the lower borders of ribs.
Rachitic rosary costo-chondral junctions on the
anterior chest wall become prominent.
Mascular hypotonia (pot-belly).
Lumbar lordosis.
Deformities knock-knees or bow-legs, coxa vera.
Wind-sweep deformity.
Quants sign T shaped depression in the left occipital
bone.
Hypophosphatemic rickets hypophosphatemia,
hypercalcemia and lower limb deformities.
X-ray:
i. Delayed appearance of epiphyses.
ii. Widening of the epiphyseal plates.
iii. Cupping of the metaphysis.
iv. Splaying of the metaphysis.
v. Fraying of the metaphysis.
vi. Pseudofractures or Loosers zone.
vii. Osteopenia.
Laboratory Findings:
Serum calcium and phosphate levels are decreased and
serum alkaline phosphatase level is increased.
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Treatment:
600000 IU oral vitamin D single dose
X-ray after 3-4 weeks
If no improvement, repeat the same dose
If no response if improves
Vitamin D resistant rickets
400 IU/day
Osteomalacia
Common in women.
Clinical feature:
Bone pains back ache.
Muscle weakness.
Spontaneous fracture of spine.
Triradiate pelvis.
Laboratory findings as above.
Summary of laboratory findings
Disease
Calcium
(8.5-10.5
mg/dl)
Phosphate
(3-4.5
mg/dl)
Alkaline
phosphatase
(5-15 IU)
Osteoporosis
Rickets and osteomalacia
Hyperparathyroidism
Renal osteodystrophy
Normal
Decreased
Increased
Decreased
Normal
Increased
Increased
Pagets disease of bone
Normal
Normal
Decreased
Decreased
Normal or
increased
Normal
Increased
MAGNESIUM METABOLISM
Hypomagnesemia
Etiology:
1. Infection giardiasis.
2. Endocrine hyperthyroidism, hypo/hyperparathyroidism.
4. Thiazide, amphotericin B.
5. Massive blood transfusion.
6. Small bowel resection.
Clinical feature:
Hypomagnesemia coexists with hypokalemia.
Associated hypocalcemia may produce Chvostek and
Trousseaus signs.
Athetoid tetany, convulsions.
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ECG QT prolongation.
Note physical findings of hypomagnesemia is due
to associated hypocalcemia and cardiac findings are
due to associated hypokalemia.
PAGETS DISEASE
It is characterized by progressive tendency of one or more
bones to bend, get thickened and spongy.
Clinical feature:
Tibia most commonly affected.
Facial pain and headache.
Backache in lumbar region.
Hearing loss.
Platybasia.
X-ray:
Multiple confluent lytic areas with interspersed new bone
formation hair-on-end appearance.
Bone scan shows increased uptake.
Increased alkaline phosphatase with normal calcium
and phosphate.
Increased urinary excretion of hydroxyproline.
Complications:
i. Pathological fracture.
ii. Urinary stones.
iii. Malignant change sarcoma.
iv. Deafness due to otosclerosis.
Treatment: Calcitonin and bisphosphonates.
MISCELLANEOUS BONE DISEASES
Hyperostosis
It is an increase in bone mass of bone per unit.
Etiology:
i. Primary hyperparathyroidism.
ii. Hypothyroidism.
iii. Radiation osteitis.
iv. Vitamin A intoxication.
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Osteopetrosis
Also called marble bone disease or Albers-Schonberg
disease.
Characterized by dense but brittle bones with a
tendency to fracture.
Clinical feature:
Most commonly affects infants with progressive anemia,
hepatosplenomegaly and hydronephrosis.
Others pancytopenia, jaw osteomyelitis and cranial
nerve palsies.
Hyperostosis Corticalis Generalisata
(Von Buchems Disease)
Characterized by osteosclerosis of skull, lower jaw, clavicle
and ribs.
Clinical feature: Blindness, deafness, facial nerve palsy.
Laboratory finding: Increased alkaline phosphatase in
serum.
Fibrous Dysplasia (McCune-Albright Syndrome)
Polyostotic fibrous dysplasia, precocious puberty and
cutaneous pigmentation in girls.
The lesions of dysplasia are focal and have a radiolucent
appearance.
Occurs equally in both sexes.
INFECTIOUS
DISEASES
SEPSIS AND SEPTIC SHOCK

Pathogenesis:
Most cases of septic shock are caused by endotoxin
producing gram-negative bacilli.
Endotoxins are bacterial wall lipopolysaccharides (LPS)
released when the cell walls are degraded.
LPS
TNF
IL-1
IL-6 / IL-8
NO, PAF and other mediators
Low quantities
Moderate quantities High quantities
1. Monocyte/
1. BrainFever
1. Heart Increased
macrophage/
2. Liver Acute
CO
neutrophil
phase reactants
2. Decreased
activation
3. Bone
peripheral
2. Endothelial cell
leukocytes
resistance
activation
Systemic effect
3. Blood vessel
3. C3a, C5a
injury
Local
thrombosis, DIC
inflammation
4. Lungs ARDA
Septic shock
Note: Normal or increased cardiac output and decreased

peripheral resistance is characteristic of septic shock and
distinguishes it from other types of shock.
Systemic Inflammatory
Response Syndrome (SIRS)
This is the systemic inflammatory response to a variety
of severe clinical insults viz infections, burn, trauma,
pancreatitis, etc.
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Manifested by 2 or more of the following conditions

1. Temperature > 38C or < 36C
2. Heart rate > 90 beats/min
3. Respiration rate > 20 breaths/min or PaCO2 < 32
torr
4. WBC count > 12000/l or
< 4000/l or
> 10 percent immature (band) cells.
Most important mediators are TNF, IL-1 and IL
6 (all secreted by macrophages).
Sepsis: Same as SIRS but with a documented microbial
origin.
Severe sepsis: Sepsis associated with organ dysfunction,
hypotension or hypoperfusion (lactic acidosis, oliguria,
altered mental state).
Septic shock: Sepsis associated with hypotension despite
adequate fluid resuscitation, along with the presence of
perfusion anomalies listed above or organ dysfunction.
Clinical Feature
Fever or hypothermia, tachypnea and tachycardia often
herald the onset of sepsis.
Hyperventilation is an early sign.
Disorientation, confusion also develop early.
Hypotension and DIC predispose to acrocyanosis
and ischemic necrosis of peripheral tissue, most
commonly the digits.
Skin lesions N. meningitidis Sepsis with cutaneous petechiae
of purpura.
Ecthyoma gangrenosum Seen exclusively in
neutropenic patients, caused by Ps. aeruginosa.
Toxic shock syndrome Generalized erythema
caused by Staphylococcus aureus or Streptococcus
pyogenes.
Complications
1. Adult respiratory distress syndrome.
2. Myocardial dysfunction, systemic vasodilatation leading
to hypotension.
3. Renal failure due to acute tubular necrosis.
4. Activation of coagulation cascade leading to DIC.
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5. Electrolytes
Early, respiratory alkalosis due to hyperventilation.
Late, metabolic (lactic) acidosis.
Diagnosis
Blood:
Leukocytosis or leukopenia.
Thrombocytopenia.
Hyperbilirubinemia.
Neutrophils may contain toxic granules, Dohle bodies
or cytoplasmic vacuoles.
Urine proteinuria.
Treatment
Pneumatic antishock garment improves cardiac filling.
Also used in aortic aneurysm rupture.
IV fluids + inotropic agent (e.g. dopamine).
Neonatal Septicemia
Cause: Through nursery personnel.
Diagnosis: Neutropenia, >20 percent immature neutrophils,
increased CRP, increased ESR.
Predisposing factors: Preterm and LBW baby, PRM, late
breastfeeding.
C/Organism: E coli, Streptococcus agalactiae.
Clinical feature: Lethargy.
FEVER OF UNKNOWN ORIGIN
Definition
It consists of
1. Temperature > 38.3o C (101oF) on several occasions.
2. A duration of fever > 3 weeks.
3. Failure to reach a diagnosis despite 1 week of inpatient
investigation.
Classification:
1. Classic FUO Fever without elucidation of a cause
by 3 outpatients visits or 3 days in hospital or 1 week
of intelligent and invasive ambulatory investigation.
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2. Nosocomial FUO Fever acquired after admission to

a hospital. Three days of investigation, including 2 days
incubation of cultures, is the minimum requirement
for diagnosis.
3. Neutropenic FUO Fever in patients whose neutrophil
count is <500/l or is expected to fall to that level
in 1 or 2 days.
Diagnosis: As above.
4. HIVassociated FUO.
Cause
I. Infections:
1. Extrapulmonary TB most common cause.
2. Intra-abdominal abscess.
3. UTI.
4. Osteomyelitis.
5. Bacterial endocarditis.
6. Malaria.
7. Fungal histoplasma, cryptococcus.
8. Viral EBV, CMV, HIV.
II. Neoplasm:
1. Hodgkins and nonHodgkins lymphoma.
2. Leukemia.
3. Renal cell Ca.
4. Hepatoma.
5. Atrial myxoma.
III. Collagen vascular diseases:
1. Stills disease.
2. Rheumatoid arthritis.
3. PAN, SLE.
IV. Granulomatous disease:
1. Sarcoidosis.
2. Crohns disease.
Stills Disease
Characterized by:
Increased ESR, leukocytosis and anemia.
Arthralgia (Rheumatoid arthritis).
Polyserositis (pleuritis, pericarditis).
Lymphadenopathy.
Splenomegaly.
Rash maculopapular.
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But no Rhfactor is found.

[C.f. Feltys syndrome arthritis, splenomegaly,
neutropenia and +Rh factor].
INFECTIVE ENDOCARDITIS
It involves the cardiac valves or mural surface of the
endocardium and characterized by formation of
vegetations.
Etiology and Classification
A. According to onset and course:
1. Acute: Microorganism Staphylococcus aureus
(overall most common). Occurs on normal valves,
rapidly destructive, produces metastatic foci and if
untreated fatal in less than 6 weeks. Most common
in drug addicts.
2. Subacute:
Microorganism Streptococcus viridans.
Occurs on damaged valves.
B. According to predisposing factors:
1. Native valve endocarditis:
Organism
Streptococcus viridans (Streptococcus sanguis)
most common source is dental infections.
Staphylococcus aureus (most common).
Enterococci.
HACEK (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella)
2. Prosthetic valve endocarditis:
Organism Staphylococcus epidermidis.
In early onset disease (< 2 months)- Streptococcus
epidermidis.
Late onset Streptococcus viridans.
3. IV drug abusers:
Organism Staphylococcus aureus, Candida
Epidemiology
Native valve endocarditis common in males > 50 years.
1. Rheumatic valvular disease
2. Congenital heart disease
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VSD (most common), PDA, TOF, coarctation of aorta,

MVP, aortic regurgitation.
Low risk in MVP without MR, ASD (Least risk).
3. Calcific aortic stenosis
IV drug abusers Common in young males. Skin is
the most common source of infection.
Pathology
Left heart (mitral valve most common) is involved in
most cases except in IV drug abusers in whom right heart
[tricuspid valve (also in septic abortion) most common]
involvement is more common.
Pathologic hallmark of bacterial endocarditis are
vegetations which are composed of platelets and fibrin
with superadded infection.
Acute BE vegetations are small and solitary
Systemic embolisation
is common
Enlarge progressively and

become bulky and friable
Abscesses can
develop at the
site of emboli
Extension of infection to
adjacent myocardium my
produce ring abscess
May produce septal perforation
Subacute bacterial endocarditis: Firm and multiple

vegetations, presence of granulation tissue at their bases.
Systemic emboli may occur but the resultant infarcts are
less likely to undergo suppuration.
Systemic embolisation: Occurs in heart, brain, kidney,
spleen, liver, extremities; may produce splenic and renal
infarcts, also myocardial infarction. Pulmonary
embolisation occurs in right sided endocarditis (large warty
vegetations). Mycotic aneurysm may develop in cerebral
arteries.
Clinical Feature
1. Fever Minimum criteria for diagnosis is unexplained
fever of 7-10 days duration in patients with known
heart disease.
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2. Changing cardiac murmur except in patients with

early acute endocarditis and in IV drug abusers with
tricuspid valve infection.
3. Splenomegaly.
4. Splinter hemorrhage subungual linear, darkred
streaks result from trauma especially in fingers.
5. Roths spot oval retinal hemorrhage (also occurs
in connective tissue disorder).
6. Oslers node small tender nodules usually on the
finger or toe pads.
7. Janeway lesions small hemorrhage on the palms
and soles.
8. Clubbing.
9. Arthralgia, myalgia.
10. Glomerulonephritis-Microscopic hematuria.
11. Normocytic normochromic anemia.
Note: Features 3-10 are due to immunologically mediated
vasculitis.
Complications
1. Pulmonary embolism in right heart endocarditis.
2. Thromboembolism most common complication.
3. Brain abscess less common, occurs with
4. Neurological cerebral infarct, encephalopathy,
meningitis.
5. Myocardial abscess most common in acute
endocarditis (Staphylococcus aureus).
6. Mycotic aneurysm.
7. Renal Focal/Diffuse glomerulonephritis.
Diagnosis
1. Blood culture repeated cultures are often needed to
establish a diagnosis.
2. All suspected cases should undergo baseline
transthoracic echocardiography (TTE). Transesophageal echo (TEE) is more sensitive than TTE in
detecting small vegetations.
Prophylaxis
Amoxycillin or erythromycin.
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479
Indications:
1. Valvular of congenital hear t disease (except
uncomplicated ASD).
2. Intracardiac prostheses.
3. Asymmetric septal hypertrophy.
4. Previous endocarditis.
Patients who do not require prophylaxis:
1. Coronary artery bypass grafts.
2. Transvenous pacemakers.
3. Patients undergoing cardiac catheterization.
Note: Anticoagulants should not be used to prevent
embolisation.
INTRA-ABDOMINAL INFECTIONS AND ABSCESS
PERITONITIS
Primary Peritonitis
It is the infection, often monobacterial, of the peritoneal
fluid without any intra-abdominal cause.
It is seen in 2 settings:
1. In children most commonly caused by Streptococcus
pneumoniae; occurs in the setting of nephritic syndrome
or SLE. Often follows an ear or URT infection.
In females genital tract infection. More common due
to spread of infection through open abdominal osteum
of fallopian tube.
2. In adults often occurs with alcoholic cirrhosis and
ascites.
Spontaneous Bacterial Peritonitis
Infection of ascitic fluid most commonly following alcoholic
cirrhosis.
Route: Hematogenous.
Organism: E. coli (most commonly) monobacterial.
Clinical feature: Fever is most common manifestation
ascites, abdominal pain.
Diagnosis: Ascitic fluid PMN count >300 /l. Ascitic fluid
culture.
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Treatment: IV antibiotic Ampicillin + Gentamicin or

3rd generation Cephalosporin.
Secondary Peritonitis
Most common form of peritonitis.
Peritoneal infection from intra-abdominal source. Most
common from rupture of hollow viscus.
Clinical feature: Abdominal pain (most common).
C/Organism: Usually mixed infection. Aerobes E. Coli
(most common), Anaerobes B. fragilis.
Treatment:
Second or third generation cephalosporin +
metronidazole.
Surgery is often life saving.
Peritoneal Dialysis Associated Peritonitis
Occurs with CAPD.
Source of infection skin flora.
C/Organism: Monobacterial; Staphylococcus aureus (most
common), Staphylococcus epidermidis, E.coli, Candida.
Treatment: Intraperitoneal Vancomycin + Gentamicin.
Tertiary Peritonitis
Persistent diffuse peritonitis following the initial treatment
of secondary peritonitis.
It represents both a failure of host response and super
infection.
Sclerosing Peritonitis
Fibrinous peritonitis caused by Practolol ( blocker)
Note: Meconium peritonitis: Intra-abdominal calcification
(in X-ray)
Note: Least irritant fluid to peritoneum is blood.
INTRA-ABDOMINAL ABSCESS
Pelvic Abscess
It is the most common intra-peritoneal abscess.
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481
Definition: It is the collection of pus in rectovesical or

rectouterine pouch (pouch of Douglas).
Cause: Appendicitis.
C/Organism: B. fragilis, E. coli.
Diagnosis: USG.
Treatment:
Antibiotics; Per rectal drainage of pus under GA.
In females, posterior colpotomy is the definitive surgery.
Subphrenic Abscess
Subphrenic spaces:
A. Intraperitoneal spaces:
1. Right anterior
2. Right posterior (Rutherford Morisons kidney pouch)
(Rt. subhepatic) most common site of subphrenic
abscess. Most common site of intra-abdominal abscess
following laparotomy.
3. Left anterior
4. Left posterior
B. Extraperitoneal spaces:
1. Right perinephric space
2. Left perinephric space
3. Midline bare area of liver.
Etiology:
Right-sided abscess Cholecystitis, appendicitis.
Left anterior space - Surgery of stomach (most
common).
Left posterior space - pancreatic pseudocyst.
Right and left perinephric abscess TB.
Midline abscess ruptured amoebic liver abscess or
pyogenic abscess of the liver.
Clinical feature: Signs of toxemia.
C/Organism: E. coli, Klebsiella, Streptococci, Anaerobes.
Treatment: Antibiotics,
Percutaneous drainage US guided,
Open drainage indicated in only 10 20 percent of
cases.
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Visceral Abscesses
Liver Abscess (Pyogenic)
Most common visceral abscess.
Source:
Ascending cholangitis (most common), hematogenous.
C/Organism:
Biliary tract E. Coli and enterococci,
Hematogenous Staphylococcus aureus, Streptococcus
milleri.
Clinical feature:
Fever most common sign. May present as PUO,
hepatomegaly, and jaundice - present in only 50 percent
cases.
Diagnosis:
LFT most reliable finding is increased alkaline
phosphatase.
Imaging USG, CT scan Investigation of choice.
Treatment:
Drainage,
Interventional radiology (CT or USG guided
aspiration) is the treatment of choice.
Splenic Abscess
Most commonly associated with bacterial endocarditis.
Route Hematogenous.
C/Organism: Streptococcus most common,
Perinephric and Renal Abscess
Most commonly associated with renal stone.
Source: Ascending infection from bladder (UTI).
C/Organism: E. coli, Proteus, Klebsiella.
Clinical feature: Flank pain and abdominal pain.
Diagnosis: USG and abdominal CT scan.
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483
INFECTIOUS DIARRHEA AND FOOD POISONING

Diarrhea
Watery Diarrhea
Produced by enterotoxins.
1. Cholera Cholera toxin has one A and 5 B subunits.
B subunit binds CT to enterocyte surface receptor, the
ganglioside GM1. A subunit activates adenylate cyclase.
Increased production of CAMP
Increased water secretion and decreased absorption
Loss of fluid in stool Rice water stool

2. Enterotoxigenic E. coli produces 2 toxins
i. Heat labile toxin (LT) acts similar to CT.
ii. Heat stable toxin (ST) acts by activation of
guanylate cyclase increased cGMP
Note: most common cause of diarrhea is neonates is
E. coli
3. Clostridium perfringens
4. B. cereus
Produce pre-formed toxin
5. Staphylococcus aureus
6. Rotavirus diarrhea most common cause of diarrhea
in infant and children.
7. Other viral diarrheas - Norwalk virus, Adenovirus,
Astrovirus, Corona virus, Calcivirus.
8. Giardia
9. Cryptosporidium important cause of diarrhea in AIDS
patients.
Inflammatory Diarrhea
1. Shigella dysentriae
2. Salmonella typhimurium
3. Enterohemorrhagic E. coli (most common serotype
O157:H7) produce shiga-like toxin.
4. Enteroinvasive E. coli
5. V. parahemolyticus
6. Clostridium difficile
7. Campylobacter jejuni
8. Yersinia enterocolitica
9. Entamoeba histolytica
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Travelers Diarrhea
Most common cause is Enterotoxigenic E. Coli

Treatment:
Bismuth Salicylate (also used for prophylaxis).
Loperamide, Diphenoxylate + Atropine.
Food Poisoning
Incubation
period
Organism
Source
1-6 hours
Staphylococcus aureus
B. cereus
Cl. perfringens
B. Cereus
Vibrio cholerae
ETEC
Salmonella, Shigella
V. parahemolyticus
Poultry, egg, salad, milk

Fried rice
Beef, poultry
Meats
Shellfish
Salads
Dairy products
Mollusks
816 hours
>16 hours
Staphylococcus aureus and B. cereus produce

neurotoxins which act on central nervous system to
produce vomiting by vagal stimulation.
B. cereus produces 2 types of syndromes 1. Emetic form with 1- 6 hours of incubation period,
occurs following eating fried rice and mediated by
enterotoxins.
2. Diarrheal form with long (8 16 hours) incubation
period, mediate a by E. coli LT type of enterotoxin.
There is diarrhea and abdominal cramps but no
vomiting.
Both types of illness are mild and self-limited requiring
no specific treatment.
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485
SEXUALLY TRANSMITTED DISEASES

Etiology
Disease
Organism
Bacterial
1. Gonorrhea
2. Nongonococcal
urethritis
3. Syphilis
4. Lymphogranuloma
venorum
5. Chancroid
6. Granuloma inguinale
(Donovanosis)
7. Bacterial vaginosis
N. gonorrhoeae most common STD

Chlamydia trachomatis most
common, Ureaplasma urealyticum
T. pallidum
Chlamydia trachomatis (L serotype)
Hemophilus ducreyi
Calymmatobacterium
granulomatosis
Gardenella vaginalis (Hemophyllus
vaginalis)
Most common STD worldwide
8. Genital chlamydiasis
Viral
1. AIDS
2. Genital herpes
3. Condyloma acuminata
(genital warts)
4. Molluscum contagiosum
5. Viral hepatitis
6. Cervical intraepithelial
neoplasia (CIN)
HIV1 and HIV2

HSV2
HPV 6 and 11
Pox virus
Hepatitis B
HPV 16, 18 and 31
Protozoal
1. Trichomonas vaginitis
2. Proctocolitis
3. Enteritis
T. vaginalis-most common
trophozoite infection
Entamoeba histolytica
Giardia lamblia
Fungal
1. Monilial vaginitis
Candida albicans
Ectoparasites
1. Scabies
2. Pediculosis pubis
Sarcoptes scabie
Phthirus pubis
Gonorrhea
Affects sexually active adults. It has affinity for columnar
and transitional epithelium.
The disease involves
a. In men urethra, prostrate, seminal vesicles and
epididymis (but not the testes).
486
b. In female urethra, Skenes gland, Bartholins gland

and the cervix. In adults, vaginitis does not occur
because squamous epithelium is resistant to it.
Most common manifestation is acute urethritis with
profuse mucopurulent discharge.
Involvement of endocervix may be asymptomatic.
Gonococcal salpingitis causes fimbrial block.
Urethritis
Etiology:
1. N. gonorrhea most common cause.
2. Chlamydia trachomatis most common cause of nongonococcal urethritis.
3. Ureaplasma urealyticum.
Genital Ulcers
Genital Herpes
Most common cause of genital ulcer in developed countries.
Now most common cause in developing countries (India),
too.
Features: Typical pastules or vesicles or a cluster of painful
ulcers that were preceded by vesicopapular lesions. May
predispose to Ca cervix.
C/Organism: HSV2.
Chancroid
Or soft-sore.
It was the most common cause of genital ulcer in
developing countries.
Incubation period 4 to 7 days.
C/Organism:
H. ducreyi.
Other Herpes hominis virus.
Ulcer: Painful with inguinal lymphadenopathy (bubo),
which is non-indurated (hence called softsore) with
fluctuance or overlying erythema. Ulcers may suppurate
and discharge on skin.
Diagnosis: Itos test.
Treatment: Cotrimoxazole/Erythromycin/Cephalosporin.
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487
Syphilis
Second most common cause world-wide.
Ulcer:
Known as chancre, single, painless papule that rapidly
becomes eroded and indurated (hard-sore).
Inguinal lymphadenopathy firm, non-tender and nonsuppurative.
Lymphogranuloma venorum (LGV)
C/Organism: Chlamydia trachomatis (L2 serotype most
common).
Ulcer Small, painless vesicle or papule often
asymptomatic and remain unnoticed; painful inguinal
lymphadenopathy which may suppurate leading to multiple
discharging sinuses; sign of groove; may produce esthiomene
(elephantiasis of the female genitalia); may cause rectal
stricture, multiple fistulae.
Diagnosis:
Freis test (Skin test).
Now-a-days cell culture is commonly used for diagnosis;
or antibody detection by CFT or micro IF.
Elementary bodies called Miyagawas granulocorpuscles.
Granuloma inguinale (Donovanosis)
C/Organism: Calymmatobacterium granulomatis.
Ulcer: Painless papule with no lymphadenopathy (hence
called pseudo-bubo). Satellite lesions.
Diagnosis: By demonstrating Donovan bodies which have
safety pin appearance. Mikulicz cells.
Treatment: Tetracycline/Erythromycin, Doxycycline drug
of choice.
Genital Ulcers at a Glance
Disease
Ulcer
1. Herpes genitalis Painful vesicles

or pustules
2. Chancroid
Painful
(soft-sore)
3. Syphilis
4. Donovanosis
5. LGV
Painless papule
Painless papule
Painless vesicles
(often unnoticed)
Lymphadenopathy
- ve
Tender (bubo),
non-indurated
(soft), may suppurate
Non-tender, indurated
- ve (pseudo-bubo)
Painful, may suppurate
488
Acute Arthritis
Most common forms of acute arthritis in sexually active
young adults are
1. Gonococcal arthritis-dermatitis syndrome.
2. Reiters syndrome.
Chlamydial Infection
C/Organism: Chlamydia trachomatis (D-K serotype).
Pathology: Chlamydia affects the columnar and transitional
epithelium of lower genital tract. There is no deep
penetration.
Clinical feature: It affects Urethra (urethritis), Bartholins
gland, cervix (cervicitis), fallopian tubes (salpingitis); may
produce infertility.
Diagnosis:
Ligase chain reaction and PCR most sensitive.
Other ELISA, cell culture, direct IFA technique.
Treatment:
Azithromycin is the drug of choice.
Also used doxycycline.
The sexual partner should also be treated with the same
regimen.
Bacterial Vaginosis
Or bacterial vaginitis.
C/organism:
Gardenella vaginalis (hemophyllus vaginalis).
Diagnosis:
Clue cells; fishy odor when mixed with 10 percent
KOH.
Number of lactobacillus and leukocytes are decreased.
Feature:
White milky non-viscous discharge adherent to vaginal
wall.
pH > 4.5, minimal vulval irritation.
Treatment: Metronidazole.
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489
Trichomonas vaginitis
Most common congenital infection in females.
C/organism: Trichomonas vaginalis (a parasite).
Clinical feature: Profuse and offensive vaginal discharge
which is greenish yellow in color.
Irritation and itching.
Diagnosis: Punctate hemorrhagic spots and strawberry
appearance of the cervix on speculum examination.
Treatment: Metronidazole; husband should also be treated.
Monilial vaginitis
C/organism: Candida albicans.
Diabetes, pregnancy, OCP use, broad-spectrum
antibiotic therapy.
Note: Candida infection is favored by a low pH (<4) [c.f.
above two which are favored at relatively high (> 4.5
5) pH].
Clinical feature:
Pruritus which is out of proportion to the discharge.
Discharge thick, curdy white and in flakes (cottage
cheese discharge).
Treatment:
Miconazole is the drug of choice.
Nystatin applied through a pessary.
Husband should also be treated with local nystatin
ointment. But treatment of partner is not routinely
indicated.
Condyloma acuminata (Genital Warts)
C/organism: HPV 6 and 11.
D/D: Verrucous Ca.
Treatment:
Cryotherapy,
20 percent podophyllin resin in liquid paraffin
produces systemic toxicity, so not used now-a-days.
490
PELVIC INFLAMMATORY DISEASE

PID implies infection of the upper genital tract (which
includes endometrium, tubes and ovaries).
Route:
Ascending infection most common route.
Hematogenous as in tuberculosis.
Etiology:
1. Sexually transmitted diseases most common cause.
i. Gonococcal 30 percent.
ii. Chlamydia 30 percent.
2. Others Mycoplasma hominis (10%), tuberculosis,
E. coli, anaerobes.
3. Rare causes include leprosy, syphilis and
schistosomiasis.
Risk factors:
1. Menstruating teenagers.
2. Sexual promiscuity (multiple sex partners).
3. Operative procedures like D and C, hCG.
4. Contraception IUCD insertion.
5. Previous history of PID.
6. Septic abortion and puerperal sepsis.
Protective:
1. Contraception barrier methods especially condom;
OCP.
2. Pregnancy.
3. Menopause.
4. Azoospermia of husband.
Clinical feature:
Temperature > 38oC.
Lower abdominal pain most common symptom.
Tenderness on movement of the cervix.
Adnexal mass.
Supportive diagnostic aids
Blood leukocytosis > 10000/cu.mm.
ESR > 15/hr.
Laparoscopic evidence of tubal affection.
Culdocentesis with purulent fluid having WBC count
> 30000/ml.
Note: Most common feature of cervicitis is profuse watery
discharge.
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491
Treatment:
All patients should receive orally 7-14 days course of
any one of the followings
Tetracycline/doxycycline/erythromycin/clindamycin.
Chronic PID
Failure to resolve the acute PID results in chronic tuboovarian masses. These include
1. Hydrosalpings.
2. Chronic pyosalpings.
3. Chronic interstitial salpingitis.
4. Tubo-ovarian cyst.
5. Tuberculous form.
Clinical feature:
Abdominal pain, low back pain, dysmenorrhea.
Fixed solid mass in pelvis frozen pelvis.
C/organism:
Staphylococcus, E.coli, gonococcus, chlamydia.
Pathology:
The tubes assume retort shape; often bilateral.
Management:
a. In young women conservative surgery - salpingectomy
or salpingo-oophorectomy.
b. In multiparous and older women abdominal
hysterectomy with bilateral salpingo-oophorectomy.
c. Tuboplasty to treat infertility. Best result is obtained
in tubo-tubo (isthmo-isthmic) anastomosis.
TUBERCULOSIS OF GENITAL TRACT
Pathogenesis:
Genital TB is almost always secondary to primary infection
elsewhere in the body.
Route:
Most common route is hematogenous spread.
Pathology
Most common site of infection is the fallopian tubes.
Both the tubes are affected simultaneously.
The initial site of infection is in the submucosal layer
(interstitial salpingitis) of the ampullary part of the tube.
492
The muscular layer gets replaced by fibrous tissue. The

walls get thickened, become calcified or even ossified.
The abdominal osteum remains patent. The tubes get
elongated and distal part distended, giving the
appearance of tobacco- pouch.
Uterus the endometrium is infected from the tubes
either by lymphatics or by direct spread through
continuity (retrograde spread).
Clinical feature:
Most common in the age group 20-30 years.
1. Infertility most common complaint.
2. Menstrual abnormalities menorrhagia or secondary
amenorrhea.
Investigation:
1. D and C best method. Time during the week before
menstruation.
2. First day menstrual fluid examination.
3. HSG is contraindicated in a proven case of genital
TB.
Features on HSG:
i. A rigid non-peristaltic pipe-like tube called the lead
pipe appearance.
ii. Beading and variation in filling density.
iii. Tobacco-pouch appearance.
4. Biopsy.
5. Marker CA 125.
Treatment:
1. Antitubercular chemotherapy is the treatment of
choice.
2. Surgery is reserved for persistent or complicated cases.
Surgery of choice total hysterectomy with bilateral
salpingo-oophorectomy.
Outcome:
Pregnancy is rare, and if occurs, chance of ectopic
pregnancy is more.
URINARY TRACT INFECTION
Pathogenesis:
Two categories of UTI:
a. Lower tract infection urethritis, cystitis and prostatitis.
b. Upper tract infection acute pyelonephritis, renal and
perinephric abscess.
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493
Route:
Lower UTI ascending infection
Upper UTI hematogenous.
Epidemiology:
Two types
1. Catheter associated (nosocomial) and
2. Non-catheter associated (community-acquired).
Etiology:
1. Community acquired UTI E. coli (most common).
2. Nosocomial UTI proteus, klebsiella, pseudomonas,
serratia.
3. UTI associated with renal calculus proteus, klebsiella.
4. Gram +ve organism coagulase negative
staphylococcus saprophyticus; enterococci and
Staphylococcus aureus in patients with calculi or
previous instrumentation.
Risk factors:
1. Catheterization.
2. Renal stone.
3. Urogenital anomalies.
4. Pregnancy high incidence of asymptomatic
bacteruria.
5. BHP in older males.
6. Vesicoureteric reflux common in children.
Clinical feature:
UTI is most common in sexually active young females.
Acute urethral syndrome dysuria, urgency and
frequency.
Pyelonephritis fever (temperature > 103oF) with
chills.
Nausea, vomiting and diarrhea.
Tachycardia.
Generalized muscle tenderness.
Abdominal pain.
Diagnosis:
Significant Bacteriuria
Sample mid-stream clean catch urine.
Count quantitative assay. Bacteria count > 105/ml
is significant.
Count less than 104/ml is of no significance and are
due to contamination during voiding.
494
Note: Children less than 2 years of age samples are

collected by suprapubic aspiration or catheterization.
Conditions where count < 104/ml may be significant
i. Symptomatic patients.
ii. Samples collected by suprapubic aspiration or inand-out catheterization and in samples from a patient
with indwelling catheter.
iii. Patients on antibacterial or diuretic therapy.
iv. Samples show evidence of some bacteria like
UTI in Pediatric Age Group
Incidence:
During infancy same in both sexes because the route
of infection is hematogenous.
Beyond infancy more common in girls.
1. Obstructive uropathy (e.g. posterior urethral valve) in
boys.
2. Vesicoureteric reflux most common cause.
3. Neurogenic bladder in girls.
Clinical feature:
Fever, jaundice, diarrhea.
Distal UTI in older children dysuria, hypogastric pain,
frequency and urgency, convulsions.
Pyelonephritis is suggested by fever with chills and
rigor, flank pain.
Diagnosis:
Uncentrifuged urine culture presence of > 10 WBC/
cu. mm are abnormal.
Grams stain > 2 bacteria/field is significant.
Significant bacteriuria see above.
Treatment:
In infants ampicillin + gentamicin/amikacin or 3rd
generation cephalosporin.
Older children cotrimoxazole/ampicillin.
Post-treatment investigation:
To detect obstruction or VUR
i. USG.
ii. MCU (for posterior urethral valve, ureterocele).
Infectious Diseases
495
iii. Renal cortical 99mTc DMSA scan to detect acute

pyelonephritis.
Indication for detailed radiological studies:
i. Age < 3 years with first UTI.
ii. Symptoms of pyelonephritis.
iii. Recurrent UTI.
iv. Abnormal voiding/persistently distended bladder.
v. Family h/o UTI or hypertension.
INFECTIONS FROM BITES
Human peptostreptococcus, Streptococcus viridans
(most common), Staphylococcus aureus.
Dog Eikenella corrodens, DF-2.
Cat Pasteurella multicoda.
Rat Streptobacillus moniliformis, spirillum minor.
Snake Pseudomonas.
INFECTIONS IN TRANSPLANT RECIPIENTS
After Bone Marrow Transplantation
Viruses
Fungi
Parasites
CMV
EBV
HSV
Hepatitis B and C
HIV
Candida
Histoplasma
Cryptococcus
P. falciparum
T. gondii
Strongyloides
T. cruzi
After Kidney Transplantation

Early, < 1 month
Middle, 1-6 months
Late, > 6 months
BacteriaE. coli,
klebsiella
UTI and pneumonia
(legionella)
UTI/lungs CMV
Nocardia
CNS
L. monocytogenes
Aspergillus
CMV retinitis
Note: CMV is the most common opportunistic infection

in organ transplant patients.
NOSOCOMIAL INFECTION
Cause:
Pseudomonas aeruginosa (gram ve bacilli) most
common cause of nosocomial pneumonia.
Staphylococcus aureus, Streptococcus pyogenes.
496
Klebsiella pneumoniae.
Enterobacteriaceae are the most common cause of
nosocomial infections.
Route: Infected hands of doctors, nurses and medical staffs.
Control: Washing of hands before and after examining
a patient best approach.
Note:
Most common nosocomial infection is UTI.
Staphylococcus epidermidis is the most common cause
of surgical site infection.
Bacteremia is most common with Staphylococcus
epidermidis.
GENERAL CONSIDERATION
BACTERIAL MORPHOLOGY AND PHYSIOLOGY
Bacteria are unicellular and prokaryotes.
Shape
Actinomycetes branching filamentous bacteria.
Mycoplasma cell wall deficient and hence do not
posses a stable morphology.
Grouping
Cocci may be grouped as
Chain streptococci.
Grape-like clusters staphylococcus.
Eight sarcina.
Cell Wall
Composition: The cell wall is composed of mucopeptide
scaffolding formed by N acetyl glucosamine and N acetyl
muramic acid molecules in alternating chains which are
linked by peptide chains.
Lipopolysaccharides (LPS):
LPS is present on the cell wall of gram ve bacteria.
Role endotoxic activity, O antigen specificity.
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497
Porins:
Transmembrane pores that serve as diffusion channels.
Comparison:
Aromatic and sulphur containing
amino acids
Teichoic acid
Gram +ve
Gram ve
Absent
Present
Present
Absent
Cytoplasm
Bacteria do not show protoplasmic streaming.
They do not possess endoplasmic reticulum or
mitochondria.
Ribosomes
This is the most active enzymatic site in bacteria.
Mesosomes
Organ of respiration.
More prominent in gram +ve bacteria.
Nucleus
Bacterial nuclei have no nuclear membrane or
nucleolus.
Genome single molecule of double-stranded DNA
arranged in a circle.
Capsule
It is polysaccharide (e.g. in pneumococcus) or
polypeptide (e.g. in anthrax bacilli) in nature.
Capsulated bacteria are Pneumococcus, B. anthracis,
Klebsiella, H. influenzae.
Diagnosis: By
i. Capsule swelling or Quellung phenomenon.
ii. Negative staining.
Flagella
They are the organs of locomotion.
Arrangement:
All around the cell peritrichous (typhoid bacilli).
498
Single polar monotrichous (cholera vibrios).

Polar in tufts lopotrichous (spirila).
At both ends amphitrichous.
Diagnosis:
By dark ground illumination.
Fimbriae
Function organs of adhesion
Spores
Spores are highly resistant resting stages of bacteria.

Seen in Bacillus and clostridium.
Sporulation occurs at stationary phase of development.
Spores are destroyed by Autoclaving at 120oC for
15 minutes.
Staining Acid fast.
Others Forms
Cell wall deficient states: In hypertonic solution or by
penicillin.
Protoplast Gram +ve bacteria.
Spheroplast - Gram ve bacteria.
Involution forms:
Swollen and aberrant cells in aging culture.
Seen in Plague bacilli and gonococcus.
L- Forms:
They resemble mycoplasma.
Toxins
Exotoxins
Endotoxins
1. Produced by Gram +ve

bacteria. Also some gram ve
bacteria viz. S. dysentery
I, V. choleri and ETEC
2. Proteins
Gram ve bacteria
3. Released by bacteria
4. Heat labile
5. Highly potent
6. Highly antigenic
7. Can be toxoided
8. Specific pharmacological
effect for each exotoxin
Polysaccharideproteinlipid
complex
Part of bacterial cell wall
Heat stable
Poor potency
Poor antigens
Can not be toxoided
Action non-specific, all
endotoxins have same effect
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499
Note: L. monocytogenes is the only Gram +ve organism

producing endotoxin.
BACTERIAL GENETICS
Transmission of Genetic Materials
Transformation
It is the transfer of genetic information through the
agency of free DNA.
Transformation has been studied in Pneumococcus
bacillus, H. influenzae (mnemonic BHP).
Transduction
Transfer of a portion of DNA from one bacterium to
other by a bacteriophage. The phage only acts as a
vector.
It has been studied in lambda phage of E. coli
Materials transferred DNA, episomes, plasmids.
Importance The plasmids determining penicillin
resistance are transferred by transduction. This has been
proposed as a method of genetic engineering.
Lysogenic Conversion
The phage DNA is incorporated in bacterial
chromosomes, multiplies synchronously with it and
transferred to the daughter cells.
Seen in Corynebacterium diphtheriae.
Conjugation
Mediated by plasmids.
The F factor: Or the fertility factor.
It contains the genetic information necessary for the
synthesis of the sex pilus and for self-transfer. But it
is devoid of other identifiable genetic markers such as
drug resistance.
F+ cells can transfer chromosomal genes to recipient
cells with high frequency and are known as Hfr cells.
Col factor:
Antibiotic substances which are lethal to other bacteria.
Produced by E.coli, pseudomonas (pyocin), diphtheria
(diphthericin).
500
Resistance transfer factor (RTF):

This is responsible for the spread of multiple drug
resistance among bacteria.
It is plasmid mediated and transferred by conjugation.
It has been demonstrated in E.coli and Shigella.
Notes:
Plasmids are extrachromosomal circular DNA present
in the cytoplasm, capable of autonomous replication.
Transporons are cytoplasmic genetic materials which
can move from site to site on the same or different
DNA molecules (transposition). Such elements are called
jumping genes. They can not replicate by themselves
but contain resistance and other genes.
STERILIZATION AND
DISINFECTION
Definition
Sterilization: is the process of destroying all
microorganisms either in the vegetative or spore state.
Disinfection: is the killing of all pathogenic organisms
outside the body by direct exposure to chemicals or
physical agents.
Antisepsis: is prevention of infection by inhibition of
growth of microorganisms. Antiseptics are agents
applied on skin to eradicate pathogenic microbes.
METHODS
Dry Heat
Incineration:
Best method of disposal of hospital waste and waste
from slaughter house.
Hot air oven:
Holding period 160oC for 1 hour.
Articles sterilized are glassware, syringes, swabs,
dressings, sharp instruments, liquid paraffin, fat and
grease and dusting powder.
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501
Moist Heat
Temperature below 100oC
Pasteurization:
Holder method 63oC for 30 minutes.
Flash method (HTST or high temperature short time
method) 72oC for 15-20 seconds.
Both processes are followed by rapid cooling to 13oC.
Result:
Pasteurization kills nearly 90 percent of the bacteria
in milk including the heat-resistant tubercle bacillus
and Q fever organism (Q fever may survive the Holder
method).
It does not kill thermoduric bacteria (like
Staphylococcus aureus, Streptococcus fecalis) and
spores.
Tests for pasteurized milk:
i. Phosphatase test
ii. Standard plate count
iii. Coliform count
Methylene blue reduction test is an indirect method
of detecting microorganisms in milk before
pasteurization.
Temperature at 100oC
Boiling:
Boiling does not kill spores or viruses.
It is not used to sterilize sharp instruments.
Tyndallisation or intermittent sterilization:
Method steam at atmospheric pressure (100oC).
For media containing sugars or gelatin, an exposure
of 100oC for 20 minutes on 3 successive days is used.
Principle:
First exposure kills all vegetative bacteria. Spores, being
in a favorable medium, germinate and are killed on
the subsequent exposure.
Temperature above 100oC
Autoclaving:
Method steam at 121oC at 15 lbs/sq. inch. pressure
for 15 minutes with air removed.
502
Articles dressings, linen, gloves, certain instruments,

culture media, suture materials except catgut.
Not suitable for plastics and sharp instruments.
Sterilization control B. stearothermophilus
(thermophilic bacteria).
Note: Vaccines are sterilized by heat inactivation.
Filtration
Types:
1. Candle filters
a. Unglazed ceramic filters, e.g. Chamberland filter.
b. Diatomaceous earth filters Berkfeld and Mandler
filters.
2. Asbestos filters e.g. Seitz filter.
3. Sintered glass filter.
4. Membrane filters made of cellulose esters (most
commonly used).
Uses:
For water purification most common use.
For separation of sera, toxins, etc.
Radiation
a. Non-ionizing radiation
i. Infrared radiation produce considerable heat,
hence considered as a form of hot air sterilization.
Use for rapid mass sterilization of syringes.
ii. UV radiation for disinfection of closed chambers
such as operation theatres.
b. Ionizing radiation X-rays, gamma rays and cosmic
rays.
Mechanism of action: Lethal to DNA. They do not
produce heat, hence referred as cold sterilization.
Use: For commercial sterilization (sharp instruments).
Chemicals
Alcohols:
They are not effective against spores (hence, not a
complete sterilizing agent).
To be effective, they must be used at a concentration
of 60-70 percent in water.
Isopropyl alcohol is used as disinfectant for catgut.
Ethyl alcohol surface disinfectation of thermometer,
skin disinfectant.
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503
Aldehyde:
Formaldehyde
Used as 2-3 percent solution (20-30 ml of 40% formalin
in 1 liter of water).
Uses formaldehyde gas is most commonly used for
disinfection of rooms.
40 percent formalin is used to sterilize all microbes
and spores.
Glutaraldehyde
Cidex is 2 percent glutaraldehyde.
Use to sterilize cystoscopes and bronchoscopes. Spores
are disinfected by glutaraldehyde.
Holding time 20 minutes.
Halogens
Bleaching powder:
Contains 33 percent of available chlorine.
It is an unstable compound.
5 percent solution is used to disinfect feces and urine.
Hypochlorites:
Most commonly used form of chlorine.
Chlorination does not affect hepatitis A, cysts of B.coli
and Giardia.
Use water purification, wound dressing and
disinfection of instruments soiled with blood.
Iodine:
1-2 percent alcoholic solution (tincture iodine) is most
effective skin disinfectant.
Disadvantage allergic reaction in some patients.
Phenols
Lysol:
Most powerful chemical disinfectant.
It is not effective against spores.
Ethylene Oxide Gas
Alkylating agent.
Effective against all kinds of microorganisms including
viruses and spores.
Use commercial sterilization of heat-sensitive medical
devices (such as prosthetic valves).
Disadvantage explosive, so can not be used as
fumigant.
504
Testing of Disinfection
Rideal Walker or phenolic co-efficient:
It is used to determine the quality or efficacy of a
disinfectant.
Note: Complete sterilizing agents i.e. those kill spores, too
are
i. Glutaraldehyde.
ii. Hydrogen peroxide.
iii. Sodium hypochlorite.
STAPHYLOCOCCUS
STAPHYLOCOCCUS AUREUS
Biochemical Reaction
Phosphatase
Coagulase
Mannitol fermentation
Staphylococcus
aureus
Staphylococcus
epidermidis
Positive
Positive
Positive
Negative
Negative
Negative
Toxins
1. Exotoxins , , and .
lysin exhibits hot-cold phenomenon or Arhenius
phenomenon.
2. Enterotoxin responsible for food poisoning.
Enterotoxin F is responsible for toxic shock syndrome
(also enterotoxins b and c).
3. Exfoliative toxin (ET) produces staphylococcal
scalded skin syndrome (SSSS).
4. Toxic shock syndrome toxin (TSST) TSST1 (formerly
called the enterotoxin F or pyrogenic exotoxin C) is
responsible for most cases of TSS.
5. Leucocidin.
Pathogenicity
Carriers: Harbor the organism in mucous membrane of
anterior nasopharynx, throat and skin.
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505
Toxic shock syndrome:

i. Menstruation.
ii. Barrier contraception highly absorbent bands or
vaginal tampons.
iii. Puerperium.
iv. Septic abortion.
Clinical feature:
Fever (temperature > 102oF).
Rash diffuse macular erythema (sun burn rash).
Hypotension (SBP 90 mmHg).
Multiorgan dysfunction.
Desquamation within 2 weeks of onset, typically on
palms and soles.
Staphylococcal scalded skin syndrome:
Termed as Ritters disease in newborns and toxic
epidermal necrolysis (TEN) in adults.
Others pemphigus neonatorum, bullous impetigo.
Food poisoning : See above.
Skin and soft tissue infections:
Boils, folliculitis, furuncles and carbuncle.
Boil infection of hair follicles.
Carbuncle infective gangrene of subcutaneous tissue,
more common in diabetics. Penicillin and excision is
the treatment of choice.
Respiratory tract infection:
Sinusitis, pharyngitis (sore throat), pneumonia most
commonly following tracheal intubation and viral
infection.
CNS: Brain abscess, subdural empyema, spinal epidural
abscess, septic intracranial thrombophlebitis.
CVS: Endocarditis of both native and prosthetic valves.
Musculoskeletal:
Acute osteomyelitis most common cause of.
Chronic osteomyelitis.
Septic arthritis most common cause of.
Psoas abscess.
506
Treatment
PenicillinG remains the drug of choice for susceptible
organisms.
-lactamase resistant penicillin methicillin, nafcillin,
oxacillin, cloxacillin.
Methicillin resistant Staphylococcus aureus (MRSA)
vancomycin.
Vancomycin resistant Staphylococcus aureus (VRSA)
teicoplanin and lenizoid.
Prevention
Staphylococcus aureus is the second most common
cause of nosocomial infection.
It can be prevented by meticulous hand washing before
and after contact with patients.
COAGULASE NEGATIVE STAPHYLOCOCCUS
Staphylococcus epidermidis
It has a predilection for growth on implanted foreign
bodies such as artificial heart valves, shunts,
intravascular catheters and prosthetic appliances.
It attains antibiotic resistance by slime production due
to biofilm formation, e.g. on catheter.
It causes stitch abscess (surgical site infection),
prosthetic valve endocarditis, nosocomial bacteremia.
Staphylococcus saprophyticus
Important cause of UTI in sexually active young
women.
STREPTOCOCCUS
Classification
Streptococcus
Aerobes and facultative

anaerobes
Hemolysis
Obligate anaerobes
Peptostreptococcus
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507
Alpha hemolytics
Beta hemolytics
Gamma no
- Greenish
- sharply defined
hemolysis
discoloration
clear colorless zone
Enterococcus
with partial
of complete
hemolysis
hemolysis
Streptococcus
| Group specific carbohydrate C
viridans
antigen (precipitation)
19 Lancefield groups (A to U except
I and J)
Group A hemolytic Streptococcus pyogenes
M protein (agglutination)
Griffith typing (1, 2, 3.... up to 80)
STREPTOCOCCUS PYOGENES
Group A -hemolytic streptococcus.
Virulence
1. Capsule strains with well marked capsule produce
mucoid colonies, corresponding in virulence to the
matt type. This is due to production of hyaluronic acid.
2. M protein acts as a virulence factor by inhibiting
phagocytosis. Antibody to M protein is protective.
Note: Capsular hyaluronic acid cross reacts with human
synovial fluid.
Toxins
1. Streptolysin (hemolysin)
Streptolysin O oxygen labile. ASO titer is increased
in serum in recent infection with streptococcus.
Streptolysin S oxygen stable, produces -hemolysis on blood agar.
2. Erythrogenic/pyrogenic toxin
Produces Scarlet fever.
Pyrogenic exotoxin A causes toxic shock like
syndrome.
Pathogenesis
1. Pharyngitis (sore throat): Most common streptococcal
lesion.
Diagnosis throat culture.
2. Scarlet fever:
Rash papules (sandpaper texture of skin), strawberry
tongue, Pastias lines accentuation of the rash in
skin folds.
Diagnosis Schultz Charlton reaction, Dick test.
508
3. Skin and subcutaneous tissue:

Impetigo superficial infection of the skin.
Cause Streptococcus pyogenes, Staphylococcus
aureus.
In rugby players it can spread to teammates called
scrum pox.
Cellulitis (erysipelas)
May also be caused by Staphylococcus aureus.
Predisposing lesion chronic lymphedema.
Ecthyma
4. Deep tissue:
Necrotizing fasciitis (Fourniers gangrene most
common in genitalia), myositis.
5. Streptococcal toxic shock-like syndrome:
Fever, hypotension, renal impairment and
respiratory distress syndrome.
Associated with necrotizing fascitis, myositis, and
cellulitis.
6. Non-suppurative complication:
Acute rheumatic fever produced by any serotype
of streptococcus pyogenes, usually follow pharyngitis.
Acute glomerulonephritis produced by
nephritogenic types, most commonly type 12,
usually follow skin infection.
Laboratory Diagnosis
Transport medium Pikes medium.
ASO titer value above 200 is significant.
High values are found in acute rheumatic fever but
not in glomerulonephritis. In glomerulonephritis, titers
are often low.
The streptolysin test passive slide agglutination test.
It is a sensitive and specific screening test.
STREPTOCOCCUS AGALACTIAE
Group B -hemolytic streptococcus.
Pathogenesis:
Neonatal meningitis and septicemia.
Endometritis and fever in parturient women.
Diagnosis: CAMP test.
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509
GROUP C -HEMOLYTIC STREPTOCOCCI

Streptococcus equisimilis
Commercial source for streptokinase.
GROUP D (ENTEROCOCCUS)
E.g. Streptococcus fecalis, Streptococcus faecium.
Characteristics:
i. Ability to grow in presence of 40 percent bile, 6.5
percent NaCl.
ii. Usually nonhemolytic, but may produce alpha or beta
hemolysis.
iii. Strains resistant to penicillin and other antibiotics
occur frequently.
iv. Ability to grow at pH 9.6, temperature 45oC, and
in 0.1 percent methylene blue milk.
Pathogenesis: UTI, may also cause endocarditis, intraabdominal abscess, peritonitis.
Treatment: Combination of penicillin or ampicillin with
an aminoglycoside.
Non-enterococcus Group D
Grow in the presence of bile but inhibited by 6.5 percent
NaCl.
Non-hemolytic.
Causes endocarditis and are common in colon Ca.
THE VIRIDANS STREPTOCOCCUS
Normal resident in the mouth and upper respiratory
tract. Produces alpha hemolysis.
Pathogenesis
Most common cause of bacterial endocarditis.
Endocarditis: Streptococcus sanguis is the most common
organism.
Produce subacute endocarditis in native damaged
valves or late onset endocarditis in prosthetic valves.
Dental extraction is the most common source.
Dental caries: Is produced by Streptococcus mutans.
510
PNEUMOCOCCUS
Gram-positive diplococci.
Capsulated.
Culture
On blood agar, produce alpha hemolysis.
Colonies have raised edges and central umbonation,
so that concentric rings are seen when viewed from
above Draughtsman or carom coin appearance.
Smear flame shaped or lanceolate appearance.
Pneumococcus Streptococcus viridans
Bile solubility
Inulin fermentation
Optochin sensitivity
+
+
+
But pneumococcus is catalase and oxidase negative.

Antigenic Properties
1. Capsular polysaccharide or specific soluble substance
It inhibits phagocytosis. It determines virulence.
It exhibits Quellung reaction or Neufeld-capsular
swelling or capsular dilineation.
It is sero-specific and antibody to it is protective.
Note: Type 3 pneumococcus is most virulent.
2. C reactive protein
An abnormal protein that precipitates with the
somatic C antigen of pneumococcus.
It appears in the acute phase sera of cases of
pneumonia.
It is not an antibody.
Produced by hepatocytes.
Its production is stimulated by bacterial infections,
inflammation, malignancies.
Also increased in liver diseases, TB, rheumatoid
arthritis, myocardial infarction and burn.
Test by capillary precipitation of the patients
sera or passive agglutination test.
Note : Other acute phase proteins are haptoglobulin, ceruloplasmin, transferrin, complements
and autolysin.
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511
3. Pneumolysin and autolysin virulence depends on

pneumolysin, too.
Pathogenesis
1. Acute otitis media and acute sinusitis: Most common
cause of.
2. Meningitis: Most common cause in adults.
Route by direct extension from mid-ear or sinuses
or by bacteremia.
CSF shows pleocytosis with predominant PMNs,
increased protein and decreased glucose.
3. Pneumonia: It is most common in extremes of age.
Characterized by:
Symptoms fever (temperature > 102-103oF), cough with
production of rusty sputum, pleuritic chest pain.
Signs gray and anxious appearance, tachycardia,
tachypnea, dullness and increased vocal fremitus on
percussion, bronchial or tubular breath sounds, crackles.
X-ray chest: Areas of infiltration involving less than a full
segment, lobar consolidation.
Complication:
Empyema most common complication.
Persistence of pain especially after first day or two of
treatment indicates empyema. Treatment is water-seal
drainage.
Treatment
Pneumonia penicillin,
Meningitis cefotaxime + vancomycin.
Prevention
Pneumococcal vaccines:
Indications
All persons above 65 years, chronic pulmonary disease,
advanced cardiovascular disease, diabetes mellitus,
alcoholism, chronic renal failure, sickle cell anemia.
Second category splenectomy, multiple myeloma,
lymphoma, HIV infection, organ transplantation.
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NEISSERIA
Gram negative, diplococci.
MENINGOCOCCUS
Morphology
Intracellular (intracytoplasmic), capsulated.
Catalase and oxidase positive.
Ferments glucose and maltose (c.f. gonococci ferment
glucose only).
Epidemiology
Source of infection nasopharynx of cases and carriers.
Carriers 5-30 percent of normal population may harbor
the organism in nasopharynx during interepidemic
period.
Incubation period 3-4 days (may vary from 2-10
days).
Case fatality of typical untreated cases is about 80
percent. It has now declined to < 10 percent.
Season dry and cold months.
Pathogenesis
Meningococcemia:
Clinical feature fever (temperature 39-41oC).
Rash most characteristic. It may be maculopapular,
petechial or ecchymotic involves skin and mucosa
early in the disease.
Pathogenic agent in meningococcal disease is an
endotoxin.
Neisseria bacteremia is favored by complements (C5C9) deficiency.
Fulminant meningococcemia or Waterhouse-Friderichsen
syndrome: Meningococcal septicemia, profound shock, DIC
and multiorgan failure (adrenal hemorrhage).
Meningitis: Common in children and young adults.
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513
Treatment
Cases 95 percent lives can be saved if antibiotics
are started within 2 days of onset of infection. Penicillin
G is the drug of choice.
Carrier rifampicin is the drug of choice.
Presence of shock is an indication of corticosteroid
therapy.
Prevention
Meningococcal vaccine: Containing the capsular
polysaccharide of groups A, C, Y and W135.
They induce good immunity in older children and adults,
but are of little value in infants.
Contraindication pregnancy.
Not recommended in infants and children less than
2 years of age.
Effective for 3 years. Booster every 3 years.
GONOCOCCUS
Morphology
It is found predominantly within polymorphs
(neutrophils).
Pili promote virulence.
Non-capsulated (c.f. meningococci).
Culture
Selective medium Thayer-Martin medium.
Gonococci ferment only glucose not maltose.
Pathogenesis
1. Gonorrhea: (means flow of seed)
Incubation period 2-8 days.
Clinical feature acute urethritis with mucopurulent
discharge.
Complication Watercan perineum, urethral stricture.
2. Disseminated infection:
Blood invasion may occur from the primary site and
may lead to metastatic lesions such as arthritis (most
common), ulcerative endocarditis and rarely meningitis.
514
3. Ophthalmia neonatarum: Only nonveneral infection.

Results form direct infection during passage through
birth canal.
Prophylaxis: CREDEs method installation of 2 percent
silver nitrate solution into the eyes of all newborn babies.
Materials: Urethral discharge, cervical swabs,
Serological tests: CFT, passive agglutination with pilus
protein.
Treatment
Single dose of ceftriaxone/cefixime/ciprofloxacin/
ofloxacin + doxycycline. Alternatively penicillin G.
For pregnant and multi-drug resistant cases
Spectinomycin (not effective in gonococcal pharyngitis).
CORYNEBACTERIUM
CORYNEBACTERIUM DIPHTHERIAE
Gram positive, non-sporing, non-capsulated and nonmobile.
Morphology
Volutin or Babes Ernst granules:
Composed of polymetaphosphate. Stained with
Loefflers methylene blue, they take up a bluish purple
color, hence called metachromatic granules.
Special stain Alberts Stain.
Culture
Media Loefflers serum slope and Tellurite blood
agar.
Advantage: Diphtheria bacilli grow on Loefflers slope media
very rapidly and colonies can be seen in 6-8 hrs. So it
is the culture medium of choice.
Colony:
Gravis daisy head colony.
Intermedius frogs egg colony.
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515
Mitis Poached egg colony.

On smear diphtheria bacilli are arranged in clusters
(Chinese letter or cuneiform arrangement) or parallel
rays (palisade).
Toxin
Type: Exotoxin.
Production:
Toxin production is dependant on a phage called tox+
phage. Nontoxigenic strains may be rendered toxigenic
by infecting them with tox+ phage ( phage). This
is called lysogenic or phage conversion.
Toxin production is influenced by concentration of iron
in medium. While low concentration favors toxin
production, high iron concentration inhibits it.
Mechanism of action: It catalyzes the transfer of adenosine
diphosphate ribose moiety from NAD to a modified his
residue on elongation factor 2 inactivation of EF2
inhibition of protein synthesis.
Source: The strain most commonly used for toxin
production is the Park Williams 8 strain.
Action:
DT acts both locally and systematically.
Local produce dermonecrosis and formation of
pseudomembrane.
Systemic produce myocarditis neuritis and focal
necrosis in various organs.
Epidemiology
Reservoir of infection human beings.
Carriers are the main sources of infection. Nasal
carriers are more dangerous than throat carriers.
Immunization does not prevent carrier state.
Period of infectivity 14 to 28 days from the onset
of the disease.
Host:
Age: particularly affects children aged 1 to 5 years.
Immunity: A herd immunity of over 70 percent is
considered necessary to prevent epidemics.
516
Clinical Feature
Respiratory tract:
Faucial diphtheria is the most common type.
Sites:
Tonsillopharyngeal most common site.
Laryngeal causes maximum mortality.
Nasal more important carriers.
Tracheobronchial.
Characterized by: Fever, dysphagia, cough, hoarseness of
voice.
Pseudomembrane formation:
It extends beyond the margin of the tonsils onto the
tonsillar pillars, palate and uvula. Gray white color.
Dislodgement of membrane causes bleeding
D/D Streptococcus pyogenes pharyngitis, infectious
mononucleosis, viral pharyngitides, Fusobacterial
infection, Candidiasis.
Bull neck: Produced by cervical lymphadenopathy. Marked
edema of the submandibular and anterior portion of the
neck is seen.
Cutaneous diphtheria:
Complications
1.
2.
3.
4.
Myocarditis most common cause of death.

Polyneuritis palatal and pharyngeal paralysis.
Pure motor neuropathy descending paralysis.
Ophthalmoplegia.
Diagnosis
Culture of throat swabs:
The tellurite medium is particularly important in isolation
of bacilli from convalescents, contacts and carriers.
Colonies grow faster on Loefflers serum slope.
Eleks gel precipitation test: in vitro virulence test.
Schick test: Susceptibility test
Aim:
I. Detect the presence of antitoxin and hence the
immunity status (resistance).
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517
II. The state of hypersensitivity to diphtheria toxin.

Result:
Readings are made 1-2 days and 5-7 days later.
Reading erythematous reaction.
I. No reaction on either arm this is negative reaction
and indicates immunity.
II. Positive reaction on test arm positive reaction
indicates susceptibility.
III. Positive reaction on both arms pseudoreaction,
indicates immunity as well as hypersensitivity to DT.
Note:
Schick test is a test where negative reaction indicates
immunity.
Schick test has been replaced by hemagglutination test.
Treatment
Case: Diphtheria antitoxin (10,000 80,000 U) IM
or IV + penicillin / erythromycin.
Carriers: Erythromycin is the drug of choice.
Contacts: Nonimmunized close contacts should receive
prophylactic penicillin or erythromycin + 1000
2000 U of antitoxin + active immunization.
They should be examined daily (by throat swabs) for
evidence of bacteria for at least 1 week after exposure.
DPT Vaccine
Composition:
Diphtheria toxoid: 25 Lf per 0.5 ml.
Tetanus toxoid: 5 Lf per 0.5 ml.
B. pertussis: 20,000 million per 0.5 ml
Aluminium phosphate: used as adjuvant.
Rationale: Pertussis component enhances the potency of
DT.
Storage: Between 4-8oC. should never be frozen. When
issued to a sub-center, the vaccine should be used within
a week.
Age: It can be safely and effectively administered as early
as 6 weeks after birth.
Administration: Deep IM in lateral aspect of thigh.
518
Complications: Excessive crying, neurological complication

including convulsions.
Contraindications: Seriously ill or hospitalized child
persistent screaming, progressive convulsions only DT
is used in such cases.
C. minutissimum
Produces erythrasma.
C. pseudotuberculosis
Preisz Nocard bacillus.
BACILLUS
They are Sporogenous, Gram positive, aerobic bacilli.
Motility: They are generally motile with peritrichous flagella
except bacillus anthracis.
B. ANTHRACIS
Morphology
Arrangement: In long chains giving a characteristic
bamboo stick appearance.
Capsule: Made of polymer of d(-) glutamic acid. It can
be demonstrated by MFadyeans reaction.
Culture
On agar plates: Medusa head colonies. Frosted glass
appearance.
On solid medium: String of pearl reaction
(differentiates with other bacilli).
On gelatin stab culture: Inverted far free appearance.
Pathogenesis
Virulence Factors
1. Capsular polypeptide: promotes virulence by inhibiting
phagocytosis. Loss of plasmid that controls capsule
production leads to loss of virulence.
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519
2. Toxin: It has 3 components protective antigen (PA),

Edema factor (EF) and Lethal factor (LF).
Anthrax
It is a zoonosis.
Cutaneous anthrax (hide porters disease):
Most common form. Characterized by a localized skin
lesion with a central eschar surrounded by marked
edema. Satellite lesions are present around it. It is called
malignant pustule. Cutaneous anthrax generally
resolves spontaneously.
Mode of transmission introduction through skin cuts
(direct contact), insect bite.
Pulmonary anthrax (wool sorters disease):
Mode: Inhalation of dust from infected wool.
Feature: Hemorrhagic mediastinitis.
Complication: Meningitis
Gastrointestinal anthrax:
Mode: Ingestion of contaminated meat.
Diagnosis
Ascolis thermoprecipitin test: demonstration of the anthrax
antigen in tissue extracts.
Treatment
Drug of choice Penicillin G.
Others Streptomycin.
B. CEREUS
Produces preformed enterotoxin.
Causes food poisoning (see above in food poisoning).
Diagnosis MYPA medium useful in isolating B.
cereus (Mannitolegg yolkpolymyxin agar).
CLOSTRIDIUM
Gram positive, obligate anaerobic, spore forming bacilli.
Motility
They are motile with peritrichate flagella except Cl.
perfringens and Cl. tetani type VI.
520
Spores
1. Central Spindle shaped bacilli Cl. bifermentans
2. Subterminal Club shaped bacilli Cl. perfringens.
3. Oval, terminal tennis racket shaped bacilli Cl.
tertium.
4. Round, terminal drumstick shaped bacilli Cl. tetani.
Pathogenesis
Cl. perfringens: Gas gangrene caused by exotoxin
production, local tissue invasion and even septicemia.
Cl. tetani: Tetanus is caused by exotoxin.
Cl. botulium: Noninvasive and non-infections, Botulism
is caused by ingestion of preformed toxin in food.
CL. PERFRINGENS
They are capsulated and nonmotile.
Culture
Medium: Robertsons cooked meat broth, Produce
Strong fermentation.
Colonies: Target hemolysis resulting from a narrow
zone of complete hemolysis due to theta toxin and
a much wider zone of incomplete hemolysis due to
alpha toxin.
Toxins
4 major toxins are alpha, beta, epsilon and iota.
toxin: It is phospholipase (lecithinase C). Responsible

for the profound toxemia of gas gangrene. The hemolytic
anemia and hemoglobinuria seen in advanced gas gangrene
is due to toxin.
Nagler reaction: Detection of lecithinase effect.
Method:
5 percent Fildes peptic digest of sheep blood
antitoxin on one half
Colonies on the other half will be surrounded by a
zone of opacity.
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521
Pathogenesis
1. Gas gangrene
Predominant agent Cl. perfringens type A. Two factors
are essential for severe disease are tissue necrosis
and low redox potential.
Clinical feature:
Sudden onset of pain at the site of trauma with local
swelling and edema accompanied by thin often
hemorrhagic exudates.
Skin is tense, white, marbled with blue and cool.
Systemic Hypotension, tachycardia, body temperature
normal, renal failure, body crepitus.
Death is due to circulatory failure (shock).
Liver foaming liver.
Treatment:
Surgery Most important prophylactic and therapeutic
measure in gas gangrene.
Antibiotics Effective in prophylaxis. Drug of choice
metronidazole IV before surgery and repeated 8 hourly
for 24 hours.
Blood transfusion to correct hypotension.
Passive immunization with antigas gangrene
serum. It contains antitoxin to Cl. perfringens, Cl.
novyi and Cl. septicum.
2. Food poisoning
Cl. perfringens type A (See above) which produce heat
labile enterotoxin.
CL. SEPTICUM
Cl. septicum produces fatal septicemia in patients with
malignancy.
Diagnosis: Citron bodies and boat or leaf shaped
pleomorphic bacilli with irregular staining.
CL. TETANI
Morphology:
Gram positive with terminal spores (drumstick
appearance).
522
Culture: The growth has marked tendency to swarm;

swarming is prevented with 4 percent agar.
Chemical reaction: Cl. tetani is week proteolytic but not
saccharolytic.
Toxin:
Exotoxin.
Tetanospasmin a neurotoxin is responsible for the
clinical manifestation of tetanus.
Sites
Action
1. Presynaptic nerve
terminals
Inhibition of release of inhibitory NTs

glycine and GABA leads to sustained
motor neuron discharge and rigidity.
Sympathetic over activity leads to
increased release of catecholamines
2. Preganglionic
sympathetic nerve
terminals in lateral
gray matter of spinal
cord
3. Muscle end plate
Inhibit NT release at NM junction leading
to weakness and paralysis
4. Brain
Note: Tetanospasmin resembles strychnine in its effect.

But it acts presynaptically, whereas strychnine acts
postsynaptically.
Types:
1. Local tetanus only the nerves supplying the affected
muscle is involved.
2. Ascending tetanus on IM injection of toxin.
3. Descending tetanus produced on IV injection of toxin.
It resembles the naturally occurring tetanus.
Epidemiology: Incubation period commonly 6-12 days.
Tetanus occurring after 30 days is called delayed.
Prognosis:
1. Short IP is associated with bad prognosis.
2. Short interval between the first symptom (trismus) and
the onset of spasms (period of onset) is also associated
with bad prognosis.
Immunity: There is no herd immunity against tetanus.
Tetanus
Generalized tetanus (most common form of tetanus)
is characterized by increased muscle tone and
generalized spasm (spastic paralysis).
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523
First muscle to be involved is masseter and first

symptom is trismus of lockjaw.
The spasticity spreads downwards (descending
paralysis).
Contration of facial muscles may produce characteristic
facies risus sardonicus.
Contraction of muscles of back may cause the body
to bend (opisthotonus).
Autonomic dysfunction- hypertension, tachycardia,
hyperpyrexia, profuse sweating (due to release of
catecholamines).
Post-exposure prophylaxis
1. Surgical management of the wound.
2. Antibiotic long acting penicillin G is drug of choice.
3. Passive immunization with ATS or human
antitetanus Ig (TIG) preparation of choice. Dose
250 U of TIG.
4. Active immunization Most effective method of
prophylaxis.
Agent: Tetanus toxoid.
Course: 3 doses of TT, first two at an interval of 4-6 weeks
and third 6-12 months after the second.
Schedule:
Wound
Wound less than 6 hours old, clean,
nonpenetrating wounds
Other wounds
Status
Treatment
Status
Treatment
A
B
C
D
Nothing
TT 1 dose
TT 1 dose
TT full course
A
B
C
D
Nothing
TT 1 dose
TT 1 dose + TIG
TT full course + TIG
A
B
C
D
complete course within 5 years.

complete course > 5 years but < 10 years.
complete course >10 years.
No course or unknown status.
Treatment:
1. Antibiotic penicillin G or metronidazole.
2. Diazepam to control spasms.
3. Human TIG 10,000 IU slow IV infusion (Paniker),
3000-6000 IU IM in divided doses(Harrison).
524
Neonatal Tetanus
Cause: Infection of umbilical stump after birth.
Clinical feature:
Onset within 2 weeks (5 15 days) after birth but
never in the first 2 days.
Symptom Excessive crying, poor feeding, apathy
(common initial symptoms), muscle spasm.
Prophylaxis:
1. Immunization of all pregnant women with 2 doses of
TT between 16-36 weeks.
2. 3 cleans during delivery clean hands (clean blade),
clean delivery surface (clean cord tie), clean cord care
(no application on cord stump).
Note: Criteria for neonatal tetanus elimination
i. Rate < 0.1 / 1000 live births.
ii. TT2 coverage > 90 percent.
iii. Attended delivery > 75 percent.
CL. BOTULINUM
Toxin
8 types of exotoxins are produced by Cl. botulinum.
Among them C 2 is cytotoxic and all others are
neurotoxic. Only types A, B, E and F cause human
disease.
Botulinum toxin is the most toxic substance known.
Uses of BT: Therapy for strabismus, blepharospasm,
other dystonias.
Pathogenesis
Cl. botulinum is non-invasive and non-infectious. Its
pahthogenicity is due to its toxin.
Three types of botulism exists
1. Food-borne botulism from ingestion of preformed
toxin in contaminated food.
2. Wound botulism from toxin produced in wounds
contaminated with organism.
3. Infant botulism most common form. Due to
ingestion of spores and production of toxin in the
intestine of infants.
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525
Mechanism of action of BT: The toxin enters the vascular

system and is transported to peripheral cholinergic nerve
terminals (including NM junction, postganglionic
parasympathetic nerve terminals and peripheral ganglia),
which leads to decrease in release of ACh (parasympatholytic) and paralysis of muscle.
Clinical Feature
Food-borne botulism:
Symmetric descending paralysis without sensory
involvement. Cranial nerves are involved first producing
diplopia, dysarthria and dysphagia.
The paralysis extends caudally to involve extremities.
GIT Nausea, vomiting, abdominal pain, severe
constipation, dry mouth, occasionally sore throat.
Eye ptosis, blurred vision, fixed or dilated pupil.
Reflexes Depressed pupillary reflex, suppressed Gag
reflex, deep tendon reflexes normal or depressed.
Others No fever, urinary retention.
Death is due to respiratory failure.
Infant botulism:
Source: honey.
Clinical feature: Failure to thrive, floppy baby, constipation,
fulminant severe paralysis with respiratory failure may cause
sudden infant death.
D/D
Myasthenia gravis, Eaton-Lambert syndrome, GB.
syndrome, poliomyelitis, tick paralysis, mushroom
intoxication, diphtheria, hypomagnesemia.
Demonstration of the bacillus or its toxin in food or
feces. The toxin in only occasionally demonstrable in
the patients blood.
Retrospective diagnosis by demonstration of antitoxin
in patients blood.
CL. DIFFICILE
It causes antibiotic associated colitis or pseudomembranous colitis by producing an enterotoxin and a
cytotoxin.
526
Causative antibiotics:
Ampicillin, tetracycline, chloramphenicol,
Clindamycin and lincomycin most common,
Cephalosporins.
Treatment: Metronidazole is the drug of choice.
Vancomycin equally effective.
LISTERIA MONOCYTOGENES
Gram positive cocco-bacilli with a tendency to occur
in chain.
They show characteristic tumbling motility at 25oC
(nonmotile at 37oC).
Intracellular pathogen.
Only gram positive bacillus to produce endotoxin.
Pathogenesis
Source of infection contaminated milk,
Listeria infections occur in neonates, pregnant women
and adults with deficient cell-mediated immunity.
Clinical Feature
They may show -hemolysis and are catalase
positive.
Neonatal listeriosis:
Meningitis and meningoencephalitis - CSF shows
pleocytosis, increased protein and normal glucose
levels.
Granulomatosis infantisepticum.
Pregnancy associated listeriosis:
Can occur in any stage but most common in third
trimester.
Cause chorioamnionitis, premature labour, abortion,
IUGR, stillbirth.
Cold enrichment technique for serial culture.
Anton test.
Treatment
Ampicillin is the most effective drug.
Infectious Diseases
527
MORAXELLA (BRANHAMELLA)
CATARRHALIS
Gram negative cocci.
Clinical Feature
Acute exacerbation of chronic bronchitis.
Purulent tracheobronchitis.
Pneumonia characterized by cough and purulent
sputum.
NON-SPORING ANAEROBES
ANAEROBIC COCCI
Peptostreptococcus: Common cause of puerperal sepsis.
ANAEROBIC BACILLI
Gram negative.
B. fragilis
Strict anaerobes.
Pathogenesis: Brain abscess, peritonitis.
Feature: Pus produced by anaerobes is characteristically
putrid.
B. melaninogenicus
Cultures or even dressings from wounds infected with the
bacillus give a characteristic red fluorescence when exposed
to UV light.
Leptotrichia buccalis (Fusobacterium fusiforme)
Vincents stomatitis or trench mouth: Necrotizing infection
of gum.
Clinical feature: Tender bleeding gums, foul breath, bad
taste, gray exudates over gingival mucosa which can be
removed on gentle pressure.
528
Cancrum oris or noma:

Gangrenous infection of buccal mucosa, teeth and
mandible or maxilla, resulting in widespread destruction
of bone and soft tissue.
It is seen in malnourished and debilitated children.
ENTEROBACTERIACEAE
Gram negative bacilli,
Motile by peritrichate flagella or non motile (Shigella
and Klebsiella).
Ferment glucose, reduce nitrates to nitrites.
Form catalase but not oxidase.
Classification
Derived from the use of lactose in MacConkeys medium.
1. Lactose fermentors: E. coli, Klebsiella.
2. Late lactose fermentors: Shigella sonnei.
3. Nonlactose fermentors: Salmonella, Shigella.
E. COLI
Gram negative, motile rod.
Aerobe and facultative anaerobe.
Culture
On MacConkeys medium, colonies are bright pink due
to lactose fermentation.
Chemical Reaction
Urease ve, IMViC ++
Antigenic Structure
Serotyping of E. coli is based on three antigens the
somatic O antigen, the capsular K antigen and the flagellar
H antigen.
Fimbriae:
Promote virulence. They are present as surface antigens.
E.g. K88 and K99 antigens causing diarrhea in
animals, CFA and CS2 causing diarrhea in man and
P-pilli for pyelonephritis.
Infectious Diseases
529
Toxins
Produce three enterotoxins (exotoxins)
1. Heat labile toxin (LT) acts by binding to GM1
ganglioside receptors in enterocyte and activates adenyl
cyclase to form cAMP, like cholera toxin.
2. Heat stable toxin (ST) acts by activation of cGMP.
3. Verotoxin (VT)/Shiga like toxin Similar to shigella
dysenteriae type 1 toxin. VT is cytotoxic to Vero or
HeLa cells.
Clinical Feature
Enteric infections:
a. Enteropathogenic E. coli (EPEC):
They cause diarrhea in infants and children; can
cause sudden infant death.
Pathogenesis The bacilli remain adherent to the
mucosa of upper small intestine (non-invasive and does
not produce enterotoxin).
b. Enterotoxigenic E. coli (ETEC):
Causes Travelers diarrhea (See above).
Produces both LT and ST.
c. Enteroinvasive E. coli (EIEC): Like shigella infection.
Non-motile, do not ferment lactose.
Pathogenesis: Invades the host cell and provokes
significant inflammatory reactions.
Feature: Fever, bloody diarrhea.
Diagnosis: Sereny test, cell penetration in HeLa or HEP2
cells.
d. Enterohemorrhagic E. coli (EHEC):
Produce VT or shiga-like toxin.
Clinical feature: EHEC, especially serotype O157:H7,
causes HUS.
Diagnosis: Demonstration of the bacilli or VT in stool
directly or in culture. Failure to ferment sorbitol (strain
O157).
(Remember: P for paedi, T for traveler, H for HUS)
UTI:
E. coli is the most common cause of naturally acquired
UTI.
Strains: Those normally found in feces, O group 1,
2, 4 etc.
Only one serotype is isolated from infected urine at
a time.
530
Strains carrying K antigens are more commonly

responsible for pyelonephritis, while most isolates from
cystitis lack K antigens.
Diagnosis
Detection of ETEC enterotoxins.
1.
2.
3.
4.
Test
LT
ST
Rabbit ileal loop

Infant mouse intragastric
Tissue culture (Y1 mouse adrenal
cells, Chinese hamster ovary cells)
Precipitin (Eikens) test
+
+
+
+
KLEBSIELLA
Or Friedlanders bacillus.
Non-motile.
Chemical reaction:
Urease + (Urease +ve bacteriae are Klebsiella,
proteins and Staphylococcus).
IM ViC ++
Klebsiella pneumoniae
Pneumonia:
Common in alcoholic men over 40 years of age with
underlying conditions like diabetes mellitus, COPD.
Features: Mimics pneumococcal pneumonia except
it progresses to produce lung abscess or empyema (red
current jelly sputum).
CXR Bulging fissure sign.
Treatment Cephalosporins.
Nosocomial Infections: UTI, RTI, etc.
PROTEUS
Chemical Reaction
Pr. mirabilis is indole ve, whereas all others are indole
+ve.
PPA test: Deamination of phenylalanine to phenylpyruvic acid (PPA).
Infectious Diseases
531
Culture
Characteristic fishy or seminal smell.
On moist agar media, Pr. Mirabilis and Pr. vulgaris
swarm over the media. Swarming does not occur on
MacConkeys medium.
Pathogenesis
1. UTI Important cause of chronic UTI often associated
with instrumentation.
Proteus possesses the enzyme urease which splits urea
into ammonium hydroxide and increases urinary pH
(alkali urine) that favors the formation of struvite stones.
2. Nosocomial infection.
Weil-Felix Reaction
Proteus (X strain) shows agglutinations with sera from
typhus fever patients - important in diagnosis of
rickettsial infections.
SHIGELLA
Culture
Selective media:
Deoxycholate citrate agar (DCA) for both Shigella
and Salmonella.
Wilson and Blairs bismuth sulphite selective for
Salmonella. Growth of Shigella is inhibited.
KLD Best selective medium.
Lactose fermentation : negative except Shigella sonnei
which is a late lactose fermentor.
Glucose fermentation produce only acid but no gas.
Mannitol fermentation produce only acid except
Shigella dysenteriae which does not ferment it.
Note: Mannitol fermentation has been used to divide shigella
into subgroups.
Classification
1. Shigella dysenteriae: especially type I is the most
virulent type. Produce 3 types of toxins
532
i. Neurotoxin
ii. Enterotoxin
iii. Exotoxin or Verotoxin earliest example of a gram
negative organism producing exotoxin.
Mechanism of action of VT: The active (A 1)
component of VT binds with host 60S ribosome
and inhibits protein synthesis. (also DT and
pseudomonas toxin).
2. Shigella flexneri: most common pathogen in India.
3. Shigella sonnei: most common pathogen in developed
countries. Produces asylum dysentery.
4. Shigella boydii.
Pathogenesis
Shigella species characteristically invade the intestinal
mucosa. Invasiveness can be demonstrated by rabbit
ileal loop test. Sereny test, penetration of HeLa or
Hep2 cells (c.f. EIEC).
Shigella is infective even in very low doses.
The invasiveness depends upon a plasmid mediated
outer membrane protein called virulence marker
antigen (VMA). Detection of VMA by ELISA serves
as a virulence test for Shigella (also for EIEC).
Bacillary dysentery:
Source: Ingestion of contaminated food.
Incubation period: 1-7 days (usually 48 hours).
Clinical feature: Frequent passage of loose, scanty stool
containing blood and mucus. Griping pain and
tenesmus. Fever and vomiting may be present.
Pathology: Invasion of distal colon with hemorrhagic
ulcers.
Extraintestinal manifestation:
Most common with Shigella dysenteriae type I.
i. Hemolytic uremic syndrome most common cause
in India.
ii. Reactive arthritis (Reiters syndrome).
iii. Toxic neuritis.
iv. Conjunctivitis.
v. Parotitis.
Isolation of bacilli from stool culture.
Infectious Diseases
533
SALMONELLA
Culture
Media:
Wilson and Blairs bismuth sulphite medium: Selective
for salmonella. Produce jet black colonies with a
metallic sheen due to production of H2S.
(Except S. paratyphi A which does not produce H2S).
Selenite F and tetrathionate both are commonly
employed as enrichment media.
All ferment glucose to produce acid and gas except
S. typhi which produces acid only (anaerogenic).
Lactose not fermented.
Antigenic Structure
1. H antigen:
Flagellar antigen.
H suspensions agglutinate rapidly and produce large,
loose, fluffy clumps.
Antibody to H antigen is formed rapidly in large
amounts and persists longer.
2. O antigen:
Cell wall antigen. O agglutination occurs slowly and
produce compact, chalky granular clumps.
3. Vi antigen:
It covers the O antigen and hence O agglutination does
not occur in fresh isolates.
Persistence of antibody to Vi antigen indicates carrier
state.
Vi antigen helps in epidemiological typing of S. typhi
according to Vi bacteriophage.
Typing
Salmonella are classified into groups on the basis of
presence of O antigen factors.
Within each group, serotyping is done by phase 1 and
phase 2 flagellar antigens. For serotyping, it is necessary
to identify flagellar antigens of both phases.
534
Enteric Fever
Pathogenesis: Ingestion of bacilli attach to epithelial
cells of intestinal villi and penetrate lamina propria and
submucosa phagocytosed by polymorphs and
macrophages, in which they multiply enter the
mesenteric lymph nodes and multiple enter blood stream
via thoracic duct invades gallbladder and multiply
sheded in intestine and invades Payers patches.
Epidemiology:
Reservoir of infection: Man is the only reservoir.
Source of infection: Carriers > cases.
It is endemic in India.
Highest incidence of the disease occurs in 5-20 years
age group.
Carriers:
Patients who continue to shed bacilli after clinical cure
For 3 weeks to 3 months convalescent carrier.
For 3 months to 1 year temporary carrier.
For > 1 year chronic carrier.
Chronic carriers are common in women over 50 years
with gallstones.
Fecal carriers are more frequent than urinary carriers,
but urinary carriers are more dangerous.
Case fatality rate (in untreated cases) 10 percent.
Clinical feature:
Gradual onset with headache, fever and anorexia.
Fever prolonged persistent fever with stepBladder
pattern, constipation or diarrhea, bradycardia,
hepatosplenomegaly.
Rose spots appear on skin during 2nd or 3rd week.
Epistaxis.
Complications:
1. Cholecystitis.
2. Typhoid ulcer may cause intestinal perforation and
hemorrhage in 3rd or 4th week of illness.
1. Blood culture: diagnostic. 90 percent +ve in first week,
also +ve in subsequent weeks.
Blood culture + bone marrow culture 100 percent
+ve.
Infectious Diseases
535
2. Feces culture: + ve in both cases and carriers (75%

in 3rd week)
3. Urine culture: +ve in 2nd and 3rd weeks.
4. Widal reaction: Tube agglutination test.
Measurement of H antigens of S. typhi, S. paratyphi
A and B and O antigens of only S. typhi. It is
maximally +ve in 3rd week.
Results: O titer 1/100 and H titer 1/200 are
significant.
Demonstration of rise of titer (4 folds or more) in serial
tests are more useful.
Amnestic reaction may occur in persons who have
had prior infection or immunization. So Widal test is
not diagnostic in endemic areas.
5. Latex agglutination and coagglutination tests for the
Vi antigen much more specific and sensitive than
classical Widal test.
6. Diagnosis of carriers: By stool or urine culture.
7. Blood count: Leukopenia with relative lymphocytosis.
Leukocytosis indicates complication (e.g. perforation).
Prevention:
Isolation of cases:
For a period till 3 bacteriologically negative stools and
urine culture are obtained on 3 separate days.
Vaccines:
Acetone killed vaccines. Gives protection about
70-85 percent for 3-4 years.
Types:
i. Monovalent S. typhi vaccine: Vaccine of choice in
India.
ii. Divalent S. typhi and S. paratyphi A vaccine.
iii. TAB vaccine.
Oral vaccine Live attenuated vaccine.
Treatment: Ciprofloxacin is the drug of choice.
Note :
S. typhimurium most common cause of food
poisoning and gastroenteritis.
S. cholerae suis may cause septicemic disease.
536
OTHER SALMONELLA SPECIES

Salmonella gastroenteritis
S. typhimurium is the most common species.
Source: Poultry and dairy products.
Clinical feature: Incubation period 24 hours. Diarrhea,
vomiting, abdominal pain and fever.
Salmonella septicemia
Most common cause is S. cholera suis.
HELICOBACTER PYLORI
Gram negative bacilli with lopotrichate flagella.
Complete genomic sequence of H. pylori has been
recognized (also E. coli).
Epidemiology
Prevalence: 80 percent in developing countries, 30 percent
in developed countries, prevalence varies with age.
Risk factors:
i. Age Most infections are acquired in childhood, but
no immunity develops.
ii. Low socio-economic status.
Reservoir of infection: Man.
Route of infection: Fecal-oral or oral-oral.
Clinical Feature
Most are asymptomatic. Diseases associated with H. pylori
infestation are
1. Gastritis It is antral predominant in developed
countries and pangastritis in developing countries.
2. Peptic ulcer.
3. Adenocarcinoma of stomach other than those arising
in the cardia.
4. Primary gastric non-Hodgkins lymphoma.
5. MALT lymphoma.
6. Large B-cell lymphoma.
Infectious Diseases
537
Diagnosis
Invasive:
1. Endoscopy based biopsy urease test quick test.
2. Microbiological culture most specific. Typical spiral
appearance on Gram stain.
Special stains Giemsa stain, silver stain (WarthinStarry stain).
Noninvasive:
3. Urea breath test most sensitive.
4. Serology (ELISA) epidemiological test.
Note: Urease activity provides protective environment to
the bacilli against gastric acidity.
Treatment
Standard triple-therapy:
1. Bismuth subsalicylate.
2. Tetracycline HCl.
3. Metronidazole.
Duration 2 weeks.
Triple-therapy with acid-reduction:
1. Omeprazole.
2. Clarithromycin.
3. Metronidazole or Amoxicillin.
Duration 1 Week.
VIBRIO
Gram negative bacilli, actively motile with polar
flagellum.
Discovered by Koch.
VIBRIO CHOLERAE
Morphology
Comma shaped bacilli, in stained films fish in stream
appearance.
Motility darting type, in culture suggests a swarm
of gnats.
538
Culture
Strongly aerobic. Growth is better in alkaline medium.
Media:
a. Holding or Transport media:
1. Venkataraman-Ramakrishnan (VR) medium.
2. Cary-Blair medium.
b. Enrichment media: Alkaline peptone water.
c. Selective media:
TCBS medium Best selective medium.
BSA (alkaline bile salt agar) and GTTA medium.
Note: Vibrio colonies can be identified by string test.
Indole is formed and nitrates are reduced to nitrites.
Cholera red reaction due to formation of nitrosoindole compound.
Enzymes liberated by vibrios Neuraminidase, catalase
oxidase.
Resistance
Cholera vibrios are susceptible to heat, drying and acids.
They are resistant to alkali.
Classification
Based on common flagellar antigen (H) Group A
and B.
Based on common somatic (O) antigen Group A
has been divided into serogroup O1 and non-serogroup
O1.
V. choleriae O-1 exists in 2 biotypes Classic and ElTor.
Each biotype is divided into serotypes Ogawa, Inaba,
Hikojima.
Note: Most infections are due to V. choleriae O1. Most
of ElTor biotypes isolated today belong to serotype ogawa.
V. Cholerae O1
1.
2.
3.
4.
5.
6.
Features
Classic Vibrio
ElTor
Hemolysis of sheep RBC

V-P reaction
Chick embryo agglutination
Gr. IV phage susceptibility
ElTor phage S susceptibility
Polymyxin B sensitivity
+
+
+
Infectious Diseases
539
Note: ElTor vibrios are resistant to Gr. IV phage and

polymyxin. All other tests are +ve with ElTor.
Epidemiology
History: Most of the epidemics before 1961 were due to
classic vibrio O1. ElTor vibrios emerged as the major
pathogen in 1961 during the 7th (current) pandemic. In
1992, a novel strain was found to cause epidemics in
Madras. This belongs to non O1 serogroup and was termed
O-139 strain. It is likely that this strain will cause the next
pandemic.
Natural habitat: Costal salt water and brackish estuaries.
Reservoir of infection: No known animal reservoir.
Mode of infection: By incidence. Most common source
is contaminated water.
Age group: In endemic areas, cholera is predominantly
a pediatric disease. But it does not occur in children less
than 2 years of age probably due to passive immunity
acquired by breast milk. In a virgin population, it affects
children and adults equally.
Blood group:
Maximum risk with group O.
Minimum risk with group AB.
Distribution: Currently, larger endemic foci are found in
Maharashtra.
Carriers: Who shed bacilli.
Incubatory carrier
Convalescent carrier
Contact or healthy carrier
Chronic carrier
During incubation period (1-5 days)

During convalescence for 2-3 weeks
Subclinical infection < 10 days
For months to years
Longest carrier state over 10 years. Chronic carriers

are more frequent with ElTor infection.
Toxin
Cholera toxin (CT): Similar to LT of ETEC.
Mechanism of action:
B subunit binds to Gm1 ganglioside receptors.
A1 fragment causes activation of cellular adenyl cyclase
leading to increased intracellular accumulation of
cAMP and secretory diarrhea.
540
Clinical Feature
Painless watery diarrhea with vomiting. No fever.
Stool rice water appearance. It is isotonic with
plasma but contains more K+ and HCO3.
Metabolic changes: decreased HCO3 level in blood.
Increased anion gap, metabolic acidosis.
ElTor cholera: Mild asymptomatic infection. Greater
endemic tendency, increased carrier rate. Less secondary
attack rate.
Specimen- Stool is the best. Vomitus never used.
Medium TCBS medium.
Control
1. Verification of diagnosis it is the first step in the
investigation of a cholera epidemic.
2. Notification Cholera is a notifiable disease within
24 hours to WHO.
3. Rehydration:
a. Oral: By ORS.
Ingredient
(in gram)
NaCl
NaHCO3
KCl
Glucose
Potable water
Or trisodium citrate dehydrate
in place of NaHCO3
Quantity
(in mmol/L)
3.5
2.5
1.5
20
1 lit.
Na +
K+
ClCitrate
Glucose
90
20
80
10
110
2.9
Total
310
Note: Addition of glucose promotes absorption of Na+

in the intestine.
Citrate based ORS has 2 advantages
i. More stable increased shelf life.
ii. Direct action of citrate to increased intestinal
absorption of Na+ and water.
b. Parenteral:
For severe dehydration.
Ringers lactate is the fluid of choice.
Composition of RL:
Na+ - 130 mmol/L
K+ - 4 mmol/L
Infectious Diseases
541
Cl- 109 mmol/L

Base 28 mmol/L
Total 271 mmol/L.
Adjuvant drug therapy:
i. Doxycycline 300 mg once drug of choice in adults.
ii. Cotrimoxazole drug of choice in children
iii. Furazolidone drug of choice in pregnant women.
5. Disinfection:
Most effective is cresol.
Bleaching powder a 5 percent solution (50 gm/lit)
is used to disinfect cholera stool.
6. Chemoprophylaxis:
For household contacts. Tetracycline is the drug of
choice. Dose 500 mg BD for 3 days (adults). But
mass chemoprophylaxis is not recommended.
7. Vaccination:
Parenteral vaccine:
Killed vaccine. Contains Ogawa and Inaba sreotypes
of V. cholerae O1.
Give protection against both classic and ElTor vibrio
but not against serotype O139.
Dose 2 equal doses at 4-6 weeks apart. Boosters
every 6 months.
Protective value 50 percent for a period of 3-6 months.
(Park). 50 percent over a 3-year evaluation period
(Harrison). Not effective in epidemics.
4.
V. PARAHEMOLYTICUS
Clinical feature: Food poisoning.

Source: Marine foods (sea fish).
Culture: It grows only on media containing NaCl.
Virulence: Produces no toxin, acts by direct invasion
of the intestinal epithelium.
V. VULNIFICUS
It also requires saline environment for growth.
Clinical feature:
Two distinct syndromes are produced
1. Primary sepsis in patients with liver disease.
2. Primary wound infection following contact of open
wounds with sea water.
542
AEROMONAS HYDROPHILA
It causes Red leg disease.
PSEUDOMONAS
Gram negative motile bacilli. Obligate aerobe.
PSEUDOMONAS AERUGINOSA
Culture
On nutrient agar, iridescent patches with a metallic sheen
are seen in cultures (greenish color of colonies).
Selective media: cetrimide agar.
Pigments
Pyocanin bluish green.
Fluorescein greenish yellow.
Pathogenesis
Produces Blue pus.
Most common cause of infections in burns.
Outside hospital, most common disease is chronic
suppurative otitis.
Skin Ecthyma gangrenosum.
Toxin
Exotoxin A functions as NADase and inhibits protein
synthesis (like diphtheria toxin).
Treatment
Antibiotics effective against pseudomonas
a. Amino glycosides: Gentamicin, amikacin
b. Third generation cephalosporin: Ceftazidine,
Cefoperazone.
c. Extended spectrum penicillin: Ticarcillin, piperacillin.
d. Carbapenems: Imipenem, Meropenem.
e. Monobatams: Aztreonam.
f. Fluoroquinolones: Ciprofloxacin, norfloxacin.
Infectious Diseases
543
HAEMOPHILUS INFLUENZAE
Gram negative with variable shape (pleomorphic
coccobacilli).
Capsulated.
Uncapsulated strains can colonize in upper respiratory
tract.
Culture
Growth requires growth factor X and V. X factor is
hemin and V factor is NAD.
H. influenzae grows poorly on blood agar (as V is
located inside RBCs) but grows well while it is heated
to chocolate agar.
Satellitism: Growth of H. influenzae is better when cultured
with Staphylococcus aureus which provides V factor on
blood agar.
Best medium: Fildes agar.
Antigenic Properties
Based on capsular polysaccharide antigen (PRP),
Haemophilus is divided into types a to f.
Most common type is type b.
Antibody to PRP is protective.
Clinical Feature
H. influenzae type b (Hib):
1. Meningitis:
Age 6 months to 3 years.
Complication Subdural effusion.
2. Epiglotitis most common cause of.
3. Pneumonia in infants.
Non-typable H. influenzae:
1. Community acquired pneumonia in adults. Second
most common cause (after pneumococcus).
2. Childhood otitis media third most common cause
(after pneumococcus and moraxella).
H. ducreyi
It causes chancroid or soft-sore (see above in veneral
diseases).
544
Gram negative coccobacilli (c.f. gonococcus) but may

be gram positive (bipolar stain).
Bacilli are arranged in chains School of fish or rail
road track appearance.
Culture:
Chocolate agar with isovitalex is a selective medium.
Fresh clotted rabbit blood.
Chorioamniotic membrane.
BORDETELLA PERTUSSIS
Gram negative coccobacilli. Obligate human parasite.
Culture
Most commonly used medium Bordet Gengou agar.
Appearances Thumb print appearance, bisected
pearls or mercury drops and aluminum paint
appearances.
Toxin
1.
2.
3.
Agglutinogens.
Pertussis toxin (PT).
Filamentous hemagglutinin (FHA)
PT and FHA promote secondary bacterial infection
a phenomenon called piracy of adhesions.
Pathogenesis
Colonization of respiratory tract leads to adhesion to cilia
and local tissue destruction (does not invade blood stream).
Epidemiology
Source of infection: a case.
The disease is never subclinical and a chronic carrier
state never occurs.
Infective period:
Most infective during catarrhal stage. Infectivity lasts
up to 3 years after onset of paroxymal stage.
Secondary attack rate 90 percent.
Age: Disease of infants and preschool children. Median
age 20-30 months.
Infectious Diseases
545
Immunity:
Maternal antibody does not protect the newborn.
Incubation period: 7 to 14 days.
Clinical Feature
Three stages
i. Catarrhal stage.
ii. Paroxymal stage.
iii. Convalescence.
Each stage lasts for two weeks.
Complications:
1. Due to pressure effect Subconjunctival hemorrhage,
subcutaneous emphysema.
2. Respiratory due to secondary infection;
bronchopneumonia and lung collapse, bronchiectasis.
3. Neurological convulsions, coma (encephalopathy),
sensory ataxia.
Diagnosis
Culture from nasopharyngeal secretion (prenasal
swab). Positive only in catarrhal and early paroxymal
stages.
Blood Lymphocytosis.
Treatment
Cases: Erythromycin is the drug of choice (prevents
secondary infection).
Protection of contacts:
Chemoprophylaxis: Erythromycin (prevents spread of
infection).
Vaccine: Booster dose of DPT/ DT to his siblings before
he is born Best.
Vaccine:
Killed whole cell preparation.
Effectivity: 70-90 percent
Contraindications: H/O epilepsy, convulsions or other
neurological disease. Acute febrile episode.
Acellular vaccine: inactivated pertussis toxin, provides
protection against disease but not against infection.
546
BRUCELLA
Gram negative bacilli.
Brucellosis is a bacterial zoonosis.
B. MELITENSIS
Most common organism.
Primarily affects goats, sheep.
Epidemiology
Route:
1. Ingestion of raw milk and milk products most
common route.
2. Direct contact.
3. Air-born infection.
Pathology
Brucellosis is primarily a disease of the RE system.
Immunity
Mainly cell mediated. Activated macrophages kill the
bacteria.
Clinical Feature
Undulant or Malta fever:
1. Fever Swinging pyrexia wit chills and rigors. May
present as PUO.
2. Sweating.
3. Headache, insomnia.
4. Joint and back pain.
5. Lymphadenopathy.
6. Mild hepatosplenomegaly.
7. Monoarticular septic arthritis.
Diagnosis
1. Blood culture most definitive method. It is positive
in only 30-50 percent cases. Castaneda method of
blood culture is employed.
2. Serology tube agglutination test most important
in acute cases.
Infectious Diseases
547
3. Rapid diagnosis in cattle Rose Bengal card test.

4. Test for food Milk ring test.
5. For chronic infection Complement fixation test,
Coombs test, ELISA are useful.
Treatment
Combination of doxycycline + rifampicin Most effective
regimen.
Prevention
Pasteurization of milk.
LEGIONELLA PNEUMOPHILA
Culture
Selective medium: Buffered charcoal, yeast extract
(BCYE) agar.
Special stain: DFA stain.
Epidemiology
Source: Human infection is typically acquired by aerosols
produced by air conditioners and showerheads. It is
common in elderly male. No man-to-man transmission.
No animal reservoir.
Risk Factors
1.
2.
3.
4.
5.
Cigarette smoking most important.

Alcoholism.
Chronic lung disease.
Advanced age.
Immunodeficiency.
Clinical Feature
1. Legionnaires pneumonia: A cause of atypical
pneumonia. Characterized by high fever, nonproductive cough and dyspnea with relative
bradycardia. Diarrhea and encephalopathy are
common. Hyponatremia, myocarditis (most common
extrapulmonary site).
548
2. Pontiac fever: acute, self-limited, flu-like disease; fever,

myalgia, fatigue.
Diagnosis
1. Detection of bacilli from sputum (best) or BAL. (most
sensitive and specific).
2. Direct fluorescent antibody (DFA) test.
3. Urinary antigen testing by latex agglutination ELISA.
4. Antibody serology by indirect IF study.
5. CXR Bilateral pulmonary infiltrates.
Treatment
Erythromycin was the drug of choice. Now azithromycin
is drug of choice.
Does not respond to -lactam drugs or aminoglycosides.
YERSINIA PESTIS
Morphology
Gram negative bacilli. In smears stained with Giemsa or
methylene blue, it shows bipolar staining (safety pin
appearance).
Culture
On ghee broth, it produces stalactite growth.
Pathogenesis
Plague bacilli are the most invasive bacteria known.
Epidemiology
Plague is a zoonosis.
Reservoir of infection: Tatera indica (field mice).
Vectors:
Rat fleas: Xenopsylla cheopis in north India, Xenopsylla
astia in south India.
Partially blocked flee is most dangerous in transmission.
Flea index: Is the average number of fleas of all species
per rat.
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549
Transmission: Propagative. The bacilli merely multiplies

in vector, but no change in form.
Plague
Bubonic plague:
Most common form.
Mode Bite of rat fleas.
IP 2-7 days.
Clinical feature: Fever with chills. Headache, arthralgia
and myalgias.
Lymphadenopathy (Bubo) Inguinal and femoral nodes
most common affected. It is hard, painful and moves under
the skin. It often suppurates. Contains large number of
bacilli.
Pneumonic plague:
Most serious, least common.
Mode droplet infection.
IP 1-3 days.
Clinical feature:
Hemorrhagic pneumonia, cyanosis very prominent,
cough productive of bloody sputum.
CXR Pleural effusion.
Septicemic plague:
Clinical feature: Petechiae, ecchymoses, bleeding from
orifices, DIC, ARDS.
Treatment
Streptomycin is the drug of choice. Buboes may require
surgical drainage.
Prevention
Chemoprophylaxis: Tetracycline is the drug of choice.
Flea control:
Insecticides of choice are DDT and BHC. Pouring
kerosene oil over the carcass is a simple method of
elimination of the fleas.
Within 48 hours of application of insecticides, the flea
index should drop to zero.
550
Vaccine
Killed vaccine. Vaccination gives some protection against
bubonic plague, but not against pneumonic plague.
Indication: Only for prevention, not for control.
Effectiveness: Immunity lasts for about 6 months.
FRANCISELLA TULARENSIS
Gram negative pleomorphic.
Tularemia
1. Ulceroglandular/Glandular tularemia most common
type. Characterized by lymphadenopathy with local
ulceration.
2. Oculoglandular type.
3. Oropharyngeal and gastrointestinal type.
4. Pulmonary tularemia.
5. Typhoidal tularemia.
BARTONELLA
Species
Disease
B. bacilliformis
B. henselae
Oraya fever, Verruga Peruana

Cat-scratch disease,
Bacillary angiomatosis in AIDS patients
Bacillary angiomatosis in AIDS patients,
Trench fever
B. quintana
Cat-scratch Disease
Causative agent: B. henselae
Clinical feature: Painful regional lymphadenopathy in the
axilla and neck.
Pathology: Granulomatous inflammation with stellate
necrosis.
MYCOBACTERIUM
Classification
a. Tubercle bacilli:
1. Human M. tuberculosis.
2. Bovine M. bovis.
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551
b. Lepra bacilli:
Human M. leprae.
c. Causing skin ulcers M. ulcerans.
d. Atypical mycobacteria 1. Photochromogens.
2. Scotochromogens.
3. Nonphotochromogens.
4. Rapid growers.
e. Johnes bacillus M. paratuberculosis (pathogenic in
animals not in human being).
Test
Human
bacilli
Bovine
bacilli
Atypical
bacilli
Niacin test
Aryl sulphatase test
Catalase test
Peroxidase test
Nitrate reduction
+ve
-ve
+ve
+ve
+ve
-ve
-ve
+ve
+ve
-ve
+ve
+++ve
-ve
M. TUBERCULOSIS
Morphology
Gram positive bacilli. Straight or slightly curved rods.
Acid fact (by Ziehl-Neelsen method).
Acid fastness is due to presence of mycolic acid and
integrity of cell wall.
Generation time 14-15 hours.
Culture
Obligate aerobe.
Selective media:
Egg containing solid media:
Lowenstein-Jensen medium Best.
Composition Coagulated hens egg (without starch),
mineral salt solution, asparagines and malachite green.
Dorset egg medium.
Liquid media: Virulent strains produce serpentine cords.
The cord factor by itself is not responsible for virulence.
Cord factor prevents phagocytosis of TB bacilli.
552
Pathogenesis
Risk factors:
1. HIV infection.
2. Chronic renal failure.
3. IDDM.
4. Malnutrition gastrectomy or jejunal bypass surgery.
Primary TB
Common in children up to 4 years of age.
Source: Droplet infection.
Course: Asymptomatic with spontaneous healing.
Site: Pulmonary TB. Most common sites are lower lobe
or lower part of upper lobe.
Pathology: Primary focus is peripheral or subpleural (Ghon
focus) with hilar and paratracheal lymphadenopathy.
CXR: Normal.
Fate: Fibrosis, consolidation or calcification (Ghon lesion).
Complication: rare.
Local spread involvement of pleura leads to pleural
effusion and empyema.
Hematogenous spread miliary tuberculosis, tubercular
meningitis.
Tubercle: Granulomatous lesion composed of central zone
containing giant cells with or without caseation necrosis,
surrounded by epithelioid cells and peripheral zone of
lymphocytes and fibroblasts.
Postprimary or Secondary TB
Age: In adults. Most common in late adolescence and
early adulthood.
Source:
Reactivation of primary infection most common.
Reactivation occurs due to high PaO2. Reinfection TB
is exclusively confined to lungs.
Exogenous reinfection.
Site: Lesion localized to the apical and posterior segments
of upper lobe, superior segments of lower lobes.
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553
Pathology: Extensive parenchymal involvement with satellite

lesions and cavity formation.
Symptoms:
Cough.
Hemoptysis due to rupture of bronchial arteries.
Rasmussens aneurysm rupture of a dilated vessel
in a cavity may also lead to hemoptysis.
Fate: May heal by resorption, fibrosis and occasionally
calcification; or progress to chronic fibrocaseous
tuberculosis with tubercle formation, caseation, cavitation
and shedding of bacilli in sputum (open TB).
Extrapulmonary TB
1. Tubercular lymphadenitis:
Most common extrapulmonary site.
Most commonly involved are cervical and
supraclavicular nodes.
Most common in HIV patients, children and young
adults.
Concomitant lung disease may or may not be
present. H/O contact or drinking infected milk.
2. Pleural TB:
a. Pleural effusion:
Exudative, straw colored or hemorrhagic.
Chemical protein > serum protein. Glucose
serum glucose. pH < 7.2.
Cytology: Neutrophils in early stage but
mononuclear cells (lymphocytes) in late stage
is typical.
Microbiology: AFB are rarely seen on direct
smear.
Diagnosis: Needle biopsy of pleura is often
needed.
b. Tuberculous empyema:
Cause: Rupture of cavity or bronchopleural
fistula.
Treatment: Chemotherapy with surgical
drainage.
3. TB pericarditis:
Nature: Exudate, often hemorrhagic.
Diagnosis: culture of fluid may detect AFB; biopsy.
Compilation: Chronic constrictive pericarditis.
554
4. Genitourinary TB:
Cause: hematogenous spread from a primary focus.
Diagnosis:
Culture ve (sterile) pyuria in acidic urine. Culture
of 3 morning urine specimen yields a definitive
diagnosis in about 90 percent cases.
IVU earliest diagnosis.
5. Skeletal TB:
Cause: Reactivation of hematogenous foci or spread
from adjacent paravertebral LN.
Site: Upper thoracic spine in children most
common. Lower thoracic and upper lumber in
adults (most common).
6. Gastrointestinal TB:
Source: Swallowing of infected sputum most
common. Hematogenous spread. Ingestion of milk
from cows affected by bovine TB (rare).
Most common site terminal ileum and caecum.
Tubercular peritonitis: Diagnosis: Peritoneal biopsy.
7. Miliary TB:
Clinical feature: Hepatosplenomegaly, lymphadenopathy. Choroidal tubercle pathognomonic of miliary
TB.
Diagnosis:
CXR interstitial infiltrates (miliary mottling).
Sputum smear negative in 80 percent cases.
Tuberculin test negative in 50 percent cases.
BAL and transbronchial biopsy more likely to
permit bacteriological confirmation.
Cryptic miliary TB: Occurs in adults with meningeal
involvement to death.
Nonreactive miliary TB: Rapidly fatal.
8. TB meningitis and tuberculoma:
Source: Hematogenous spread of primary or postprimary pulmonary disease or rupture of a
subependymal tubercle into the subarachnoid space.
Clinical feature: Cranial nerve palsy (most commonly
ocular nerves). Involvement of cerebral arteries may
prduce focal ischemia. Hydrocephalus.
Diagnosis:
Lumbar puncture CSF shows increased leukocyte
count (predominantly lymphocytes), increased
protein and decreased glucose.
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555
CSF culture is diagnostic in 80 percent cases.

CT and MRI: show hydrocephalus and abnormal
enhancement of basal cisterns or ependyma.
Treatment: Steroids are useful adjunct to chemotherapy.
Tuberculoma: Appears as SOL in brain.
9. Cutaneous TB:
i. Lupus vulgaris: most common type.
Source: From lesions elsewhere in the body usually
in the lung or lymph nodes.
Clinical feature:
Most common site head and neck.
Apple jelly nodules.
Lesion with central scaring.
May be associated with nasal TB (butterfly
appearance) produces perforation of septal
cartilage.
ii. Scrofuloderma:
Source: Direct extension of infection from
underlying focus, i.e. infected LN, muscles or bones.
Diagnosis
1. Chest X-ray:
Normal in primary TB.
Classic picture upper lobe infiltrates with cavitation.
Atypical picture in late stages of HIV infection diffuse
interstitial or miliary infiltrates with little or no cavitation
(resembling primary TB).
2. AFB microscopy:
Sputum smear examination by direct microscopy
is now considered the method of choice for
diagnosis of pulmonary TB.
At least 10000 acid fast bacilli should be present
per ml of sputum for them to be readily
demonstrable in direct smears.
The frequency of sputum smear negativity is
increased in HIV patients.
Rapid diagnosis: Auraminerhodamine staining and
fluorescent microscopy is the quickest method of
diagnosis.
3. Culture: Very sensitive in detecting tubercle bacilli.
Media:
Solid medium LJ medium.
556
Liquid medium with radiometric growth detection

(e.g. BACTEC 460) and identification of isolates
by nucleic acid probes is more commonly used now.
4. Biopsy: Often needed in extrapulmonary TB (e.g.
pleural or peritoneal TB). The specimen should not
be preserved in formaldehyde.
5. Tuberculin test: For screening.
It detects the prevalence of infection.
Reagent:
Purified protein derivative (PPD). The standard PPD
contains 50000 TU/mg.
1 TU = 0.00002 mg PPD.
Dose: Three doses 1TU, 5TU and 250TU. For routine
testing, 1 TU dose is advocated in India.
Test: 1TU of PPD in 0.1 ml is injected intradermally
on the flexor aspect of forearm with a tuberculin syringe,
raising a wheal.
Result:
Read after 72 hours. Indurations is read.
> 10 mm Positive.
< 6 mm negative.
6-9 mm doubtful.
Interpretation:
Positive tuberculin test:
It indicates hypersensitivity to tuberculoprotein,
denoting infection or BCG immunization, recent or
past, with or without clinical disease. The test becomes
positive 4-6 weeks after infection or immunization.
A positive test is significant in children < 2 years and
indicate evidence of active lesion.
False negative test: Occurs in immunosuppression, e.g.
malignancy, Hodgkins disease, defective CMI, miliary TB,
convalescence from measles, sarcoidosis, severe
malnutrition, steroid therapy. A positive reaction may
occasionally revert to negative upon INH therapy.
Epidemiology
Prevalence of infection: It is the percent of individuals
who show a positive reaction to the standard tuberculin
test. Prevalence in India is about 30 percent.
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557
Incidence of infection (Annual infection rate):

It is the percent of population under study who
will be newly infected with M. tuberculosis. In India
1 to 2 percent.
Also known as tuberculin conversion index. It is one
of the best indicators for evaluating TB problem and
its trend.
Prevalence of disease: 4 cases/1000 i.e., 0.4 percent.
It is the percent of individuals whose sputum is positive
for tubercle bacilli on microscopic examination. It
reflects the case load in a community.
Incidence of disease: 1.5 cases/1000 = 0.15 percent.
New case: A patient with sputum positive pulmonary
tuberculosis who has never had treatment for tuberculosis
or has taken anti-tuberculosis drugs for less than
4 weeks.
Failure case: Smear positive at 5 months or later.
Default: Smear positive after having left treatment for at
least 2 months.
Treatment
Long-course regimens:
a. Daily regimens most frequently used combination
in India is INH plus thioacetazone. Duration 18
months.
b. Bi-weekly regimens Streptomycin + INH + Pyridoxine supervised.
Short-course chemotherapy:
Advantages:
1. Rapid bacteriological conversion.
2. Lower failure rates.
3. Reduction in frequency of emergence of drug-resistance.
4. Low toxicity.
Disadvantages: High cost.
Course: Intensive phase HRZE 2 months; Continuation
phase HT 6 months.
558
DOTS:
DOTS (directly observed treatment, short-course)
Category Type of patients
Regimen
Test at
month
Reviews
I.
2(HRZE)3
4(HR)3
4 and 6
months
2(HRZES)3
1(HRZE)3
5(HRE)3
2(HRZ)3
4(HR)3
5 and 6
months
II.
III.
New case
Seriously ill sputum
smear ve
Extrapulmonary TB
Relapse
Failure
Sputum ve or
Extrapulmonary
not seriously ill
Drugs taken on alternate days, i.e. thrice a week.

H = Isoniazid (600 mg)
R = Rifampicin (450 mg or 10 mg/ kg in children)
Z = Pyrazinamide (1500 mg)
E = Ethambutol (1200 mg)
S = Streptomycin (750 mg)
Patients > 60 kg should receive additional 150 mg
of R.
Pyridoxine 10 20 mg daily to prevent INH induced
neuropathy.
Extrapulmonary TB
Serious
Not serious
Meningitis
Miliary TB
Pericarditis
Spinal/GI tract
Lymph node
Peripheral joint
Skin
Category I
Category III
During intensive phase all the drugs are administered

under supervision.
During continuation phase drugs are selfadministered. Medicines for 1 week are supplied in a
multiblister combipack of which the first drug is swallowed
under supervision.
Domiciliary treatment:
Advantages Cheaper than hospital treatment.
Disadvantages Irregular treatment.
Monitoring for antitubercular chemotherapy:
With standard 6 months regimen, more than 80 percent
patients should have negative sputum at the end of 2nd
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559
month. By the end of third month, virtually all patients

should be sputum ve. When patients sputum culture
remains +ve at or beyond 3 months, treatment failure or
drug resistance should be suspected. Smears +ve after 5
months should be considered indicative of treatment failure.
Special cases:
Renal failure: INZ + RM + PZ.
Pregnancy: INZ + RM for 9 months (2HRZ + 4HR)
+ E for first 2 months.
Breastfeeding: Continue + ATT to mother + INH
prophylaxis and BCG vaccination to baby,
Prevention
BCG vaccination:
Live attenuated vaccine consisting of bovine strain of
tubercle bacilli. WHO recommendation Danish 1331
strain.
Diluent: Normal saline.
Dose: 0.1 mg in 0.1 ml.
Administration: Intradermal injection.
Storage: 4oC (2-8oC)
Reaction: Papule reaches a diameter of 4-8 mm at 5
weeks subsides or form a shallow ulcer usually covered
with a crust spontaneous healing occurs within
6-12 weeks.
Contraindication: Generalized eczema, infective
dermatosis, hypogammaglobulinemia, immunodeficiency
BCG is not effective in AIDS.
Protective value: 80 percent, varies in different parts of
the world.
ATYPICAL MYCOBACTERIA
General features:
1. They are not transmitted directly form man-to-man.
2. They are resistant to antitubercular drugs.
Runyons Classification
Group I: Photochromogens:
Produce yellow-orange pigment in light.
M. Kansasii: Most important pathogen. Produces
chronic pulmonary disease in old persons with pre-
560
existing lung disease lady Windermeres syndromes.

It is sensitive to AT drugs.
M. marinum: Produces swimming pool granuloma.
Group II: Scotochromogens:
Produce pigmented colonies even in the dark.
M. scrofulaceum: May cause scrofula (cervical adenitis
in children.
Group III: Nonphotochromogens:
Don not produce any pigment.
M. avium intracellular: Common in AIDS patients with
CD4 count <50/l.
Group IV: Rapid growers:
M. smegmatis and M. phlei: Saprophytes and
incapable of infecting humans.
Skin Pathogens
M. ulcerans produces Buruli ulcer.
M. marinum swimming pool granuloma.
MYCOBACTERIUM LEPRAE
Morphology
Acid fast bacilli.
Globi: are spheroidal mass of bacilli arranged in a cigar
bundle appearance found within the lepra cells.
Virchow or lepra cells: Foaming macrophages laden
with acid-fast bacilli (large undifferentiated histiocytes).
Culture
Lepra bacilli cannot be cultured in artificial media or
tissue culture. They can be propagated in the footpads
of mice and the nine-banded armadillo.
Generation time of lepra bacillus 12-13 days.
Epidemiology
Prevalence:
It is highest in Orissa.
Overall prevalence 6.7/10000.
Leprosy is considered to be a public health problem
when the prevalence exceeds 1 in 10000.
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561
Transmission:
1. Droplet infection.
2. Contact transmission.
3. By insect bite, breast milk, tattooing.
Incubation period: Is calculated from mode.
Classification
a. Early or Intermediate leprosy:
Hypopigmented patch with definite sensory impairment.
Peripheral nerves are normal. May heal spontaneously.
b. Tuberculoid leprosy:
CMI is high and bacillary load is low (Lepromin
+ve).
Clinical feature:
Hypopigmented macule with hypoesthesia-usually
single or a few.
Nerve involvement superficial nerves [such as the
ulnar nerve (most common), common peroneal
nerve and greater auricular nerves] maybe enlarged.
Muscle atrophy (due to neural involvement) is
common in small muscles of hand. Clumsiness in
hand is due to involvement of interossei muscles.
Neuropathy:
Sensory changes are more marked. DTR are never
lost. Loss of fine touch, pain and temperature but
position and vibration senses are spared.
Plantar ulceration of metatarsal head is the most
common complication.
Histology:
Noncaseating granuloma in nerve with epithelioid
and giant cells.
c. Lepromatous leprosy:
CMI is low and bacillary load is high (Lepromin
ve).
Clinical feature:
Widespread bilateral cutaneous involvement.
Lesions vary from macules, nodules, and plaques
to papules (never vesicles), non-anesthetic.
Facial involvement:
Madorasis loss of lateral portions of eyebrows.
Leonine facies due to loss of nasal septum.
Sterility, gynecomastia.
Nerve involvement is infrequent.
562
Histology:
Lepra cells with globi, no epitheloid or giant cells
(subepithelial free zone); normal skin contain bacilli
demonstrable by staining.
Note: Lazarine leprosy is a variant of LL.
Note: ovary is not involved in leprosy. Testes not in
gonorrhea. Vas not in syphilis.
Note: Iris pearls are seen in leprosy.
d. Borderline leprosy:
All kinds (bizarre) of lesions in a single patient
distributed asymmetrically.
Inverted saucer shaped lesions are seen.
Borderline tuberculoid:
Most common type in India. BB represents the
most unstable form of leprosy.
Shows satellite lesions.
Multibacillary leprosy:
Includes Borderline, BL and LL.
Bacterial index 2. Bacilli are present in large
numbers in the skin granulomas.
Paucibacillary leprosy:
Includes BT and TT and intermediate leprosy.
Bacterial index < 2.
WHO study group classification for treatment:
Treatment
Paucibacillary
Single skin lesion
Multibacillary
2-5 skin lesions
>5 skin lesion
Immunity
Cell mediated immunity is deficient in leprosy.
CMI deficiency is very specific for lepra bacilli and other
infections (e.g. viral, parasitic) are not increased.
Patients with LL show increase in CD8 cell count.
Patients with TT show increase in CD4 cell count.
The albumin: Globulin ratio is reversed.
TT is associated with HLA DR2 and LL is associated
with HLA MT1 and HLA DQ1.
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563
Reactional States
Type 1 or Reversal reaction:
Seen in BT (most common), BB, BL patients.
Mechanism - Cell mediated hypersensitivity.
Clinical feature Painful tender nerves, loss of function,
swollen and erythematous skin lesions and new lesions
may appear. No fever.
Treatment Mild Aspirin; Severe Prednisolone.
Type 2 or Erythema Nodosum Leprosum (ENL):
Seen in LL and BL patients.
Most frequently in the latter half of initial year of
treatment.
Mechanism immune complex (Arthrus reaction)
Clinical feature Tender, inflamed subcutaneous
nodules, may ulcerate. Fever, arthralgia, iritis, orchitis.
Treatment MildAspirin; Severe Thalidomide (100
300 mg / day), clofazimine, steroids, chloroquine.
Downgrading reaction: Clinically similar to reversal
reactions. Common in untreated patients and in women
during the third trimester of pregnancy.
Complications
Lucio phenomenon: Characterized by arteritis, seen
in patients with diffuse, infiltrative non-nodular
lepromatous leprosy.
Secondary amyloidosis: in severe LL especially those
complicated by ENL reaction.
Diagnosis
1. Skin biopsy: Shows periappendageal lymphocytes. It
is ve in primary neuritic leprosy.
2. Bacterial index: Seven sites should be examined at
least. These include four skin lesions, nasal smear
and both ear lobule.
WHO grading of smears:
Negative: No bacilli in 100 fields.
+ : 1 bacilli in each field.
++ : Bacilli found in all fields.
+++ : Many bacilli in all fields.
564
Use:
1. Only objective way of monitoring the benefit of
treatment.
2. Classification of leprosy as paucibacillary (with BI <2)
and multibacillary (BI 2)
3. Lepromin test: Delayed hypersensitivity test.
i. Early Fernandez reaction: Read at 48 hours. Consists
of erythema and indurations.
ii. Late Mitsuda reaction: Read at 21 days. Consists
on an indurated skin nodule that may ulcerate.
Use: Not diagnostic.
1. To test the status of CMI of leprosy patients.
2. To assess the prognosis and response to treatment.
3. To classify the lesions Lepromin test is +ve in
TT, it is ve in LL and equivocal in intermediate
leprosy.
4. Tests for humoral response:
i. FLAABS: Used to identify subclinical infection.
ii. Monoclonal antibodies.
iii. ELISA test.
5. Morphological index: Is the percent of solid staining
bacilli in stained smears.
6. Histamine test: Very reliable in detecting at an early
stage peripheral nerve involvement due to leprosy.
7. Mice footpad culture.
Treatment
Multidrug chemotherapy:
WHO regimen:
Multibacillary leprosy
Rifampicin 600 mg once monthly supervised.
Dapsone 100 mg daily, self-administered.
Clofazimine 300 mg once monthly, supervised
and 50 mg daily self-administered
Duration 2 years (1 year now).
Paucibacillary leprosy
Rifampicin 600 mg once monthly supervised.
Dapsone 100 mg daily, self-administered.
Duration 6 months.
Drugs should be continued till the signs of disease
activity have subsided.
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565
Surveillance:
Multibacillary: Both clinically and bacteriologically at
least once a year for 5 years after completion of therapy.
Paucibacillary: Only clinically at least once a year for
2 years after completion of therapy.
Reaction states:
Type 1: High dose prednisolone.
Type 2 (ENL): Thalidomide (200 mg BD), clofazimine.
Note: Rifampicin is most rapidly acting and most potent
bactericidal drug in leprosy. Clofazimine is used both in
chronic and acute (reactional states) stages of leprosy.
Treatment of nerve abscess in leprosy surgical excision.
Treatment of single skin lesion Rifampicin + Ofloxacin
+ Minocyclin (ROM regimen).
Prevention
Best method is early detection and treatment
(secondary prevention).
Early detection: By
Contact survey in areas with low prevalence (< 1
case per 1000).
Group survey in areas with prevalence 1 in 1000
Mass survey in hyperendemic areas prevalence 10
in 1000.
Treatment by multidrug therapy. Only bactericidal
drugs are used.
Evaluation
Incidence rate: Most sensitive index of transmission
of disease. Also the only index for measuring the
effectiveness of measures taken, i.e. reduction in
transmission.
Bacteriological index: Only objective way of monitoring
the benefit of treatment.
SPIROCHETES
TREPONEMA
Pathogens
1. T. pallidum Veneral syphilis.
2. T. endemicum Endemic syphilis or Bejel.
566
3. T. pertenue Yaws.
4. T. carateum Pinta.
[mnemonic: P not for P]
T. PALLIDUM
Discovered by Schandiun and Hoffmann.
Morphology
Actively motile spiral rods.
They are seen by negative staining with Indian ink.
Dark ground or phase contrast microscopy.
Stained by Silver impregnated method. Fontanas
method for staining film and Levaditis method for
tissue sections.
Cultivation
They do not grow on artificial culture media. Strains
can be maintained by serial testicular passage in rabbits.
Nichols strain is the strain used for diagnostic and
research purposes.
Non-virulent strains can be grown on artificial media
e.g. Reiter strains used in group specific tests for syphilis.
Syphilis
Routes of transmission:
1. Sexual contact most common.
2. Direct contact.
3. Transplacental.
4. Blood transfusion.
Incubation period: 10 to 90 days.
Manifestations
Primary syphilis:
Chancre: Painless papule, indurated, superficially ulcerated.
Most common sites:
In heterosexual male - penis; in homosexual male rectum and anal canal.
In female - cervix and labia.
Primary chancre heals within 4-6 weeks leaving a scar.
Regional lymphadenopathy firm, rubbery, non-tender
and non-suppurative.
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567
Secondary syphilis: Occurs 2-6 months after primary lesion

heals.
Features:
May be asymptomatic.
Diffuse symmetrical mucocutaneous lesions ranges
from macules, papules, papulosquamous and pustular
(but not vesicular).
Occurs on trunk and extremities, face and scalp,
palm and soles, (non-itching).
In mouth superficial erosions cause snail-track ulcers.
Generalized non-tender lymphadenopathy.
Condyloma lata: Seen in secondary syphilis.
Broad, moist pink papules in moist, warm areas
perianal area, vulva, scrotum, axillae, etc. Highly
infectious.
Constitutional symptoms.
Complications: Hepatitis, nephropathyproteinuria, G.I.
involvementgastritis, UC, arthritis, periostitis, moth
eaten alopecia.
Latent syphilis:
Quiescent stage, lasts from 2 years to a lifetime.
No clinical features and normal CSF study but positive
serological tests.
Late syphilis:(Tertiary): Occurs only in 35 percent untreated
patients after 5-15 years.
a. Neurosyphilis:
Meningeal:
Meningovascular most common presentation is
a stroke syndrome involving the MCA in young
adults.
General paresis includes abnormalities of itals
personality, affect, reflexes increased, eye (Argyll
Robertson pupil), sensorium (illusions, delusions,
hallucinations), intellect (decrease recent memory)
and speech. (Mnemonic PARESIS).
Tabes dorsalis: Demyelination of posterior columns,
dorsal roots and dorsal root ganglia.
Symptoms: Ataxic wide based gait (sensory ataxia),
paresthesia, bladder disturbance, impotence, areflexia,
and loss of position, deep pain and temperature
sensations.
568
Charcots joint:
Trophic joint degeneration due to loss of pain
sensation. Most commonly in the knees.
Optic atrophy.
b. Cardiovascular syphilis:
Affects the vasa vesorum (endarteritis obliterans
leads to medial necrosis) of mainly ascending and
transverse segments of aortic arch.
Clinical feature Aortic regurgitation, saccular
aneurysm, coronary osteal stenosis.
Symptoms appear 10-40 years after infection.
X-ray shows linear calcification of the ascending
aorta.
c. Eyes: Pain, photophobia, dimness of vision,
chorioretinitis, fixed pupil.
d. Gumma
It is a late benign lesion.
Most common in skin.
Histology:
Granulomatous inflammation with central necrosis
surrounded by mononuclear, epithelioid and
fibroblastic cells; occasionally giant cells and
perivasculitis are seen.
Treponema are scant in gumma and difficult to
demonstrate. Gumma in liver may produce hepar
lobatum.
Sloughing of a subcutaneous gumma produces
painless, punched out ulcer with a wash-leather
base.
Congenital Syphilis
Transplacental transmission can occur at any stage of
pregnancy but the lesions generally develop after the fourth
month of gestation.
Results: Stillbirth, abortion, prematurity, neonatal death,
congenital syphilis.
Manifestations of congenital syphilis:
Early manifestations within 2 years of life.
Features:
Earliest sign is rhinitis (snuffles).
Mucocutaneous lesions primary bullous lesions
(syphilitic pemphigus) vesicles.
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569
Note: Bullae / vesicles are only seen in congenital syphilis.

Osteochondritis and osteitis most common early
manifestation. Involves the metaphysis of long bones.
Hepatosplenomegaly, lymphadenopathy, jaundice,
thrombocytopenia, leukocytosis.
Late manifestations appears after 2 years.
Consists of Hutchinsons classic triad of late congenital
syphilis
i. Interstitial keratitis,
ii. 8th nerve deafness (seen in tertiary congenital syphilis)
iii. Hutchinsons teeth.
Recurrent arthropathy.
Cluttons joint: Bilateral knee effusions.
Residual stigmata (in late disease as a sequele of early
disease)
Hutchinsons teeth centrally notched, widely spaced,
peg shaped upper central incisors.
Mulberry molars (Moons molars).
Facies Frontal bossing, saddle nose and poorly
developed maxillae, collapsed nasal septum
(perforation of bony septum).
Saber tibia.
Rhagades linear scars at the angles of mouth and
nose, caused by secondary bacterial infection.
Perforation of palate.
Note: Thymus gland abscess in congenital syphilis is called
Dubois abscess.
Diagnosis
Serological tests:
1. Non-specific (Reagin antibody) tests:
Using cardiolipin antigen (standard tests for syphilis)E.g. Wasserman CFT, Kahn tube flocculation test,
VDRL slide flocculation test, Rapid plasma regain
(RPR) test.
STS become positive 7-10 days after appearance of
primary chancre (3-5 weeks after acquiring infection).
2. Group specific Reiter protein CFT.
3. Species specific tests Using Nichols strain.
FTA-ABS and TPI are both equally specific called
standard reference test.
570
Note:
Sensitive tests RPR and VDRL.
Specific tests TPHA and FTA-ABS
TPI test is most specific.
FTA-ABS is the earliest test to be +ve (most sensitive).
Uses of serology:
1. For screening and diagnosis RPR and VDRL.
2. For monitoring the response to therapy VDRL, RPR.
3. For confirmation of diagnosis FTAABS or MHA
TP.
Causes of biological false positive VDRL and RPR tests
a. Acute (< 6 months)
i. Recent viral infection (genital herpes, HIV).
ii. M. pneumonia.
iii. Malaria.
iv. Parenteral drug use.
b. Chronic (> 6 months)
i. Aging.
ii. Autoimmune disorders SLE, RA.
iii. Parenteral drug use.
4. Detection of specific IgM antibodies IgM antibodies disappear soon after elimination of
infection by treatment.
Presence of IgM in neonatal serum confirms the
diagnosis of congenital syphilis (because IgM does not
cross the placenta).
Tests for detection of IgM:
VDRL test.
19S IgM FTAABS used to diagnose congenital
syphilis.
Treatment
Benzathine penicillin G is drug of choice for all stages.
Neurosyphilis use of Benzathine penicillin G alone
is not recommended.
Syphilis in pregnancy drug of choice is penicillin G.
Monitoring:
By VDRL and RPR (become ve after treatment).
The FTA-ABS and hemagglutination tests remain +ve
in most patients treated for seropositive early syphilis
so they are not recommended for monitoring.
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571
To indicate effective control VDRL titer should fall 4

fold.
Jarisch-Herxheimer Reaction:
Follow the initiation of treatment of syphilis most
commonly in secondary syphilis.
Features: Fever, headache, myalgias, tachycardia,
tachypnea, increased circulating neutrophil count, mild
hypotension.
ENDEMIC SYPHILIS
Transmission: Nonvenerally.
Clinical feature: Common in children, primary chancre is
not usually seen except sometimes on the nipples of mothers
infected by their children. The disease mimics secondary
syphilis.
YAWS
Causative organism: T. pertenue which is antigenically and
morphologically indistinguishable from T. pallidum.
Transmission: By direct contact (not STD).
Clinical feature: Primary lesion is an extragenital papule
that enlarges and breaks down to form an ulcerating
granuloma. (Most commonly seen on legs of children).
Secondary and tertiary stages are seen.
PINTA
Causative organism: T. carateum which is antigenically
different from T. pallidum.
Clinical feature: Primary lesion extragenital papule that
does not ulcerate but develops into a lichenoid or
psoriaform patch. Skin is involved and hypo/
hyperpigmentation is seen in secondary stage.
BORRELIA
Organisms
B. recurrentis Relapsing fever.
B. burgdorferi Lyme disease.
B. vincenti Vincents angina.
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Relapsing Fever
Vector: Louse and soft tick.
Clinical feature: Fever and bacteremia which is followed
by afebrile episodes, splenomegaly, jaundice.
Culture: BSK medium.
Lyme Disease
Vector: Ticks (ixodes).
Clinical feature: Expanding annular skin lesion (erythema
chronicum migrans) with fever, headache, myalgia and
lymphadenopathy. Arthritis is a late sequel.
Vincents Angina
B. vincenti is always associated with fusiform bacilli
(Fusobacterium fusiforme). This symbiotic infection is
known as fusospirochetosis.
Clinical feature: Ulcerative gingivostomatitis or
oropharyngitis.
LEPTOSPIRA
Weils Disease
Causative organism:
L. icterohemorrhagiae (belongs to genus L.
interrogans).
Vector: Rat.
Route: Water contaminated with urine of vector animal.
Clinical feature:
High fever with chills, jaundice, and hemorrhagic
diasthesis purpura,
Renal dysfunction albuminuria is a constant feature.
Farm workers in rice fields are in greatest risk.
Diagnosis: Microscopic agglutination test (MAT), antibody
titer 1:100 in MAT is significant. Isolation of organism
in EMJH medium. Indirect hemagglutination test.
Treatment: Penicillin G is the drug of choice.
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573
MYCOPLASMA
Smallest freeliving microorganism.
Cell wall deficient (so resistant to lactam antibiotics).
Mycoplasma represents stable L forms. But current
evidences are against this possibility.
Not an obligate parasite.
They can pass through bacterial filters (Eaton agent).
Multiply by binary fission.
Can grow in cell free media.
M. PNEUMONIAE
Culture
Colonies have fried egg appearance.
Staining by Dienes method.
Clinical Feature
Common in older children and adolescents.
Tracheobronchitis most common manifestation;
bronchiolitis pharyngitis.
Walking or atypical pneumonia:
Symptoms: Fever with chills, headache, sore throat,
paroxysmal cough with blood stained sputum.
Characteristically paucity of physical findings but marked
radiological features.
CXR: Evidence of consolidation, usually unilateral,
involving lower lobe, starting at the hilum and fanning
out to the periphery.
Complications: Bullous meningitis and otitis,
meningoencephalitis, erythematous maculopapular and
vesicular exanthems, hemolytic anemia (cold agglutinins).
Diagnosis
Routine laboratory tests are often normal.
Cold agglutinins are produced in less than 50 percent
cases.
Serology ELISA is preferred.
Clinical, radiological and laboratory findings are
indistinct to sever as a basis for accurate diagnosis.
Treatment
Erythromycin is the drug of choice.
574
UREAPLASMA UREALYTICUM
Second most common cause of non-gonococcal
urethritis.
In men urethritis, proctitis, balanoposthitis and
Reiters syndrome.
In women acute salpingitis, PID, cervicitis and
vaginitis.
OTHER MYCOPLASMA
M. hominis postpartum fever, salpingitis.
M. genitalium urethral infection.
RICKETTSIA
Morphology
Gram negative bacilli, obligate intracellular pathogen; they
are parasites in arthropods.
Culture
Can not grow in cell free media.
Classification
Diseases
Species
Vector
Typhus group
a. Epidemic typhus
R. prowazekii
R. typhi
Louse (Pediculosis
corporis)
Rat Flea
R. tsutsugamushi
Mite
R. rickettsii
Tick
R. conorii
R. akari
Tick
Mite
C. burnetii
No vector for
human infection
Louse
b. Endemic typhus
(murine)
c. Scrub typhus
Spotted fever group
a. Rocky mountain
spotted fever
b. Indian tick typhus
c. Rickettsial pox
Others
a. Q fever
b. Trench fever
R. quintana
Pathogenesis
They are maintained by transovarian transmission in mite
(i.e. scrub typhus and R. pox). They multiply in the
endothelium of small vessels.
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575
Epidemic Typhus
Fever and chills.
Characteristic rash macular of maculopapular.
Starting on the trunk and spreading over the limbs but
sparing the face, palms and soles.
Clouding of consciousness.
Rocky Mountain Spotted Fever
(Indian Tick Typhus)
Resembles epidemic typhus except the rash.
Rash is macular initially and becomes petechial later.
Appears first on the flexor aspects of the wrist and
ankle and then spreads all over the body including the
palms, soles and even the buccal mucosa.
Rickettsial Pox
Mildest of rickettsial infection.
Q Fever
Highly infectious zoonotic disease.
Ticks act as vectors as well as reservoir. There is no
vector in human disease.
Human Q fever is by inhalation of infected dust fro
soil previously contaminated by urine or faeces of
diseased animals.
It is also transmitted by milk.
Clinical feature: There is no rash. May cause pneumonia.
Diagnosis
Neill-Mooser or Tunica reaction: Positive in endemic typhi.
Helps to differentiate between epidemic and endemic typhi.
Well-Felix reaction: Antigen O antigen of proteus.
Disease
Antigens
Epidemic typhus
Endemic typhus
Spotted fever
Scrub typhus
Q fever
Agglutination with
OX 19
+++
+++
OX2
++
OXK
+++
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ACTINOMYCETES
They are gram positive, filamentous true bacteria.
ACTINOMYCES
Anaerobic actinomycetes.
Most common organism is Actinomyces israelli which
causes human disease.
Actinomycosis
Pathology: Chronic granulomatous infection with
development of indurated swelling which suppurates and
discharges sulphur granule. The lesion often points towards
the skin leading to multiple draining sinuses.
Clinical feature: Three types:
1. Cervicofacial Indurated lesions on cheek and
submaxillary region (jaw) most common type.
2. Thoracic Lungs and pleura.
3. Abdominal Liver.
4. Pelvis Most commonly with the use of IUD.
Diagnosis:
a. Demonstrating lesion by microscopy.
b. Isolation in culture.
Specimen Pus.
Findings: Sulphur granules which are white to yellow.
These represent bacterial colonies. Surrounded by club
shaped structures which represent antigen-antibody complex
and gives a sun-ray appearance.
Treatment: Penicillin.
Nocardia
Aerobic actinomycetes.
Acid fast, gram positive, filamentous.
Pathogenesis:
Cutaneous Local abscess, cellulitis and
lymphocutaneous lesions.
Subcutaneous Actinomycotic mycetoma.
Systemic Pulmonary disease (pneumonia most
common disease).
Diagnosis: Culture on paraffin bait.
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577
Actinomycotic Mycetoma (Maduramycosis)

Granulomatous lesion of subcutaneous tissue.
Common sites foot and less often the hands.
Features Multiple sinuses that discharge white to
yellow granules (c.f. mycotic mycetoma which
discharges black granules).
Treatment: Sulfonamides are drug of choice.
CHLAMYDIAE
Obligate intracellular pathogen (hence considered to
be virus once).
Gram negative bacteria. They are bacteria because
they
i. Possess both DNA and RNA.
ii. Have cell walls and ribosomes.
iii. Replicate by binary fission.
iv. Susceptible to antibiotics.
Morphology
They occur in two forms
1. Elementary body: Extracellular and infective form.
2. Reticulate body: Intracellular and replicative form.
The developing intracellular Chlamydial micro colonies
are called inclusion bodies.
Human Diseases
Species
Serotype
Disease
Trachoma
Inclusion conjunctivitis
(neonatal and adult).
Genital chlamydiasis.
Infant pneumonia.
Chl. trachomatis L1, L2, L3
Lymphogranuloma
venereum.
Chl. psittici
Psittacosis.
Chl. pneumoniae Only one serotype Acute respiratory diseases.
Chl. trachomatis
Chl. trachomatis
A, B, C
D to K
Trachoma
Signs:
1. Papillary hypertrophy.
2. Follicular hypertrophy seen in upper tarsal
conjunctiva, the limbus (leading to Herberts pit
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pathognomonic), the bulbar conjunctiva (also pathognomonic).

3. Pannus Sub-epithelial neovascularization.
4. Cicatrization Stellate shaped scar on cornea; late
sequele.
MacCanans Classification:
Stage I : Incipient trachoma, immature follicles in upper
palpebral conjunctiva with no scarring.
Stage II : Established trachoma.
IIA: Follicular hypertrophy predominant
IIB: Papillary hypertrophy predominant.
Stage III : Cicatrizing trachoma follicles and scarring
at upper tarsal conjunctiva.
Stage IV : Healed trachoma.
Diagnosis:
Any two of the following criteria should be present
1. Follicles at upper tarsal conjunctiva.
2. Limbal follicles and Herberts pit.
3. Stellate shaped scar.
4. Vascular pannus mostly at upper limbus.
Complications:
Entropion.
Treatment:
i. Oral sulphonamide in full dose.
ii. Local sulphacetamide drop.
Note: Prevalence of trachoma > 5 percent (in children
< 10 years) is an indication for mass or blanket
treatment.
Treatment
Veneral infection Tetracycline.
Neonatal conjunctivitis and infant pneumonia
Erythromycin.
Diagnosis
a. Non-cell culture:
1. Direct IF antibody (DFA) Sensitivity 70-85 percent.
2. ELISA Sensitivity 60-80 percent; Specificity
97-99 percent.
3. Ligase chain reaction and PCR Most sensitive.
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579
b. Serology: CFT and micro IF test (for infant pneumonia).

c. Microscopic demonstration of inclusion or elementary
bodies by Giemsa stain (in conjunctivitis) or iodine
stain.
d. Isolation in yolk cell, mice brain and cell cultures
(McCoy, HeLa and BHK cell lines).
VIROLOGY
GENERAL PROPERTIES
Viruses are obligate intracellular parasites.
They contain only one type of nucleic acid ether DNA
or RNA.
Morphology
Size:
Virion The extracellular infections virus particle is
called the virion.
Elementary bodies Stained viruses seen under light
microscope (e.g. poxvirus).
Largest virus Poxvirus.
Smallest virus Parvovirus.
Structure and shape:
The virion consists of a nucleic acid core surrounded
by a protein coat, the capsid.
2 types of symmetry are met within the capsid icosahedral (cubical) and helical.
Peplomers: Protein subunits projecting as spikes on the
surface of envelope. Influenza virus carries two types of
peplomers the hemagglutinin and the neuraminidase.
Shape:
Rabies virus is bullet shaped.
Poxviruses are brick shaped.
Resistance:
Lyophilisation or freeze drying drying the frozen virus
under vacuum.
Use for prolonged storage of viruses.
Hemagglutination: Elution Release of virus from
hemagglutinated red cells. It is seen only in myxovirus that
possesses neuraminidase.
580
Viral biosynthesis:
Positive strand RNA viruses the viral RNA itself acts
as the mRNA. E.g. picorna, togaviruses.
Negative strand RNA viruses possess their own RNA
polymerase for mRNA transcription. E.g.rhabdo -,
orthomyxo -, paramyxoviruses.
Retroviruses oncogenic RNA viruses. Contain reverse
transcriptase (RNA dependent DNA polymerase) that
converts ssRNA to dsDNA.
Abnormal replication: Von Magnus phenomenon the virus
yield will have high hemagglutination titer but low infectivity.
Cultivation
1. Animal inoculation.
2. Embryonated egg.
Inoculation on the chorioallantoic membrane (CAM)
produces visible lesions (Pocks).
Pock count can be used for the assay of pock forming
viruses such as variola and vaccinia.
Chick embryo vaccines influenza vaccine, 17D
vaccine (yellow fever), flury strain (rabies).
3. Cell cultures most widely employed.
Types:
i. Primary cell cultures normal cells freshly taken from
body and cultured.
ii. Diploid cell culture.
iii. Continuous cell line usually derived from cancer
cells. Capable of continuous serial cultivation
infinitely. E.g. HeLa, Hep2, KB cell lines.
Cell line:
HeLa Ca cervix,
Hep-2 Ca larynx.
KB Ca nasopharynx.
Detection of virus growth in cell cultures:
1. Cytopathic effect enterovirus, measles virus, herpes,
adenovirus.
2. Hemadsorption when hemagglutinating viruses (e.g.
influenza and parainfluenza) grow in cell cultures, their
presence can be indicated by addition of guinea pig
erythrocytes to the cultures.
3. Interference one virus inhibits simultaneous or
subsequent growth of another virus.
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581
Assay of infectivity:
a. Quantal assay only indicate the presence (or absence)
of infectious viruses (e.g. tissue cultures).
b. Quantitative assay measures the actual number of
infectious particles in the inoculum.
Types:
Plaque assay in monolayer cell culture. Pock assay in chick
embryo (CAM).
i. Plaque assay: Each plaque indicates infectious virus.
Plaque test is used to separate specific clone of virus.
ii. Pock assay: E.g. Vaccinia.
Classification
DNA viruses:
All contain dsDNA except parvovirus.
1. Poxviridae.
2. Herpesviridae.
3. Adenoviridae.
4. Parvoviridae genome consists of ssDNA.
5. Hepadnaviridae Hepatitis B virus.
6. Papovaviridae.
RNA viruses:
All contain ssRNA except reoviridae.
1. Picornaviridae Entero (polio), Coxsackie, Echo,
Rhinovirus. HeparnaHepatitis A.
2. Orthomyxoviridae Influenza virus. Genome contains
ssRNA in 8 pieces (segmented).
3. Paramyxoviridae.
4. Toga.
5. Flavi.
6. Bunya.
7. Arena.
8. Rhabdoviridae rabies virus.
9. Reoviridae genome contains dsRNA in 10-12 pieces.
Reovirus, orbivirus, rotavirus.
10. Corona.
11. Retroviridae.
12. Calci.
13. Filo.
Note: Segmented genome is seen in bunyavirus,
orthomyxovirus, reovirus and arenavirus (mnemonic
BORA).
582
Some Definitions
Virusoids: Virusoids are nucleic acids that depend on helper
viruses to package the nucleic acids into virus like
particles.
Viroids: Subviral agents without an extracellular dormant
phase (i.e. virion) and contain a much smaller genome.
Prions: Prions are abnormal cellular proteins that can
spread from cell to cell and effect changes in normal cellular
proteins, thereby disrupting cellular function and
propagating themselves.
Prion diseases: Creutzfeldt-Jacob disease, Kuru,
Gerstmann-Strassler syndrome, Bovine spongiform
encephalopathy.
VIRUS INFECTIONS
Inclusion Bodies
Negri bodies (intracytoplasmic eosinophilic) Rabies.

Guarnieri bodies Vaccinia.
Bollinger bodies Fowl pox.
Henderson Peterson bodies Molluscum contagiosum.
Cowdry type A Herpes virus.
Note:
Poxvirus contains intracytoplasmic inclusions. Herpes
virus contains intranuclear inclusions. Measles contains
both.
Inclusions of adenovirus are basophilic.
Interferon
Nature: Protein. Species specific.
Production: Produced by cells on induction by viral and
nonviral inducers.
Mechanism of action: They have no direct action on viruses.
They act on other cells of the same species, rendering
them refractory to virus infection. On exposure to IFN,
cells produce translation inhibiting protein which selectively
inhibits translation of viral mRNA.
Types:
IFN: (leukocyte IFN) produced by leukocytes.
IFN: (fibroblast IFN) produced by fibroblasts and
epithelial cells.
IFN: (immune IFN) produced by T lymphocytes.
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583
Uses:
IFN
i. Chronic HBV infection.
ii. Chronic hepatitis non-A, non-B/C infections.
iii. Condyloma acuminata.
iv. Hairy cell leukemia.
v. Kaposis sarcoma.
IFN has significant activity in Bladder CA,
Laryngeal papilloma, non-Hodgkins lymphoma, and
Cutaneous T cell lymphoma.
IFN therapy also effective in Herpes keratitis, HZ
varicella infection, Rhinovirus infection, CMV infection.
IFN Chronic granulomatous disease.
Side effects: Hypotension, prostration, fever, abnormal liver
function.
Bacteriophage
Life cycle: 2 types
1. Virulent or lytic cycle: intracellular multiplication of
the phage culminates in the lysis of the host bacterium
and the release of progeny virions.
2. Temperate or Lysogenic cycle the phage DNA
becomes integrated with the bacterial genome,
replicating synchronously with it, causing no harm to
host cell.
Phage typing:
Application: Intra-species typing of bacteria, as in the
phage typing of S. typhi and staphylococci. Also V.
cholerae.
Bacteriophage are mostly used for epidemiology.
POXVIRUSES
VARIOLA AND VACCINIA
Morphology
Brick shaped virion. Can be seen under light
microscope.
Culture
CAM: Both viruses form pocks on CAM.
584
Tissue culture: Eosinophilic inclusion bodies called

Guarnieri bodies.
MOLLUSCUM CONTAGIOSUM
Clinical feature: Umbilicated skin lesion especially in genital
region.
Transmission: By close contact (sexual intercourse).
Diagnosis: Eosinophilic hyaline inclusion bodies
Henderson-Peterson bodies.
Treatment: Physical ablation.
HERPES VIRUS
Morphology
The nucleocapsid is surrounded by a lipid envelope. Intranuclear inclusion bodies (Cowdry type A Lipschutz) are
seen.
Classification
Herpes
Herpes
Herpes
Herpes
Herpes
virus type 1 Herpes simplex virus 1.

virus type 2 Herpes simplex virus 2.
virus type 3 Varicella-Zoster.
virus type 4 Epstein-Barr virus.
virus type 5 Cytomegalovirus.
Herpes Simplex
Pathogenesis:
HSV1: Lesions in and around the mouth. Transmitted
by direct contact or droplet spread.
HSV2: Genital tract infections. Transmitted by sexual
contacts.
The virus remains latent in ganglia, particularly of the
trigeminal nerve (HSV1) and sacral (HSV2) nerves.
Clinical feature:
1. Cutaneous lesions: Most common site is the face. Fever
blisters or herpes febrilis is due to viral reactivation
in febrile patients. Herpetic whitlow is seen in doctors,
nurses.
Eczema herpeticum caused by HS hominis virus.
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585
2. Mucosal: Most common site is buccal mucosa.

Gingivostomatitis and pharyngitis primary infection.
Recurrent herpes labialis.
3. Ophthalmic: Most common cause of corneal blindness
in USA. Acute keratoconjunctivitis. Follicular
conjunctivitis.
4. CNS: HSV encephalitis most common viral infection
in CNS. Caused by HSV1.
Clinical feature Acute onset of fever and focal
neurological (especially temporal lobe) symptoms.
Diagnosis Most sensitive noninvasive method is
demonstration of HSV DNA in CSF by PCR.
Treatment IV acyclovir.
5. Visceral: Esophagitis.
6. Genital:
HSV2 (also caused by HSV1).
Male lesions on the penis, urethra urethritis.
Female cervix, vagina, perineum and vulva.
7. Congenital:
Most commonly due to HSV2.
Mode due to contact with genital secretions at the
time of delivery.
Prevention Elective CS in women with genital herpes
lesions.
Clinical feature
Hallmark vesicular ulcerative skin lesion, skin lesion
may be absent in 1/3 rd cases, Neonatal encephalitis.
Diagnosis:
1. Microscopy Tzanck smear.
2. Tissue culture Method of choice for virus isolation.
On CAM produce white shiny pocks.
3. Serology.
Treatment:
Acyclovir is the most commonly used drug.
Idoxuridine is the drug of choice for H. simplex
keratoconjunctivitis.
Chickenpox
Epidemiology:
Agent: the virus can be grown in tissue culture. VaricellaZoster virus (herpes virus type 3).
586
Infectivity: From 1-2 days before the appearance of

rash to 4-5 days thereafter. Scabs are not infective.
Transmission: Droplet infection from a case most
common. Transplacental transmission.
Secondary attack rate: 90 percent.
Clinical feature:
Prodrome of 1-2 days.
Rash: appears on the day the fever starts. Rashes first
appear on trunk and face and then spread centripetaly.
Rashes are seen in various stages of development
macule, papule, vesicles and scabs (pleomorphism).
Vesicles are filled with clear fluid and look like dew
drops (most characteristic lesion). Symmetrical in
distribution.
Complications:
1. Secondary bacterial infection most common
complication.
Causative organism Streptococcus pyogenes and
2. Varicella pneumonia most serious complication in
adults.
3. CNS most common extracutaneous site in children.
Clinical feature: acute cerebellar ataxia, meningeal
irritation. Aseptic meningitis. Encephalitis. Transverse
myelitis. G-B syndrome.
Reyes syndrome Acute encephalopathy with fatty
liver.
4. Hemorrhage.
5. Glomerulonephritis.
6. Arthritis.
7. Hepatitis.
Perinatal Varicella
Associated with high mortality rate when maternal
disease develops within 5 days before delivery or within
48 hours thereafter.
Congenital varicella limb hypoplasia. cicatrical skin
lesions, microcephaly at birth.
Herpes Zoster (Shingles)
Cause: Reactivation of latent VZV from the dorsal root
ganglia.
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587
Clinical feature: Neuritic pain that precedes rash.

Rash: Unilateral vesicular eruption within a dermatome
with severe pain. Most common dermatomes involved
are T3 to L3 (thoracic region) and ophthalmic branch
of trigeminal nerve (Zoster ophthalmicus).
Risk factors: Immunodeficiency, Hodgkins and nonHodgkins lymphoma.
Diagnosis: Tzanck smear shows multi-nucleated giant
cells (Ballooning).
Ramsay-Hunt syndrome:
Cause: Involvement of facial nerve (the geniculate ganglion
of the sensory branch of facial nerve).
Clinical feature: Pain and vesicles in external auditory canal
and tympanic membrane. Loss of taste in the anterion
2/3 of tongue. Ipsilateral facial nerve palsy.
Treatment: Indications of systemic antiviral therapy
1. Involvement of mandibular nerve.
2. Involvement of motor nerve.
3. Very painful cutaneous lesions.
Epstein-Barr Virus
Pathogenesis:
EB virus specifically affects B lymphocytes. EB virus
receptors (CD21) are present on the surface of B cells
and epithelial cells.
Acute infection with EBV causes polyclonal activation
of B cells and antibodies are produced to both host
cell and viral proteins.
The number of T cells are increased with inverted
CD4:CD3 ratio.
In vitro, infected B cells are transformed so that they
can proliferate indefinitely.
Disease associations:
1. Infectious mononucleosis.
2. Malignancies
i. Nasopharyngeal carcinoma.
ii. Burkitts lymphoma.
iii. Hodgkins disease mixed cellularity type.
iv. T cell lymphoma.
v. Thymoma.
vi. Gastric carcinoma.
588
vii. Primary CNS lymphoma (especially in AIDS

patients).
3. Others
Chronic
fatigue
syndrome.
Meningoencephalitis.
Infectious mononucleosis (Glandular fever)
Route: Intimate oral contact as in kissing; called the kissing
disease.
Clinical feature:
Most infections in infants and young children are
asymptomatic, whereas most infections in adolescents
present as IM.
Symptoms Fever, sore throat, abdominal pain,
nausea, vomiting.
Sign Lymphadenopathy, pharyngitis or tonsillitis,
hepatosplenomegaly, rash.
Blood increased WBC count, anemia, lymphocytosis
with > 10 percent atypical lymphocytes,
thrombocytopenia.
LFT Increased serum levels of aminotransferase and
alkaline phosphatase.
Complications:
Disease is usually self-limited.
Meningitis and encephalitis are the most common
neurologic complications.
Autoimmune hemolytic anemia (Coombs +ve).
Hepatitis, myocarditis, pneumonia.
Diagnosis:
Heterophile antibody test (IgM type) cold antibody.
Standard test PaulBunnel test.
Sensitive test Monospot test.
Cytomegalovirus
Congenital CMV infection
Most common viral infection of the fetus. The disease
is called cytomegalic inclusion disease.
Clinical feature:
Petechial rash (due to thrombocytopenia).
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589
Hepatosplenomegaly, jaundice.
Microcephaly most common cause.
Chorioretinitis.
Cerebral calcification Sparse (c.f. toxoplasma) and
usually periventricular.
Inguinal hernia, 1UGR and prematurity.
CMV mononucleosis
Most common clinical manifestation in normal hosts
beyond neonatal period is a heterophile-negative
mononucleosis syndrome (c.f. EB virus with is heterophile
+ve).
CMV infection in immuno compromised host
Most common infection in organ transplant recipient.

Organ transplant Febrile leukopenia.
BM transplant Pneumonia, gastrointestinal disease.
AIDS infection occurs when CD4+ cell count falls
below 50 100 /L. CMV retinitis is the most common
manifestation.
Treatment:
1. CMV immunoglobulin.
2. Ganciclovir.
3. Foscarnet.
Vaccine: Live attenuated vaccine (Tower strain). Not effective
in immunodeficient patients.
Human Herpes Virus Type 6
HHV-6B causes exanthem subitum (roseola infantum
or sixth disease).
It is common in early infancy.
Clinical feature: Fever with subsequent rash which
disappears in 12 days without pigmentation or
desquamation.
PARVOVIRUS
Smallest virus.
Genome contains single stranded DNA.
B19 strain is a human pathogen.
590
Clinical Feature
1. In children Erythema infectiosum or 5th disease.
Characterized by facial rash with a slappedcheek
appearance. Spreads to involve palm and soles. Rash
disappears in 2 weeks. There is no fever.
2. In adults Acute arthralgia and arthritis.
3. Most common cause of transient aplastic crisis
developing suddenly in patients with chronic hemolytic
disease.
4. May produce non-immune hydrops in fetus.
PAPOVAVIRUS
Classification
Papovaviridae
Polyomavirus
Simian vacuolating virus
(SV40) and polyomavirus
Both produce malignant
tumors in mice
Papillomavirus
Human papilloma virus (HPV)
Morphology
Non-enveloped, icosahedral virus containing DNA (also
adenovirus).
Diseases by HPV
1. Common warts (verruca vulgaris) occurs on hands
in young children.
2. Plantar warts (verruca plantaris) painful, occurs in
adolescent and young adults (myrmecia warts).
3. Flat warts (verruca plana) most common in children.
Occur on face, neck, chest and flexor aspects of
forearms and legs.
4. Condyloma acuminata (or anogenital warts)
Sexually transmitted.
Most common pathogens HPV 6 and 11.
Sites in men frenum or coronal sulcus of penis.
In female appears first at the posterior introitus and
adjacent labia.
Features moist, soft, pedunculated wart on external
genitalia.
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591
Treatment Cryosurgery is the initial treatment of

choice. Also used Topical podophyllin preparation
(C/I in pregnancy), IF. Imiquimod drug of choice
in women.
5. CIN by HPV 16, 18, 31,
JC Virus
Produces progressive multifocal leukoencephalopathy
(PML).
ADENOVIRUS
Morphology
Non-enveloped, possesses DNA and a capsid with
icosahedral symmetry.
Diseases
1.
2.
3.
4.
5.
6.
In children acute URTI with prominent rhinitis.

In adults acute respiratory disease in military recruits.
Epidemic keratoconjunctivitis.
Acute follicular conjunctivitis.
Acute hemorrhagic cystitis.
Diarrhea by enteric types (types 40, 41) that produce
enterotoxins.
PICORNAVIRUSES
ENTEROVIRUS
Polio Virus
Morphology: Virion shows icosahedral symmetry with
genome containing single stranded RNA.
Epidemiology:
Prevalence:
A rough estimate of all clinical cases of poliomyelitis
can be done by multiplying the prevalence rate of
residual paralysis due to polio by 1.33, i.e. prevalence
of polio = prevalence of residual paralysis1.33. But
prevalence of residual paralysis = prevalence of
lameness1.25.
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Agent: Most outbreaks of paralytic polio are due to type

1 virus.
Most cases of vaccine induced paralysis are due to
type 3 virus.
Type 2 most effective antigen.
For 1 clinical case, there may be 1000 subclinical cases
in children and 75 in adults.
Route:
Fecal-oral route most common.
Droplet infection may occur in the acute phase.
Manifestations:
a. Inapparent (subclinical) infection 95 percent cases,
most common manifestation.
b. Abortive polio or minor illness fever, headache, sore
throat and malaise.
c. Nonparalytic polio (aseptic meningitis) 1 percent
of cases, fever comes back along with headache and
neck rigidity. Lasts for 2-10 days.
d. Paralytic polio least common manifestation (<1%).
Asymmetrical flaccid paralysis. Proximal more than
distal.
Usually involves the legs. Descending, i.e. starting at
the hip and moving down to distal parts.
Decreased muscle tone. Decreased or absent reflexes.
No sensory loss (pure motor neuropathy). May be
precipitated by fatigue, trauma, IM injection.
Note:
Most common muscle affected is the quadriceps. The
muscle which undergoes complete paralysis is the
tibialis anterior. The muscle in the hand affected most
commonly is the opponens pollicis.
Deformities:
Triple deformity (at knee) flexion, posterior
subluxation and external rotation.
Equinovarus deformity at the foot.
Tests:
Tripod sign, Kiss the knee test, Head drop sign (in
non-paralytic polio).
Death is due to respiratory failure (bilateral phrenic
nerve palsy is seen in polio).
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593
Laboratory diagnosis: Isolation of virus from throat in early

stage, feces throughout the course of the disease and the
convalescence.
Serodiagnosis is least commonly employed.
Prevention:
Polio vaccine:
1. Inactivated (Salk) vaccine
Course 4 doses. One or two doses of OPV can be
given as boosters.
Disadvantages
i. It induces humoral antibodies, but does not induce
intestinal or local immunity. The circulating antibodies
protect against paralytic polio but do not prevent
reinfection of gut by the virus no herd immunity.
ii. It is unsuitable during epidemics.
Advantage
Safe to administer in persons with immunodeficiency.
2. OPV:
Live attenuated vaccine containing
300,000 TCID50 of type 1 virus.
Result It results in widespread herd-immunity.
Contraindication -immunodeficiency.
Complication vaccine-associated paralytic polio due
to type 3.
Dose 3 drops.
Storage stabilization by adding MgCl2 can be stored
at 4oC for a year. Non-stabilized vaccine should be
stored at 20oC in a deep freeze.
Administration:
Polio is subject to international surveillance. All cases
of AFP should be followed up for 60 days to detect
residual paralysis. Even a single case is scaled as an
outbreak. Reporting of all cases with AFP in children
less than 15 years is mandatory.
Treatment of deformities:
Tendon transfer operation should not be performed before
5 years of age.
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Coxsackie Virus
Epidemiology: Transmission by fecal-oral rout. The virus
is shed in stool.
Diseases:
1. Herpengina (vesicular pharyngitis) Coxsackie group A.
2. Aseptic meningitis Group A and B.
3. Hand, foot and mouth disease.
4. Epidemic pleurodynia or Bornholm disease Group B.
5. Myocarditis and pericarditis in newborn Group B.
6. Juvenile diabetes Group B4.
7. Orchitis.
8. Acute follicular conjunctivitis Coxsackie A-24.
Echo Virus
Also called the orphan virus.
It is the most common cause of aseptic meningitis.
Others
Acute hemorrhagic conjunctivitis caused by enterovirus
type 70 and Coxsackie type A24. It occurs in pandemic.
Note: Viruses causing conjunctivitis:
1. Adenovirus Acute follicular conjunctivitis, also
epidemic keratoconjunctivitis.
2. Enterovirus (type 70) Hemorrhagic (pandemic)
conjunctivitis.
3. Coxsackie A24.
4. HSV follicular conjunctivitis.
ORTHOMYXOVIRUS
INFLUENZA
Morphology
Genome contains single stranded RNA in 8 pieces
(segmented).
Hemagglutination
Influenza virus agglutinates RBC due to presence of
hemagglutinin. This is followed by release of virus form
the agglutinated cell surface due to presence of
neuraminidase. This is called elution.
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595
Antigenic Structure
Internal antigen: Ribonucleoprotein or RNP antigen
which is type specific.
Surface antigen: Hemagglutinin and neuraminidase
which are strain specific.
Antigenic variations:
Antigenic drift: (Gradual change at frequent intervals)
Cause: Mutation and selection.
Effect: causes epidemics by type.
Antigenic shift: (Abrupt drastic discontinuous variation)
Cause: Genetic recombination of human with animal
or avian virus.
Effect: Major pandemics by type A.
Antigenic variation is highest in type A virus, less in
type B virus. Type C virus is antigenically stable.
Note: H5N1 is a novel strain causing human infection.
It is the Avian flue influenza a virus, also called the bird
flu virus.
Complications
1. Pneumonia most common complications. It is mostly
due to mixed bacterial and viral infection. Secondary
bacterial infection most commonly due to
Streptococcus, Staphylococcus aureus and H.
influenzae.
2. CVS congestive failure or myocarditis.
3. CNS encephalitis.
4. Reyes syndrome most common complication of type
B infection.
Laboratory diagnosis
Rapid diagnosis: By demonstration of virus antigen of the
surface of the nasopharyngeal cells by immunofluorescence.
Treatment
Amantadine active only against influenza A.
Prevention
Chemoprophylaxis with amantadine.
Vaccine: Live attenuated vaccine. May be administrated
as nasal drops.
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PARAMYXOVIRUSES
PARAMYXOVIRUSES
Mumps
Pathogenesis: Infection is acquired by droplet inhalation.
The virus replicates in the epithelium of URT.
Epidemiology:
Immunity one attack provides life long immunity.
Clinical feature: 30-40 percent cases are clinically
inapparent. Parotid swelling is often the first symptom.
It is generally bilateral and painful. The orifice of Stensens
duct is red and swollen. The swelling subsides in 6-10 days.
Submandibular and sublingual glands are also affected.
No fever.
Complication:
1. Meningoencephalitis most common complication in
children.
Aseptic meningitis
Occurs in both children and adults. Self- limited, may
lead to cranial nerve palsy with permanent sequele,
particularly deafness.
Other CNS problems cerebellar ataxia, facial nerve
palsy.
2. Orchitis most common complication in postpubertal
male. It is usually unilateral, may lead to testicular
atrophy. If bilateral, may lead to sterility (rare).
3. Pancreatitis.
4. Oophoritis in female.
5. Nephritis.
Prevention:
Vaccine: Live attenuated vaccine (from Jeryl-Lynn strain).
Recommended after one year of age because of possible
interference with maternal antibodies earlier than that.
Isolation: Till the swelling subsides.
Gestational mumps: May lead to spontaneous abortion
if occurs in first trimester.
PNEUMOVIRUS
Respiratory Syncytial Virus
RSV is the most common cause of lower respiratory
tract infection in infants. (Bronchiolitis).
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597
Epidemiology:
Transmission through close contact, through
contaminated fingers and fomites.
Common in winter season.
Most common in the age group 1-6 months.
Clinical feature:
The disease starts as febrile rhinorrhea with cough and
wheezing. May progress to pneumonia, bronchiolitis,
tracheobronchitis. Breathing is fast with respiratory
distress. Retraction of lower intercostals spaces and
suprasternal notch, cyanosis.
Auscultation Rales and ronchi, breadth sounds are
faint.
Respiratory distress is out of proportion to the extent
of the physical signs in the lungs.
CXR: Hyperinflation and infiltrates.
Course: Self - limited. Chance of development of bronchial
asthma in later life.
Treatment:
Humid atmosphere.
O2 is the mainstay of treatment.
Antibiotics have no role.
Antiviral Ribavirin.
MORBILLIVIRUS
Measles
Epidemiology:
No secondary attack rate, no subclinical infection, most
common in the age group 6 months to 3 years. Infants
are protected with maternal antibody up to 6 months
of age.
Measles tend to be severe in malnourished child.
Incubation period 10 days from exposure to onset
of fever, 14 days from exposure to appearance of rash.
Clinical feature: (Note the sequence.)
1. Prodrome (2-4 day) malaise, cough, coryza,
lacrimation, fever.
2. Kopliks spots appear 1-2 days before the appearance
of rash. Blue white spots on a bright red background
on buccal mucosa opposite the first and second upper
molars. The spots disappear as rashes appear.
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3. Rash appears on 4-5th day as fever subsides.

Erythematous, non-pruritic maculopapular rash. First
appears behind the ears, near the hairline and spreads
down the trunk and limbs to involve palms and soles.
By fourth day, rash begins to fade in the order in which
it appeared, leaving a brownish discoloration of skin
and desquamation.
Moderate generalized lymphadenopathy.
Morphology: Lymphoid organs contain giant cell called
Warthin-Finkeldey cells.
Complications:
a. Respiratory tract :
1. Otitis media most common complication in
children,
2. Interstitial pneumonia and bronchopneumonia
occurs due to immunomodulation.
b. CNS encephalomyelitis, transverse myelitis, subacute
sclerosing panencephalitis (SSPE).
c. GI tract diarrhea, appendicitis.
d. CVS myocarditis.
e. Blood thrombocytopenic purpura.
f. Malnutrition all patients should receive vitamin A
as vitamin A deficiency can lead to keratomalacia and
corneal blindness.
g. Death due to measles are almost always due to
pneumonia.
Prevention:
Vaccine: Live attenuated vaccine.
Administration: Subcutaneous injection. The vaccine once
opened should be used within 1 hour.
Storage: In Freezer compartment (heat labile). The
reconstituting fluid is stored at 4-8oC.
Immunity: Develops 11-12 days after vaccination. 1 dose
provides 95 percent protection.
Contacts:
Incubation period of measles induced by vaccine is
about 7 days.
Hence post-exposure prophylaxis is effective if given
within 3 days.
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599
Contraindication: Pregnancy.
Note: Heat stable vaccine has also been developed.
RUBELLA
Congenital Rubella
Transmission: Maximum chance of infection and
maximum congenital abnormalities during first trimester.
(Max. first 5-6 weeks, chance 90%).
Features: Causes maximum abnormalities among the
congenital infection.
1. Sensorineural deafness most common abnormality.
2. Cardiac PDA (most common cardiac anomaly), PS,
VSD.
3. Eye Cataract, retinopathy, glaucoma.
4. Neurology Microcephaly, mental retardation.
5. Hepatosplenomegaly Jaundice.
6. Blood Thrombocytopenia.
7. IUGR.
Diagnosis: Serology demonstration of IgM antibody in
fetal blood by ELISA.
Postnatally Acquired Rubella
Clinical feature:
1. Fever.
2. Lymphadenopathy Posterior auricular, cervical and
suboccipital.
3. Rash Maculopapular, first appears on the face and
spreads down the body. Rapidly progressive and clears
in 4 days.
Forschheimer spots: Petechial exanthem on the soft
palate.
Complications:
1. Conjunctivitis.
2. Arthritis.
3. Hemorrhage due to thrombocytopenia.
4. Encephalitis more common in adults.
Rubella vaccine:
Live attenuated vaccine.
Absolute contraindication Pregnancy.
600
ARBOVIRUSES
These are arthropod-borne viruses.
TOGAVIRUS
Alphavirus
Chikungunya fever: The only group A arbovirus (alphavirus)
causing epidemic disease in India is Chikungunya fever.
FLAVIVIRUS
Japanese Encephalitis
Epidemiology: Incidence: Ratio of overt disease to
inapparent infection is 1:300 to 1:1000 (i.e. cases show
only the tip of iceberg).
Host:
Pond herons act as reservoir host.
Pigs amplifier host.
Man accidental, deadend host.
Transmission: Bite of infected mosquito. Man-to-man
transfer has not been recorded.
Vector: Culex tritaeniorhynchus. Culex vishnui.
Case fatality rate: 20-40 percent.
Control: Vector control Vector mosquitoes of JE are
widely scattered and not easily amenable to control.
Vaccine: Protective immunity develops in about a months
time after the second dose. Revaccination after 3 years.
Yellow Fever
Causative agent: Flavivirus fabricus.
Vector: Aedes aegypti.
Vaccine: 17D vaccine a live attenuated vaccine. Immunity
appears on 7th day.
Quarantine: For 6 days from the date of leaving an infected
area.
Airports and seaports are kept free from the breeding
of insect vectors over an area extending at least 400
meters around their perimeters. The Aedes aegypti
is kept below 1.
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601
International certificate of vaccination: India requires this

even if the traveler has been in transit. Validity begins 10
days after immunization and lasts for 10 years.
Dengue Syndrome
Epidemiology:
Agent: Dengue virus has 4 serotypes. All the serotypes
are found in India.
Agent: Aedes aegypti.
Transmission: Transovarian transmission occurs.
Clinical feature:
a. Dengue fever:
Fever: typically biphasic (saddle back fever). Pain in
the back and limbs (breakbone fever). Associated with
lymphadenopathy, maculopapular rash.
b. Dengue hemorrhagic fever:
Occurs due to double infection with dengue virus. More
common in previously healthy children in the indigenous
populations of the endemic areas.
Clinical feature:
Fever acute onset, high and continuous.
Hemorrhagic manifestation Purpura, gum bleeding,
decrease platelet count, positive tourniquet test.
c. Dengue shock syndrome:
Treatment: Fluid replacement with 5 percent DNS.
Aspirin should be avoided particularly in endemic areas
as it may cause gastritis, bleeding and acidosis.
Note: IgM ELISA is the most common test for dengue.
Neutralization test is most sensitive and specific.
Kyasanur-Forest Disease
Vector: Ticks (Haemaphysalis spinigera and H. turtura).
Reservoir: Monkeys.
Distribution: In Karnataka state.
Clinical feature: Hemorrhagic fever.
Control:
i. Spraying.
ii. Restriction of cattle movement.
iii. Killed KFD vaccine.
iv. Personal protection.
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West Nile Fever

Endemic in India.
Note: Arboviruses prevalent in India Chikungunya fever,
Dengue, KFD, JE, West Nile.
BUNYAVIRIDAE
Hantavirus
RNA virus.
Natural pathogen of rodents. Transmission to human
is by inhalation of virus in rodent urine and feces.
Causes hemorrhagic fever with renal syndrome (HFRS)
also called epidemic nephrosonephritis.
RHABDOVIRUS
Rabies
Morphology:
Virion is bullet shaped.
RNA virus (single stranded with a negative sense).
It has only a single serotype.
Epidemiology:
Distribution: Rabies virus is not present in Australia and
Antarctica. In India, it is not found in Andaman and
Lakshadweep.
Mode of transmission:
i. Animal bites.
ii. Licks.
iii. Aerosols.
Incubation period: Highly variable, commonly 3-8 weeks
following exposure. It depends on the site of injury and
the distance of brain form it.
Clinical feature:
Stages:
i. Prodrome.
ii. Acute encephalitis.
iii. Brainstem dysfunction.
iv. Death or recovery (very rare).
Pathology: Pathological hallmark is Negri bodies
intracytoplasmic inclusions with characteristic basophilic
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603
inner granules. Most commonly found in cerebellum and

hippocampus.
Diagnosis: Fluorescent antibody staining for detection of
viral antigen of skin biopsy.
Antemortem corneal smears,
facial skin biopsy
Specimen
Postmortem - brain
Prevention:
Post-exposure prophylaxis:
a. Local wound toilet Rabies is sensitive to ethanol.
b. Immunization fixed virus is used for vaccine
preparation.
Vaccine 3 types (killed inactivated vaccine)
1. Nervous tissue vaccine e.g. BPL vaccine from adult
sheep brain (Semple type).
Complication neurological complication.
2. Duck embryo vaccine.
3. Cell culture vaccine, e.g. Human diploid cell culture
(HDCC) vaccine.
Advantages Less immunologic reaction.
Note: Inactivation is done by treatment with phenol or
propionolactone.
Doses:
BPL vaccine
Category
I. Lick on intact
II. Minor scratches or abrasions
without bleeding. Licks
on broken skin
III. Single/multiple transdermal
bites or scratches
Dose
Duration
Booster
2 ml
5 ml
7 days
10 days
1 after
3 weeks
5 ml
10 days
2 after 7
days and
21 days
HDCC vaccine: 6 doses on days 0, 3, 7, 14, 28 and 90

IM (in deltoid).
Antirabies serum: Should be given within 24 hours.
c. Pre-exposure prophylaxis: 3 doses at 0, 7 and 28 days
of HDCC vaccine.
Control of urban rabies:
1. Elimination of stray and ownerless dogs.
604
2. Program of swift mass immunization.

3. Registration and licensing of all domestic dogs.
SLOW VIRUSES
Classification
Group A:
1. Visna.
2. Maedi.
Group B:
3. Scrapie.
4. Crautzfeldt-Jacob disease equivalent to mad cow
disease.
Characterized by Spongiform degeneration of the
brain.
5. Kuru.
Group C:
6. Subacute sclerosing panencephalitis (SSPE).
7. Progressive multifocal leucoencephalopathy (PML)
JC virus.
FILOVIRIDAE
Marburg disease,
Ebola fever (hemorrhagic fever).
ROTAVIRUS
It is the most common cause of diarrhea in infants
and children.
It has 5 antigenic groups (A to E).
Diagnosis: Serology for demonstration of viral antigen in
stools. Human rotavirus does not grow readily in cell
cultures. Only some Rota A can be cultivated.
Pathogenesis: Increased secretion by villi leads to secretory
diarrhea.
Pathology: Terminal ileum villi destroyed.
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605
Vaccines:
Life attenuated vaccine produced by genetic
reassortment.
Rotavirus immunity develops by the age of 3 years.
ONCOGENIC VIRUSES
RNA VIRUSES
Retrovirus
Morphology:
The genome consists of 2 single stranded RNA. The
virion contains RNA dependant DNA polymerase or
Reverse transcriptase. It prepares a DNA copy of the
retroviral RNA genome.
Classification:
1. The avian leukosis complex.
2. Human T cell leukemia (lymphotropic) viruses (HTLV)
HTLV-I causes T cell lymphoma (Mycosis fungoides).
Adult T cell leukemia (Sezarys syndrome). Tropical
spastic paraparesis.
HTLV-II causes Hairy cell leukemia.
Slow transforming viruses:
E.g. chronic leukemia viruses.
They are so called because they have a low oncogenic
potential and induce malignant changes after a long
latent period.
DNA VIRUSES
Papovavirus: HPV 16, 18 and 31 Ca cervix.
EB virus: see above.
Hepatitis B virus: Hepatocellular Ca.
MYCOLOGY
GENERAL CONSIDERATION
Classification
Morphology:
1. Yeast Unicellular, possess true nuclei with nuclear
membrane and paired chromosomes. The only
pathogenic yeast is Cryptococcus neoformans.
606
2. Yeast like fungi partly as yeast and partly as

pseudohyphae, e.g. Candida albicans.
3. Moulds or filamentous fungi form true mycelia, e.g.
dermatophytes.
4. Dimorphic fungi they are rounded yeast in tissue but
grow like moulds when cultured at room temperature.
e.g. Histoplasma, blastomyces, sporotrichos,
rhinosporidium, coccidioidomyces, paracoccidioidomyces.
Most fungi causing systemic infections are dimorphic.
Systemic classification: Four classes.
Classes
1. Phycomycetes
2. Ascomycetes
(yeast + moulds)
3. Basidiomycetes
4. Fungi imperfecti
Sexual spores
Asexual spores
Oospores, zygospores
Ascospores
Sporangiospores
Conidia
Basidiospores
No sexual phases
Conidia
Diagnosis
Media most common medium is Sabourauds
glucose agar.
Stain PAS and methanamine silver strains.
SUPERFICIAL MYCOSIS
DERMATOPHYTOSES (TINEA OR RING WORM)
Pathogenesis
Infect only superficial keratinized tissues skin, hair.
Involve only the stratum corneum in skin.
Epidemiology
According to habitat, they are of 3 types
1. Anthropophilic in man
2. Zoophilic natural parasites of animals, e.g. T.
verrucosum in cattle.
3. Geophilic in soil.
Classification
According to asexual spores (conidia) they produce:
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607
1. Trichophyton
Microconidia are abundant. They infect skin, hair
and nails.
T. rubrum is the most common species affecting
human beings.
2. Microsporum
Macroconidia are predominant (single) and single
microconidia.
Infect only skin and hair.
3. Epidermophyton:
Microconidia are absent. Macroconidia in groups.
Infect only skin and nails.
Remember - T all, M not N (Nail), E not H (Hair).
Clinical Feature
According to site involved
1. Tinea capitis:
Infection of scalp.
Most common species Trichophyton tonsurans.
Endothrix the hair shaft breaks at skin surface,
leaving the hairs visible as black dots on the scalp.
Favus chronic infection with crust (scutula)
formation lead to alopecia and scarring.
Kerion boggy lesion with marked inflammatory
reaction (easily plicable hair).
2. T. corporis:
On smooth or non-hairy skin.
May produce typical annular appearance of ring
worm.
3. T. pedis:
Most common infection.
Also called athletes foot.
The web space between 4th and 5th toes is almost
invariably involved.
4. T. cruris: groin, most common in male.
5. T. barbae: On bearded skin.
6. T. unguinum: infection of nail plate (onychomycosis).
Diagnosis
Routine method: Examination of KOH mounts.
608
Treatment
Topical Imidazoles. Topical therapy is not effective
in T. capitis and T. unguinum.
Oral griseofulvin is the drug of choice.
Note: Ciclopirox, oleamine new drugs.
PITYRIASIS (TINEA) VERSICOLOR
Causative organism: Malassezia furfur.
Clinical feature: Scaly, hypo/hyperpigmented macule on
trunk with branny scales. Coupid nale or stoke of the
nail.
Treatment:
Selenium sulfide shampoo.
Ketoconazole/Clotrimazole.
Diagnosis:
KOH smear.
Woods lamp pale yellow fluorescence.
TINEA NIGRA
Causative organism: Exophiala wernickii.
Clinical feature: Infection of stratum corneum, particularly
of the palms, producing black or brownish macular lesions.
PIEDRA
Causative organism:
Black piedra Piedraia hortai.
White piedra Trichosporon beigellii.
Clinical feature: Infection of hair. Appearance of firm,
irregular nodules along the hair shaft.
CANDIDIASIS
Morphology
Yeast like fungus. Hyphae and pseudohyphae are
formed (except C. glabrata).
Pathogenesis
Commensals of humans. Candidiasis is an opportunistic
endogenous infection.
Infectious Diseases
609
1. Diabetes mellitus most common.
2. OCP.
3. Pregnancy.
4. Immunodeficiency.
5. Leukemia.
Diseases
a. Cutaneous candidiasis:
Sites Intertriginous (in skin folds) and paronychial.
Intertriginous infection occurs in macerated skin.
Paronychial infection associated with frequent
hand washing.
Chronic mucocutaneous candidiasis or candida
granuloma
Circumscribed hyperkeratotic skin lesions, common
in immunodeficiency.
b. Mucosal candidiasis:
Vaginitis common in 3rd trimester of pregnancy.
Oral thrush common in bottle fed neonates.
Clinical feature creamy white patches appear on
the tongue or buccal mucosa that leave a red oozing
surface on removal.
c. Intestinal candidiasis: Sequel to oral antibiotic therapy.
May present as diarrhea not responding to treatment.
d. Bronchopulmonary candidiasis.
e. Systemic infections: Septicemia, endocarditis and
meningitis.
Common in immunosuppressed persons.
Chronic disseminated candidiasis common in
patients with acute leukemia.
Note:
1. C. parapsilosis may cause endocarditis.
2. C. tropicalis causes deep infection in neutropenic
patients.
Diagnosis
Superficial Infection: Demonstration of pseudohyphae on
wet smear. Confirmation by culture on Saboureuds
media produce white creamy colonies.
Deep infection:
By histological section of biopsy specimen.
Culture of blood, CSF, joint fluid or surgical specimens.
610
Characteristics of C. albicans:
1. Formation of chlamydiospores.
2. Presence of hyphal elements in addition to yeast forms
in stained specimen.
3. Ability to form germ tubes in serum rapid diagnosis
method (called Reynolds-Braude phenomenon).
4. Biochemical sugar assimilation and fermentation
tests.
DEEP MYCOSIS
SUBCUTANEOUS INFECTIONS
Mycotic Mycetoma
Commonly affects the foot.
Clinical Feature: Subcutaneous nodule which enlarges,
burrowing into deep tissue and tracking to the surface as
multiple sinuses discharging viscid, seropurulent fluid
containing granules.
Diagnosis: The granules are microcolonies and their
demonstration is of diagnostic valve.
Chromoblastomycosis
Also called verrucous dermatitis.
Causative organism:
Soil inhabiting fungi called Dematiacea.
F. pedrois, P. verrucosa, and Cladosporum carrionii.
Clinical feature: Warty cutaneous nodules that resemble
the florets of cauliflower.
Diagnosis: The fungi present as dark brown, yeast like bodies
with septae, called sclerotic cells.
Sporotrichosis
Causative organism: Sporothrix schenckii a dimorphic
fungi.
Clinical feature: Development on the skin, in subcutaneous
tissues and in lymph nodes, of nodules which soften and
break down to form indolent ulcer. Common in wood
cutters.
Diagnosis: Asteroid bodies.
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611
Rhinosporidiosis
Causative organism: R. seeberi a dimorphic fungi. It
has been successfully cultivated in epithelial cell culture.
SYSTEMIC INFECTIONS
Cryptococcosis
Causative organism: Cryptococcus neoformans. It has a
polysaccharide capsule. It has 4 serological types (A to
D) based on capsular polysaccharide. It is particularly
abundant in feces of pigeons.
Route: Acquired by inhalation. Initial site of cryptococcal
infection is lung.
Clinical feature:
1. Pulmonary cryptococcosis.
2. Meningitis most serious infection. Common in HIV
and neutropenic patients.
3. Infections of bones and joints.
4. Cutaneous infection.
Diagnosis:
1. Grows at 37oC.
2. Hydrolyses urea.
3. Staining With methenamine silver or PAS. A strongly
positive result upon mucicarmine staining of tissue is
diagnostic.
4. Demonstration of capsules in Indian ink preparations.
5. Serology demonstration of capsular antigen in CSF
or serum by latex agglutination test.
Treatment: Patients with AIDS and cryptococcosis are
treated initially with IV amphotericin B and later with
fluconazole.
Immunity: Anticapsular antibodies appear but are not
protective.
Blastomycosis
Dimorphic fungi. Disease is largely confined to North
America North American disease.
Clinical feature: Formation of suppurative and
granulomatous lesions in any part of the body but with
a marked predilection for lungs and skin.
612
Diagnosis: Grows as mould at room temperature. But

appears yeast like in body or at 37oC.
Paracoccidioidomycosis
South American disease.
Coccidioidomycosis
Causative organism: C. immitis Dimorphic fungi.
Clinical feature: Produces valley fever or desert
rheumatism fever with arthralgia.
Diagnosis: Demonstration of spherule containing
endospores (endosporulating spherules) in tissue.
Histoplasmosis
Causative organism: H. capsulatum Dimorphic fungi.
Clinical feature: Majority of infections are asymptomatic
or mild. Disease resembles TB with cough, fever and CXR
showing hilar adenopathy with or without infiltrates.
Chronic infections may lead to granuloma formation.
OPPORTUNISTIC SYSTEMIC MYCOSIS
Aspergillosis
Causative organism: A. fumigatus most common.
Pathogenesis:
It is common in immunodeficient and neutropenic
patients.
Aspergillus infection is characterized by hyphal invasion
of blood vessels, thrombosis, necrosis and hemorrhagic
infarction.
Chronic granulomatous disease of childhood also
predisposes to invasive pulmonary aspergillosis.
Aspergillus infection is a combination of type I and
type III hypersensitivity.
Diseases: Most common infection is otomycosis (Aspergillus
niger is the most common organism).
Infectious Diseases
613
Pulmonary aspergillosis:
1. Aspergillus asthma occurs in atopic individuals
(allergic bronchopulmonary aspergillosis) with
eosinophilia and IgE antibody to aspergillus. Malt
workers lung.
2. Bronchopulmonary aspergillosis the fungus grows
within the lumen of bronchioles which are blocked by
fungus plugs.
3. Aspergilloma occurs in preexisting pulmonary cavity
e.g. in tuberculosis usually in the upper lobe and
visible on CXR. The disease presents as massive
hemoptysis.
Disseminated aspergillosis: May produce cerebral infarcts.
Diagnosis:
Aspergilli have septate hyphae.
Immediate type hypersensitivity reaction to aspergillus
protein.
Treatment: Aspergilloma may require surgical removal.
Mucormycosis
Caused by Phycomycetes.
Aseptate hyphae.
2. Organ transplantation.
3. Leukemias.
4. Long-term desferoxamine therapy.
Clinical feature:
Most commonly invades the nose and paranasal
sinuses.
May spread to adjacent tissues e.g.
Orbit produce blindness.
Brain cavernous sinus thrombosis.
614
PARASITOLOGY
Classification
Parasites
Protozoa
(unicellular)
Amoebae
Helminths
(multicellular)
Flagellates
Sporozoa
Cestodes
Ciliates
Nematodes
Trematodes
Cestodes
Nematodes
Trematodes
Feature:
Tape like,
segmented
Leaf-like,
unsegmented
Alimentary
canal:
Body cavity:
Sex:
Head:
Absent
Elongated,
cylindrical,
unsegmented
Complete
Absent
Not separate
Hooks an
suckers
Present
Separate
No hooks
or suckers
Absent
Not separate
Only suckers
Incomplete
AMOEBAE
Intestinal Amoeba
Entamoeba histolytica
Morphology: It exists as 2 forms cyst and trophozoite.
Cyst: 12-15 m (5-20 g). Contains 1-4 refractile
chromatid bars and a glycogen mass which stains brown
with iodine. Contains 1-4 nuclei.
Trophozoite: Single nucleus with centrally located
karyosome.
Life cycle: Cyst is the infective form. Both cyst and
trophozoite are found in colon.
Pathogenesis: Trophozoites attach to epithelium in the
caecum, sigmoid colon or rectum and produce
microulceration (earliest change).
Amoebic ulcer: Button-hole size. Flask shaped.
Infectious Diseases
615
Liver abscess:
Always preceded by intestinal colonization which may
be asymptomatic. Infection reaches liver from colon
via portal vein. Liver parenchyma is replaced by necrotic
material called anchovy paste.
It is bacteriologically sterile with few or no cells.
Trophozoites may be found in parenchyma.
Epidemiology:
Reservoir man is the only reservoir.
Incubation period 2 to 4 weeks.
Young adults of low socioeconomic status are most
commonly affected by massive amoebiasis.
Clinical feature:
Intestinal amoebiasis:
Most cases (90 percent) are asymptomatic.
Produces amoebic dysentery.
Amoeboma chronic granulomatous mass usually in
colon.
Amoebic liver abscess:
Usually single, located in superoanterior quadrant of
right lobe.
Point tenderness over liver and right sided pleural
effusion are common.
Less than 1/3rd patients have active diarrhea. Always
have increased ESR.
Complications: Pleuropulmonary involvement - sterile
effusion, contiguous spread from liver, rupture into
pleural sac.
Other extraintestinal sties:
Genitourinary, lung, brain.
Cutaneous amoebiasis It is a spreading necrotizing
inflammation of skin and subcutaneous tissue. Occurs
by direct contact.
Diagnosis:
Stool:
Presence of Charcot-Leyden crystals.
Trophozoites which show erythrophagocytosis and
motility.
Pathogenic and non-pathogenic strains can be
differentiated by the electrophoretic study of zymodens.
616
Serology: For extraintestinal amoebiasis.

i. ELISA most sensitive (best test).
ii. Indirect hemagglutination most widely used.
Liver biopsy: Shows presence of trophozoites.
Imaging:
USG most commonly used.
CT scan Imaging of choice.
Treatment:
1. Invasive intestinal amoebiasis Metronidazole/
Tinidazole drug of choice.
2. Chronic intestinal amoebiasis/asymptomatic cyst
passers Diloxanide furoate drug of choice (luminal
amoebicide).
3. Extraintestinal amoebiasis Metronidazole/Tinidazole
drug of choice. Chloroquine is also used.
Free-living Amoebas
Naegleria fowleri
Causes Acute primary amoebic meningoencephalitis
(PAM).
Diagnosis Mobile trophozoites in wet mounts of fresh
spinal fluid.
Acanthamoeba infections
Causes:
1. Granulomatous amoebic encephalitis (GAE). Presents
as SOL in brain. Common in chronically ill and
immunosuppressed patients.
2. Acanthamoeba keratitis.
Risk factors:
i. Contact lens Extended wear, homemade saline,
wearing of lenses while swimming, inadequate
disinfection.
ii. Trauma Vegetable foreign body.
Clinical feature: Severe pain, paracentral ring-shaped ulcer.
Treatment:
1st line drug chlorhexidine or polyhexamethylin
biguanides.
2nd line drug Propamidine isethionate, neomycin.
Keratoplasty.
Note: Neuropathogenic amoebae are Naegleria and
Acanthamoeba.
Infectious Diseases
617
SPOROZOA
MALARIA
History
Laveran discovered the malaria parasite. Ronald Ross
discovered the transmission by anopheline mosquito.
Life Cycle
Hosts: Two hosts
1. Man: Intermediate host. Occurs in liver and RBC,
asexual cycle (Schizogony) and products are merozoites
and gametocytes.
2. Mosquito: Female anopheles mosquito definitive host.
Anopheles is the main vector of urban malaria. Sexual
cycle (Sporogony) and products are called sporozoites.
Life cycle in mosquito is cyclopropagative i.e. the
parasites change in form and number in mosquito.
Vectors: Of major importance are Anopheles culicifacies
in rural areas and Anopheles stephensi in urban area.
Cycle:
Sporozoites in saliva
Mosquito
Human liver (exoerythrocytic

schizogony)
- Produces schizonts which are
not found in blood
Gametocytes
Releases merozoites
RBC
RBC
Erythrocytic schizogony
Duration
72 hours for P. malariae and
48 hours for the rest.
Forms trophozoites
Hypnozoites in liver are the cause of relapse in P. vivax

and P. ovale infections. P. malariae relapse occurs due to
persistence in blood rather than in liver.
Epidemiology
Extrinsic incubation period: time for sexual cycle in
mosquito. It is about 10-20 days.
Measurements:
1. Spleen rate measures the endemicity of malaria.
618
2. Infant parasite rate most sensitive index of recent

transmission of malaria in a locality.
3. Annual parasite incidence (API)
API = (Confirmed cases during one year)/(Population
under surveillance) 1000
It measures malaria incidence. It is based on active
and passive surveillance. Cases are confined by blood
examination.
4. Annul blood examination rate (ABER)
It is an index of operational efficiency. In MPO, a
minimum prescribed is 10 percent of the population
in a year.
5. Others
Slide positivity rate.
Provide information on the
Slide falciparum rate. trend of malaria transmission
Methods of transmission:
i. Sporozoite induced: By mosquito bite.
ii. Trophozoite induced: Transfusion malaria, congenital
malaria, malaria in drug addicts. Characteristically
pre erythrocytic schizogony is absent.
Protection against malaria:
1. Duffy negative persons are resistant to vivax malaria.
2. G6-PD deficiency, sickle cell disease, thalassemia
protect from death due to falciparum malaria.
3. Newborns and persons with sickle cell trait are resistant
to P. falciparum infection due to high concentration
of HbF in RBC.
Plasmodium Parasites
Features
P. falciparum
Incubation
12
period (days)
RBC affected Any age
(multiple
infection)
Morphology
Ring
(in peripheral trophozoites,
blood)
bananashaped
gametocytes
Maurers dot
Pigment
Black
(contains iron,
porphyrin,
hematin)
P. vivax
P. ovale
P. malariae
14
14
30 (Max.)
Reticulocytes Reticulocytes Old cells

(young)
(young)
All forms,
enlarged
RBC,
Schuffners
dots
Enlarged
oval RBC,
James
dots
Band
trophozoites
Ziemanns
dots
Yellow
brown
Dark
brown
(does not
occur in
India)
Brown
black
Infectious Diseases
619
Clinical Feature
1. Fever: Three stages the cold stage, the hot stage,
the sweating stage.
P. vivax causes benign tertian malaria interval
48 hours.
P. falciparum malignant tertian malaria interval
48 hours.
P. malariae quartan malaria interval 72 hours.
P. ovale tertian malaria- interval 48 hours
Interval corresponds to erythrocytic schizogony.
2. Anemia normocytic normochromic.
3. Splenomegaly.
Complications
Severe falciparum malaria:
i. Cerebral malaria:
Diffuse symmetric encephalopathy leads to
convulsions and coma.
Focal neurological signs and signs of meningeal
irritation are absent.
Tendon reflexes variable. Plantar reflexes flexor
or extensor. Abdominal and cremasteric reflexes
absent.
Eye retinal hemorrhage.
DIC signs of bleeding.
ii. Metabolic hypoglycemia, hyperkalemia,
hypoalbuminemia, lactic acidosis.
iii. Hematological anemia, mild thrombocytopenia,
hypogammaglobulinemia.
Note: Pancreatitis is the most rare complication of
falciparum malaria.
Tropical splenomegaly:
Features:
Splenomegaly, anemia, pancytopenia.
Increased serum IgM against CD8 and CD5.
Increased CD4:CD8 ratio.
Nephropathy: Nephrotic syndrome may occur in P. malariae
infection (Quartan malaria).
Other Entities
Transfusion malaria:
Most commonly due to P. vivax.
620
Infective form is trophozoite. No pre-erythrocytic stage.

Most common sources are whole blood and packed
RBCs.
Screening IFA test.
Pernicious malaria: Results from anoxia due to obstruction
of capillaries in various organs followed by necrosis of
tissues.
Malaria in pregnancy:
Malaria in primi and secundigravida is associated with
LBW.
Falciparum malaria is an important cause of fetal death.
Diagnosis
Thick smear preparation. Best detected if blood films are
taken during chills.
Other methods:
Plasmodium LDH test.
PfHRP2 test.
Microtube concentration method with acridine orange
staining.
Treatment
1. In high-risk areas (Pf. predominant and drug resistance
areas):
a. Presumptive treatment
Tab. Chloroquine 600 mg in 1st and 2nd days,
300 mg on 3rd day. Tab. Primaquine 45 mg on
1st day.
b. Radical treatment
P. vivax Tab. Primaquine 15 mg daily for 5 days.
P. falciparum no further treatment required.
2. Severe and complicated cases: Choice of antimalarial
is quinine injection. Others Artemisinin.
Chemoprophylaxis:
Chloroquine + Proguanil (drug of choice).
It should begin a week before arrival in the malarious
area and continued for at least 4 weeks or preferably
6 weeks after leaving the area.
Treatment for tropical splenomegaly:
In endemic areas Proguanil.
In non-endemic areas Antimalarials.
In chloroquine resistant Pf. cases: Combination of
Sulfalene/Sulfadoxine and Pyrimethamine single dose.
Infectious Diseases
621
In chloroquine and sulfa-pyrimethamine resistant cases of

Pf. infection (Multi-drug resistant): Halofantrine. Also
Mefloquine.
TOXOPLASMA GONDII
Life Cycle
Hosts:
Definitive host - Cat
Host
Intermediate host - Man
Cycle:
Cysts containing bradyzoites or sporulated oocyst
Cat
Man
Gametocytes
Tachyzoites
Transmission:
1. Oral ingestion of sporulated oocyst from soil or
bradyzoites from under cooked meat.
2. Direct transmission by blood or organ products during
transplantation.
3. Transplacental:
In 1st trimester Lowest chance but severe disease
in newborn.
In 3rd trimester Greatest transmission but
asymptomatic in newborn.
Women who are seropositive are protected against acute
infection and do not cause congenital infection.
Clinical Feature
In normal individuals, infection is usually
asymptomatic.
Toxoplasmosis in immunocompetent persons: Cervical
lymphadenopathy most common manifestation,
chorioretinitis.
In immunocompromised person: CNS disease
encephalopathy.
Congenital Toxoplasmosis
1. Fever, rash.
2. Bone age < chronological age.
3. CNS convulsions, seizures, hydrocephalus or
microcephaly, mental retardation, cerebral calcification
(dense) c.f. CMV infection.
622
4. Eye chorioretinitis, cataract, glaucoma.

5. Hepatosplenomegaly.
6. Thrombocytopenia.
Diagnosis
Serology: The Sabin-Feldman dye test for detection of
IgG antibody against toxoplasma.
Congenital toxoplasmosis:
Definitive diagnosis is by direct inoculation of placental
tissue or of newborn blood or CSF into susceptible
mice.
Presence of IgM specific antibody in serum.
Double sandwich ELISA most sensitive.
Treatment
Pyrimethamine + Sulfadiazine/Clindamycin.
In pregnant women Spiramycin decrease the risk of
transplacental transmission of infection and prevents
recurrent abortion.
FLAGELLATES
BLOOD AND TISSUE FLAGELLATES
(HAEMOFLAGELLATES)
Characteristics:
1. They all require and insect vector as an intermediate
host.
2. Most haemoflagellates can be cultured in vitro.
3. They possess an undulating membrane in their
structure.
Leishmaniasis
L. donovani visceral leishmaniasis or Kala-azar.
L. tropica cutaneous leishmaniasis (oriental sore of
Chicleros disease).
L. braziliensis mucocutaneous leishmaniasis
(Espundia or New world leishmaniasis).
Infectious Diseases
623
L. donovani Kala-azar
Life cycle:
Vertebrate (man) amastigote form
of LD body
2 Hosts
Insect (sand fly) promastigote form
Epidemiology:
Vector: Female phlebotomus sand fly, P. argentipes in
India.
Reservoir: Indian Kala-azar is non-zoonotic with man
as the sole reservoir.
Habitat: Amastigote forms are seen in reticuloendothelial cells of vertebrate hosts.
Clinical feature: Fever, hepatosplenomegaly, anemia, weight
loss. Darkening of skin.
Diagnosis:
a. Blood:
Anemia, leukopenia (neutropenia with relative
lymphocytosis and monocytosis), thrombocytopenia (pancytopenia).
Hypergammaglobulinemia (increase IgG).
Reversed albumin-globulin ratio.
The normal WBC:RBC ratio of 1:750 is altered
to 1:1500.
ESR increased.
Note: Antibodies are not protective.
b. Napiers aldehyde test:
Usually becomes +ve 2-3 months (8 weeks) after
onset of the disease.
Use not diagnostic, useful in surveillance.
c. Demonstration of LD bodies in tissue aspirates:
diagnostic. Aspirates are taken from spleen (most
sensitive), bone marrow, liver and lymph nodes.
d. Culture: Medium NNN medium.
e. Serology: ELISA and indirect fluorescent antibody test
(IFAT) are most suitable. CFT.
Treatment:
Sodium stibogluconate drug of choice (if fails)
Pentamidine isethionate (if fails) IV Amphotericin B.
Resistant Kala-azar: Persistence of splenomegaly,
hyperglobulinemia and LD bodies in > 5 percent cells in
BM despite adequate therapy.
624
Sequel:
Post-kala-azar dermal leishmaniasis (PKDL): It occurs in
2-10 percent cases of visceral leishmaniasis in endemic
areas (e.g. India) about 2 years after recovery form visceral
disease.
Clinical feature: Depigmented macules, erythema or
nodules never ulcerate (differentiates from oriental sore
and espundia).
Diagnosis: Biopsy from skin lesions.
Treatment: Pentavalent antimonials.
L. tropica Cutaneous Leishmaniasis
Vector: P. sergenti.
Clinical feature: Painful ulcers over legs, arms or face. Starts
as papule leads to ulcer with central depression surrounded
by raised border (prominent central crusting).
Diagnosis: Skin biopsy.
L. braziliensis Mucocutaneous Leishmaniasis
Ulcerative granuloma of skin that extends to mucosa
especially in mouth, nose, pharynx and larynx.
Treatment: Pentavalent antimonials.
TRYPANOSOMA
Chagas Disease (American trypanosomiasis)
Agent T. cruzi.
Vector Reduvid bugs.
Clinical feature:
Romanas sign facial swelling and pronounced edema
of the eyelids.
Chagoma Skin erythema and swelling.
Heart (most commonly involved) arrhythmia,
cardiomyopathy and thromboembolism.
Sleeping sickness (African trypanosomiasis)
Agent T. brucei.
Vector Tsetse fly.
Infectious Diseases
625
Clinical feature:
Trypanosomal chancre.
Winterbottoms sign posterior cervical lymphadenopathy.
Keranadels sign Pressure on palms or ulnar nerve
produces pain after the pressure is removed.
INTESTINAL FLAGELLATES
Giardiasis
Agent: Giardia lamblia.
Habitat: Duodenum and upper part of jejunum.
Morphology: It exists in two forms trophozoites (tennis
racket appearance) and cyst.
Transmission: Waterborne. Cyst is the infective stage.
Pathology: Trophozoites only adhere to the epithelium but
do not cause invasive or locally destructive lesions.
Risk factors: Hypogammaglobulinemia. Common variable
immunodeficiency is associated with chronic giardiasis (also
Xlinked agammaglobulinemia of Bruton).
Clinical feature:
Fulminant diarrhea.
Lactose intolerance, malabsorption.
Fever and blood in stool uncommon.
Diagnosis:
Stool contains only cyst. But liquid stool contain
both cyst and trophozoite.
Intestinal biopsy shows atrophy of villi, nodular
lymphatic hyperplasia, increase in intraepithelial
lymphocytes and cellular infiltration of the lamina
propria.
Treatment: Metronidazole drug of choice.
Trichomonas vaginalis
Most common trophozoite infection as STD.
Occurs in only trophozoite form. No cystic form.
Habitat: Lower genital tract in females, urethra and prostrate
in males.
Treatment: Metronidazole drug of choice.
626
CILIATES
Balantidium coli
Largest protozoan.
OTHERS
Babesiosis
Vector: ticks.
Habitat: RBCs in human blood.
Co-exists with Lyme disease.
Cryptosporidiosis
Agent: Cryptosporidium parvum.
Clinical feature: Chronic persistent diarrhea in AIDS
patients. May cause diarrhea in immunocompetent
hosts, too.
Diagnosis: Stool shows small oocysts.
Treatment: Paromomycin.
Isosporiasis
Agent: Isospora belli.
Clinical feature: In AIDS patients diarrhea,
malabsorption.
Pneumocystis carinii
Most common opportunistic infection in AIDS.
It is now regarded as a fungus.
Clinical feature: Pneumonia (interstitial plasma cell
pneumonia), fever, cough (nonproductive) and shortness
of breath.
Diagnosis:
CXR diffuse mottling in lung fields.
Demonstration of octanucleate cyst in sputum, BAL
or biopsy.
Stain Methenamine silver. Immunofluorescence.
Treatment: Co-trimoxazole drug of choice.
Infectious Diseases
627
HELMINTHS
NEMATODES
Tissue Nematodes
Trichinella spiralis: Smallest nematode.
Trichinosis:
Phase
Symptoms
Enteric invasion
Larva migrans
Muscle encystment
Diarrhea
Eosinophilia
Retinal hge, splinter hge, myocarditis
Treatment: Albendazole. Thiabendazole is drug of choice

for muscle symptoms.
Visceral and ocular larva migrans:
Causative organism: Canine ascarid Toxocara canis.
Clinical feature: Liver is the most common viscus
involved.
Treatment: Diethylcarbamazine.
Cutaneous larva migrans:
Causative organism: Dog and cat hookworm
Ancylostoma braziliense.
Clinical feature: Creeping eruption serpiginous skin
eruption caused by burrowing larvae.
Treatment: Thiabendazole, Ivermectin.
Angiostrongylus cantonensis:
Causes: Eosinophilic meningoencephalitis.
Dracunculiasis
Causative agent:
Drucunculus medinensis (Guinea worm).
Also called Dragon or Serpent worm. It is the largest
nematode.
Life cycle:
Definitive host: Man
Host
Intermediate host or vector: Cyclops
Location: Adult female worm resides in subcutaneous
tissue.
628
Epidemiology: India is free of dracunculiasis.

Methods of eradication:
1. Provision of safe drinking water.
2. Control of Cyclops.
3. Health education.
4. Surveillance.
Treatment:
No drug is suitable for effective mass treatment.
Niridazole (drug of choice). Metronidazole.
Intestinal Nematodes
Features
Ascaris
lumbricoides
(Round
worm)
Necator
americanus
Ancylostoma
duodenale
(Hookworm)
Strongyloides
stercoralis
Trichuris
trichuria
(Whip
worm)
Enterobius
vermicularis
(Pin
worm)
Infective
stage
Route of
infection
Egg
Falciform
larva
Percutaneous
Falciform
larva
Percutaneous
or autoinfection
Sexual
transmission
Small bowel
mucosa
Yes
Egg
Egg
Oral
Oral or
retroinfection
Caecum,
colon
No
Caecum,
appendix
No
Oral
GI
Jejunum
location
(lumen)
Pulmonary Yes
passage of
larvae
(produce
eosinophilia)
Symptoms Fever, cough,
dyspnea, rarely
GI or biliary
obstruction.
Anorexia
Malabsorption
Diagnosis
Others
Egg in stool
Jejunum
(mucosa)
Yes
Pruritic
dermatitis,
abdominal
pain, diarrhea,
iron
deficiency
anemia
Egg in stool
Recurrent
Colitis,
urticaria
anemia
(larva currens)
Larvae in stool Egg in

stool
CXR:
Infective stage+ Common in
eosinophilic
- Rhabditiform immunopneumonitis
larva after 2
compromised
(Loefflers
moldings.
patients.
syndrome)
Chandlers
Completes
In children
index: average entire life
usually
number of
cycle in man
asymptomatic eggs per gram
of faeces
Perianal
pruritus,
vaginitis,
abdominal pain
Egg from
skin
Also called
Threadworm,
Seatworm
(Contd...)
Infectious Diseases
629
(Contd...)
Features
Ascaris
lumbricoides
(Round
worm)
Necator
americanus
Ancylostoma
duodenale
(Hookworm)
Treatment
Mebendazole Mebex, PP
(Mebex),
Pyrantal
pamoate (PP),
levimasole
tonic paralysis
Strongyloides
stercoralis
Trichuris
trichuria
(Whip
worm)
Thiabendazole, Mebex
Ivermectin
Drug of choice.
Enterobius
vermicularis
(Pin
worm)
Mebex, PP
Note: Autoinfection occurs in Strongyloides, Enterobius (also H. nana)
FILARIASIS
Features
Wuchereria
bancrofti
Brugia malayi
Loa loa
Onchocerca
volvulus
Vector
Location of
adult
Microfilarae
Sheath
Tail tip
Culex fatigans
Lymphatics
Mansonia
Lymphatics
Blood
+
Free of nuclei
Blood
+
2 terminal
nuclei, blunt
Deerfly
Subcutaneous
tissue
Blood
+
Nuclei up to
tail tip, pointed
Blackfly
Subcutaneous
tissue
Skin, eye
Free
W. bancrofti
Life cycle:
Host
Intermediate host: Culex mosquito
In mosquitoes, the parasite does not multiply but
undergoes only cyclic change cyclo-developmental
transmission.
Third stage larva is infective. Female parasites are
viviparous.
Adult parasites live in lymphatics in man.
Clinical feature:
In endemic areas most cases are asymptomatic with
microfilarae in blood.
Hydrocele.
Lymphangitis: develops in retrograde or descending
fashion.
Lymphatic obstruction: by adult worms. Elephantiasis
brawny edema of skin followed by pitting edema,
630
thickening of subcutaneous tissue (hyperkeratosis),

fissuring of skin and hyperplasia.
Complications: Secondary bacterial infection, dilatation
and rupture of lymphatics may lead to chyluria,
chylothorax, chylous ascites.
Site: most commonly the legs. Other sites are scrotum,
arms, penis, vulva and breasts.
Occult filariasis:
No classical symptoms, no microfilarae in blood.
Cause: hypersensitivity to filarial antigens.
E.g. tropical pulmonary eosinophilia.
Diagnosis:
Demonstration of microfilarae in blood by
concentration method (passage of fluid through a
polycarbonate cylindrical pore filter with pore size 3
m or by centrifugation of fluid in 2 percent formalin
Knotls technique) in early adenolymphangitis stage.
Blood is best collected between 10 pm and 2 am.
Blood: Eosinophilia. Increase serum IgE and antifilarial
antibody.
Epidemiology: Extrinsic incubation period 10 to 14 days.
Parasitological parameters:
1. Microfilaria rate.
2. Filarial endemicity rate - percent of persons examined
showing microfilarae in blood or disease manifestation
or both.
3. Microfilaria density.
Entomological parameter:
Percent of mosquitoes positive for infective (stage III)
larvae.
Endemic areas: UP, Bihar, Orissa, Tamil Nadu.
Treatment:
DEC is the drug of choice.
Note: DEC has highly selective action on microfilarae.
Prolonged use may kill adult worm of B. malayi and
W. bancrofti.
Control: Best measure is personal prophylaxis (avoidance
of mosquito bite).
Infectious Diseases
631
B. malayi
Similar to W. bancrofti except that it rarely involves genital
organs. B. malayi is the most common nematode in south
India.
Tropical Pulmonary Eosinophilia
Caused by lymphatic filarial species (W. bancrofti and B.
malayi).
Pathology: Hypersensitivity to filarial antigens.
Clinical feature: Paroxymal cough and nocturnal wheezing.
Diagnosis:
Blood pronounced eosinophilia (> 3000 /l).
CXR increased bronchovascular markings, diffuse
miliary lesions or mottled opacities in middle or lower
lung fields.
Loiasis
Clinical feature: Produces Calabar/Fugative swelling.
Diagnosis: Isolation of adult worm from eye or from
subcutaneous biopsy.
Treatment: DEC.
Onchocerciasis
Primarily affects skin, eyes and lymph nodes. Damage is
produced by adult worms (c.f. lymphatic filariasis).
Clinical feature:
Pruritus and rash most common manifestation.
Onchocercomata subcutaneous nodules.
Eye visual impairment (river blindness).
Diagnosis: Microfilarae in skin snip.
Treatment:
Ivermectin drug of choice.
Surgery for nodules on head.
632
TREMATODES-FLUKES
Schistosomiasis
Life Cycle:
Host
Intermediate host: Snails
Infective stage is called cercariae.
Difference with other trematodes:
1. Both sexes are separate.
2. Adult worm resides in bloodstreams.
3. Humans are infected by free-swimming cercariae that
invade the skin.
Mode of transmission:
Fresh water, undercooked fish, crustacea, contaminated
vegetations.
Pickled or smoked fish.
Species:
S. mansoni
Reside in the venules of intestine
S. japonicum and produce acute disease of liver
S. hematobium Resides in venules of urinary tract
and causes lesions primarily in ureter and bladder.
Clinical feature:
1. Acute disease: Katayama fever.
2. Liver fibrosis: most important complication of intestinal
schistosomiasis.
Features: Periportal or Symmers fibrosis and portal
hypertension (hepatosplenic schistosomiasis).
3. Glomerulonephritis and pulmonary hypertension:
complication of the above.
Diagnosis:
Eosinophilia in acute stage.
Definitive diagnosis:
1. Eggs in stool or sputum.
Eggs:
S. mansoni
S. japonicum
S. hematobium
Lat. Spine
Round with
small knob
Terminal spine
2. Biopsy of infected tissue.
Infectious Diseases
633
Treatment: Praziquantel is the drug of choice for all

trematode infections except fascioliasis (F. hepatica) for
which Bithionol is the drug of choice.
Clonorchis sinensis
3 hosts: Man, snail and cyprinoid fish.
Habitat: Bile duct and gallbladder.
Complication: Ascending cholangitis, cholangiocarcinoma, pancreatic Ca.
Fasciola hepatica
Habitat: Liver. May cause biliary obstruction.
Fasciola buski
Largest trematode.
Habitat: Intestine.
Paragonimus westermani
Habitat: Lung.
CESTODES-TAPEWORM
They produce hexacanth embryo.
Host:
Organism
Definitive host
Intermediate host
T. solium
T. saginata
Diphylobothrium
Man
Man
Man
Pigs
Cow or buffalo
1st Cyclops
2nd Fresh water fish
H. nana
Echynococcus
Man
Dog
Man
Note: H. nana requires no intermediate host.

Taeniasis solium
Pathogenesis: Adult tapeworm in intestine (upper jejunum).
Source: Ingestion of undercooked pork containing cysticerci
(T. saginata by uncooked beef).
Clinical feature: Epigastric discomfort, nausea, hunger,
weight loss.
634
Diagnosis: Eggs in stool.

Treatment:
Praziquantel drug of choice.
Niclosemide is not given.
Cysticercus cellulose - Cysticercosis
Pathogenesis: Larvae (cysticercus cellulose) in tissues.
Site: Brain most common, striated muscle of neck, tongue
and trunk, eye and subcutaneous tissue.
Source: Ingestion of food contaminated with eggs,
autoinfection.
Clinical feature:
Neurocysticercosis most common manifestation of
cysticercosis.
Seizures most common manifestation of
neurocysticercosis.
Focal neurological deficits, hydrocephalus, meningitis.
Signs of increase ICT: headache, nausea and vomiting,
changes in vision, confusion.
Abnormal psychiatric manifestation.
Recemose form:
Characterized by grapelike clusters of proliferating larva
membranes.
Site: base of the brain or subarachnoid space.
Clinical feature: chronic meningitis and arachnoiditis.
Diagnosis:
CT scan shows multiple calcified (or noncalcified)
cysts in brain.
MRI cysts with highintensity rim around them.
Serology Immunoblotting.
Treatment:
Praziquantel or Albendazole (drug of choice)/
Flubendazole.
Niclosemide is ineffective.
Echynococcus granulosus (Hydatid disease)
Definitive host: Dog.
Sites in human body location of cysts: Liver (most
common 70%), lungs, brain, kidneys, spleen, bones.
Infectious Diseases
635
Clinical feature:
Most common manifestation of hepatic cyst is
asymptomatic.
May produce SOL abdominal pain and right upper
quadrant mass.
Lungs pain, cough, hemoptysis, most common in
lower lobes. Rarely associated with liver cyst.
Brain SOL. May produce spinal cord compression.
Kidneys Hematuria.
Diagnosis:
Imaging CT scan (most sensitive), USG, MRI.
Test for hypersensitivity Casonis test.
Serology detection of antibody to echynococcus
antigen 5 (C5 antigen).
Treatment:
Albendazole (medical management indicated in
moribund patients).
Surgery is the definitive treatment (enucleation).
Complication:
Rupture may produce allergic symptoms.
Calcification least common in lung, most common
in liver.
Diphyllobothrium latum (Fish Tapeworm)
Size: Largest tapeworm (may be as long as 15 mt).
Intermediate hosts:
First cyclops
Two
Second Fresh water fish (trout, salmon, etc.)
Clinical feature: May produce vitamin B12 deficiency
(megaloblastic anemia).
Hymenolepsis nana
It is the most common cestode infecting man.
Size: Smallest tapeworm Dwarf tapeworm.
Eggs: Contain polar filaments arising from either end of
the ambryophore. Eggs float on saturated salt solution.
636
Note: Eggs that float on a saturated solution of saline.

1. Ancylostoma eggs.
2. Trichuris eggs.
3. Fertilized eggs of Ascaris.
4. Enterobius eggs.
5. H. nana eggs.
(Mnemonic FATEH)
Note: Man is secondary host for Malaria, Toxoplasma
and Echynococcus.
10
HEMATOLOGY
BLOOD
Normal blood volume is 7 percent of body weight (or 70

ml/kg).
HEMATOPOIESIS
Source
1. Yolk sac
2. Liver and spleen
Period
First few weeks of gestation.
From 3rd month to 2 weeks after
birth. Liver predominates up to 6
month of gestations.
3. Bone marrow
Begins at 4th/5th month of
gestation and becomes fully active
by 7th and 8th month.
In adults, hematopoietic marrow is confined to the
central skeleton (vertebrae, sternum, ribs, skull, sacrum
and pelvis the flat bones) and proximal ends of femur,
tibia and humerus.
Normal myeloid: erythroid ratio in bone marrow is 3:1.
Factors Regulating Hematopoiesis
1. Erythropoietin: A glycoprotein that regulates
erythropoiesis.
Source:
During neonatal and fetal life Liver.
In adults Kidneys (85%) peritubular interstitial
cell, liver (15%).
Regulators:
Increased secretion main stimulus is hypoxia,
various anemias (except anemia of chronic disease),
alkalosis, ascend to high altitude.
Decreased secretion in polycythemia rubra vera.
2. Granulocyte colony stimulating factor (G-CSF).
3. Granulocyte macrophage CSF (GM CSF).
4. Thrombopoietin.
638
RED BLOOD CELLS

Erythropoiesis
Erythroid Series
1.
2.
3.
4.
5.
Pronormoblast earliest recognizable cell.

Early normoblast basophilic.
Intermediate normoblast polychromatic, Hb appears.
Late normoblast acidophilic.
Reticulocyte juvenile RBC devoid of nucleus but
contains ribosomal RNA
Normal count 0.5-2.5 percent in adults, 26
percent in infants.
Reticulocytes are stained by vital staining with
methylene blue or brilliant cresyl blue.
Reticulocytosis occurs in hemorrhage and hemolytic
anemias.
6. RBC.
Red Cell
They are non-nucleated biconcave discs. The biconcave
shape increases surface area.
Survival:
Half life of neonatal RBC is 100 days.
Half life of adult RBC is 120 days.
Red cell fragility (Hemolysis):
Red cells begin to hemolyse when suspended in 0.5
percent saline.
Hemolysis is 50 percent in 0.40-0.42 percent saline.
Hemolysis is complete in 0.35 percent saline.
Fragility is increased in: Hereditary spherocytosis.
Fragility is decreased in: -thalassemia.
Features of fetal RBC:
1. Low 2, 3DPG binding.
2. Low carbonic anhydrase activity.
3. Short life span.
4. High RBC volume (larger than adult RBC).
5. Contains less iron.
Hemoglobin
Hb Gower: First Hb to appear in fetus.
Hematology
639
HbA (22): Or adult hemoglobin - replaces HbF at 6

month.
HbA2 (22): Present in normal blood only 2.5 percent.
It is increased in -thalassemia.
HbF (22): Or fetal Hb - Level at birth= 70 percent.
At 6-12 month only traces of HbF present (<2%).
Features of HbF:
i. Alkali resistant.
ii. Binds 2, 3- DPG less avidly.
HbF - increased in - thalassemia, juvenile CML, sickle
cell anemia, hydroxyurea therapy.
HbS: Substitution of Glutamate by Valine at 6 position,
seen in sickle cell anemia.
HbE: Substitution of Glutamate by lysine at 26 position,
seen in HbE disease.
Note:
Methods of Hb estimation:
i. Sahlis method (acid-hematin method).
ii. Drabkins method (cyano-methemoglobin
method).
iii. Oxyhemoglobin method simplest and quickest.
iv. Spectrophotometry most accurate method.
All Hbs migrate slower on paper electrophoresis than
type A except Hb barts.
Other functionally similar Hb of HbA:
Substitution of Val at 67 by
Aspartate Hb Bristol.
Glutamate Hb Milwaukee.
Alanine Hb Sydney.
Red Cell Indices
1. Hematocrit: Value 47 percent in males, 42 percent
in females. Hematocrit value is 3 percent greater in
venous blood.
2. Mean corpuscular volume (MCV) 90 9 fl.
3. Mean corpuscular volume Hb (MCH) 32 2 pg.
4. Mean corpuscular Hb concentration (MCHC) 33
3 percent:
MCHC is independent of red cell count and size
and hence considered the best index.
640
Red Cell Morphology

Variation in size (anisocytosis):
1. Macrocytes Cells with MCV > 100 fl.
Causes of macrocytosis:
i. Cobalamin and folate deficiency
ii. Hemolysis
iii. Liver disease
iv. Alcoholism
v. Hypothyroidism
vi. Aplastic anemia
vii. Orotic aciduria
viii. N2O inhalation
ix. As poisoning
x. Kwashiorkor
xi. Thiamine deficiency.
2. Microcytes Cells with MCV < 80 fl.
Causes of microcytosis:
i. Iron deficiency anemia
ii. Thalassemia
iii. Spherocytosis
iv. Lead poisoning due to inhibition of enzymes involved
in heme synthesis.
v. Vitamin C deficiency.
Variation in shape (poikilocytosis): Seen in
Megaloblastic anemia,
Thalassemia,
Myelosclerosis and
Microangiopathic hemolytic anemia.
Hb Concentration:
Hypochromasia MCH< 25 g/dl.
i. Iron deficiency anemia
ii. Chronic infection
iii. Thalassemia
iv. Sideroblastic anemia.
Hyperchromacia
i. Megaloblastic anemia
ii. Spherocytosis
iii. Neonatal blood.
Compensatory erythropoiesis:
i. Polychromasia represent reticulocytes.
ii. Punctate basophilia Aplastic anemia, thalassemia,
myelodysplasia, infections, lead poisoning.
Hematology
641
iii. Howell-Jolly bodies are nuclear remnants seen in

megaloblastic anemia, after splenectomy, severe
hemolytic anemia.
Miscellaneous:
a. Spherocytes (Loss of membrane): Seen in hereditary
spherocytosis, autoimmune hemolytic anemia, ABO
hemolytic disease of newborn.
b. Schistocytes (Fragmentation of RBC): Seen in
Microangiopathic hemolytic anemia, DIC, patient on
cardiac valves.
c. Target cells Increased ratio of RBC surface area to
volume: Seen in Thalassemia, HbS and HbC
diseases, chronic liver disease, after splenectomy.
d. Heinz-bodies Precipitated Hb: Seen in G6PD
deficiency, -thalassemia.
e. Burr cells: Seen in uremia (CRF).
f. Acanthocytes or spur cells Severe liver disease mainly
advanced Laennecs cirrhosis.
WHITE BLOOD CELLS
Total count 4000-11,000/ml.
Granulocytes: Polymorphonuclear cells mainly
neutrophils also eosinophil, basophil, and monocyte.
Agranulocytes: Lymphocyte.
Granulopoiesis
Myeloid series:
1. Myeloblasts Devoid of granules.
2. Promyelocyte Contains primary granules.
3. Myelocyte Secondary granules appears.
4. Metamyelocyte Most abundant cell in bone marrow.
5. Band forms.
6. Segmented granulocytes.
Lymphopoiesis
Primary lymphopoietic organs Bone marrow and
processed by thymus or bursal equivalent.
Secondary/reactive lymphoid tissue After birth.
Lymph nodes, spleen and gut associated lymphoid
tissue (GALT)
Polymorphs (Neutrophils)
Lobes: 2-5 in nucleus.
T = 4-8 hours in blood.
642
Granules:
Predominantly secondary granules.
Source Lysosome.
Primary granules contain myeloperoxidase, acid
phosphatase, other acid hydrolases.
Secondary granules contain alkaline phosphatase,
lysosome, lactoferrin.
Arneth count: It is counting of neutrophils by lobes.
Note: Lactoferrin binds iron and exerts an antimicrobial
activity. It is present in many exocrine secretions, e.g. milk,
tears, saliva, etc.
Variations
In Count
Neutrophilic leukocytosis:
Most common cause is acute bacterial infection.
Drug Steroids.
Leukemoid reaction: Persistent neutrophilia of 30,000 to
50,000 cells/l or greater, seen in acute infections.
Neutropenia:
Causes:
Typhoid, miliary TB, septicemia.
Viral Hepatitis, HIV, influenza, measles, IM.
Drugs.
Note: Most common opportunistic infection in neutropenia
Staphylococcus aureus. Most common fungal infection
Candida.
In Size
1. Dohle bodies are cytoplasmic inclusions (represent
rER and glycogen granules).
2. Sex chromatin found in 2-3 percent of neutrophils
in normal females.
3. Pelger-Huet anomaly decreased number (1-2) of nuclei
in cells.
Lymphocytes
20-40 of total count.
Nucleus - 1 lobe.
Hematology
643
Small lymphocytes are predominant in blood.

T cells mediate cell mediated immunity and delayed
hypersensitivity reaction.
B cells mediate humoral immunity.
Activated B cells proliferate and differentiate into
memory cells and plasma cells, the later produce
immunoglobulins.
T cells, most commonly CD4+ TH cells are the most
abundant cells.
Lymphocytosis:
Absolute:
1. Acute infections pertussis, IM, viral hepatitis.
2. Chronic infections brucellosis, TB, secondary syphilis.
3. Leukemias, lymphosarcoma, heavy chain disease.
Relative:
1. Viral exanthem.
2. Convalescence from acute infections.
3. Conditions causing neutropenia.
Monocytes
Source: bone marrow.
In blood they act as blood macrophages and when
enter the tissue they become tissue macrophages.
Half-life of blood monocyte is 1 to 3 days.
Eosinophilia
Cause:
1. Allergy to drugs such as aspirin.
2. Pemphigus.
3. Collagen vascular disease Rheumatoid arthritis, PAN.
4. Malignancies Hodgkins lymphoma, Mycosis
fungoides, CML, Ca lung.
5. Helminthic infections, HIV.
6. Loefflers syndrome.
Note:
Eosinophiluria is seen in antibiotic induced allergic
nephritis, atheroembolic ARF.
Treatment of eosinophilic leukemia is glucocorticoids.
Eosinophils produce major basic protein.
CD Antigen Markers
CD1 to CD8 (except CD6) T cell (CD3 is pan T
cell marker).
644
CD10 19, 20 to 23 B cell.

CD13 to 15, 33 monocyte, macrophage.
CD16, 56 NK cell.
CD34 stem cell and progenitor cell.
CD45 all leucocytes.
ANEMIA
Definition
WHO definition: Hb level< 11 gm/dl in children 6 months
to 6 years and < 12 gm/dl in older children (6-14 years).
Note: Anemia in neonate of 1 week is considered if Hb
< 16 gm/dl.
Anemia in pregnancy: WHO Hb 11gm/dl in developed
countries, Hb 10 gm/dl in India.
Adult anemia: WHO Adult male < 13 gm/dl, female
< 12 gm/dl.
IRON DEFICIENCY ANEMIA

IRON
Absorption
From duodenum and jejunum (proximal small intestine)
in Fe+2 form.
Iron absorption increased by Ascorbic acid, Citric
Acid, Amino acid, Sugars, Gastric secretions and HCl
(All reduce Fe+3 present in food to Fe+2 and increase
iron absorption).
Iron absorption decreased by Antacids, Milk,
Phytates, Phosphates, Pancreatic secretions, EDTA,
Tetracycline.
Normal Values
SI 50-150 g/dl.
TIBC 300-360 g/dl.
Percent Saturation 30-50 percent.
Ferritin 30-200 g/dl.
Hematology
645
Total body iron 2-6 gm, 80 percent in Hb.

Daily loss of iron 0.5 to 1 mg.
Transport
In plasma bound to transferrin (a -globulin secreted
from liver).
Storage
5-20 percent of total body iron.
In the form of ferritin (main storage form) and
hemosiderin (in gut, spleen and liver, also BM, skeletal
muscle).
IRON DEFICIENCY ANEMIA
Stages of Iron Deficiency
1. Iron store depletion: 1st stage.
Measured by the serum ferritin level and marrow iron
stain.
2. Iron-deficient erythropoiesis.
3. Iron-deficient anemia
Microcytic hypochoromic anemia (microcytosis
precedes hypochromia).
Laboratory Finding
Serum iron (SI) decreased.
Total iron binding capacity (TIBC) increased (< 10%
saturation).
Ferritin Level decreased.
Increased TRP (transferrin receptor protein).
Increased RBC protoporphyrin (due to less iron in serum)
c.f. Thalassemia.
Note: Serum ferritin estimation is the single most sensitive
test to detect iron status in a community.
Treatment
Prophylaxis in pregnancy: 200 mg ferrous sulphate
(containing 60 mg elemental iron) once daily.
Oral therapy: 200 mg ferrous sulphate (60 mg elemental
iron) thrice daily before food.
646
Parenteral therapy
a. Total dose infusion Iron-dextran.
b. IM route Iron-sorbitol-ascorbic acid complex in dextrin.
Indicators of response:
Earliest response of iron therapy is increased
reticulocytes.
Erythropoietin therapy reticulocyte count increases
3-4 days after the initiation of therapy and reaches
a peak at about 10 days.
OTHER HYPOPROLIFERATIVE
ANEMIA
Causes
1.
2.
3.
4.
5.
Acute and chronic inflammation.

End-stage renal disease.
Hypothyroidism.
Protein deprivation.
Liver disease.
Anemia of Chronic Disease

Causes:
Chronic inflammatory conditions such as:
a. Chronic infections osteomyelitis, bacterial endocarditis
and lung abscess.
b. Chronic immune disorders rheumatoid arthritis,
Crohns disease.
c. Neoplasms Hodgkins lymphoma, Ca lung and breast.
Pathology:
1. Reduced erythropoietin response.
2. Inhibition of iron delivery.
3. Inhibition of erythroid precursor growth.
Features: Anemia either normocytic normochromic or
microcytic hypochromic.
Laboratory findings: Decreased SI, decreased TIBC and
increased ferritin, increased storage iron in marrow
macrophages.
Treatment: Erythropoietin.
Hematology
647
Anemia of Renal Disease

Anemia Normocytic normochromic.
Laboratory findings SI, TIBC, ferritin all normal.
Anemia of Liver Disease
Increased ferritin, normal iron store in marrow.
D/D of ANEMIA
D/D of anemia
Type
SI
TIBC
Serum ferritin
Iron deficiency
Decreased
Decreased
Chronic diseases
Liver disease
Renal disease
Sideroblastic
anemia
Hemochromatosis
Decreased
Increased
Increased
(< 10%
saturation)
Decreased
Decreased
Decreased
(> 50%
saturation)
Increased
Increased
Increased
Increased
Increased
Note:
Serum iron is increased in:
1. Thalassemia.
2. Sideroblastic anemia.
3. Chronic hemolytic anemia.
4. Myelodysplastic syndrome.
Increased ferritin level is seen in: Leukemia, CRF, rheumatoid arthritis.
Sideroblastic Anemia
Microcytic/normocytic (dimorphic) hypochromic
anemia.
X-linked disorder associated with defective enzyme ALA
synthetase.
Acquired causes:
2. Pyridoxine deficiency.
3. Lead poisoning.
Laboratory findings: SI increased, ferritin increased, TIBC
decreased.
Treatment: Responds to pyridoxine.
648
MEGALOBLASTIC ANEMIA
Etiology
Cobalamin deficiency:
i. Malabsorption a. Inadequate production of intrinsic factor
Pernicious anemia, most common cause in
temperate countries.
b. Defect in terminal ileum - Tropical suture, Crohns
disease, infants fed on goats milk, intestinal
resection.
c. Competition for cobalamin - Fish tapeworm
(Diphylobothrium), blind loop syndrome.
ii. Others Nitrous oxide inhalation.
Folic acid deficiency:
i. Increased requirements Pregnancy, chronic
hemolytic anemia.
ii. Impaired metabolism
a. Inhibitors of DHFR Methotrexate, Pyrimethamine,
Pentamidine, Trimethoprim, Triamterene.
b. Alcohol.
iii. Malabsorption Tropical sprue.
Others:
i. Drugs that impair DNA metabolism
a. Purine antagonist 6-mercaptopurine,
Azathioprine.
b. Pyrimidine antagonist 5 -FU, Cytosine arabniose.
c. Metabolic Hereditary orotic aciduria
Pathogenesis
Basic defect maturation of nucleus is delayed relative
to that of cytoplasm due to defect in DNA synthesis.
DHFR = Dihydrofolate reductase
Hematology
649
Clinical Feature
Cobalamin deficiency:
Sore tongue smooth and beefy red on inspection.
Demyelination of the posterior and lateral columns of
spinal cord, peripheral nerves and cerebellar
involvement lead to numbness and paresthesia in the
extremities (the earliest neurological manifestation),
weakness and ataxia.
Laboratory Finding
Macrocytic anemia, macroovalocytes are typical of
megaloblastic anemia
Hypersegmentation of the nucleus of neutrophils earliest sign.
Note:
Normal blood level of:
Vitamin B12 140-180 pg /ml.
Folic acid 165-760 pg /ml.
Tests for Vitamin B12 Deficiency
A. Serum assay
a. Microbiological assay.
b. Radio assay.
B. Schilling test 30-40 percent of radioactive cobalamin
is excreted in case of malabsorption.
Test for Folate Deficiency
1. Urinary excretion of FIGLU after His load.
2. Folate assay.
Treatment
Cobalamin deficiency :
Replacement therapy with IM cyanocobalamin.
Reticulocytosis begins 4-5 days after therapy is started
and peaks at about day 7.
Folate deficiency :
Folate replacement therapy with 2 mg/day oral dose.
Folate can correct the megaloblastic anemia of
cobalamin deficiency without altering neurological
symptoms.
650
HEMOLYTIC ANEMIA
Classification
Intracorpuscular hemolysis
A. Hereditary:
I. Abnormalities of RBC interior
a. Enzyme defects G-6 PD, hexokinase, pyruvate
kinase.
b. Hemoglobinopathies.
II. RBC membrane defects
a. Hereditary spherocytosis.
B. Acquired: RBC membrane defect.
a. Paroxysmal nocturnal hemoglobinuria.
b. Spur cell anemia.
Extracorpuscular hemolysis:
Acquired:
a. Hypersplenism.
b. Antibody : Autoimmune hemolysis.
c. Microangiopathic hemolysis.
d. Infections, toxins, etc.
Laboratory Evaluation
General:
a. Increased reticulocyte count most useful indicator.
b. Increased unconjugated bilirubin.
c. Erythroid hyperplasia in bone marrow.
d. Abnormal red cell morphology.
Note: Causes of reticulocytosis.
a. Hemolysis Hereditary spherocytosis, PNH.
b. Active blood loss.
c. Myelophthisis.
Others:
Plasma
Haptoglobin
Plasma Hb
Lactate
dehydrogenase
Urine
Hemosiderin
Hemoglobin
Extravascular
hemolysis
Intravascular
hemolysis
Decreased or absent
Normal to increased
Increased
Absent
Markedly increased
Markedly increased
None
None
Present
Present
Hematology
651
Note: Hemoglobinuria is detected by spectrophotometry.

Haptoglobin
It is an alpha globulin that is present in high
concentration in plasma.
It binds free Hb in plasma. It binds specifically and
tightly to globin in Hb. The Hb-haptoglobin complex
is cleared within minutes by mononuclear phagocyte
system.
It is decreased in
a. Hemolysis.
b. Hepatocellular disease.
Increased in Inflammatory states.
Note: Causes of positive Benzidine reaction of urine
a. Hemoglobinuria intravascular hemolysis.
b. Hematuria.
c. Myoglobinuria rhabdomyolysis.
Hereditary Spherocytosis
Inheritance: Autosomal dominant (most common),
autosomal recessive, spontaneous mutation.
Pathology: Spherocytes decreased ratio of surface area
to volume.
Defect:
In cytoskeleton of RBC membrane.
50 percent defect in ankyrin.
25 percent defect in protein 3.
25 percent defect in spectrin (most common defect).
Clinical feature:
3 major features
Anemia.
Splenomegaly.
Jaundice.
Others: Pigmentary gallstones, chronic leg ulcer.
Anemia MCV is normal or slightly decreased.
MCHC is decreased.
Normo/microcytic hyperchromic anemia
652
Osmotic fragility: In hypoosmotic solutions, it is increased,

i.e. the spherocytes lyse at a higher concentration.
Auto-hemolysis test: Increased lysis of RBCs.
Treatment: Splenectomy is the only mode of treatment.
Done at the age of 3-4 years.
Hereditary Elliptocytosis
Autosomal dominant.
Elliptocytes are due to defect in spectrin.
Osmotic fragility is usually normal.
Treatment: Splenectomy.
G6PD Deficiency
X-linked recessive.
It is the most common enzyme deficiency in body.
Drugs causing hemolysis in G6 PD deficiency:
1. Aminosalicylic acid
2. Primaquine, chloroquine, quinine
3. Sulfamethoxazole
4. Dapsone
5. Nitrofurantoin
6. Furazolidone
7. Fava beans (Favism).
Pathology: Reduced production of NADPH (by HMP
pathway) leads to decreased production of reduced
glutathione which protects the RBCs from oxidative stress.
Varieties:
G6PD has 3 varieties
Type B normal variant.
Type A+ - in blacks.
Type A- - most common and significant variant in black
males. This type confers protection against malaria.
Clinical feature:
Self-limiting hemolytic anemia.
Increased plasma Hb, increased unconjugated bilirubin
and decreased plasma haptoglobin.
Heinz bodies.
Hematology
653
AUTOIMMUNE HEMOLYTIC ANEMIA

Classification
I. Warm-antibody usually IgG, may be IgA.
1. CLL.
2. Non-Hodgkins lymphoma.
3. SLE.
4. Drugs - -methyldopa, penicillin, quinidine.
II. Cold-antibody usually IgM.
a. Cold agglutinin disease 1. Acute Mycoplasma pneumonia, infectious
mononucleosis.
2. Chronic lymphoma.
b. Paroxysmal cold hemoglobinuria IgG type.
Diagnosis
Positive direct Coombs test (Coombs +ve immune
hemolytic anemia).
Reaction with
Anti-IgG
AntiC3
Causes
+
+
Antibodies to Rh protein
(Penicillin, -methyldopa)
Antibodies to glycoprotein (SLE)
Cold antibodies
Treatment: Glucocorticoids in warm antibody diseases.

Paroxysmal Cold Hemoglobinuria
Donath-Landsteiner antibody (IgG type) against P antigen.
Etiology:
Tertiary syphilis (most common).
Now most commonly due to viral infection or are
autoimmune.
Evans Syndrome
Immune hemolytic anemia plus thrombocytopenia.
MICROANGIOPATHIC HEMOLYTIC ANEMIA
Cause:
Mechanical trauma to RBCs (e.g.-prosthetic value).
Other causes DIC, malignant hypertension, TTP,
HUS, SLE, eclampsia, and scleroderma.
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Characterized by: Fragmented RBCs (schistocytes).

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
Pathology
Acquired red cell defect. Undue sensitivity of red cells to
complement due to defective synthesis of membrane
proteins DAF and CD59 (complement mediated RBC lysis).
(Decreased membrane glycoprotein anchor).
Clinical Feature
3 cardinal features hemolytic anemia, venous
thrombosis and deficient hematopoiesis
pancytopenia.
Hemolytic anemia intravascular hemolysis.
Venous thrombosis primarily intraabdominal veins.
Results in the Budd-Chiari syndrome, congestive
splenomegaly and pain.
Cerebral venous thrombosis common cause of death.
Pancytopenia leukopenia and/ or thrombocytopenia.
Note: PNH affects all 3 blood cell lineage i.e. RBC, WBC
and platelets.
Diagnosis
Features of intravascular hemolysis:
Hemoglobinemia, hemoglobinuria (intermittent),
hemosiderinuria,
Elevated LDH of erythrocyte type.
Others: Decreased LAP score, decreased acetyl
cholinesterase.
Diagnostic tests:
Hams test.
Flow cytometry to detect lack of CD59 and DAF
most sensitive and specific.
Bone marrow is cellular.
Treatment
1. Washed RBC infusion.
2. Iron therapy.
3. Thrombolytics.
Hematology
655
HEMOGLOBINOPATHIES
SICKLE CELL ANEMIA
Epidemiology
Sickle cell anemia is prevalent in central Africa.
HbS in blood gives protection against falciparum
malaria.
Pathophysiology
HbS is characterized by substitution of valine for
glutamate at 6 position as a result of point mutation
(i.e. glutamate is replaced by valine).
There are 2 types
Sickle cell trait HbS:HbA = 40:60 in RBCs.
Sickle cell anemia - HbS:HbA = 100:0 (i.e. no RBCs.)
Red cells with HbS show tendency to form sickles
when exposed to low O2 tension; this results in
hemolytic anemia and infarction of spleen, lungs,
kidney and brain.
Sickle cell trait does not manifest because 40 percent
HbS is insufficient to produce sickling and HbA has
low affinity for HbS.
Factors favoring sickling: Hypoxia, HbS concentration, fall
in pH.
Clinical Feature
Does not manifest before 6 months of age.
Anemia due to chronic hemolysis (primarily
extravascular), also leads to jaundice and gallstone
formation.
Lung Pulmonary infarction leads to pulmonary
hypertension.
Acute chest syndrome fever, chest pain and
pulmonary infiltrates.
Eye Retinal hemorrhage, detachment and blindness.
Kidney Renal papillary necrosis with hematuria.
Spleen Repeated splenic infarction leads to autosplenectomy predispose to pneumococcal (most
common), hemophilus and meningococcal infections.
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Heart Cardiomegaly, heart failure.

Bone Salmonella osteomyelitis. Bone pain most
common manifestation. Aseptic necrosis of femoral
head. Fish-mouth vertebrae.
Others Leg ulcers, Priapism, Hand-foot syndrome.
leukocytosis, stroke, fat embolism.
Crises
Acute episodes in chronic course:
1. Infarctive or painful crisis most common type.
Characterized by severe bone pain, fever, normal
Hb concentration.
2. Sequestration crisis sudden massive pooling of blood
in spleen acute decrease in Hb concentration
Most common between 6 month and 3 years.
Most common cause of death is sepsis and acute chest
syndrome.
3. Hemolytic crisis decrease in Hb concentration and
increase in jaundice.
Diagnosis
1. Sickling phenomenon demonstration of red cell
sickling under conditions of decrease O2 tension by
an oxygen consuming agent sodium metabisulfite.
2. Hb electrophoresis.
3. Gandy-gamma bodies.
Note: Dithionate test is done to detect HbS.
Treatment
Chronic transfusion therapy.
Drug hydroxyurea (anti-sickling agent).
THALASSEMIAS
Thalassemias are due to quantitative deficiency of
globin chain (either or ) synthesis.
Thalassemia
Due to defective production of chain, chains
accumulate to form tetramers Hb barts (4) in children
and HbH (4) in adults. These tetramers are deposited
in blood vessels and cause hemolysis.
Hematology
657
-genes are located on chromosome 16 and the genetic

defect in thalassemia is deletion.
Clinical feature:
1. Deletion of all loci Hb barts or Hydrops fetalis
(most common cause of hydrops in SE Asia) Babies
are stillborn or die shortly after birth.
Hb barts have very high affinity for O2 and they can
not deliver O2 to tissues.
2. Deletion of 3 loci HbH disease.
Clinical feature - Microcytic hypochromic anemia,
Splenomegaly, target cells and Heinz bodies in blood.
3. Deletion of 2 loci - thalassemia trait.
Clinical feature: Mild anemia and moderate
microcytosis and hypochromia.
4. Deletion of 1 locus asymptomatic carriers.
Diagnosis:
Hb electrophoresis to detect Hb barts and HbH.
Prenatal diagnosis by DNA analysis from chorion villous
sampling or amniocentesis.
Treatment:
1. No treatment available for hydrops fetalis.
2. Splenectomy in HbH disease.
3. No treatment required for others.
Thalassemia
Due to defective production of chains, the excess
chains precipitate in RBCs as Heinz bodies and
produce red cell membrane defect.
genes are located on chromosome 11 and the genetic
defect is mutation
Types of mutation - Splicing (most common), promoter
region, chain termination stop codon (frame shift
mutation).
Clinical feature:
Cooleys anemia.
Extravascular hemolysis.
a. thalassemia major or homozygous form (o o) Severe anemia within first 4-6 months of life.
Massive splenomegaly.
Growth retardation.
658
Expansion of marrow space due to erythroid

hyperplasia chipmunk facies (except mandible).
Copper color skin due to pallor, jaundice and
melanin deposition.
Bone changes: Earliest changes occur in small bones
of hand which show rectangular appearance,
Diploic spaces of skull are widened, Hair on end
appearance of skull in X-ray, bossing of skull.
b. thalassemia minor or heterozygous form Late
presentation with modest anemia with marked
microcytosis.
c. thalassemia intermedia (also homozygous)
intermediate between above two. Does not require blood
transfusion.
Diagnosis:
Hb electrophoresis.
-thalassemia major
Increased HbF (90-100%) and increased HbA2.
Increased serum iron.
Decreased osmotic fragility.
-thalassemia minor (trait)
Increased HbA2 and increased HbF (1-5%).
-thalassemia intermedia
Decreased HbA (20-40%)
Increased HbF (60-80%)
Increased HbA2.
Blood: Microcytic hypochromic anemia. Anisocytosis,
reticulocytosis, nucleated red cells, target cells.
Note: Nestrof test: Screening test to detect carriers of
thalassemia.
Treatment:
1. Periodic blood transfusion Washed RBC is product
of choice.
Complication Iron overload.
Treatment IV or SC desferrioxamine.
2. Splenectomy.
3. Bone marrow transplantation curative.
Hereditary Persistence of HbF
It is a condition where HbF is markedly increased (about
95%) but patient remains asymptomatic and does not
require blood transfusion.
Hematology
659
APLASTIC ANEMIA
Etiology
Most cases are Idiopathic.
A. Acquired
1. Drug Antimetabolites, Chloramphenicol,
Phenylbutazone, Sulfonamides, Gold.
2. Radiation.
3. Chemical benzene.
4. Viruses Hepatitis D, HIV, EBV.
5. Others Pregnancy, SLE.
B. Hereditary
1. Fanconis anemia.
2. Dyskeratosis congenital.
3. Shwachman Diamond syndrome.
Clinical Feature
Normocytic normochromic anemia.

Decrease granulocytes with relative lymphocytosis.
Thrombocytopenia.
BM aspiration may yield a dry tap.
No splenomegaly (c.f. hypersplenism).
Treatment
Treatment of choice is bone marrow transplantation.
Fanconis Anemia
Affects older children (median age 7.5 years).
Characterized by:
Progressive pancytopenia.
Increased predisposition to malignancy.
Increased chromosomal fragility or cellular
hypersensitivity to mutagenic chemicals.
Congenital defects Short stature, caf au lait spots,
kidney and urinary tract abnormalities, microphthalmia
and mental retardation, skeletal abnormalities most
often affecting thumbs, radius.
Myelophthisic Anemia
Infiltration of bone marrow because of:
1. Hematologic malignancy leukemia, lymphoma
multiple myeloma.
660
2. Metastatic deposits from Ca breast, prostrate, lung,

stomach (most common cause).
3. Advanced TB.
4. Lipid storage diseases (Gauchers, Niemann-Picks
disease).
5. Osteopetrosis and myelofibrosis.
Features:
Leucoerythroblastosis (presence of immature erythroid
and myeloid cells in circulation).
Tear drop cells, giant platelets.
BM fibrosis. May yield a dry tap.
Pure Red Cell Aplasia
a. Congenital Idiopathic.
BlackfanDiamond syndrome.
b. Acquired Parvovirus infection.
Parvovirus B19 causes transient aplastic crisis in the
course of chronic hemolytic anemias.
MYELODYSPLASTIC SYNDROME
Preleukemic disorders.
Characterized by
Anemia normocytic normochromic.

Decreased reticulocyte counts.
Neutropenia and thrombocytopenia (pancytopenia).
Increased monocytes.
0-5 percent normoblasts in peripheral blood.
Pseudo-PelgerHuet anomaly (hyposegmented
neutrophil).
Bone marrow:
Is normocellular or hypercellular.
Cells show overt morphological abnormalities or
dysplastic changes.
Chromosomal Abnormality
Monosomy 7 (most common).
5q, 20q deletions.
Trisomy 8.
Hematology
661
FAB Classification
RA Refractory anemia.
RARS Refractory anemia with ring sideroblast.
RAEB RA with excess blast.
CMML Chronic myelomonocytic leukemia (see
below).
RAEBt RA with excess blast in transformation.
Note: Ring sideroblasts are seen in myelodysplastic
syndrome.
Chronic Myelomonocytic Leukemia
FAB criteria:
1. Absolute monocytosis > 1 109/L in peripheral blood.
2. Peripheral blasts < 5 percent.
3. BM blast up to 20 percent.
Others: pH chromosome negative; absent or minimal
dysplasia in myeloid lineage.
MYELOPROLIFERATIVE
DISORDERS
They include four entities:
1. Polycythemia vera most common.
2. Idiopathic myelofibrosis.
3. Essential thrombocytosis.
4. Chronic myeloid leukemia.
Note: Transient myeloproliferative syndrome is seen in
infants with Downs syndrome.
POLYCYTHEMIA VERA
There is overproduction of normal RBCs, granulocytes and
platelets.
Etiology
Idiopathic.
Causes of secondary erythrocytosis:
i. Hypoxia cor pulmonale.
ii. Renal disease such as hydronephrosis, renal artery
stenosis.
iii. Tumors Hypernephroma, hepatoma, adrenal
adenoma, cerebellar hemangioblastoma.
iv. Bartters syndrome.
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Clinical Feature
i. Erythrocytosis vertigo, tinnitus, headache and visual
disturbances.
ii. Massive splenomegaly.
iii. Aquagenic pruritus.
iv. Systolic hypertension.
v. Hemorrhagic manifestations easy bruising, epistaxis
or GI hemorrhage.
vi. Ocular congestion.
Complications
1. Increase in blood viscosity leads to venous or arterial
thrombosis most significant. Intra-abdominal venous
thrombosis is particularly common and when involves
hepatic vein results in Budd-Chiari syndrome.
Digital ischemia.
2. Increase production of histamine leads to peptic ulcer,
pruritus.
3. Increase uric acid production Gout and urate stones.
4. Erythromelalgia erythema, pain and warmth in lower
extremities.
Treatment: Salicylates.
Diagnosis
1.
2.
3.
4.
Elevated red cell mass.

Normal arterial O2 saturation.
Splenomegaly.
In the absence of splenomegaly leukocytosis and
thrombocytosis.
5. Decrease plasma erythropoietin.
Others:
Decreased serum iron (due to overproduction of RBC).
Increased LAP score.
Increased Vitamin B12 (due to increased transcobalamin
III level).
Decreased ESR.
Increased uric acid.
Treatment
Phlebotomy.
32P.
Hematology
663
Chance of Malignancy
Increased risk of AML, NHL and multiple myeloma.
IDIOPATHIC MYELOFIBROSIS
Characterized by
Marrow fibrosis, myeloid metaplasia with
extramedullary hematopoiesis and splenomegaly.
Clinical Feature
1. Mild anemia.
2. Leukocyte and platelet counts either normal or
increased.
3. Huge splenomegaly.
4. Mild hepatomegaly.
Blood:
Tear drop-shaped red cells (dacryocytes).
Nucleated red cells.
Giant platelets.
Promyelocyte, myelocyte.
Bone marrow;
Generally yields a dry tap.
Aspirate shows hypercellular marrow with trilineage
hyperplasia and increased megakaryocytes.
ESSENTIAL THROMBOCYTOSIS
Characterized by overproduction of platelets without any
identifiable cause.
Clinical Feature
1. Arterial or venous thrombosis.
2. Bleeding manifestations.
3. TIA and stroke.
Diagnosis
Increased platelet count with normal LAP score (c.f.
polycythemia).
664
Treatment
To decrease platelet count: Hydroxyurea treatment
of choice. Interferon , Anagrelide, radioactive
phosphorus.
To stop bleeding: Eamino caproic acid (may be used
prophylactically).
Note: Causes of secondary (reactive) thrombocytosis:
i. Postsplenectomy.
ii. Hemorrhage.
iii. Post-surgery.
LEUKEMIAS
MYELOID LEUKEMIAS
ACUTE MYELOID LEUKEMIA
Incidence
Incidence of AML increases with age. It occurs in all ages
but maximum incidence in age above 65 years.
Etiology
Heredity
Downs syndrome better prognosis, .
Klinefelters syndrome, Patau syndrome, Fanconis
anemia, Bloom syndrome, Ataxia telangiectasia.
Classification
M0: Minimally differentiated Ph chromosome +,
worse prognosis.
M1: AML without maturation Auer rods +.
M2: AML with maturation Auer rods +, t (8:21),
chloroma.
M3: Acute promyelocytic leukemia Auer rods +
(most abundant), t (15:17), DIC.
M 4 : Acute myelocytic leukemia meningeal
involvement, gum hyperplasia.
M 5 : Acute monocytic leukemia meningeal
involvement, gum hyperplasia.
M6: Acute erythroid leukemia.
M7: Acute megakaryocytic leukemia.
Hematology
665
Note:
Auer rods are seen in M1, M2 and M3.
Myeloperoxidase +ve in M1, M2, M3, M4.
Nonspecific esterase +ve in M4, M5.
PAS +ve in M6
Platelet peroxidase +ve in M7.
Note:
Myeloblasts are myeloperoxidase positive, Sudan black
positive.
Lymphoblasts are PAS positive.
Clinical Feature
Fatigue is most often the first symptom.
Splenomegaly, hepatomegaly, sternal tenderness,
hemorrhagic manifestations, infections.
Chloroma is a mass lesion of leukemic cells in soft
tissues and other viscera. It is now called the
granulocytic sarcoma or extramedullary myeloid tumor.
Marker CD117.
Blood Picture

Leukocytosis (>15,000 /L) or leukopenia.
Thrombocytopenia.
> 30 percent myeloblasts in blood and/or bone marrow.
Treatment
Induction chemotherapy: Cytarabine + an anthracycline
(daunorubicin or idarubicin).
Allogenic BM transplantation: In first complete remission.
CNS prophylaxis: As ALL.
Note: All-trans-retinoic acid can induce remission in acute
promyelocytic leukemia (M3).
Prognosis
Single most prognostic factor is attainment of complete
remission.
Complete remission:
Blood neutrophil 1500/L, platelet 1 lac/L,
no blast.
BM cellularity 20 percent with trilinear maturation,
<5 percent blasts, no Auer rods.
Age is most important prognostic factor (>60 years
poor).
Median survival is 12-18 months.
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Other poor prognostic factors:

Leukocytosis > 1 lac/L.
Secondary leukemias.
Auer rods positive.
MDRI gene.
Good prognosis: t (8:21), t (15:17), inv (16).
Aleukemic Leukemia
Acute leukemia presenting with pancytopenia without
peripheral blast.
Diagnosis: Bone marrow blasts > 30 percent.
CHRONIC MYELOID LEUKEMIA
Incidence
CML is most common in middle age.
Pathology
Hallmark of CML is the presence of Philadelphia
chromosome in all cell lines.
It is formed due to reciprocal translocation between
chromosomes 9 and 22 (long arms) resulting in fusion
of BCR gene on 22 with ABL gene on 9.
Patients with Downs syndrome are more prone to
develop juvenile CML.
Clinical Feature
Massive splenomegaly almost always present. May
lead to splenic infarction.
Hepatomegaly, bleeding tendencies, gout, priapism,
lymphadenopathy.
Types
Features
Adult type CML

(Common
in children)
Juvenile CML
(Common in
< 2 years)
Thrombocytopenia
Ph chromosome
HbF
Uncommon
+
Normal
Common
Increased
Hematology
667
Diagnosis
Blood
Normocytic normochromic anemia.
Marked leukocytosis (>100000 / L) with basophilia
(>10%).
Thrombocytosis present in 50 percent cases.
< 5 percent circulating blasts and < 10 percent blasts
and promyelocyte.
Others:
Decreased LAP score.
Increased serum vitamin B12 (c.f. leukemoid reaction).
Disease
LAP score
Serum vitamin B12
PNH
Polycythemia vera
Leukemoid reaction
CML
Decrease
Increase
Increase
Decrease
Increase
Decrease
Increase
Phases
1. Chronic phase as outlined above.
2. Disease acceleration refractoriness of anemia to
therapy characterized by
Blasts 15 percent but < 30 percent, blasts and
promyelocytes 30 percent, basophil 20 percent,
platelet count < 100000/L.
3. Blast crisis
Blood or marrow blast 30 percent, hyposegmented
neutrophils (Pelger-Huet anomaly).
Treatment
1. Allogenic BM transplantation: in chronic stage. It is
the only curative therapy for CML, and when feasible,
is the treatment of choice.
2. Chemotherapy: Hydroxyurea induces rapid disease
control. Busulphan may produce pulmonary,
endocardial and marrow fibrosis. IFN/Imatinib is now
considered the drug of choice when BMT is not feasible.
Prognosis
Sokal index:
i. Percent of circulating blast.
ii. Spleen size.
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iii. Platelet count.

iv. Age.
v. Cytogenetic clonal evaluation.
LYMPHOID LEUKEMIAS
ACUTE LYMPHOBLASTIC LEUKEMIA
Incidence
ALL is the most common childhood malignancy. It is
common in children and young adults.
Classification
They are aggressive B cell malignancies.
REAL classification:
Markers:
PreB ALL (Classic childhood ALL) CD19, CD10
and CD20 (in 50% cases). Surface Ig negative most
common childhood leukemia.
T cell ALL (adult ALL) CD2, CD7, CD3, CD5.
B cell ALL CD19, CD20 CD22, CD24, surface
Ig +ve.
Null cell ALL Pre B reactive to CD22 only.
For all ALL:
Cells react to common ALL antigen (CALLA+)
CD10.
95 percent cases present terminal deoxynucleotidyl
transferase (TdT).
Clinical Feature
Signs and symptoms of marrow failure
Thrombocytopenia bleeding manifestations.
Neutropenia opportunistic infection (especially when
count <500 / L). Most common organism Staph.
aureus.
Others Splenomegaly and splenic infarction
(particularly in pre-B ALL).
T cell ALL Involvement of mediastinum (anterior
mediastinal mass) and CNS (particularly as a site of
relapse) in T cell ALL.
Hematology
669
B cell ALL Extramedullary presentation (involvement

of liver, skin, testes) and metabolic abnormalities
(hyperuricemia, hyperkalemia and hypocalcemia).
Diagnosis
Marrow or blood lymphoblast 30 percent.
Specific cell markers.
Treatment
Chemotherapy:
a. Induction of remission Daunorubicin + vincristine
+ prednisolone L-asparaginase.
b. CNS prophylaxis in early post remission period.
Intrathecal and/or IV methotrexate + cytosine
arabinose.
c. Maintenance Methotrexate + 6mercaptopurine +
vincristine + prednisolone.
Note: L-asparaginase can be used in both induction of
remission and consolidation.
BM transplantation: Role in first remission is unclear, 30
percent cure rate in second remission.
Prognosis
Age is the most important factor. Age > 35 years
worsens prognosis.
Mediastinal and CNS involvement in T cell ALL is
a poor prognostic factor, as is hypoploidy.
Other poor indicators: CNS secondaries, WBC > 500000/
L, age <1 and >9 years, male sex, translocations (9:
22, 8:14, 4:11).
Good prognosis: t (12:21).
CHRONIC LYMPHOCYTIC LEUKEMIA
Most common type of adult leukemia.
Incidence
Common in adults. Median age of presentation is 60 years
(seventh decade).
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Pathology
CLL is mainly an indolent neoplasm of mature B cell.
B cell CLL express cell surface IgM/D (most common
chronic leukemia / lymphoma).
T cell CLL express CD 2, 3, 4, 5, 7, 11a.
Clinical Feature
B cell CLL asymptomatic lymphocytosis, generalized
lymphadenopathy (small lymphocytic lymphoma - see
later).
T cell CLL prominent splenomegaly and extensive
skin lesions with a rapidly progressive course.
Diagnosis
Autoimmune hemolytic anemia warm antibody type
Coombs +ve.
Thrombocytopenia and pure red cell aplasia.
Hypogammaglobulinemia.
Blood - TLC > 5 109 /L, 90 percent of cells are
small lymphocytes.
Treatment
No therapy for stages 0, I and II.
Chemotherapy chlorambucil.
Nucleoside analogues fludarabine, pentostatin,
cladribine.
Prognosis
Clinical staging is most important prognostic factor.
Bad prognosis: Deletion of 11q and 17p, also trisomy 12.
Good prognosis: 13q14 (most common).
HAIRY CELL LEUKEMIA
Neoplasm of activated B cells.
Express IL-2 receptors (CD25) and specific adhesion
molecules, also CD19 and 20 (B cell).
Incidence
Rare. Predominantly occurs in males over age 40.
Hematology
671
Clinical Feature
Pancytopenia, massive splenomegaly.
Diagnosis
Hairy cells are abnormal mononuclear cells with hairy
projections in cytoplasm present in bone marrow,
peripheral blood and spleen.
Positive staining with tartarate-resistant acid
phosphatase.
Treatment
1. Splenectomy standard treatment for cytopenias.
2. Chemotherapy
Purine analogues cladribine (drug of choice),
Pentostatin (adenosine deaminase inhibitor),
fludarabine.
Interferon .
LYMPHOMAS
General Consideration
Lymphomas are neoplasm of lymph nodes and other
extranodal tissues that arise from B (most common) or
T lymphocytes and are closely related to lymphoid
leukemias.
They are basically 2 types Non-Hodgkins and
Hodgkins. NHL resembles lymphoid leukemias whereas
HL is a separate entity completely.
NHL may have widespread dissemination at the time
of diagnosis and hence only systemic therapies are curative.
HL often presents at a single site and spreads methodically.
So local therapy may be helpful early in the disease.
NON-HODGKINS LYMPHOMA
They are primarily neoplasms of B cells (most common
85%).
They have 2 basic architectural patterns1. Follicular the nodular architecture of lymph nodes
is preserved better prognosis.
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2. Diffuse the nodular architecture of lymph nodes is

lost worse prognosis.
Markers
Lymphoblasts TdT.
Precursor B cells CD 19, 20, 10.
Mature B cells CD 19, 20, 21, 22; surface Ig.
Precursor T cells CD 1, 2, 5, 7.
T cells CD 2, 3, 4, 8.
NK cells CD 16 and 56.
Basic Differences Between NHL and HL

Features
NHL
HL
Cellular derivation
Sites of disease Localized
Nodal spread
Extranodal
Mediastinal
Abdominal
Bone marrow
B. symptoms
Chromosomal
anomalies
Curability
90% B 10% T
Unresolved
Discontiguous
+
+
+
Translocations and
deletion
30-40%
+
Contiguous
+
Aneuploidy
75-85%
+ = common
= uncommon
Classification
REAL classification:
I. B-cell origin:
a. Indolent 1. CLL/small lymphocytic lymphoma (SLL).
2. Hairy cell leukemia.
3. Follicular lymphomas (grade I small cleaved
cells, grade II mixed small and large cells)
4. Lymphoplasmacytoid lymphoma/Waldenstroms macroglobulinemia.
5. Marginal zone lymphoma (MALT).
b. Aggressive 1. Diffuse large cell lymphoma.
2. Follicular large cell lymphoma (grade III).
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673
3. Mantle cell lymphoma.

4. Burkitts lymphoma.
5. Plasmacytoma.
II. T-cell origin:
a. Indolent 1. T-CLL, T-PLL.
2. Cutaneous T cell lymphoma (Sezarys syndrome
and mycosis fungoides).
b. Aggressive 1. Peripheral T cell NHL.
2. Angioimmunoblastic T cell lymphoma.
3. Intestinal T-cell lymphoma.
4. Adult T-ALL.
INDOLENT B-CELL
Small Lymphocytic Lymphoma
It is the lymphomatous presentation of CLL. Patient
presents with asymptomatic generalized lymphadenopathy.
Unlike CLL, peripheral blood may appear normal or reveal
only mild lymphocytosis. But bone marrow is involved in
90 percent cases.
Markers mature B-cell (CD19, 20, 23), Ig, kappa
or lambda light chains, also express CD5.
Lymph node biopsy shows characteristic
prolymphocyte. The foci of mitotically active
prolymphocytes are called the proliferation centers
(pathognomonic).
Follicular Lymphoma
Grade I small cleaved cell most common type
of NHL indolent.
Grade II mixed small and large cell indolent.
Grade III large cell aggressive.
Characteristic translocation t (14:18) present.
Clinical feature:
They occur predominantly in older persons (> 20
years).
Present as painless peripheral lymphadenopathy with
waxing and waning.
Extranodal involvement is uncommon.
Bone marrow is almost always involved.
40 percent cases progress to diffuse large B-cell
lymphoma.
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Extranodal Marginal Zone Lymphoma (MALT)

They arise form mucosa-associated lymphoid tissue
(MALT) such as salivary glands, small and large bowel
and lungs.
Associations Sjgrens syndrome, Hashimotos
thyroiditis, H. pylori infection.
AGGRESSIVE B-CELL
Diffuse Large B-cell Lymphoma
Most common type of adult lymphoma.
Most malignant form of NHL.
Associations:
1. E-B virus.
2. Human herpes virus type 8.
3. Mediastinal large B-cell lymphoma.
Clinical feature:
Median age is 60 years.
Presents as rapidly enlarging, often symptomatic mass
at a single nodal or extranodal site.
Extranodal involvement (GI tract, skin, bone or brain)
is very common.
But spleen and bone marrow are not commonly
involved.
Markers:
Mature B-cell (CD 19, 20), CD79a, surface Ig, light
chains.
Mantle Cell Lymphoma
Translocation t (11:14).
Markers:
Pan B-cell CD19, 20, 22 and also precursor T-cell CD5
(these are positive also in CLL). But CD79b and FMC
7 are positive only in mantle cell lymphoma and not
in CLL.
CD 23 negative (c.f. SLL), CD 10 negative.
Increased level of cyclin D1 is seen.
B cell presents bright kappa positivity.
Clinical feature: Lymphadenopathy or systemic involvement
of spleen, liver and GI tract.
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Burkitts Lymphoma
Endemic form (in Africa) is associated with E-B virus.
This shows translocation t (8:14) involving the MYC
gene.
They express surface IgM, CD 19 and CD 10.
Clinical feature: Involvement of jaw is the common mode
of presentation.
Morphology: Starry sky appearance.
INDOLENT T-CELL
Mycosis Fungoides and Sezary Syndrome
These are cutaneous T-cell lymphomas involving CD4+
T cells (helper T cells).
Histologically, there is infiltration of the epidermis and
upper dermis by neoplastic T cells.
The tumor has mushroom-like appearance (hence the
name).
With progressive disease, both nodal and visceral
dissemination occurs.
Sezary syndrome is related to generalize exfoliative
erythroderma along with an associated leukemia of
Sezary cells.
Sezary cells have characteristic cerebriform nucleus.
AGGRESSIVE T-CELL
Intestinal T-cell Lymphoma
Predominantly involves the ileum and presents as
abdominal pain, obstruction and perforation.
Adult T-cell Lymphoma
This is associated with human T-cell lymphotrophic virus
1 (HTLV-1).
OTHERS
AIDS-related Lymphomas
1. Diffuse large B-cell lymphoma.
2. Burkitts lymphoma.
3. Primary CNS lymphoma.
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Clinical Feature of NHL

NHL occurs in all ages. Incidence increases with age.
Persistent, painless peripheral lymphadenopathy,
Involvement of Waldeyers ring, epitrochlear, mesenteric
and pelvic nodes.
Extranodal involvement: Liver, lungs, bone (most common
sites are femur, pelvis and vertebrae), GI tract (most
common site is stomach), skin, brain, spinal cord and
kidneys.
Treatment
Radiotherapy in early stage disease (stage I and II).
Chemotherapy in advanced disease.
MOPP Methotrexate, vincristine (oncovin),
procarbazine and prednisolone.
CHOP Cyclophosphamide, doxorubicin, oncovin,
prednisone.
Treatment for Mycosis fungoides:
Full skin electron beam radiation therapy.
Local application of nitrogen mustard.
Others Anti CD20 antibody.
Prognosis
Age ( 60 vs. > 60) is the most important factor.
Depends on histological subtype.
Follicular lymphoma (Grade I) best prognosis.
Diffuse large B cell lymphoma worst prognosis.
Note: Post transplant lymphomas are B-cell origin.
HODGKINS LYMPHOMA
Incidence
Age: It has bimodal peak. One in young adults (15-35
years) and another after age 50. It is rare before age 5
years.
Sex: All types are more common in males except the nodular
sclerosis variety which is more common in females.
Pathology with Types
Reed-Sternberg (RS) cell:
It is the classical diagnostic feature of Hodgkins
lymphoma.
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677
It characteristically has a bilobed nucleus (occasionally

multilobed) appearing as mirror images of each other.
Each lobe contains an inclusion like nucleolus giving
an owl-eye appearance.
Variants of RS cells:
1. Lacunar cells.
2. Polyploid cells.
3. Pleomorphic cells.
Note: RS cells are also found in infections mononucleosis
and mycosis fungoides.
RYE Classification
1. Lymphocyte predominant Polyploid or popcorn cells
(both lymphocytes and histiocytes L and H cells).
Follicular B cell origin - it is distinct from other types
both clinically and histologically.
2. Nodular sclerosis Lacunar cells. Most common type
(70%) in developed countries. More common in women
and children.
3. Mixed cellularity More common in India, also most
common above age 50. Most commonly associated
with systemic symptoms. Typical RS cells are seen.
4. Lymphocyte depleted Pleomorphic cells.
Clinical Feature
Usually presents as localized disease with involvement
of single lymph node region and subsequently spreads
contiguously.
Lymph nodes Painless, freely movable and rubbery.
Site Nodes are centripetal or axial. Most commonly
involves cervical nodes. Mediastinal nodes are involved
more often in nodular sclerosis variety.
CNS involvement is very rare.
Constitutional or B symptoms:
1. Low grade fever (most common) which persists for
several weeks followed by afebrile intervals (Pel-Ebstein
fever).
2. Night sweats.
3. Weight loss of > 10 percent over 6 months or less.
Abdomen Splenomegaly (50%) and hepatomegaly.
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Others Generalized pruritus, nephrotic syndrome,

Paraneoplastic cerebellar degenerative changes.
Diagnosis
Blood: Normocytic normochromic anemia; decreased SI
and decreased TIBC but increased marrow iron store.
Absolute monocytosis.
Immunological:
Defective cellular immunity. Reverse CD4: CD8 ratio.
Markers Most cases are neoplasms of transformed germinal
center B cells.
Lymphocyte predominant HL express B cell markers.
Markers for RS cells CD15 and CD30.
Lymph node biopsy: Confirmatory.
Ann Arbor Staging
Stage I Involvement of single LN region.
Stage II Involvement of 2 or more LN region on
the same side of diaphragm.
Stage III Involvement of LN regions on both sides
of diaphragm.
Stage IV Disseminated involvement of extranodal
organs.
B Presence of weight loss, fever, night sweets.
A Absence of above constitutional symptoms.
Treatment
I. Radiation Dose 3000 5000 rads. For early stage
(I and II) disease.
II. Chemotherapy for advanced disease (III and IV).
MOPP regime mechlorethmine, vincristine,
procarbazine and prednisolone.
S/E Infertility.
ABVD regime Adryamicin, bleomycin, vinblastine
and dacarbazine.
S/E Fatal pulmonary toxicity.
Choice of treatment:
Localized disease chemo + radiotherapy.
Extensive disease chemotherapy.
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Prognosis
Lymphocyte predominant best prognosis.
Lymphocyte depleted worst prognosis.
Bad prognostic factors:
Sex male.
Age > 45 years.
Hb < 10.5 gm/dl.
Leukocytosis > 15000/l.
Lymphocytopenia < 600/l or < 8 percent of WBC.
Serum albumin < 4 gm/dl.
PLASMA CELL DISORDERS

Also called monoclonal gammopathy or paraproteinemia.
Plasma cells are derived from activated B cells and
they give rise to immunoglobulins.
M Component
Igs are gammaglobulins. In plasma cell disorders there
is increase in gammaglobulin fraction on electrophoresis. This is called the M component or paraprotein.
It may be immunoglobulin, heavy chain or light chain.
M components are found in blood and urine and
detected by electrophoresis.
M components are increased in:
1. Plasma cell disorders (multiple myeloma,
Waldenstroms macroglobulinemia, primary
amyloidosis and heavy chain disease)
2. B-cell lymphomas
3. CLL, CML
4. Cryoglobulinemia
5. Breast and colonic carcinoma
6. Rheumatoid arthritis
7. Cirrhosis
8. Sarcoidosis.
Due to disproportionate increase in M component, there
is otherwise hypogammaglobulinemia in plasma cell
disorders.
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M component is absent in:

1. IgD myeloma
2. Light chain disease.
MULTIPLE MYELOMA
Incidence
It is rare before 40 years of age (median age is 68
years).
Slightly more common in males.
Pathology
There is increased cellularity and plasmacytosis in bone
marrow.
Causes of plasmacytosis:
Multiple myeloma,
Aplastic anemia,
Rheumatoid arthritis,
SLE,
Metastatic cancer,
Chronic inflammation.
Note:
Myeloma cells contain characteristic inclusion bodies
in their cytoplasm called the Russell bodies.
These are hyaline globules composed of Igs.
Clinical Feature
1. Bone pain: most common presentation.
Involves the back and ribs and precipitated by
movement.
Skeletal involvement vertebrae (most common), ribs,
skull.
2. Pathological fracture: due to osteopenia and
osteoporosis.
Bone lesions in multiple myeloma are lytic in nature
with no osteoblastic activity leads to hypercalcemia
with normal alkaline phosphatase levels.
3. Susceptibility to infection: most common extraosseous
manifestation.
i. Pneumonia Streptococcus pyogenes, Staphylococcus aureus, Klebsiella.
Hematology
4.
5.
6.
7.
8.
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ii. Pyelonephritis E.coli.

Cause Hypogammaglobulinemia.
Renal failure: leading to azotemia.
It is a late feature.
Causes Hypercalcemia (most common cause),
Glomerular deposit of amyloid, hyperuricemia,
Infiltration of kidneys with myeloma cells.
Pathology:
i. Precipitated Bence Jones proteins in DCT.
ii. Tamm-Horsfall protein.
iii. Tubular cast.
iv. Renal tubular necrosis.
v. Fanconis syndrome.
Electrolytes: Hypercalcemia, pseudohyponatremia,
hyperuricemia, decreased anion gap.
Hyperviscosity syndrome: More common in IgM
paraproteinemia.
Defined as serum viscosity > 5 to 6. (Normal serum
viscosity is 1.8).
Features:
Raynauds phenomenon,
CNS headache, fatigue, visual disturbances and
retinopathy.
Increased ESR.
Bleeding manifestations.
Primary amyloidosis: systemic (AL amyloid).
Diagnosis
The
i.
ii.
iii.
classical triad of myeloma is

Marrow plasmacytosis (> 10%).
Lytic bone lesions.
Serum/urine M component > 3 gm/dl.
Major criteria:
i. Plasmacytoma on tissue biopsy.
ii. Marrow plasmacytosis > 30%.
iii. Mspike on electrophoresis > 3.5 gm/dl for IgG or
> 2 gm/dl for IgA
Minor criteria:
i. Marrow plasmacytosis 10-30%.
ii. M spike less than levels mentioned above.
iii. Lytic bone lesions.
iv. Normal IgM < 0.05 gm/dl, IgA < 0.1 gm/dl or IgG
< 0.6 gm/dl.
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Blood: Normocytic normochromic anemia.

X-ray: Lytic bone lesions, punched out lesions in the skull.
Electrophoresis:
M component most commonly IgG (53%), less
commonly IgA and IgD.
20 percent patients will have only light chains (Bence
Jones proteins) in serum and urine.
M component is absent in light chain myeloma in which
renal catabolism has made the light chains
undetectable in urine.
Enzymes: Serum alkaline phosphatase is normal due to
lack of osteoblastic activity.
Urine: Proteinuria, glycosuria, amino aciduria.
Variants
Two variants of myeloma do not show the classical triad
in that they show no plasmacytosis.
1. Solitary bone plasmacytoma.
2. Extramedullary plasmacytoma usually involves the
submucosal lymphoid tissue of the nasopharynx and
paranasal sinuses.
They have better prognosis.
Staging
Serum 2-microglobulin is the most powerful predictor of
survival and can substitute for staging.
Bad prognostic indicators:
Increased serum LDH level.
DNA hyperploidy.
Blood urea > 80 mg/dl.
Hb < 7 gm/dl.
Hypoalbuminemia.
Treatment
1. Systemic chemotherapy intermittent pulse
chemotherapy with an alkylating agent (melphalan is
the drug of choice, also used cyclophosphamide).
2. Supportive therapy symptomatic.
3. Local radiotherapy in solitary bone plasmacytoma
and extramedullary plasmacytoma.
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683
Monoclonal Gammopathy
of Unknown Significance
Asymptomatic; with M protein < 3 gm/dl, bone marrow
plasma cells < 10 percent and no Bence Jones protein.
Indolent Myeloma
Same as multiple myeloma but asymptomatic.
POEMS Syndrome
Poyneuropathy, organomegaly, endocrinopathy, multiple
myeloma, skin changes.
WALDENSTROMS MACROGLOBULINEMIA
M component is IgM.
Differences with Multiple Myeloma
i. Involves bone marrow, but does not cause lytic bone
lesions or hypercalcemia.
ii. Renal disease is not common.
iii. Associated with lymphadenopathy and hepatosplenomegaly.
Clinical Feature
Major clinical manifestation is hyperviscosity syndrome.
Peripheral neuropathy.
Diagnosis
Serum M component IgM > 30 gm/dl.
Increased ESR.
HEAVY CHAIN DISEASE
Gamma Chain Disease (Franklins Disease)
Hepatosplenomegaly, involvement of Waldeyers ring, fever.
Alpha Chain Disease (Seligmanns Disease)
Most common type.
Characterized by chronic diarrhea, malabsorption,
weight loss, enlargement of abdominal lymph nodes.
Mu Chain Disease
Rarest.
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LANGERHANS CELL
HISTIOCYTOSIS OR
HISTIOCYTOSIS X
Origin
They arise from dendritic cells, which are antigen-presenting
cells most predominantly found in skin.
Pathology
Hallmark of LCH is Birbeck granules in their cytoplasm.
Langerhans cells are HLA-DR and 5-100 positive and
express CD1 a antigen.
TYPES WITH FEATURES
Eosinophilic Granuloma
Unifocal most common (60%).
Multifocal disease is a component of Hand-SchllerChristian disease.
Feature:
Solitary bone lesion, most commonly on skull (most
common), long bones (femur), ribs and vertebrae.
X-ray shows lytic lesions with non-healing borders
(no new bone formation).
Common in children and young adults.
Hand-Schller-Christian Disease
Triad of multifocal bony lesions, diabetes insipidus
and exophthalmos.
Develops in children younger than 5 years of age.
Letterer-Siwe Disease
Characterized by:
Seborrheic skin lesions in the scalp and back, lymphadenopathy, hepatosplenomegaly, pulmonary
infiltration and destructive osteolytic bone lesions.
Extensive infiltration of marrow may lead to anemia,
thrombocytopenia and recurrent infections like otitis
media and mastoiditis.
Occurs in children < 2 years of age.
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685
HEMOSTASIS AND DISORDERS

OF PLATELETS
PLATELETS
Platelets are non-nucleated cells.
Origin:
Megakaryoblast promegakaryocyte megakaryocytes platelets.
Younger platelets are characterized by larger and stickier.
Half-life: 7-10 days.
Granules: They contain 2 types of granules
1. granules contain fibrinogen, fibronectin, factor V
and VIII, platelet factor 4, platelet derived growth factor
(PDGF) and transforming growth factor (TGF ).
2. Dense bodies or granules contain nucleotides (ADP
and ATP), Ca++, histamine, serotonin and epinephrine.
Note:
Large platelets are seen in ITP, Bernard-Soulier
syndrome, myelofibrosis.
Small platelets are seen in Wiskott-Aldrich syndrome.
NORMAL HEMOSTASIS
Fluidity of Blood
Normally, fluidity of blood is maintained by
1. Flow of blood it is laminar in normal conditions.
2. Adsorption of coagulation factors to surfaces.
3. Presence of multiple inhibitors in plasma- antithrombin,
proteins C and S and TFPI.
4. Smooth, vascular endothelium coated with glycocalyx.
Role of Endothelium
Endothelial cells are induced by
1. Cytokines (most Important) TNF and IL-1 (mediators
of acute inflammation).
2. Bacterial endotoxin.
3. Plasmin mediators.
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Antithrombic properties:
a. Antiplatelete effects Endothelium secrete prostacyclin
(PGI2) and NO which are potent vasodilators and
inhibitors of platelet aggregation.
Adenosine diphosphatase also inhibits platelet
aggregation.
b. Anticoagulant properties mediated by membrane
associated heparin like molecules and thrombomodulin.
c. Fibrinolytic properties By t-PA.
Prothrombic activity:
1. Damaged endothelium promotes platelet adhesion by
vWF.
2. They also secrete tissue factor which activates extrinsic
clotting pathway.
Primary Hemostasis
It is the process of platelet plug formation at the site
of injury. It occurs within seconds.
Common in capillaries, small arterioles and venules.
Events:
Three cardinal events
1. Platelet adhesion:
Injury to endothelium exposes the ECM which
contains collagen (most important), proteoglycans,
fibronectin and other adhesive glycoprotein.
Platelet adhesion to ECM is mediated by vWF which
acts as a bridge between platelet surface receptors
(e.g. glycoprotein Ib) and exposed collagen. This
interaction stabilizes the platelet adhesion.
2. Secretion (release reaction):
Following adhesion, and granules in platelets
release their contents.
Thromboxane
synthetase
Membrane phospholipids
Phospholipase C and A2
Arachidonic acid
Cyclooxygenase
Endoperoxidase
Prostacyclin
(PGG 2, PGH2)
synthase
Thromboxane A2
Thromboxane B2
(in platelets)
Prostacyclin (PGI2)
6 keto PGF 1
(in endothelial cells)
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687
3. Platelet aggregation:
Proaggregatory factors:
1. TXA2 (secreted from platelets, is also a potent
vasoconstrictor).
2. ADP
3. Fibrinogen.
Antiaggregatory factors:
1. Prostacyclin (PGI2) by
increased intra-platelet
cAMP.
2. Nitric oxide.
All derived from
3. Adenosine diphosphatase.
endothelium
4. Aspirin blocks cyclooxygenase and inhibits
synthesis of TXA2.
Note: GpIIbIIIa receptors present on platelet surface and
bind fibrinogen which connects multiple platelets to form
large aggregates. Deficiency of GpIIbIIIa results in
Glanzmann thromboasthenia.
Secondary Hemostasis
It consists of the reactions of the plasma coagulation system
that results in fibrin formation.
Coagulation cascade: Please see a textbook.
Fibrinolytic cascade:
This limits the size of the final clot by promoting clot
lysis.
This is primarily achieved by the activation of plasmin
which degrades fibrin polymer into smaller fragments
that are cleared by monocyte macrophage scavenger
system.
Plasminogen
Plasmin
Plasminogen activators (PA)
1. Tissue PA (tPA) most important.
2. Urinary PA (uPA) or urokinase.
3. Hageman factor (XII) fragments.
Natural Anticoagulants
1. Antithrombin III inhibits activity of thrombin and
other serine proteases factors IXa, Xa, XIa and XIIa.
It is activated by binding to heparin-like molecules on
endothelial cells (see above).
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2. Protein C and S vitamin K dependant proteins that

inactivate the cofactors Va and VIIIa.
Procoagulant thrombin
Thrombomodulin
anticoagulant thrombin
Activated protein C
Protein C
Protein S
Cleavage of cofactors Va and VIIIa.
They are secreted by endothelial cells.

Note:
In factor V Leiden defect, antithrombin C fails to
inactivate factor Va.
Factor V Leiden is the most common inherited
thrombophilia that causes resistance to activated protein
C and leads to thromboembolism during pregnancy.
THROMBOSIS
This is the pathologic converse of normal hemostasis
in which blood clots (thrombus) are formed in uninjured
vessels or following minor trauma.
Thrombotic Disorders
A. Primary:
1. Factor V mutations (Leiden mutations).
2. Prothrombin mutations.
3. Antithrombin III deficiency.
4. Protein C and S deficiency.
5. Homocystinuria.
B. Acquired:
High risk:
1. Prolonged bed rest or immobilization.
2. Myocardial infarction.
3. Tissue damage (surgery, fracture, burns)
4. Malignancy.
5. Prosthetic cardiac valves.
6. DIC.
7. Lupus anticoagulant.
Low risk:
1. Atrial fibrillation.
2. Cardiomyopathy.
Hematology
3.
4.
5.
6.
7.
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Nephrotic syndrome.
Hyperestrogenic states.
OCP.
Sickle cell disease.
Smoking.
Others: PNH, Behets syndrome, hyperlipidemia,

myeloproliferative syndrome, Hyperviscosity syndrome,
pregnancy, obesity.
Pathogenesis
Virchows triad:
1. Endothelial injury.
2. Stasis or turbulence of blood flow and
3. Blood hypercoagulability.
Types
Red thrombi: Those formed in veins are rich in fibrin and
red cells and contain few platelets.
White thrombi: Those formed in arteries are rich in platelets
and have little fibrin.
Venous thrombi:
Formed in superficial and deep veins most commonly
in lower extremities following blood stasis.
Almost invariably occlusive cause congestion and
edema distal to obstruction.
Complications: Venous ulcer, poor wound healing,
pulmonary embolism.
Arterial thrombi:
They are formed following endothelial injury commonly
in coronary, cerebral and femoral arteries.
Usually mural, do not occlude the lumen completely.
When formed in heart or aorta, thrombi may have
grossly apparent laminations called lines of Zahn. These
are produced due to pale layers of platelets that
alternate with darker layers containing red cells.
Complications: TIAs and stroke, amaurosis fugax,
myocardial infarction.
Note: Thrombus undergoes fibrosis in 2 weeks.
690
INVESTIGATIONS
Clinical Preview
Features
Defects of primary
hemostasis (platelet
defects)
Defects of secondary
hemostasis (plasma
protein defects)
Site of
bleeding
Superficial skin,
mucous membranes,
nose, gastrointestinal
and genitourinary tracts
Immediate
Deep joints, muscles,

retroperitoneum
Petechiae, ecchymoses
Hematomas, hemarthrosis
Autosomal dominant
Autosomal or
X-linked recessive.
Requires sustained
systemic therapy
Onset after
trauma
Physical
findings
Family
history
Response
to therapy
Immediate; local
measures effective
Delayed hours to days.
Laboratory Tests
A. Primary hemostasis:
1. Bleeding time a sensitive measure of platelet
function.
Normal range 3-8 min.
BT is prolonged in Thrombocytopenia, disorders
of platelet function von Willebrands disease,
vascular abnormalities.
2. Platelet count
Normal 150000-400000/L.
Count < 50000/L easy bruising after minor
trauma.
Count < 20000/L spontaneous bleeding.
B. Secondary hemostasis Coagulation system:
1. Partial thromboplastin time (PTT) measures the
intrinsic pathway.
Normal value 30-40 sec.
PTT is prolonged in parenteral heparin therapy,
DIC, liver disease.
2. Prothrombin time (PT) screens the extrinsic
pathway (factor VII activity).
Normal value 10-14 sec.
PT is prolonged in oral anticoagulant therapy,
vitamin K deficiency, liver disease, DIC.
PT is used to monitor oral anticoagulant therapy.
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691
3. Thrombin time (TT) screening test for fibrinogen

deficiency.
Normal value 20 sec.
TT is prolonged in hypofibrinogenemia (e.g. DIC),
raised FDP, heparin administration.
4. Clot solubility Factor XIII deficiency.
5. Clot lysis 2 plasmin inhibitor.
Note: Heparin therapy is monitored with PTT (which is
kept at 50-80S) and clotting time.
HEMORRHAGIC DISORDERS
DUE TO PLATELETS
THROMBOCYTOPENIA
Most common coagulopathy in surgical patients.
Etiology
a. Impaired production: Most common causes are marrow
aplasia, fibrosis and metastatic infiltrates.
b. Splenic sequestration: Splenomegaly due to - liver
disease, myeloproliferative disorders, lymphoproliferative disorders, Gauchers disease, WiskottAldrich syndrome.
c. Accelerated destruction:
I. Non-immunogenic:
1. Vasculitis (SLE).
2. HUS.
3. TTP.
4. DIC.
II. Immunogenic:
1. ITP.
2. Drug induced most patients recover in 7-10
days and do not require therapy.
IDIOPATHIC THROMBOCYTOPENIC PURPURA
Pathogenesis
Immunogenic - Acute ITP is an immune complex
disease. Chronic ITP is an autoimmune disease with
antibody directed against platelets (direct Coombs test
+ve).
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Acute ITP
Common in children.
Clinical feature: Explosive onset of thrombocytopenia
following recovery from a viral exanthema or URTI.
Recovery: 60 percent recovers in 4-6 weeks and over 90
percent recover within 3-6 months.
Chronic ITP
Common in young adult women (20-40 years).
Clinical feature: Most often present with H/O easy bruising
or menorrhagia.
Course: Disease may persist for years.
Diagnosis
No splenomegaly.
BM shows megakaryocytes.
Blood isolated thrombocytopenia.
Treatment
1. Glucocorticoids drug of choice in childhood ITP.
2. IV immunoglobulin drug of choice in neonatal ITP.
3. Emergency splenectomy.
FUNCTIONAL PLATELET DISORDERS
von Willebrands Disease
vWD is the most common inherited bleeding disorder.
vWF is a glycoprotein which serves 2 functions
1. Adhere platelets to collagen in the ECM of damaged
endothelium.
2. Carrier of factor VIII.
So, in vWD, there is both defective platelet adhesion
and decrease factor VIII concentration in blood.
Inheritance:
Most commonly autosomal dominant (except type III).
Diagnosis:
1. Prolonged BT (also increased APTT) but normal PT.
2. Decreased plasma vWF concentration.
3. Decrease in biological activity in Ristocetin cofactor
assay.
4. Decreased factor VIII activity.
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693
Treatment:
1. Cryoprecipitate which is rich in vWF.
2. Factor VIII concentrates.
3. Desmopressin in patients with type I disease.
PLATELET MEMBRANE DEFECT
Bernard-Soulier Syndrome
Defective platelet adhesion due to deficiency of platelet
membrane glycoprotein complex (Ib-Ix).
Giant platelets are seen.
Glanzmanns Thromboasthenia
Defect in platelet aggregation due to deficiency of
receptor for fibrinogen (GpIIbIIIa).
Note: Thromboasthenin is a contractive protein in platelet.
VESSEL WALL DISORDER
Thrombotic Thrombocytopenic Purpura
Pathology:
Deposition of hyaline thrombi throughout the
microcirculation in the body. These thrombi consist
of platelets and fibrin.
Etiology:
Pregnancy, metastatic cancer, mitomycin c, high dose
chemotherapy.
Features:
Thrombocytopenia, microangiopathic hemolytic
anemia, fever, renal failure, fluctuating levels of
consciousness and evanescent focal neurological
deficits.
Diagnosis:
Gingival biopsy.
Blood presence of Coombs ve hemolytic anemia
with schistocytes or fragmented red cells in peripheral
blood.
Thrombocytopenia.
Coagulation tests are normal.
694
Treatment:
Exchange transfusion or intensive plasmapharesis coupled
with infusion of FFP.
Hemolytic Uremic Syndrome
Pathology:
Hyaline thrombi only in the afferent arterioles and
glomerular capillaries in the kidney (c.f. TTP).
Features:
Occurs in infancy and early childhood ( 1-3 years).
Clinical feature:
Anemia, thrombocytopenia and ARF - classical triad
of HUS.
Fever, abdominal pain, diarrhea and vomiting.
Thrombocytopenia, leukemoid reaction.
Microangiopathic hemolytic anemia (Coombs ve).
Hypertension.
Acute renal failure uremia.
Metabolic: Hyponatremia, hypoglycemia, hyperkalemia.
CNS abnormalities.
Etiology:
Follows a minor febrile or viral illness. May follow an
episode of diarrhea.
Shigella dysentriae type 1 infection (producing
verotoxin) has been implicated as the cause (more
important in India).
EHEC O157 is most important worldwide.
Diagnosis:
Verotoxin in faces.
Helmet cells.
Normal coagulation tests (Normal C 3 ) except
hypofibrinogenemia (increased FDP).
Henoch-Schnlein Purpura
Pathology:
It is due to anaphylaxis (hypersensitivity angitis). It is a
self- limited vasculitis in capillaries, mesangial tissues and
small arterioles that cause increased vascular permeability,
exudation and hemorrhage. Vessel lesions contain IgA and
complements.
Hematology
695
Features:
Occurs in children and young adults.
Follows an acute episode of URTI or streptococcal
pharyngitis.
Clinical feature:
Purpuric rash on extensor surfaces of the arms and
legs and on the buttocks (palpable purpura).
Polyarthralgia or arthritis.
Colicy abdominal pain.
Hematuria due to focal glomerulonephritis, proteinuria.
Melena.
Acute renal failure or chronic nephritis.
Diagnosis:
All coagulation tests are normal. IgA levels may be elevated.
Treatment:
Glucocorticoids.
Prognosis:
Excellent. Usually resolves in 6 weeks.
DISORDERS OF COAGULATION
Causes
a. Inherited X-linked recessive.
1. Factor VIII deficiency or hemophilia A.
2. Factor IX deficiency or hemophilia B.
b. Acquired 1. DIC.
2. Liver disease.
3. Vitamin K deficiency.
4. Anticoagulant therapy.
FACTOR VIII DEFICIENCY HEMOPHILIA A
Factor VIII
It is synthesized in liver and circulated complexed to vWF
protein. Normal hemostasis requires about 25 percent factor
VIII activity. But symptoms appear only when factor VIII
activity falls below 5 percent. Hemophilia A is due to
quantitative reduction of factor VIII in 90 percent cases
and only 10 percent have a reduced activity of factor VIII.
696
Features
With severe disease extensive cephalhematoma or
profuse bleeding at circumcision.
Hemophilic bleeding typically occurs in soft-tissue,
muscles and weight bearing joints.
Hemophilic Arthropathy
Most common manifestation of hemophilia is painful
swelling at weight-bearing joints most commonly the knees.
Repeated bleeding erodes articular cartilage and causes
osteoarthritis, articular fibrosis, and joint ankylosis.
X-ray features:
1. Juxta-articular osteopenia (no sclerosis or bone
formation).
2. Marginal erosions.
3. Subchondral cyst.
4. Reduced joint space.
5. Widening of femoral intercondylar notch.
6. Squaring of patella.
Others
1. Hematuria.
2. Oropharyngeal and intracerebreal bleeding most
dreaded complication.
3. Muscle hematoma, necrosis of muscle (compartment
syndrome) most commonly involves psoas muscle.
4. Venous congestion (pseudophlebitis).
5. Ischemic neuropathy femoral neuropathy is common
due to pressure by a retroperitoneal hematoma.
6. Pseudotumor syndrome large calcified masses of blood
and inflammatory tissue that are mistaken for softtissue sarcomas.
Diagnosis
Increased PTT with all others tests normal.
Treatment
Infusion of cryoprecipitate or purified factor VIII
concentrate.
Desmopressin in mild hemophilia.
Hematology
697
Eaminocaproic acid (EACA) potent antifibrinolytic

agent. Indicated in oral bleeding; contraindicated
in hematuria.
Prednisolone in spontaneous hematuria.
Complications of Therapy
1. Liver Hepatosplenomegaly chronic active or persistent
hepatitis or cirrhosis.
2. HIV infection and AIDS diffuse lymphadenopathy
and immune thrombocytopenia.
3. Multiple infusions cause production of IgG antibodies
against factor VIII.
Prenatal Diagnosis
Familial investigation of RFLP linked to factor VIII
gene.
Chromosomal defect (inversion) can be detected by
PCR or southern blotting.
Prenatal diagnosis from CVS or amniocentesis using
PCR.
FACTOR IX DEFICIENCY HEMOPHILIA B
Also called Christmas disease.
Treatment
Fresh frozen plasma.
Rosenthals Syndrome
Deficiency of factor XI.
FACTOR XIII DEFICIENCY
Factor XIII = Fibrin stabilizing factor.
Clinical Feature
Bleeding from umbilical stump or during circumcision.
Mild bruising, delayed separation of umbilical stump.
Recurrent abortion.
Diagnosis
Conglutination tests normal.
Increased clot solubility.
698
VITAMIN K DEFICIENCY
Causes
1. Inadequate dietary intake.
2. Malabsorption bile duct obstruction.
3. Loss o storage sites due to hepatocellular disease
especially primary biliary cirrhosis.
Acute vitamin K deficiency is common in
i. Patient recovering from biliary tract surgery.
ii. T-tube drainage of bile and
iii. Broad-spectrum antibiotics.
Pathology
In liver, vitamin k is converted to an active epoxide which
serves as a cofactor in the post translational modification
(carboxylation of glutamic acid residues) on prothrombin
complex proteins (Factors II, VII, IX, X, protein C and
protein S).
Hemorrhagic Disease of the Newborn

Due to neonatal deficiency of vitamin K.
Causes:
1. Liver cell immaturity.
2. Lack of gut bacterial synthesis of the vitamin.
3. Low quantities in breast milk.
Manifested as hemorrhage on second to fourth day
of life. It is now rare in developed countries due to routine
administration of vitamin K to all newborn infants.
Diagnosis:
Increased PT and normal PTT (PTT is prolonged in severe
disease).
Hematology
699
Treatment:
Injection vitamin K 10 mg IM.
DISSEMINATED INTRAVASCULAR
COAGULATION (DIC)
Pathology
It is characterized by intravascular coagulation and
bleeding.
Note: Most common site of thrombin formation is brain.
Etiology
I. Massive tissue injury:
a. Obstetrical syndromes
1. Abruptio placentae.
2. Amniotic fluid embolism.
3. Retained dead fetus.
4. Second trimester abortion.
b. Neoplasms 1. Mucinous adenocarcinoma.
2. Acute promyelocytic leukemia.
3. Ca prostrate.
c. Tissue damage burn.
II. Endothelial damage: Aortic aneurysm, HUS, acute
glomerulonephritis.
III. Infections: Endotoxemia, Gram ve and meningococcal septicemia, malaria.
IV. Others: Snake bite.
V. Endocrinal: Fredrich-Hausen Syndrome (adrenal
hemorrhage), Sheehans syndrome (pituitary
hemorrhage).
Clinical Feature
a. Bleeding: most common manifestation.
Most patients have extensive skin and mucous
membrane bleeding and hemorrhage from multiple
sites usually surgical incisions or venipuncture or
catheter sites.
b. Tissue ischemia: Peripheral acrocyanosis, thrombosis
and pregangrenous changes in digits, genitalia and nose.
700
Diagnosis
Blood:
Thrombocytopenia, microangiopathic hemolytic anemia
schistocytes or fragmented red cells.
Laboratory tests:
Increased PT, increased PTT and increased TT.
Decreased plasma fibrinogen level most important
marker (best correlates with bleeding).
Increased FDPs, increased plasmin.
Treatment
1. Attempt to correct any reversible cause.
2. To stop bleeding FFP and platelet concentrate.
3. To prevent thrombosis heparin.
COAGULATION DISORDERS IN LIVER DISEASE
Characterized by: increased PT and increased PTT, mild
thrombocytopenia and normal fibrinogen level. Among
them PT has good correlation with risk of bleeding.
Treatment: Vitamin K supplementation, FFP.
CIRCULATING ANTICOAGULANTS
They are IgG in type.
Specific: Autoantibody against factor VIII are seen in
1. Hemophiliacs with repeated transfusion.
2. Postpartum females.
3. SLE.
4. Normal elderly individuals.
5. AIDS.
Nonspecific:
Lupus anticoagulant against phospholipids is classically
seen in SLE.
LA is associated with increased risk of
i. Thromboembolism and
ii. Recurrent mid-trimester abortion.
Hematology
701
BLOOD GROUPS AND BLOOD

TRANSFUSION
Blood group antigens are located on the cell membrane
of red cells.
Blood group antibodies are of 2 types
1. Natural antibodies most important are anti-A and
anti-B antibodies, usually of IgM class.
2. Immune antibodies are acquired after transfusion
or transplacental passage during pregnancy, are warm
antibodies of IgG class.
ABO SYSTEM
ABO blood group antigens were discovered by
Landsteiner.
It is the most important of systems because natural
antibodies are present in plasma in all individuals
against the blood group antigen they lack.
A, B and H antigens are glycoprotein. Apart from RBCs,
they are also secreted in saliva, gastric juice, semen,
sweat (not CSF).
H antigen is precursor of A and B and all the blood
groups contain H antigen.
Bombay group in rare cases, person of O blood group
lacks H antigen and are called Bombay or OH group.
They contain anti A, anti B and anti H antibodies
in their sera.
Blood group antigens are inherited according to
Mendelian dominance (autosomal).
Group A antigen has been divided into two subtypes
A1 and A2 depending upon the number of antigen
present on cell surface.
Most common blood group is O and least common
is AB.
Rh SYSTEM
Most potent Rh antigen is D antigen. Consequently
persons with D antigen present are called Rh +ve and
those with D antigen absent are called Rh ve.
Genotype is CDe /Cde and CDe/CDe.
Rh antigens have no naturally occurring antibodies in
serum. Immune antibodies (IgG) appear following
702
blood transfusion and fetomaternal transmission during

pregnancy.
As IgG can cross placenta, subsequent child may suffer
from hemolytic disease.
Percent of Rh positivity in India is 93 percent.
DUFFY SYSTEM
Duffy antigens serve as receptors for P. vivax malaria. So
Duffy ve group gives protection against the disease.
BLOOD COMPONENTS
1. Whole blood: Provides both O2-carrying capacity and
volume expansion. They lack in factor V and VIII.
2. Packed red cells: Contain RBCs with variable leukocyte
content and small amount of plasma.
Provides O2 carrying capacity in anemic patients.
3. Platelets:
Platelets in stored blood remain functional up to 24
hours. In platelet concentrate they survive for 72 hours.
Indications ITP, DIC.
Repeated transfusions cause alloimmunisation and
refractoriness.
4. Fresh frozen plasma: contains stable coagulation factors
and plasma proteins fibrinogen, antithrombin,
albumin as well as protein C and S.
Indications TTP, DIC, hemophilia.
5. Cryoprecipitate:
Contains Fibrinogen, factor VIII and vWF.
6. Plasma derivatives.
Note: 1 unit blood raises Hb level by 1 gm percent
(0.8 gm% in India).
TRANSFUSION REACTIONS
Immunologic
1. Hemolytic transfusion reaction:
a. Immediate intravascular hemolysis occurs in ABO
incompatibility.
Clinical feature: decrease in BP, tachycardia,
tachypnea, hemoglobinuria, chest pain.
b. Delayed extravascular hemolysis occurs in Rh
incompatibility.
Hematology
703
2. Febrile reaction:
Most common with cellular blood components.
Treatment: Stop transfusion, antipyretics. Also reducing
pore size of transfusion set filter.
3. Allergic reaction Urticaria, purpura.
Non-immunologic
1. Circulatory overload: Resulting in pulmonary
congestion and acute heart failure is most common
complication that may result in death following
transfusion.
2. Massive transfusion: May cause dilutional
thrombocytopenia. Also hypothermia and DIC.
3. Electrolytes: With repeated transfusion
Hypocalcemia, hyperkalemia, metabolic alkalosis (due
to citrate).
4. Infections HCV is the most common cause of transfusion
associated viral hepatitis.
Others Hepatitis G, Parvo B-19, CMV, HIV,
hepatitis B.
5. Iron overload.
BONE MARROW
TRANSPLANTATION
Indications
Blood:
1. Leukemias AML in first remission, ALL in second
remission, CML in chronic stage.
2. Aplastic anemia.
3. Thalassemia.
4. Myelodysplastic syndrome.
5. Lymphoma, myeloma.
Others:
1. Osteopetrosis.
2. Severe combined immunodeficiency.
3. Storage diseases e.g. Gauchers, Hurlers, Hunters,
Infantile metachromatic leukodystrophy.
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Bone Marrow Examination

Essential in Aplastic anemia, megaloblastic anemia,
Aleukemic leukemia, myelofibrosis, myelosclerosis, multiple
myeloma.
ESR
Increased in: Pregnancy, menstruation, multiple
myeloma, anemia other than sickle cell, leukocytosis,
newborn and DLE.
Decreased in: Polycythemia, CHF, sickle cell anemia,
afibrinogenemia.
11
ONCOLOGY
GENERAL ONCOLOGY
NOMENCLATURE
Metaplasia
Metaplasia means replacement of one mature cell type
with another. It is non-neoplastic. For example, squamous
metaplasia - most common type; seen in endocervix and
bronchial mucosa.
Glandular metaplasia is seen in Barrets esophagus.
Dysplasia
Dysplasia is a loss in the uniformity of the individual cells
and a loss in their architectural orientation. It is encountered
principally in the epithelia. It is non-neoplastic with
maximum potential for malignant change.
Carcinoma In Situ
When dysplastic changes are marked and involve the entire
thickness of the epithelium, the lesion is referred to as
carcinoma in situ. It is a preinvasive stage of cancer.
Anaplasia
Loss of differentiation of cells is known as anaplasia. It
is the hallmark of malignancy.
Features of anaplastic cells:
1. Pleomorphism (variation in size and shape).
2. Nuclei are hyperchromatic and large.
3. The nucleus : cytoplasm ratio of normal 1:4 or 1:6
may approach 1:1.
4. Anaplastic nuclei are variable and bizarre in size and
shape.
5. Mitoses are often numerous and distinctly atypical.
706
Desmoplasia
Tumors with dense, abundant fibrous stroma are called
desmoplastic or scirrhous carcinoma.
Differences between cellular changes
Metaplasia
Dysplasia
Neoplasia
Abnormal
differentiation
Abnormal
differentiation
and maturation
Loss of uniformity
of cells
Abnormal
differentiation
and maturation
Marked variation
in size, shape and
cell number
Variable loss of
control and
organization
Irreversible
Replacement of one
mature cell type
with another
Regular organization
of tissue maintained
Reversible
Partial loss of
control and
organization
Partially reversible
Tumors
Malignant tumors:
Sarcoma - that arises from mesenchymal tissue.
Carcinoma - that arises from epithelial tissue.
Features of malignancy:
1. Anaplasia or lack of differentiation.
2. Rate of growth erratic and rapid.
3. Locally invasive.
4. Metastases to distant sites - most characteristic of
neoplasm.
Mixed tumors: Tumors composed of a single type of
parenchymal cells that differentiate towards more than
one cell line are called mixed tumors.
For example, pleomorphic adenoma of parotid gland.
Teratoma: Tumors composed of a number of parenchymal
cell types arising from totipotent cells derived from more
than one germ cell layer.
Choriostoma: Congenital anomaly defined as ectopic rests
of normal cells.
Hamartoma: It is a congenital malformation defined as
a mass of disorganized but mature cells of tissues
indigenous to the particular site.
Oncology
707
METASTASIS
Routes
1. Lymphatic spread: Carcinomas spread via lymphatics.
Sarcomas that spread via lymphatics
1.
2.
3.
4.
5.
6.
7.
Synovial sarcoma
Clear cell sarcoma
Angiosarcoma
Rhabdomyosarcoma
Fibrosarcoma
Epithelioid sarcoma
Malignant fibrous histiocytoma
2. Hematogenous spread: Hematogenous route is favored

by sarcomas, but carcinomas also spread by this route
especially those of lungs, breast, kidney, thyroid and
prostrate.
3. Seeding within body cavity: e.g. peritoneal deposits in
colonic carcinoma.
4. Other routes:
Spread along epithelium-lined surfaces.
Spread via CSF.
Direct implantation by surgeons instruments.
Site
Some important sites for metastasis
Breast
Kidney
Lung
Melanoma
Prostate
Bone
Lung
Liver
Brain
Max.
Max.
Max.
Max.
+
+
++
+
Max.
++
+
Most common metastasis:

TO
FROM
Brain - melanoma, lung
Bone - prostrate (male), breast (female)
Lungs - liver
Liver - GI tract, neuroblastoma in children, adrenals,
melanoma, and lungs.
Overall most common sites of metastasis are lymph
nodes and liver.
708
EPIDEMIOLOGY
Incidence
Most common sites of cancer in male are prostrate (world
wide) and oral cavity (in India). Most common sites of
cancer in female are breast (worldwide) and cervix (in
India). Maximum mortality is from lung cancer.
Most common cancer in children is leukemia (ALL).
Heredity
I. Inherited cancer syndrome (autosomal dominant):
1. Familial retinoblastoma
2. Familial adenomatous polyposis of the colon
3. Multiple endocrine neoplasia (MEN) syndrome
4. Neurofibromatosis type 1 and 2
5. von Hippel-Lindau syndrome.
II. Familial cancers:
1. Breast carcinoma
2. Ovarian carcinoma
3. Colonic carcinoma
III. Autosomal recessive syndroms of defective DNA repair
(chromosomal breakage syndrome):
1. Xeroderma pigmentosa
2. Ataxia telangiectasia
3. Bloom syndrome
4. Fanconis anemia
CELL CYCLE AND REGULATION
Phases
G0 : Resting phase.
G1 : First gap phase during which the cell determines
its readiness to commit to DNA synthesis.
S : Phase of DNA synthesis (replication).
G2 : Second gap phase during which the fidelity of
DNA replication is determined and errors are corrected.
M : Phase of mitosis.
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709
Regulation
RB + cyclin D
(CDK 4 and 6)
Cyclin B (CDK 1)
Regulation of cell cycle
Interphase
Regulator
G1 S
Product of retinoblastoma gene (pRB) and cyclin D

along with CDK 4 and 6
Cyclin A along with CDK 1 and 2
Cyclin B along with CDK 1
S G2
G2 M
CDK = Cyclin dependant kinase
CDK inhibitors:
p15, p16, p18, p19 inhibit CDK 4 and 6 (G1 S
interphase).
p21, p27, p57 inhibit all the CDKs.
RB protein is regulated by four genes
RB gene
CDK4
Cyclin D and
CDKN2A (p16)
Transforming growth factor (TGF- ): has
antiproliferative effects by cell arrest at G1 phase.
Mutation of TGF- is associated with pancreatic
carcinoma (100%) and colonic carcinoma.
CANCER GENETICS
Proto-oncogenes
Genes that promote normal cell growth are called protooncogenes. Activation of such genes converts them to
710
oncogenes which produce oncoproteins. Their production

or function is independent of any external regulator.
Oncogenes transferred to in vitro animal cells turn them
neoplastic.
Mechanism of activation of proto-oncogenes:
a. Point mutation:
i. RAS gene: RAS gene is associated with
Neurofibromatosis type 1. RAS is activated by
binding to GTP and inactivated by conversion of
GTP to GDP by guanosine triphosphatase
(GTPase). GTPase activity is controlled by GTPase
activating protein (GAPs). Thus, GAPs prevent
uncontrolled activation of RAS gene and control
cell growth.
Disabling mutation of neurofibrin 1 (NF 1), a
GAP is associated with neurofibromatosis type 1.
ii. Ret gene:
Gain of function in the protooncogene Ret on
chromosome 10 is associated with Multiple
Endocrine Neoplasia (MEN) syndrome type 2.
Loss of function of Ret causes Hirschsprungs
disease.
b. DNA amplification: Over expression of these genes cause
growth autonomy by binding to nucleus and increasing
transcription of DNA.
i. erbB gene:
erbB1 is associated with squamous cell
carcinoma of lung.
erbB2 (Her2/neu) is associated with breast
cancer, adenocarcinoma of lung.
ii. MYC genes:
N-MYC gene is associated with neuroblastoma.
L-MYC gene is associated with small cell Ca
of lung.
C-MYC gene is associated with familial polyposis
coli.
c. Chromosomal alterations:
i. Translocation:
t (8:14) causes dysregulation of MYC gene and
produces Burkitts lymphoma.
Balanced translocation between ABL gene on
chromosome 9 and BCR gene on chromosome
Oncology
711
22 produces Philadelphia chromosome in

chronic myeloid leukemia.
t (14:18) causes follicular B cell lymphoma.
ii. Deletions:
13q14 deletion is associated with
retinoblastoma.
18q deletion is associated with colorectal Ca.
3p deletion is associated with small cell Ca of
lung.
11p13 deletion is associated with WAGR
syndrome.
Tumor Suppressor Genes
Genes that normally restrain cell growth are called tumor
suppressor genes. They usually regulate at the G1 S
interphase.
Majority of inherited autosomal dominant traits are
due to suppression of function of tumor suppressor genes.
Examples:
RB gene (on chromosome 13) - retinoblastoma,
osteosarcoma.
BRCA 1 (on chromosome 17) - breast, ovary, colon,
prostatic Ca.
BRCA 2 (on chromosome 13) - breast, ovary (lower
risk), male breast Ca.
WT 1 - Wilms tumor, WAGR syndrome.
NF 1 - neurofibromatosis type 1 (neurofibromas,
neurofibrosarcomas, brain tumor).
NF 2 - neurofibromatosis type 2 (acoustic neuroma,
meningioma).
p16 (CDKN2A) - melanoma, pancreatic Ca.
p53 - sarcoma, breast, colon, lung Ca.
APC - intestinal polyposis, colorectal Ca (loss of APC
gene causes decreased degradation of -catenin and
increased WNT signaling).
p53 gene:
It is a 53 kD protein
It is located on short arm of chromosome 17.
It blocks cyclins and CDK and prevents cell to enter
G1 phase transiently and allows DNA repair.
The wild type is normal and acts as a tumor supressor
gene.
712
p53 gene plays a major function in

1. Antiproliferative effect
2. DNA repair
3. Apoptosis
That is why it is called guardian of genomes.
Mutations in p53 gene causes Li-Fraumeni syndrome
where affected individuals may develop a variety of
sarcomas, brain tumors and leukemia.
Mutations in p53 gene are the most common genetic
alteration in human cancer.
DNA Repair Genes
i. Hereditary nonpolyposis colon cancer (HNPCC or
Lynchs syndrome): due to mutation of one of four
DNA mismatch repair genes.
ii. Autosomal recessive disorders:
Xeroderma pigmentosa - nucleotide excision repair
defect.
Ataxia telangiectasia - mutation of ATM protein.
Bloom syndrome.
Fanconis anemia.
iii. BRCA 1 and BRCA 2 genes: defective repair of
double stranded break.
Genes Regulating Apoptosis
Genes that promote apoptosis:
p53, BAD, BAX, BID.
All these genes favor cytochrome C release and promote
apoptosis.
Genes that inhibit apoptosis:
BCL 2 and BCL-XL.
They prevent release of cytochrome C.
CARCINOGENESIS
Chemical Carcinogens
1.
2.
3.
4.
5.
Alkylating agents such as anticancer drugs.

Acylating agents.
Aromatic hydrocarbons.
Aromatic amines (azo dyes) - bladder Ca.
Others Vinyl chloride - liver Ca (angiosarcoma).
Oncology
713
Asbestos - Ca lung, pleura (mesothelioma) and

peritoneum.
Arsenic - Ca lung, skin.
Benzene - acute myelocytic leukemia.
Hormones
1. Androgens - prostatic Ca.
2. Diethylstilbestrol (prenatal exposure) - vaginal Ca (clear
cell Ca) in female offspring.
3. Estrogen - carcinoma endometrium, liver (adenoma),
breast.
Viruses
1. Human T cell lymphotropic virus type 1 (HTL V 1)adult T cell leukemia/lymphoma.
2. Human papilloma virus (HPV) - benign squamous
papillomas (warts), squamous cell Ca of cervix and
anal canal, perianal, vulvar and penile Ca.
3. EB virus - Burkitts lymphoma, nasopharyngeal Ca.
4. Hepatitis B and C virus - liver Ca.
5. HIV - non-Hodgkins lymphoma, Kaposis sarcoma,
squamous cell Ca.
Other Microorganisms
1. H. pylori - gastric Ca.
2. Schistosoma - urinary bladder Ca (squamous cell type).
Radiation
1. Acute and chronic myelocytic leukemia.
2. Papillary Ca thyroid in those exposed during infancy
and childhood to head and neck irradiation.
CLINICAL FEATURES OF NEOPLASIA
Cancer Cachexia
It is the combination of asthenia (emaciation) and anorexia
seen in patients with advanced cancer.
Mediators: Cachectin or tumor necrosis factor (TNF) and
IL-1 liberated by activated macrophages.
714
Paraneoplastic Syndromes
Paraneoplastic syndromes are seen in 10-15 percent of
patients with cancer. They may represent the earliest
manifestation of an occult neoplasm.
Endocrinal syndromes:
Hypercalcemia seen in squamous cell carcinoma of
lung, breast Ca, renal cell Ca, bladder Ca.
Cause PTH-related protein, TGF, vitamin D.
Cushings syndrome seen in small cell Ca of lung,
pancreatic Ca. Cause ACTH.
SIADH seen in small cell Ca of lung, head and neck
tumors. Cause AVP and ANP.
Carcinoid syndrome seen in bronchial carcinoid (most
common), pancreatic Ca, gastric Ca. Cause serotonin,
bradykinin, histamine.
Polycythemia seen in renal cell Ca, cerebellar
hemangioblastoma, hepatocellular Ca. Cause
erythropoietin.
Acromegaly seen in carcinoid tumors, small cell of
lung.
Hematological syndromes:
Superficial thrombophlebitis or peripheral vascular
thrombosis seen in pancreatic Ca (Trousseaus sign),
GI tract Ca, breast Ca, lung Ca.
Non-bacterial thrombotic endocarditis.
Neurological syndromes:
Central nervous system
Progressive multifocal encephalopathy seen in small
cell Ca of lung.
Subacute cortical cerebellar degeneration seen in small
cell Ca of lung.
Opsoclonus-myoclonus seen in bronchial Ca.
Peripheral nerves
G-B syndrome seen in Hodgkins lymphoma.
Chronic demyelinating polyneuropathy.
Neuromuscular junction
Lambert-Eaton syndrome seen in small cell Ca of
lung.
Myasthenia gravis seen in thymoma.
Bone and soft tissue:
Hypertrophic osteoarthropathy seen in non-small cell
Ca of lung.
Clubbing seen in non-small cell Ca of lung.
Oncology
715
Metabolic:
Hyperglycemia seen in fibrosarcoma, liposarcoma
and other sarcomas, hepatocellular Ca.
Note: Paraneoplastic syndromes associated with thymoma:
1. Hypogammaglobulinemia
2. Pure red cell aplasia
3. Myasthenia gravis
4. Graves disease
5. Pernicious anemia
6. Polymyositis.
GRADING AND STAGING
Grading
Grading is done on the basis of:
1. Grading of anaplasia (cell differentiation) and
2. Rate of growth.
Broders grading of squamous cell carcinoma:
Grade I: Well-differentiated (< 25% anaplastic cells).
Grade II : Moderately differentiated (25-50% anaplastic
cells).
Grade III: Moderately differentiated (50-75% anaplastic
cells).
Grade IV: Poorly differentiated (>75% anaplastic cells).
Staging
Staging is done on the basis of:
1. Primary tumor (size) - T
2. Lymph node involvement - N
3. Metastasis - M
Staging is based on clinical and radiological
examination - clinicoradiological.
DIAGNOSIS OF TUMORS
Tumor Markers
Tumor markers
Marker
Neoplasm
Human chorionic Choriocarcinoma,

gonadotropin
seminoma,
(hCG)
teratocarcinoma
Non-neoplastic
condition
Pregnancy
Contd...
716
Contd...
Marker
Neoplasm
Non-neoplastic
condition
Calcitonin
Medullary Ca of thyroid
Catecholamines
Pheochromocytoma
-fetoprotein
Hepatocellular Ca,
endodermal sinus
tumor (yolk sac),
embryonal Ca,
teratoma
Alkaline
phosphatase
Placental seminoma Pregnancy
Cirrhosis of liver,
pregnancy
choriocarcinoma
Liver hepatoblastoma,
hepatocellular Ca
Prostatic acid
phosphatase
Prostatic Ca
Prostate specific
antigen (PSA)
Prostatic Ca
Lactate
dyhydrogenase
Lymphoma, Ewings
sarcoma, seminoma
Benign prostatic
hyperplasia
Carcinoembryonic Adenocarcinoma of
antigen (CEA)
colon, carcinoma of
pancreas, stomach,
lung, breast, ovary
Cirrhosis, emphysema,
diabetes mellitus,
ulcerative colitis,
pancreatitis, Crohns
disease, healthy
smokers
CA-125
Endometriosis,
tuberculosis of
genital tract
Ovarian Ca
Use of tumor markers:

1. Tumor markers are useful to assess the response to
treatment.
2. For detection of recurrence after excision, e.g. CEA
after colonic resection.
Exfoliative Cytology
It is useful for detection of Ca cervix, endometrium, lung,
urinary bladder, prostrate, stomach.
Fine Needle Aspiration Cytology
FNAC is useful for detection of ca breast, thyroid, lymph
nodes and salivary glands. FNA needle size is 22-26G.
Oncology
717
Immunohistology
Immunohistology is used for detection of
1. Intermediate filaments
Cytokeratin - carcinoma (undifferentiated).
Vimentin sarcomas.
Desmin sarcomas (myogenic tumors).
2. Prostrate specific antigen.
3. Estrogen receptors and Her2/neu.
Flow Cytometry
Flow cytometry is used for
1. Classification of leukemia and lymphomas on the basis
of CDs.
2. Assessment of DNA content (ploidy) of tumor cells.
CANCER THERAPY
Surgery
Uses of surgery:
1. Diagnosis - biopsy.
2. Staging - e.g. exploratory laparotomy for staging of
Hodgkins lymphoma.
3. Treatment.
Aims of therapeutic surgery:
i. Resection of metastatic disease with the intent to cure.
ii. For palliation of advanced disease.
iii. To achieve cytoreduction when complete excision in
not possible, e.g. in Wilms tumor.
iv. Reconstruction after definitive surgery, e.g. breast
reconstruction.
v. Prevention - e.g. colectomy in patients with familial
polyposis coli.
Radiotherapy
Physical characteristics:
Ionizing radiation:
a. Electromagnetic (photons)They have the highest penetrating potential.
1. X-ray: Produced by electron-level transition
within the atom.
718
2. Gamma rays: Produced by radioactive decay,

typically from cobalt-60, cesium-137 and
radium-226.
b. Particles1. Electron - electron beam therapy is used for
skin cancers.
2. Proton.
3. Neutron.
4. Alpha particle - produced by helium atom.
Unit of radiation:
Gray (Gy) - 1 Gy is the absorption of 1 joule of energy
per kg of tissue.
1 Gy = 100 rad.
Biological characteristics:
Photons act by dislodging orbital electrons of the
tissues through which they pass.
This collision produces a fast electron

(Compton effect)
This ionizes molecules along its path producing

secondary electrons and free hydroxyl (OH) radicals
Local cellular damage, especially of DNA

DNA is the primary target for radiation-induced cell
death. The damage caused to DNA is double-strand
break.
Cells are most sensitive to radiation at G2 - M interface
(mostly G2).
Sensitivity to radiation:
Most radiosensitive tissue is bone marrow (othersintestinal mucosa and skin).
Least radiosensitive tissue is the nervous tissue.
Most radiosensitive blood cells are lymphocytes.
Therapy:
Types:
a. External beam therapy or teletherapy - radiation
delivered from a source outside the body.
b. Brachytherapyi. Interstitial brachytherapy Source: Most commonly used metal is iridium192.
Oncology
719
Use: Commonly used in the treatment for Ca

cervix.
ii. Intracavitary brachytherapy
Source 32P
Use: early ovarian cancer.
Isotopes used in brachytherapy:
1. Cesmium-137
2. Gold-198
3. Cobalt-60 - half-life 5.26 years.
4. lridium-192
5. Radium-226 - half-life 1640 years (longest halflife).
Use: Radiotherapy is used as a sole modality of
treatment in highly radio-sensitive tumors like 1. Limited stage Hodgkins lymphoma.
2. Some non-Hodgkins lymphomas.
3. Seminoma testis.
4. Head and neck cancer.
5. Ewings sarcoma.
6. Medulloblastoma.
Complications:
a. Stochastic effects - not related to dose, e.g.
leukemia (secondary), solid tumors.
b. Non-stochastic effects - dose related, e.g. cataracts,
sterility.
c. Acute radiation sickness - at doses above 100 rem.
They include Hematopoietic syndrome - bone marrow
suppression.
GI syndrome - nausea, vomiting.
CNS, CVS syndromes.
d. Long-term effects Skin - erythema (most common).
CVS - asymptomatic pericardial effusion (most
common).
Toxic doses:
Minimum lethal dose is about 200 rem.
Some selected doses for organ damage
Kidney - 2500 rad.
Liver - 4000 rad.
Ovary - 2300 rad.
Radiosensitizing agents:
1. 5-fluorouracil
2. Hydroxyurea
720
3. BUDR
4. Cisplatin
5. Actinomycin D
6. O2
7. Metronidazole.
Radioprotecting agent
Amifostil.
Chemotherapy
Chemotherapeutic agents:
I. Alkylating agents:
1. Busulfan
2. Cyclophosphamide, Ifosfamide
3. Chlorambucil
4. Cisplatin
5. Melphalan
6. Nitrogen mustard, nitrosoureas
7. Thiotepa
II. Antimetabolites:
a. Pyrimidine analogues
1. Cytarabine
2. 5-Fluorouracil (5FU)
3. Gemcitabine
b. Purine analogues
1. Cladirabine
2. Fludarabine
3. Pentostatin
4. 6-mercaptopurine
5. Azathioprine
c. Folate antagonist: Methotrexate
d. Others: Hydroxyurea
III. Topoisomerase inhibitors:
a. Anthracyclines
1. Daunorubicin
2. Doxorubicin
b. Epipodophyllotoxins: Etoposide
IV. Plant alkaloids:
a. Taxanes: Paclitaxel
b. Vincas
1. Vinblastine
2. Vincristine
Oncology
721
V. Antibiotics:
1. Bleomycin
2. Mitomycin C
VI. Miscellaneous:
1. Dacarbazine
2. L-asparaginase
3. Procarbazine.
Alkylating Agents
They produce carbonium ion binds to guanine residues
in DNA cross linking/abnormal base pairing/scission of
DNA strand.
Side effects:
1. Azoospermia and male infertility.
2. Secondary leukemia.
3. Myelosuppression - most common.
Chemotherapeutic agents
Drug
Indication
Side effects
Nitrogen mustard
Single dose therapy

in Hodgkins
lymphoma
Local invasion
so always given IV,
poor wound healing
Cyclophosphamide Ovarian tumor,

Wegners
granulomatosis
drug of choice
Alopecia, hemorrhagic
cystitis due to
metabolite acrolein. It is
prevented by mesna.
Paralytic ileus
Melphalan
Multiple myeloma
drug of choice
Bone marrow
suppression
Busulfan
Chronic myeloid
leukemia durg
of choice
Hyperuricemia,
hyperpigmentaion,
pulmonary fibrosis
Chlorambucil
Chronic lymphocytic
leukemia drug
of choice
Nitrosoureas
Meningeal leukemia
and brain tumors
(because they
cross BBB)
722
Antimetabolites
Antimetabolites
Drug
Mechanism
of action
Indication
Side effects
Methotrexate
Inhibits dihydrofolate
reductaseprimarily
inhibits DNA
synthesis and kills
cells in S phase.
Non-proliferating
cells are resistant to
methotrexate
Choriocarcinoma,
osteosarcoma, head
and neck tumors,
others psoriasis
and rheumatoid
arthritis
Megaloblastic anemia
and pancytopenia.
This can be prevented
by folinic acid.
Leukoencephalopathy
6-Mercaptopurine and
Azathioprine
Inhibit conversion
of IMP to ATP
and GTP
They are metabolized by

xanthene
oxidase which
is blocked by
allopurinol. So
dose should be
reduced in
concurrent use
Bone marrow
suppression most
common, jaundice,
hyperuricemia can
be reduced by
allopurinol
Other purine
analogues
Pentostatin
irreversible inhibitor
of adenosine
deaminase
Cladirabine
drug of choice
in hairy cell
leukemia,
Fludarabine
CLL,
Pentostatin
hairy cell leukemia
Immunosuppression
especially T cell
mediated immunity
5-fluorouracil
Inhibits thymidylate
synthetase and
blocks conversion
of deoxyuridylate
to deoxythymidylate
Solid tumors like

Ca breast, colon,
urinary bladder,
liver, stomach
Bone marrow
suppression (with
bolus infusion),
GI toxicity (with
continuous infusion).
Hand-foot syndrome,
stomatitis most
common
Cytarabine
(cytosine
arabinose)
Inhibits DNA
polymerase and
blocks cytidilic acid
Induction of
remission in
AML
Gemcitabine
Pancreatic Ca
Vinca Alkaloids
Mechanism of action: They inhibit mitosis by binding to
tubulin; cause metaphase arrest.
Drugs:
Vincristine
Indication ALL, side effects peripheral neuropathy,
alopecia.
Oncology
723
Vinblastine
Indication bladder Ca.
Taxanes
Indication bladder Ca.
Topoisomerase Inhibitors
Mechanism of action: Topoisomerase II inhibitor.
Side effects: Cardiomyopathy, bone marrow suppression.
Drugs:
Daunorubicin
Indication induction of remission in AML.
Side effects cardiomyopathy.
Doxorubicin (adriamycin)
Indication solid tumors like thyroid Ca,
leiomyosarcoma.
Side effects cardiomyopathy, retinal pigmentation.
Note: Mitroxantrone is a new doxorubicin analogue with
less cardiotoxicity.
Antibiotics
Drugs:
Bleomycin Side effects pulmonary fibrosis, nonischemic heart pain.
Mitomycin C Side effects renal failure with
microangiopathic anemia (HUS).
Actinomycin D Indication Wilms tumor,
rhabdomyosarcoma, methotrexate resistant
choriocarcinoma.
Others
Drugs:
L-asparaginase Side effects liver damage,
pancreatitis, CNS damage.
Cisplatin Side effects emesis (most potent emetic),
acute tubular necrosis most common toxicity (most
nephrotoxic chemotherapeutic agent), deafness,
peripheral neuropathy, least bone marrow suppression.
Response of tumors to chemotherapy:
a. Curable by chemotherapy 1. Acute leukemia - ALL and AML.
2. Lymphomas - Hodgkins and few non-Hodgkins
lymphomas.
724
3. Carcinomas i. Testicular Ca
ii. Gestational trophoblastic Ca (choriocarcinoma)
iii. Wilms tumor
iv. Neuroblastoma
4. Sarcomas i. Ewings sarcoma
ii. Rhabdomyosarcoma
iii. Osteosarcoma
b. Chemotherapy has significant activity in
1. Chronic leukemias
2. Hairy cell leukemia
3. Carcinomas i. Small cell Ca of lung
ii. Breast, bladder and anal canal Ca
c. Minor activity 1. Cervical Ca
2. Melanoma
Combination Therapy
Surgery + chemotherapy:
Neoadjuvant chemotherapy:
It refers to the administration of chemotherapy before
definite surgery.
Used in Ca breast, lung, esophagus and osteosarcoma.
Surgery followed by chemotherapy:
Used in Wilms tumor.
Chemoradiation: It is the treatment of choice for squamous
cell carcinoma of anal canal.
Hormone Therapy
Hormone responsive tumors are
1. Breast Ca
i. Estrogen diethylstilbestrol, estradiol.
ii. Antiestrogens tamoxifen.
iii. Progestins medroxyprogesterone acetate,
megestrol acetate.
iv. Aromatase inhibitor aminoglutethimide (medical
castration).
2. Endometrial carcinoma - progestins.
3. Prostatic carcinoma i. Antiandrogens - Flutamide.
ii. GnRH agonist - Leuprolide.
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725
4. Carcinoid tumors (metastatic)

Somatostatin analogue - Octreotide.
Biological Therapy
Interferons: Interferon is used in the treatment of CML,
hairy cell leukemia, AIDS associated Kaposis sarcoma,
high risk melanoma.
Interleukins: IL-2 is used in metastatic renal cell Ca and
melanoma.
Supportive Care
Pain relief:
WHO ladder - rational titration of oral analgesics.
i. Mild-to-moderate pain - oral NSAIDs.
ii. Pain persists and increases - opioid like codeine or
hydrocodeine is added to above therapy.
iii. Moderate to severe pain - oral morphine.
Nausea:
Acute emesis - within 24 hours of treatment.
i. Mild-to-moderate emetogenic agents-prochlorperazine
and dexamethasone.
ii. Highly emetic agents - ondansetron, ganisetron.
Delayed emesis 1 to 7 days after treatment.
Oral dexamethasone + metoclopramide.
Infection:
Infection is the most common cause of death in cancer
patients.
Sweets syndrome:
Also called febrile neutrophilic dermatitis.
Treatment is by high dose steroids.
Typhilitis (necrotizing colitis):
Almost always seen in neutropenic patients after
chemotherapy.
Treatment - broad spectrum antibiotic.
Infectons in granulocytopenic patients:
1. Staphylococcus epidermidis
2. Staphylococcus aureus
3. Streptococcus viridans
4. E. coli
5. Klebsiella
6. Pseudomonas
7. Candida albicans
726
Depression:
Most common psychiatric manifestation in cancer
patients is depression.
Treatment - Fluoxetine.
SCREENING FOR CANCER
Screening for cancer
Cancer
Method of screening
Breast Ca
Self-examination - best approach

Clinical examination by a care-giver
Mammography - best investigation
Papanicolaou smears
Fecal occult blood testing
Sigmoidoscopy
Barium enema X-ray
Colonoscopy
Chest X-ray and sputum cytology
Transvaginal ultrasonography
Adnexal palpation
Serum CA-125 determination
Digital rectal examination
Assays for serum PSA
Cervical Ca
Colorectal Ca
Lung cancer
Ovarian Ca
Prostatic Ca
TUMOR RELATED EMERGENCIES

Tumor Lysis Syndrome
Characterized by:
Hyperuricemia, hyperkalemia, hyperphosphatemia,
lactic acidosis and hypocalcemia.
It is caused by mass destruction of a large number
of neoplastic cells especially during treatment of
Burkitts lymphoma, ALL etc.
It often leads to acute renal failure.
Superior Vena Cava Syndrome
Cause:
1. Lung cancer - small cell Ca and squamous cell Ca
- most common cause.
2. Lymphoma.
3. Metastatic tumors to mediastinum, e.g. testicular and
breast Ca.
Oncology
727
Others
Structural:
1. Spinal cord compression
2. Pericardial effusion and tamponade
3. Intestinal or urinary obstruction
4. Increased ICT.
Metabolic:
1. Hypoglycemia
2. Hypercalcemia
3. SIADH
4. Lactic acidosis
5. Adrenal insufficiency.
SKIN TUMORS
VASCULAR MALFORMATIONS
Hemangioma
It is the most common congenital malformation
(hamartoma).
Most commonly seen in skin and subcutaneous tissues,
but may occur elsewhere in the body (liver, lung, brain,
etc.).
Capillary Hemangioma
Strawberry hemangioma: Child is normal at birth. A red
mark is noticed at 1-3 months after birth. It increases in
size from 3 months up to 1 year. After 1 year, it starts
to regress and complete involution occurs within 9 years.
Systemic associations:
i. Kasabach-Merritt syndrome - disseminated
intravascular coagulation, thrombocytopenia.
ii. Maffucis syndrome dyschondroplasia.
Cutaneous lesions
Lesion
Appearance
Disappearance
Strawberry hemangioma
Port wine stain
Salmon patch
Cavernous hemangioma
1-3 months
Birth
Birth
Birth
9 years
Persists for life
1 year
Persists for life
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Treatment: Masterly inactivity.

Port Wine Stain (Naevus flammens)
Present since birth and persists for life.
Site: most common on face and scalp.
Systemic associations: Sturge-Weber syndrome.
Treatment: Pulsed tunable dye laser (argon).
Cavernous Hemangioma
Present since birth with no tendency for spontaneous
involution.
Consists of multiple venous channels.
Site: face, cheek, ears, lips, tongue (others -liver, kidney
and brain).
Glomus Tumor
Benign tumors that differentiate towards modified smooth
muscle cells called glomus cells.
Origin: It arises from arterial portion of the glomus body
(Sucquet-Hoyer canal) which is an arteriovenous shunt in
the dermis that contributes to temperature regulation.
Site: Most commonly the subungual areas of fingers and
toes.
NAEVI
A naevus is a hamartoma of melanocytes.
Pathology
In normal skin melanocytes appear as clear cells in the
basal layer of the epidermis. They may increase in number
to form benign pigmented naevi (moles) which include:
i. Lentigo - within basal layer of epidermis.
ii. Junctional - localized aggregation projecting into the
dermis. They are most likely to turn malignant.
iii. Dermal - entirely within the dermis.
iv. Compound - features of both junctional and dermal
naevi present.
Oncology
729
Types
1. Congenital naevi: They are darkly pigmented with hairy
or papillary appearance. They may turn malignant even
during childhood.
2. Naevi appearing in childhood and adolescence: They
are very common, usually junctional or compound type
and may turn malignant.
3. Blue naevi: They are dermal naevi, most commonly
on face dorsum of hands and feet and over the sacrum
(Mongolian spot). Malignant change is rare.
4. Dysplastic naevi: They occur sporadically or in a familial
form (autosomal dominant). They occur in both sunexposed and non-exposed areas of skin. Familial form
has high risk of turning malignant (maximum risk).
PREMALIGNANT LESIONS
1. Actinic keratoses (also called senile or solar keratoses):
They are scaly lesions over the sun-exposed skin. They
predispose to squamous cell carcinoma.
2. Bowens disease: It is an intraepidermal squamous cell
carcinoma that is potentially malignant.
Risk factors - exposure to sun, arsenic poisoning.
Erythroplasia of Querat is a Bowens disease of the
glans penis seen in uncircumcised males.
3. Radiodermatitis.
4. Chronic scars - develop into Marjolins ulcer.
5. Sebaceous epidermal naevus.
6. Porokeratosis.
MALIGNANT LESIONS
Basal Cell Carcinoma (BCC)
BCC is the most common malignant skin tumor.
Source: It arises from the basal layer of epidermis.
Risk factors:
1. Exposure to ultraviolet rays.
2. Fair complexion.
3. Immunosuppression.
4. Ionising radiation.
5. Xeroderma pigmentosa.
6. Naevoid BCC syndrome.
7. Exposure to arsenic.
730
Site: More than 85 percent of these tumors occur in the

head and neck region. Most common site is the face, on
the cheeks. It is also called tear cancer.
Nature: BCC grows slowly, but become locally invasive
and penetrates deeper tissues - hence called rodent ulcer.
It rarely metastasizes.
Histology:
It arises from pluripotent epithelial cells of the epidermis
and hair follicles.
Basaloid cells form islands in which peripheral cells
are arranged in a palisaded fashion.
Clinical feature: It presents as pearly papules with superficial
dilated vessels and ulcerates later. Some tumor contains
melanin pigments.
Types:
i. Noduloulcerative (most common).
ii. Superficial (mimics eczema).
iii. Pigmented (may be mistaken for melanoma).
iv. Morpheaform (plaquelike lesion with telangiectasiawith keratosis is most aggressive).
v. Keratotic (basosquamous carcinoma).
Diagnosis: Incisional biopsy.
Treatment:
1. Surgical excision is the treatment of choice.
2. Electrodessication and curettage - most commonly used
method.
3. Radiotherapy - BCC is very radiosensitive.
4. Mohs micrographic surgery (chemosurgery) - for
morpheaform (fibrosing) BCC.
Squamous Cell Carcinoma (SCC)
SCC is less common than BCC but is more likely to
metastasize.
Risk factors:
SCC arises in areas with some premalignant lesions
listed above.
Risk factors are same as BCC.
Oncology
731
Others - burn scars, venous ulcers, Bazins uIcer,

Marjolins ulcer, lupus vulgaris, osteomyelitis sinus,
albinism, lichen planus, persistent heat injury (Khangri
cancer).
Histology:
SCC arises from the malphigian or squamous cell layer
of the skin.
Characteristically, malignant cells have whorled
arrangement forming keratin pearls or horn cells.
Clinical appearance: SCC presents as an ulcerative lesion
with induration and raised, everted edge.
Metastasis: Through lymphatics to regional lymph nodes
which become enlarged.
Treatment: Surgical excision, radiotherapy, Mohs
micrographic surgery.
Variants:
Marjolins ulcer: It is a well-differentiated SCC occurring
in chronic scars (most commonly burns) or ulcers (most
commonly chronic venous ulcer).
Features:
It grows slowly as the scar is relatively avascular.
It is painless as there are no nerves left in the scars.
No lymph node involvement as the lymphatics are
destroyed in a chronic scar.
Treatment:
Wide excision.
Radiotherapy should not be used.
Verrucous Carcinoma
It is a well-differentiated SCC.
Features:
Large, soft, wart like (papillomatous).
Invades locally but rarely metastasizes.
Commonly occurs on the palm and sole - carcinoma
ciniculatum.
Treatment: Wide excision.
Keratoacanthoma (Molluscum sebaceum)
It arises as a rapid proliferation of squamous epidermal
cells over 6-8 weeks after which it regresses spontaneously.
732
Malignant Melanoma
It is a malignant neoplasm arising from melanocytes in
the epidermis of skin (epidermal cells).
Other sites: Oral and anogenital mucosal surfaces, the
esophagus, the meninges, the eyes.
1. Exposure to sun rays.
2. Fair complexion, blonde hair, blue eyes.
3. Family history of melanoma.
4. Dysplastic naevus syndrome.
5. Giant congenital naevi.
6. Genetics - albinism, xeroderma pigmentation.
Site:
Most common sites
In females - lower legs.
In males - front or back of the trunk.
In Bantus - the sole of the foot.
Genetics:
Mutations of CKDN2A (p16) gene are found in 50
percent of melanoma patients.
Mutational loss of PTEN gene is also common.
Immunohistological marker for melanoma: S-100,
HMB-45.
Incidence: Incidence has increased over decades. There
is no overall sex predilection.
Histology: Radial growth phase - atypical proliferation of
intraepidermal melanocytes which precedes the
development of dermal invasion (vertical growth phase)
in all except nodular melanoma.
Types:
1. Superficial spreading: Most common; it occurs in any
part of the body.
2. Lentigo maligna: Least common and least malignant,
lentigo maligna (Hutchinsons melanotic freckle) is
precursor lesion, most common in elderly and in sunexposed areas (especially face).
3. Acral lentiginous: Most common form in darkly
pigmented people; occurs on palms and soles, mucosal
surfaces, in nail beds and mucocutaneous junctions;
similar to lentigo maligna melanoma but with more
aggressive biologic behavior, poor prognosis.
Oncology
733
4. Nodular: most malignant having invasive growth from

onset.
5. Amelanotic: worst prognosis.
Metastasis:
Via lymphatics to the regional lymph nodes; in-transit
nodules or satellite nodules may be present.
Through blood to liver (most common distant site),
lungs, brain (most commonly from melanoma of
choroids).
Staging:
It depends on the depth of invasion.
Breslows classification
i. Up to papillary dermis 0.75 mm.
ii. In reticular dermis 0.75-1.5 mm.
iii. Up to subcutaneous layer 1.5 mm.
Clarks layers
i. Restricted to epidermis and appendages.
ii. Invading papillary dermis without filling it.
iii. Filling papillary dermis and impinging on reticular
dermis.
iv. Invading reticular dermis.
v. Invading subcutaneous tissue.
Diagnosis: Any suspicious lesion should be biopsied. The
recommended technique is full-thickness excisional biopsy.
Treatment: Complete surgical excision with a margin of
minimum 1 cm to maximum 2 cm.
Course and prognosis:
Regression may occur in some thin melanomas.
The most important prognostic factor is depth of
invasion or the stage of the disease.
Women have better prognosis than men.
HEAD AND NECK TUMORS

ORAL AND OROPHARYNGEAL CANCER
Oral and oropharyngeal cancers are the most common
type of cancer in India. Most commonly they are squamous
cell carcinoma.
734
Premalignant Lesions
Definite risk of malignancy
1. Leucoplakia most common lesion.
2. Erythroplakia maximum risk.
3. Chronic hyperplastic candidiasis.
Increased incidence of malignancy
1. Oral submucosal fibrosis.
2. Syphilitic glossitis painless ulcer.
3. Sideropenic dysphagia.
Oral cancer is casual or causal
1. Oral lichen planus.
2. Discoid lupus erythematosis.
3. Dyskeratosis congenital
Leucoplakia
Leucoplakia is the most common premalignant lesion.
It refers to a whitish, well-differentiated mucosal patch
or plaque caused by epidermal thickening or
hyperkeratosis.
It is most commonly associated with the cancer of
floor of mouth.
Risk factors:
1. Smoking and tobacco chewing.
2. Alcohol intake.
3. Chronic friction.
Treatment: On stopping tobacco use 60 percent lesions
resolve spontaneously.
Surgical excision.
Erythroplakia
It appears as red, velvety plaque.
Histology: Parakeratosis with severe epithelial dysplasia.
Chance of malignancy: 17 times higher than that of
leucoplakia.
Chronic Hyperplastic Candidiasis
Feature: Dense chalky plaques of keratin which are
thicker and more opaque than leucoplakia.
Site: Most common sites are the oral commissures.
Oncology
735
Oral Submucosal Fibrosis

It is a progressive fibrosis deep to the mucosa of oral cavity
which causes trismus and ankyloglossia.
Etiology:
Hypersensitivity to chilly, betel nut and tobacco.
Vitamin deficiency.
Chance of malignancy: 30-33 percent.
Treatment:
Intralesional steroid injection.
Surgical - excision and grafting.
Carcinoma Cheek
Most commonly squamous cell Ca.
Site: Most commonly at the commissure or along the
occlusal plain to the retromolar area, the majority being
situated posteriorly.
Clinical feature: It may involve three nerves Hypoglossal nerve causing deviation of tongue to the
same side of lesion.
Spinal accessory nerve causing defective shrugging of
shoulder.
Cervical sympathetic chain causing Horners syndrome.
Eventually it causes fungation and bleeding from major
vessels - carotid blow out.
Metastasis: Ca of buccal mucosa metastasizes to
submandibular and upper deep cervical lymph nodes.
Treatment:
For early growth - radiotherapy using 192 iridium wires
(brachytherapy).
In case of mandibular involvement - wide excision of
the primary lesion plus hemimandibulectomy/ segmental
resection of mandible/marginal mandibulectomy.
In case of lymph node involvement - Same side - radical
neck dissection. Opposite site - functional block
dissection.
Reconstruction by using
Muscle flap - pectoralis major, trapezius and latissimus
dorsi.
736
Free tissue transfer based on microvascular techniques.

Mandible reconstruction by cortical bone graft or rib,
fibula or synthetic material.
Chemotherapy - Cis-platinum:
Radical neck dissection
Structures removed in
Radical neck dissection
Structures retained in
functional block dissection
1.
2.
3.
4.
5.
1. Internal jugular vein

2. Sternocleidomastoid muscle
3. Spinal accessory nerve
Cervical lymphatics
Internal jugular vein
Accessory nerve
Submandibular gland
Sternocleidomastoid muscle
Carcinoma of Tongue
Type:
Microscopic - most commonly squamous cell Ca.
Gross - ulcerative or ulceroproliferative.
Site: most commonly on the middle third of the lateral
margins.
Clinical feature:
The growth is exophytic with areas of ulceration.
Pain which radiates to neck and ears.
Difficulty in speech and swallowing.
Metastasis: To regional lymph nodes.
Treatment:
Principle:
< 1 cm surgery as primary therapy
Tumour
> 1 cm radiotherapy is primary
therapy, surgery for salvage
Surgery:
i. Wide excision for early growth < 1 cm, tumor at
the tip of tongue (primary therapy).
ii. Hemiglossectomy in growth> 1 cm (for salvage).
In case of mandible and lymph node involvement
surgery same as in Ca cheek.
Note: Wide excision or hemigolssectomy + hemimandibulectomy + radical neck dissection together is called
Commando operation.
Oncology
737
Radiotherapy:
Primary therapy for larger (> 1 cm) tumors.
For tumors located in the anterior 2/3rd of tongueinterstitial brachytherapy.
For tumors located in the posterior 1/3rd of tongueteletherapy.
Reconstruction:
< 1/3rd of resection - nothing.
1/3rd to 2/3rd resection - radial forearm flap.
> 2/3rd resection - pectoralis major flap.
Carcinoma of Lip
This is the most common type of oral cancer worldwide.
But in India, alveolobuccal Ca is most common.
Site: Most commonly the vermilion border of the lower
lip.
Feature: The tumor tends to spread laterally. Lymph node
involvement is a late feature.
Type: Squamous cell Ca.
Metastasis: First involves upper cervical lymph node
(submandibular and submental).
Treatment: Both surgery and radiotherapy are highly
effective.
For lesion < 2 cm surgical excision
is the primary therapy
Tumour
For lesion > 2 cm radiotherapy
is the primary therapy
Reconstruction:
Excision of lower lip up to 1/3rd can be sutured primarily
without causing microstomia.
Excision > 1/3rd of the lip requires reconstruction.
A full thickness loss of middle 1/3rd of upper lip is
best reconstructed by - Abbey flap and Estlanders flap
(basedon labial artery).
Prognosis: Best among oral cancers.
Note: Lymph node metastasis is least common in
carcinoma of hard palate.
738
Staging of Oral Cancers

Staging of oral cancers
Tumor
Node
Metastasis
T1tumor < 2 cm
N1single homolateral
node 3 cm
N2 single homolateral
node > 3 to 6 cm or
multiple homolateral
nodes < 6 cm
N3 homolateral
node > 6 cm or bilateral
or contralateral node
M0 no
metastasis
M1 distant
metastasis
T2tumor > 2 cm
T3tumor > 4 cm
SALIVARY GLAND NEOPLASM

Classification
a. Epithelial:
1. Adenoma
Pleomorphic adenoma - most common salivary
gland tumor.
Warthin s tumor (adenolymphoma) - second most
common.
2. Carcinoma
Mucoepidermoid Ca - most common malignancy
Adenoid cystic Ca - most aggressive.
b. Non-epithelial:
1. In children hemangioma, lymphangioma.
2. In adults neurofibroma, neurilemmoma.
Incidence
Most common sites for salivary neoplasm are the
parotids and most of them are benign.
Most common salivary gland tumor in children is
mucoepidermoid Ca.
Parotid Gland Tumors
Pleomorphic adenoma:
Overall most common tumor.
It is a mixed tumor arising from epithelium and
mesenchyma.
Benign in nature, but may turn to malignant.
Sometimes it involves only the deep lobes - dumbbell
tumor.
Oncology
739
Warthins tumor:
Occurs only in the parotid glands.
More common in males, in 6-7th decade.
More often bilateral (10%) or multicentric.
It is due to trapping of jugular lymph sacs in parotid
during developmental period.
It produces hot spot in 99mTc scan.
It does not undergo malignant change.
It can be enucleated without the danger of recurrence.
Mucoepidermoid Ca:
It is the most common malignant tumor of salivary
glands.
It is very low grade histologically, slowly progressive
and does not involve facial nerve.
Radical treatment often not needed.
Adenoid cystic Ca:
It is the most aggressive salivary gland tumor.
Characterized by relentless perineural spread along the
cranial nerves and into the brain.
Distant metastasis may occur to lungs producing
cannon ball shadow.
Diagnosis of parotid gland tumors:
CT and MRI scan - best method.
FNAC is also useful.
Management of parotid gland tumors:
Surgery:
1. Superficial parotidectomy for all benign tumors in
superficial lobe.
2. Total parotidectomy for all benign tumors in deep
lobe and dumb bell tumor.
Complication of surgery:
Freys syndrome:
It is due to injury to auriculo-temporal nerve wherein postganglionic parasympathetic fibres from otic ganglion
become united to sympathetic nerves from the superior
cervical ganglion.
Clinical features - flushing, sweating, pain and
hyperesthesia in the face whenever salivation is stimulated
(e.g. during mastication).
740
Radiotherapy:
Indication - Deep lobe tumors, microscopically positive
margin, malignant recurrence.
Submandibular Gland Tumors
Benign - pleomorphic adenoma is most common.
Treatment - excision of both superficial and deep lobes
of the gland.
MalignantTreatment - wide excision with removal of adjacent
muscles, soft tissues and mandible + postoperative
radiotherapy.
Complications of submandibular gland surgery: Three
cranial nerves are at risk during removal of the
submandibular glands namely 1. The mandibular branch of the facial nerve.
2. The lingual nerve.
3. The hypoglossal nerve.
Minor Salivary Glands
Most common site of minor salivary glands is the palate
(40%).
Most common tumor of minor salivary glands is
adenoid cystic carcinoma (malignant).
TUMORS OF THE LARYNX
Non-neoplastic
Vocal Nodule (singers nodule)
This is a fibrous thickening of the vocal cord due to epithelial
hyperplasia.
Site: Most common site is the junction of anterior 1/3rd
and posterior 2/3rd of the vocal cord.
Cause: speech abuse.
Clinical feature:
Increasing hoarseness is the main symptom.
Treatment:
Speech therapy - preferred method, most lesions resolve
spontaneously.
Oncology
741
Surgery - removal of nodule by micro-laryngeal

technique.
Vocal Cord Polyps
Usually unilateral at the same site as of vocal nodule.
Treatment: Microdissection and speech therapy.
Reinkes Edema (Bilateral Diffuse Polyposis)
Bilateral multiple polyps along the length of the vocal
cord.
Cause: Collection of edema fluid in the subepithelial
space of Reinke.
Treatment: Vocal cord stripping.
Contact Ulcer
Ulceration and granuloma formation over the vocal
processes of arytenoids.
Cause: Speech abuse.
Intubation Granuloma
Bilateral involving posterior thirds of the true cords.
Cause: Faulty intubation (most common cause of
laryngeal granuloma).
Treatment: Voice rest and endoscopic removal of the
granuloma.
Leucoplakia or Keratosis
Epithelial hyperplasia involving upper surface of one
or both cords.
It is a premalignant lesion.
Treatment
Stripping of the vocal cords.
Biopsy and radiotherapy in case of carcinoma in situ.
Laryngocele
It is an air-filled cystic swelling due to dilatation of
the ventricular saccule.
It is seen in glass blowers, trumpet players and weight
lifters.
742
An external laryngocele presents as a reducible swelling

in the neck which increases in size on coughing or
performing Valsalva maneuver.
Neoplastic Tumors
Benign: Squamous Papilloma
Juvenile squamous papilloma:
Multiple.
Viral (HPV) in origin.
Most commonly on the true and false cords and the
epiglottis.
Not premalignant.
Treatment - CO2 laser is the treatment of choice;
removal by direct laryngoscopy under GA.
Chance of recurrence after removal.
Adult squamous papilloma:
Single.
More common in male.
Site - anterior half of vocal cord or anterior commissure.
Premalignant.
Treatment - CO2 laser excision.
Malignant: Carcinoma of Larynx
Etiology:
1. Smoking and alcohol.
2. Leucoplakia or keratosis of larynx.
3. Adult papilloma.
4. Viral infection - herpes simplex virus.
5. Pachyderma larynx.
Epidemiology: More common in males between 40-70 years
of age.
Histology: Most commonly squamous cell Ca.
Types with features:
Features of laryngeal carcinoma
Supraglottic
Glottic
Incidence
Most common
in Indians
Most common
worldwide
Spread
Rich lymphatic Paucity of

supply favours lymphatics, so
Subglottic
Lymphatic
metastasis to
Contd...
Oncology
743
Contd...
Supraglottic
Glottic
early spread to metastasis

deep cervical
is late
nodes
Subglottic
prelaryngeal,
pretracheal,
paratracheal
and lower
jugular nodes
Site
Epiglottis
Most common
on the free
edge of vocal
cord in its
anterior and
middle third
Hoarseness
Late feature
Early feature
Late feature
Other
symptoms
Discomfort and
pain in neck,
difficulty in
breathing and
stridor
Stridor (most
common cause
of stridor in
adults)
Stridor,
hemoptysis
Diagnosis:
Direct laryngoscopy and biopsy - diagnostic.
CT scan is very useful to detect lymph node
involvement.
Management:
Radiotherapy:
For early supraglottic and glottic tumors in stage I and
II (mobile cord, no neck node).
Surgery:
CIS is best treated by transoral endoscopic CO2 laser.
Total laryngectomy is indicated in:
1. T3 lesions (with cord fixed).
2. All T4 lesions.
3. Invasion of thyroid or cricoid cartilage.
4. Bilateral arytenoid involvement.
5. Transglottic Ca.
Neck dissection - is indicated in T3 and T4 lesions
(stage III), in subgottic Ca.
Chemotherapy: Chemotherapy is indicated in advanced
(stage IV) cases.
Speech therapy:
Esophageal speech.
Artificial larynx.
Tracheoesophageal speech.
744
NEOPLASMS OF LUNG
BRONCHOGENIC CARCINOMA
Bronchogenic Ca is the leading cause of death worldwide.
Epidemiology
Male: female = 2:1 (incidence is increasing among
females).
Age of onset - most commonly between 55-65 years.
Risk factors:
1. Cigarette smoking - both active and passive.
There is dose-response relationship between the lung
cancer death rate and the total amount of smoking
(expressed in cigarette pack-years).
Smoking is most commonly associated with squamous
cell Ca and small cell Ca. It is least associated with
adenocarcinoma.
Combination of smoking and asbestos exposure greatly
increases the risk
2. Chronic exposure to asbestos.
3. Others - exposure to nickel, chromium, arsenic, coaltar.
Types
1. Small cell lung Ca (SCLC)/Oat cell Ca:
SCLC is the most malignant type.
Bloodstream metastasis occurs early, hence not
amenable to surgery.
Treatment is by chemotherapy with or without
radiotherapy.
It is the most radiosensitive of lung cancers.
It has the worst prognosis.
2. Non-small cell Ca: They have slow course and amenable
to surgery and/ or radiotherapy.
i. Squamous cell Ca (epidermoid Ca) It is the most common type in India. It has the best
prognosis.
ii. Adenocarcinoma including bronchoalveolar Ca Adenocarcinoma is the most common lung cancer
nowadays worldwide.
Oncology
745
It is also the most common type in non-smokers,

women and young patients (<45 years).
iii. Large cell Ca.
Pathology
Squamous cell Ca and SCLC usually present as central
masses with endobronchial growth.
Adenocarcinoma and large cell Ca present as peripheral
nodules or masses, frequently with pleural involvement.
Cavitation - common in epidermoid and large cell Ca.
Bronchoalveolar Ca arises from peripheral airways and
is characterized by their growth along pre-existing
structures and preservation of alveolar architecture.
Genetics
3p deletion is the most common abnormality found
in both SCLC and NSCLC.
p53 and RB gene mutations are common in SCLC.
p16/CDKN2A is commonly activated in NSCLC.
K-RAS oncogene mutations are seen in adenocarcinoma.
c-erbBl over expression is seen in 80 percent cases of
squamous cell Ca.
Clinical Features
Features due to regional spread in thorax:
Recurrent laryngeal nerve palsy - hoarseness.
Phrenic nerve palsy - elevation of hemidiaphragm and
dyspnea.
Cervical sympathetic chain involvement: Horners
syndrome.
Pancoast tumor (superior sulcus tumor): Usually
squamous cell Ca which extends to the apex of lung
with involvement of C8, T1, and T2 nerves causing
shoulder pain that characteristically radiates along the
distribution of ulnar nerve in arm often with radiological
destruction of the first and second ribs. These symptoms
along with Horners syndrome are together called
Pancoast syndrome.
Superior vena cava syndrome: Most commonly due
to SCLC.
746
Bronchoalveolar Ca can spread transbronchially and

produce respiratory insufficiency.
Extrathoracic metastasis:
Most commonly seen with SCLC.
Most common site of metastasis is liver.
Metastasis to the adrenal glands is common with
SCLC. Adenocarcinoma may metastasize to the
opposite lung.
Paraneoplastic syndrome: They may be the first
presenting feature or the first sign of recurrence.
Paraneoplastic syndromes of lung cancers
System
Manifestation
Cancer
Endocrine
Hypercalcemia
Squamous Ectopic PTH

cell Ca
or PTH related
protein
Do
Do
SCLC
Ectopic ADH
or ANP
SCLC
Do and ACTH
SCLC
SCLC
ACTH
Hypophosphatemia
Hyponatremia
(SIADH)
Hypokalemia
Hyperglycemia
Cushings syndrome
Skeletal
Clubbing
Hypertrophic
pulmonary
osteoarthropathy
Neurological
Myasthenia gravis
SCLC
Lambert Eaton
SCLC
syndrome
Retinal blindness
SCLC
Peripheral
neuropathy
foot drop
Subacute cerebellar
degeneration ataxia
Cortical degeneration
Polymyositis
Cutaneous
Dermatomyositis
Acanthosis nigricans
Hematological Migratory venous

thrombophlebitis
(Trousseaus sign)
Renal
Nephritic syndrome
or acute
glomerulonephritis
Cause
NSCLC
Adenocarcinoma
Adenocarcinoma
Oncology
747
Diagnosis
Biopsy:
Tissue biopsy by fiber optic bronchoscopy.
Node biopsy during mediastinoscopy.
CT guided FNAC - for thoracic and extrathoracic
tumors.
Chest X-ray: A solitary pulmonary nodule is indicative
of malignancy if doubling time is 2 weeks.
Management
NSCLC
Stages I and II: Pulmonary resection is the treatment
of choice.
Stage III: Radiotherapy.
Combined surgery + radiotherapy is indicated for
Pancoast tumor.
SCLC
Chemotherapy with or without radiotherapy is the
treatment of choice.
Chemotherapeutic agents used - most commonly
etoposide plus cisplatin.
Pulmonary resection:
First step during surgery is to ligate the pulmonary artery.
Contraindication - malignant pleural effusion.
Most serious complication - bronchopleural fistula.
BENIGN NEOPLASMS OF LUNG
Bronchial Adenomas
Bronchial carcinoid - most common.
Adenocystic tumors (cylindromas).
Mucoepidermoid tumor.
Bronchial Carcinoid
It arises from Kulchitsky cells (neuroendocrinal cells lining
the bronchial epithelium from which SCLC also arises).
K-cells are part of APUD system.
Clinical feature:
Often present as chronic cough, recurrent hemoptysis
(most common) and pulmonary infection.
748
Rarely metastasizes - least chance of producing

carcinoid syndrome.
Note: Blood stained sputum may be the only symptom
in bronchial adenoma.
Pathology: Usually central, slow-growing, endobronchial
growth.
Treatment: Surgical resection.
Hamartoma
Most common benign tumor of lung.
Pathognomonic radiological feature is popcorn
calcification.
Bronchial Cyst
Mostly medial mediastinal, usually multiloculated, quite
often infected.
NEOPLASMS OF PLEURA
Malignant Mesothelioma
It arises from the mesothelial cells in the parietal or visceral
pleura.
Nature: Mostly, but not always malignant.
Other sites: Peritoneum, pericardium.
Risk factors: Chronic exposure to asbestos. The disease
appears after 5-10 years of exposure. Once established,
the disease progresses even after cessation of exposure.
Pathology: It is preceded by pulmonary fibrosis and plaque
formation. May cause hemorrhagic pleural effusion.
Clinical features: Dyspnea which is out of proportion to
clinical signs in the lungs.
Diagnosis: sputum shows asbestos bodies.
X-ray chest shows ground glass appearance.
TUMORS OF LIVER AND

BILIARY TRACT
BENIGN LIVER TUMORS
Hemangioma
Most common benign tumor of the liver.
Usually found incidentally and requires no treatment.
Oncology
749
Hepatic Adenomas
Common in females in their third or fourth decade who
are taking OCP.
Pathology: It consists of cords or acini of hepatocytes
without bile ducts or portal tracts, and fibrous tissue septa
are sparse. It may be encapsulated. There is little or no
disturbance in liver function and alpha-fetoprotein
concentrations are normal. Malignant potential is there.
Treatment: Resection.
Focal Nodular Hyperplasia
Common in females.
Not associated with any underlying liver disease or OCP.
Pathology: The lesion is composed mainly of hepatocytes
and Kupffer cells. Typically it has a central stellate scar
with radiating septa containing arterial and venous channels
and bile ductules.
Diagnosis: Doppler ultrasound may show an arterial signal
within the tumor and biliary scintiscanning may show a
late hotspot in the tumor.
Nodular Regenerative Hyperplasia
Associated with underlying liver disease.
Portal hypertension is the most common manifestation.
CARCINOMA OF LIVER
Hepatocellular Carcinoma (HCC)
Epidemiology:
Prevalent in Asia and sub Saharan Africa due to high
prevalence of hepatitis B.
Four times more common in males.
It occurs in older age group (fifth to sixth decade).
Risk factors:
60-80 percent HCC arises in cirrhotic liver (particularly
macronodular form).
1. Chronic hepatitis B and C (most common cause
in India is hepatitis B infection).
2. Aflatoxin B1.
750
3. Other chronic liver diseases like - alcoholic liver

disease, 1 antitrypsin deficiency, hemochromatosis.
4. Exposure to thorium dioxide or vinyl chloride.
Clinical features:
Pain and mass in right upper quadrant of abdomen.
Jaundice is rare.
Diagnosis:
Increased serum levels of alpha-fetoprotein (> 500
g/L) in 30-40 percent cases.
Increased serum levels of alkaline phosphatase.
An abnormal prothrombin called des--carboxy
prothrombin.
Ultrasonography - best screening procedure; also the
first line investigation.
Metastasis: Vascular invasion into hepatic venous channels,
portal vein and IVC may occur.
Staging: Based on Childs classification.
Treatment:
Resection is only possible in about 10 percent of cases.
Liver transplantation for unresectable tumors.
Other Tumors
Fibrolamellar carcinoma:
It tends to occur in young adults without any underlying
cirrhosis.
Equal incidence among male and female.
Serum AFP level is not increased.
It has the best prognosis.
Hepatoblastoma:
Occurs in infancy.
Associated with high levels of AFP.
Angiosarcoma (Kupffer-cell sarcoma):
This is a highly malignant tumor and curative resection
is rarely possible.
Hepatic Metastases
Secondary metastatic tumors are more common than
primary tumors in liver.
Oncology
751
Source: GI tract (most common), lung, breast, melanoma.

Treatment: Chemotherapy is the treatment of choice
depending upon the source of primary.
CARCINOMA OF BILIARY TREE
Cholangiocarcinoma
It may arise in any part of the biliary tree from the small
intrahepatic bile ducts down to the lower end of the
common bile duct. Two clinical varieties occur in the liver1. A peripheral form, which consists of one single or
multiple nodules.
2. A hilar form, which is usually situated at the confluence
of the right and left hepatic duct (much commoner)known as Klatskin tumor.
Pathology:
It is an adenocarcinoma usually with a prominent fibrous
stroma (desmoplasia) - scirrhous type.
Risk factors:
1. Chronic infection with Clonorchis sinensis (liver fluke).
2. Thorium dioxide (Thorotrast).
3. Ulcerative colitis.
4. Sclerosing cholangitis.
5. Cystic diseases of the biliary tree such an congenital
hepatic fibrosis, polycystic disease of the liver, and
Carolis disease.
Unlike hepatocellular carcinoma neither long-standing
HBV or HCV infection nor cirrhosis seems to predispose
to cholangiocarcinoma.
Clinical feature:
The peak age is in the sixth and seventh decades.
In hilar type, there is obstruction of the bile duct and
patient presents with jaundice with collapsed gallbladder.
Diagnosis: Alpha-fetoprotein concentrations are usually
normal.
Carcinoma of the Gallbladder
Epidemiology:
Common in Asia.
752
1. Gallstones with chronic cholecystitis - present in 90
percent cases.
2. Chronic infection of gallbladder such as typhoid
carriers.
3. Gallbladder wall calcification - porcelain gallbladder.
4. Choledochal cyst.
5. Adenomatous polyp.
Pathology:
Most commonly adenocarcinoma.
Grossly, it appears very firm (scirrhous type).
Metastasis: It directly invades the mucosa and serosa and
spreads to the liver. Distant metastasis may occur via
lymphatics and veins.
Clinical feature: Liver secondaries may cause jaundice.
An extensive mass is found in the liver during investigation
of the jaundice.
Treatment: Wide resection with wedge resection of adjacent
liver.
Note: if a gallbladder carcinoma is found incidentally after
cholecystectomy, nothing more than regular follow-up is
needed.
Prognosis:
Those limited to mucosa - good.
Those with transmural involvement or with obstructive
jaundice - poor.
PANCREATIC TUMORS
Carcinoma of Pancreas
Risk factors:
2. Chronic pancreatitis.
Pathology:
Mostly duct cell adenocarcinoma.
Most common site is the head of the pancreas.
Clinical feature:
Painless jaundice - most common sign and symptom.
Epigastric discomfort.
Oncology
753
Weight loss.
Migratory thrombophlebitis - Trousseaus sign.
Investigation:
Spiral CT scan. If the CT shows:
i. Tumor is small (4 cm),
ii. Confined to the head,
iii. No evidence of distant spread or vascular invasion
- then the patient is considered for operative
interventions.
Treatment:
1. 95 percent cases - unsuitable for resection.
Palliative treatment- Choledochoduodenostomy and
gastrojejunostomy.
2. Resection - Pancreatoduodenectomy (Whipples
procedure).
Structures removed are:
i. Bile duct, structures of porta hepatis and lymphatics.
ii. Gallbladder (cholecystectomy).
iii. Fourth part of duodenum.
iv. Retroperitoneal lymph nodes.
Along with intraoperative radiotherapy.
3. Chemotherapy - Gemcitabine is the drug of choice.
ENDOCRINE TUMORS OF THE PANCREAS
Insulinoma
Insulinoma is the most common endocrine tumor of
the pancreas.
It may be associated with MEN I.
Nature: Most are small, benign, and hard to find, but 10
per cent are multifocal or malignant.
Source: It arises from pancreatic cells. It is distributed
equally in head, body and tail.
Clinical feature:
Whipples triad:
1. Fasting hypoglycemia (glucose < 2.8 mmol/l or <
50 mg/dl).
2. Symptoms of hypoglycemia, and
3. Relief after intravenous glucose.
Weight gain - due to over consumption.
754
Diagnosis:
Normal or elevated serum insulin levels in the presence
of fasting hypoglycemia are diagnostic (fasting
hypoglycemia: insulin ratio> 0.3).
Increased level of C-peptide (differentiates it from
factitious hyperinsulinemia).
Endoscopic USG.
Treatment:
Enucleation of the localized tumors.
Pancreatic resection or total pancreatectomy.
Gastrinoma (Zollinger-Ellison Syndrome)
Source: They arise from G cells of the pancreas (non-
non- cells).
Sites:
G cells in the duodenum (most common site).
Pancreatic head.
Distal small bowel, stomach, spleen, liver, lymph nodes
and ovary (mucinous cystadenoma).
Pathogenesis:
Gastrinomas secrete high levels of gastrin
hypersecretion of gastric acid consequent duodenal
and jejunal ulcer.
Gastrin secreted by gastrinomas is heptadecapeptide
gastrin (G-l7) whereas normal gastrin is G-34.
Other than gastrin, they secrete ACTH.
Clinical feature:
Peptic ulceration.
Watery diarrhea/steatorrhea.
Hypercalcemia hypokalemia.
Kidney stone.
Diagnosis:
1. Fasting gastrin assay - gastrin level> 1000 pg/ml is
almost definitive.
2. Detection of acid output by one of the following
methods
i. Calcium infusion test - in children.
ii. Provocative test by secretin injection - most sensitive
and specific.
iii. Pentagastrin test - increased ratio of basal acid output
to maximum acid output.
Oncology
755
3. Imaging study - somatostatin receptor scintigraphy is

the best.
Treatment:
Proton pump inhibitors e.g. omeprazole are the drug
of choice.
Surgery - chance of recurrence is high.
Glucagonoma
They arise from the cells in the pancreas.
Clinical feature:
Necrolytic migratory erythema - a characteristic red,
raised, scaly rash usually located on the face, abdomen,
perineum, and distal extremities.
Diabetes mellitus, diarrhea and weight loss.
Stomatitis.
Diagnosis: Glucagon levels >1000 pg/L not suppressed
by glucose are diagnostic.
VIPoma
Pancreatic islet tumors that produce vasoactive intestinal
polypeptide (VIP).
A syndrome of watery diarrhea (hence also called
pancreatic cholera), hypokalemia, achlorhydria (collectively
called WDHA syndrome), and renal failure.
Somatostatinoma
The classic triad of somatostatinoma is diabetes mellitus,
steatorrhea, and cholelithiasis.
Diagnosis:
Tolbutamide enhances somatostatin secretion by
somatostatinomas.
Principles of Management of Pancreatic
Endocrine Tumors
Investigation: Investigation of choice for pancreatic islet
cell tumors is nuclear scan (somatostatin receptor
scintigraphy or SRS) except for Insulinoma.
Treatment:
Tumor is surgically removed, if possible.
Octreotide inhibits hormone secretion in the majority
of cases. Interferon- may reduce symptoms.
756
Streptozotocin plus doxorubicin combination

chemotherapy may produce responses in 60-90 percent
of cases.
Embolisation of hepatic metastases may be palliative.
TUMORS OF THE GI TRACT

Esophageal Carcinoma
Types:
1. Squamous cell carcinoma - Involves the upper 2/3rd
(most commonly the middle 1/3rd) of esophagus - most
common.
2. Adenocarcinoma - Involves the lower 1/3rd.
Risk factors:
Chronic achlasia.
Plummer-Vinson syndrome (causes malignancy in postcricoid region).
Tylosis - Congenital hyperkeratosis and pitting of the
palms and soles.
Chronic gastroesophageal reflux - Barrettes esophagus
(replacement of the squamous epithelium by an
abnormal columnar, metaplastic epithelium) for
adenocarcinoma.
Clinical feature:
1. Sense of stickiness behind the sternum while taking
food - earliest symptom.
2. Dysphagia (to both liquid and solids) and weight loss.
3. Hypercalcemia - In squamous cell Ca.
Investigations:
1. Barium-swallow X-ray shows - Irregular filling defect
which in mid and lower third of esophagus produces
rat tail deformity.
2. Esophagoscopy and Biopsy - confirmatory.
3. Endoscopic USG - Best for staging.
Management:
1. Surgery - mainly for lower third carcinoma.
Subtotal esophagectomy (Ivor Lewis) -is the method
of choice.
Esophagogastric continuity is maintained by using left
colon (more commonly) or small intestine.
Complication - Anastomotic leakage.
Oncology
757
2. Radiotherapy - Curative. Mainly used for upper and

middle third carcinoma.
3. Chemotherapy - Not curative. Regimens always contain
cis-platinum.
TUMORS OF STOMACH
Gastric Polyp
Benign:
1. Metaplastic - most common type, associated with H.
pylori infection.
2. Inflammatory.
3. Fundic gland polyps - associated with NSAIDs and
familial polyposis.
With malignant potential: Adenomas.
Gastric Carcinoma
1. Chronic gastric ulcer.
2. H. pylori infection - adenocarcinoma and lymphoma.
3. Atrophic gastritis with/without pernicious anemia.
4. Intestinal metaplasia.
6. Prior gastric surgery - particularly Billroth II or Polya
gastrectomy.
7. Blood group A.
8. Diet.
Site:
Most common site is pre-pyloric region.
Proximal stomach in western countries.
Classification:
According to pathology:
1. Ulcerative - most common and most malignant.
Note: Features of malignant ulcer:
i. Eccentric
ii. Margins are heaped up and everted
iii. Mucosal rugae stop far off the ulcer
2. Proliferative or Cauliflower like (superficial spreading)
- best prognosis.
3. Linitis plastica.
4. Colloid or mucoid.
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Lauren classification:
1. Diffuse type Common in young adults
Develops throughout the stomach including cardia.
Infiltrates deeply into the walls of stomach - stomach
capacity is grossly decreased, also loss of
distensibility of stomach - Linitis plastica or leather
bottle appearance.
2. Intestinal type Common in antrum and lesser curvature of
stomach.
Frequently forms polyps or ulcers.
Microscopic types: Adenocarcinoma - most common
type.
According to stage:
1. Early gastric cancer - cancer limited to the mucosa
and submucosa with or without lymph node
involvement - curable.
2. Advanced - involves the musculature. Type III and
Type IV are incurable.
Spread:
1. Direct spread.
2. Lymphatic spread - involves supraclavicular nodes
(Trosiers sign).
3. Blood borne metastasis - first to liver.
4. Transplacental spread - to ovaries (Krukenbergs
tumors), to umbilicus (Sister Josephs nodule).
Symptoms:
1. Dyspepsia.
2. Pain - common first symptom.
3. Bleeding - iron deficiency anemia.
4. Obstruction - dysphagia, vomiting.
5. Para neoplastic syndromes- superficial vein
thrombophlebitis (Trousseaus sign) and DVT.
Investigations:
1. Stained Endoscopic biopsy - investigation of choice
for early gastric Ca.
2. Barium meal X-ray - irregular feeling defect.
Management:
Surgery:
1. Total gastrectomy - removal of whole of the stomach,
lesser curvature and greater omentum, lymph nodes,
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759
spleen and distant pancreas. Continuity by Roux-enY loop (esophagojejunostomy).

2. Subtotal gastrectomy - (65-80% of stomach) when the
tumors are situated distally.
3. Near-total gastrectomy (nearly 90% of stomach is
resected).
4. Palliative surgery - for patients suffering from symptoms
of either obstruction or bleeding - palliative resection
of growth.
Criteria for inoperability:
1. Fixation to surrounding structures.
2. Palpable metastasis in pelvis and the peritoneum with/
without ascites.
3. Multiple metastases to liver.
4. Distant hematogenous metastasis to lungs and bones.
5. Distal lymph node involvement (N4) - left
supraclavicular node.
Radiotherapy: for palliative treatment of painful bony
metastasis.
Gastric Stromal Tumors (Leiomyoma
and Leiomyosarcoma)
Stomach is the most common site for such tumors
in GI tract.
Frequently presents with bleeding - most common gastric
ca to bleed.
Gastric Lymphoma
Most common site in GI tract is stomach.
They are B-cell in origin and arise from MALT (mucosaassociated lymphoid tissue); associated with H. pylori
infection.
Associated with E-B virus infection.
Usually treated conservatively with chemotherapy.
TUMORS OF THE SMALL INTESTINE
Benign
Peutz-Jeghers syndrome:
1. Peutz-Jeghers polyp-hamartomatous polyp, affects
jejunum. They have malignant potential.
2. Melanosis of the oral mucous membrane and the lips.
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Malignant
Small Gut Adenocarcinoma
Site: Duodenum (at or near ampulla of Vater) is the most
common site for adenocarcinoma arising in GI tract.
Risk factors:
1. Peutz-Jeghers syndrome.
2. Celiac disease.
Treatment: Pancreatoduodenectomy (Whipples
procedure).
Lymphoma of the Small Bowel
Occurs most frequently in the ileum.
Immunoproliferative small-intestinal disease (IPSID): Bcell, non-Hodgkins lymphomas. It can present as intestinal
malabsorption. It involves extensive areas of the small
bowel so that surgical resection is often impossible. It tends
to occur proximally and is associated with the production
of monoclonal immunoglobulin heavy chains, which may
be detectable in the serum.
Enteropathy-associated T-cell lymphoma (EATCL): The
condition develops in patients with long-standing celiac
disease or dermatitis herpetiformis. They are high-grade
tumors unresponsive to chemotherapy.
TUMORS OF THE LARGE

INTESTINE
GASTROINTESTINAL POLYPS AND THE
POLYPOSIS SYNDROMES
Benign
Hyperplastic Polyps
Incidentally found polyps are asymptomatic and they have
no malignant potential.
Large hyperplastic polyps are frequently found on the
right side of the colon and are associated with the
development of carcinoma.
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761
Multiple hyperplastic polyps (hyperplastic polyposis) are

strongly associated with a family history of colorectal cancer.
Hamartomatous Polyps
Hamartomatous polyps are traditionally considered nonmalignant.
Peutz-Jeghers syndrome:
It is an autosomal dominant disease characterized by
hamartomatous polyps throughout the gastrointestinal
tract, particularly in the jejunum, with mucocutaneous
pigmentation of the buccal mucosa, perioral region and
digits.
Pathology: They contain frond-like epithelium with cystic
dilatation of glands overlying a network of characteristic
fibromuscular bundles.
Patients with the Peutz-Jeghers syndrome are at a very
high risk for both gastrointestinal and non-gastrointestinal
cancers.
Juvenile Intestinal Polyposis
It is an autosomal dominantly inherited hamartomatous
polyposis syndrome.
Juvenile polyps are pedunculated hamartomas, prone
to surface ulceration, which can cause bleeding.
May be associated with mutation in the PTEN tumorsuppressor gene.
Association:
Cowden disease or Bannayan-Zonana syndrome: In
both of which hamartomas in multiple tissues and
macrocephaly occur.
Gorlin syndrome: An autosomal dominant disease
primarily characterized by basal-cell carcinomas of the
skin and odontogenic keratocysts in the mouth.
Risk of malignancy:
Solitary juvenile polyps do not predispose to malignancy
in children but Juvenile intestinal polyposis predisposes to
adenomatous transformation and an increased risk of
colorectal cancer and cancers elsewhere in the
gastrointestinal tract.
762
Neoplastic Polyps (Adenomas)

Tubular Adenomas
They are pedunculated or sessile; usually asymptomatic.
Overall risk of malignant degeneration correlates with
size (< 2% if <1.5 cm diameter; >10% if >2.5 cm
diameter) and is higher in sessile polyps.
65 percent polyps are found in rectosigmoid colon.
Treatment by endoscopic resection.
Villous Adenoma
Often sessile; high risk of malignancy (up to 30% when
>2 cm).
They are more prevalent in left colon.
Occasionally associated with potassium-rich secretory
diarrhea.
Treatment by endoscopic resection.
Familial Adenomatous Polyposis
Diffuse pancolonic adenomatous polyposis.
Autosomal dominant inheritance associated with
deletion in adenomatous polyposis coli (APC) gene on
chromosome 5.
Colon carcinoma from malignant degeneration of polyp
occurs in 100 percent by age 40 years.
Diagnosis: Screening by flexible sigmoidoscopy with biopsy
of polyps for histological diagnosis.
Treatment:
Prophylactic total colectomy or subtotal colectomy with
ileoproctostomy before age 30 years.
Sulindac and other NSAIDs cause regression of polyps
and inhibit their development.
Gardner syndrome:
Variant of FPC with associated soft tissue tumors
(epidermoid cysts, osteomas of the mandible and skull,
dental abnormalities, sebaceous cysts, lipomas,
fibromas, desmoids).
Higher incidence of gastroduodenal polyps, ampullary
adenocarcinoma.
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763
Turcots syndrome:
It is a rare variant of FPC with associated malignant
brain tumors.
50 percent have germ line APC (adenomatous
polyposis coli) mutations and develop cerebellar
medulloblastoma.
50 percent have germ line mutations in their DNA
mismatch repair genes (HNPCC) and develop
glioblastoma multiforme.
Nonpolyposis Syndrome
Familial syndrome with up to 50 percent risk of colon
carcinoma.
Peak incidence in fifth decade.
Associated with multiple primary cancers (esp.
endometrial).
Autosomal dominant; due to defective DNA mismatch
repair (HNPCC gene).
MALIGNANT TUMORS OF THE COLON
Adenocarcinoma of Colon
Etiology and risk factors:
2. Implantation of the ureters into the sigmoid colon
(ureterosigmoidostomy).
3. Ulcerative colitis of over 20 years duration (and
probably also Crohns colitis).
4. Ileorectal anastomosis.
5. Hereditary non-polyposis colon cancer (Lynch
syndromes type 1 and 2) due to germ line mutation
in the DNA mismatch repair gene HNPCC.
Dukes classification:
A - Confined to bowel wall.
B - Through the bowel wall but not involving the free
peritoneal space.
C - Lymph nodes involved.
D - Advanced local disease or liver metastasis.
Clinical feature:
Age> 50 years.
Colonic bleeding.
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20 percent cases presents as emergency with intestinal

obstruction or peritonitis.
Left colon i. Increasing intestinal obstruction - main symptom.
ii. Alteration of bowel habit.
Caecum - Anemia which is severe and unyielding to
treatment.
Sigmoid colon - Pain and tenesmus.
On X-ray: Apple core appearance.
Spread: Rectosigmoid tumors may spread to lungs early
because of systemic paravertebral venous drainage of this
area.
Diagnosis:
Screening asymptomatic persons with fecal occult blood
testing. Flexible sigmoidoscopy.
Air-contrast barium enema.
Colonoscopy is most sensitive and specific.
Carcinoembryonic antigen (CEA) levels are of some
value in postoperative management and in the detection
of tumor recurrence.
Operations:
Secondaries in liver is not a contraindication to resection
as the best palliative treatment is removal of the tumor.
Caecal carcinomas are treated by right hemicolectomy;
Ascending and transverse colon tumors by extended
right hemicolectomy;
Left hemicolectomy for descending colon cancer and
Sigmoid colectomy for sigmoid tumors.
Prognosis: Degree of invasiveness at surgery (Dukes
classification) is the single best predictor of prognosis.
Other predictors of poor prognosis are Preoperative serum carcinoembryonic antigen (CEA)
>5 ng/mL (>5 g/L),
Poorly differentiated histology,
Bowel perforation,
Venous invasion,
Adherence to adjacent organs,
Aneuploidy,
Specific deletions in chromosomes 5, 17, 18, and
Mutation of ras protooncogene.
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765
Tumors of Rectum and Anal Canal

Rectal Carcinoma
Rectum is the most common site of malignancy in large
gut.
Type:
Adenocarcinoma is the most common type.
The more malignant varieties frequently contain large
numbers of mucin-producing cells.
Clinical feature:
1. Bleeding - most common.
2. Sense of incomplete evacuation.
3. Alteration of bowel habit.
4. Pain.
Treatment
1. Anterior resection - For carcinoma in upper 2/3rd of
rectum, followed by end-to-end anastomosis.
Principle- sphincter saving operation.
Structures removed are i. Radical excision of neoplasm with at least 2 cm
margin of normal bowel below the lower edge.
ii. Total mesorectal excision.
iii. High proximal ligation of the inferior mesenteric
lymphovascular pedicle.
2. Abdominoperineal excision -For carcinoma in lower
1/3rd of rectum, followed by permanent colostomy.
Carcinoma of Anal Canal
Type: Squamous cell carcinoma.
Treatment:
1. Chemoradiation - a combination of chemotherapy
(5-FU and mitomycin) and radiation (Nigro regimen)
preferred method.
2. Surgery - abdominoperineal excision with permanent
colostomy for large tumors (>3 cm).
ENDOCRINE TUMORS OF THE GI TRACT
APUD Cells
APUD = Amine precursor uptake and decarboxylation.
APUD cells secrete monoamine neurotransmitters like
serotonin, histamine and dopamine.
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Distribution:
APUD cells
Origin
Tumor
GI tract (enterochromaffin cells)

Pancreas
CNS (glial cells and neuroblast)
Thyroid (C cells)
Skin (melanocytes)
Adrenal medulla
Lungs (neuroendocrine cells)
Carcinoid tumor
Islet cell carcinoma
Glial cell tumors
Medullary carcinoma
Melanoma
Pheochromocytoma
Carcinoid tumor, SCLC
Carcinoid Tumors
These are the most common endocrine tumors of the GI
tract.
GI tract is the overall most common site for carcinoid
tumors; but the single most common site is bronchus.
Site: Ileum> rectum> appendix.
Source: They arise from the enterochromaffin cells or
Kulchitsky cells found in the crypts of Liberkhn.
Character:
Fore gut carcinoids - produce low levels of serotonin.
Mid gut carcinoids - produce high levels of serotonin
most commonly produce carcinoid syndrome.
Hind gut carcinoids - rarely produce serotonin, but
produce somatostatin and peptide YY.
Carcinoid Tumor of the Appendix
Appendix is the single most common site of carcinoid
tumor in the GI tract.
Carcinoid tumors arise in Argentaffin cells.
Site: most commonly the distal third.
Pathology: On transection, carcinoid tumors appear as
solid, yellow-tan due to lipochrome deposition.
Feature: Appendicular carcinoids have the lowest chance
of distant metastasis in the GI tract and rarely produce
carcinoid syndrome.
Note: Least malignant carcinoid tumor is of bronchus.
Treatment:
i. Appendicectomy if the tumor size is < 2 cm.
ii. Right hemicolectomy when tumor size is > 2 cm,
caecal wall is involved or lymph nodes are involved.
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767
Carcinoid Syndrome
About 5 percent of patients with carcinoid tumors develop
symptoms of the carcinoid syndrome. Carcinoid tumors
of the small bowel and pancreas have a more malignant
course than tumors of other sites. In the GI tract,
appendicular carcinoid is least likely to metastasize.
For tumors of GI tract origin, symptoms imply
metastases to liver.
Carcinoid tumors
Location
Pancreas
Bronchus
Small gut
Appendix
Rectum
Incidence of
metastasis
Incidence of
carcinoid
syndrome
71.9
(most common)
27.9% of total
(most common)
16.7%
4.8%
5.7
58.4
38.8
3.9
(least common)
13
9
< 1
Nil
Mediators: Serotonin (most common), kinins,

prostaglandins, histamine and indoles. They are produced
by enterochromaffin cells.
Clinical feature:
The classic triad of cutaneous flushing (most common
symptom), diarrhea, and valvular heart disease.
Heart disease in carcinoid syndrome - commonly
involves the right heart and cause tricuspid regurgitation
(most common) or pulmonary stenosis.
Others - telangiectasia, wheezing, paroxysmal
hypotension, pellagra like dermatitis.
Diagnosis:
Production of more than 15 mg/day of the serotonin
metabolite, 5-hydroxyindoleacetic acid (5HIAA) in the
urine.
Octreotide scintigraphy identifies sites of primary and
metastatic tumor in about 2/3rd of cases.
Treatment:
Symptoms may be controlled with histamine blockers
and octreotide.
768
Hepatic artery embolization and chemotherapy have

been used for metastatic disease.
GENITOURINARY TUMORS
CANCER OF THE URINARY BLADDER
Classification:
Transitional cell carcinoma - most common type.
Adenocarcinoma - arises from urechal remnant or in
extrophy bladder or from glandular metaplasia.
Squamous cell carcinoma - arises from long standing
bladder stone or schistosomiasis infection.
Risk factors:
1. Chemical carcinogens - most commonly aniline dyes.
It is related to several occupations like textile, dye,
petrol, painting, leather workers.
3. Chronic cyclophosphamide exposure.
4. Bladder calculus - commonly squamous cell carcinoma.
5. Schistosoma hematobium infection - most commonly
squamous cell carcinoma.
6. Therapeutic pelvic irradiation in women.
Transitional Cell Carcinoma
Classification:
Carcinoma in situ - occurs in association with a new
tumor (concomitant CIS) or in patients with previous
disease (secondary CIS).
Superficial tumors Non-muscle invasive tumor without involving lamina
propria (pTa) - most common type with excellent
prognosis.
Non-muscle invasive tumor with involvement of lamina
propria (pTl)
Muscle invasive tumors (pT2)
The most common histological type is a low grade
papillary tumor that grows on a central stalk.
Sites:
Most common site for superficial tumors is the lateral
wall of the bladder.
Next common site is the trigone.
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769
Clinical feature:
Median age is 65 years. More common in males.
Painless hematuria - most common and earliest
symptom.
Features of cystitis with suprapubic pain, frequency of
urine, dysuria - more common with CIS.
Metastasis:
Via lymphatics - to the pelvic nodes.
Via blood - to lungs (most common distant site), liver
and bones.
Distant metastasis is more common with squamous
cell type.
Recurrence:
Superficial tumors tend to recur after treatment.
Chance of recurrence is high in cases of - high grade
tumor, concomitant CIS, multiple primaries.
Diagnosis:
Intravenous urogram - first investigation in case of
hematuria. Bladder Ca appears as a filling defect.
Ultrasonography.
Cystourethroscopy - mainstay of diagnosis.
Treatment:
CIS - surgery (transurethral resection of tumor or TURT).
pTa - transurethral resection with a single instillation
of an intravesical agent.
pTl- TURT followed by multiple intravesical therapy.
Note: Intravesical instillation of bacille Calmette-Guerin
(BCG) reduces the risk of recurrence by 40-45 percent.
Recurrence is monitored every 3 months.
Muscle-invasive disease - radical cystectomy + urinary
diversion external beam radiotherapy.
Metastatic disease is treated with combination
chemotherapy, either CMV (cyclophosphamide,
methotrexate, and vinblastine) or M-VAC
(methotrexate, vinblastine, doxorubicin, cisplatin).
Note: Complications of ureterosigmoidostomy:
i. Hyperchloremic acidosis,
ii. Hypokalemia,
iii. Hypercalcemia,
iv. Uremia.
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Prognosis: Histological grade influences survival. Lesion

recurrence is influenced by size, number, and growth pattern
of the primary tumor.
PROSTATE
Benign Prostatic Hyperplasia
Pathology:
BHP arises from the periurethral transition zone. It
typically affects the submucous glands of transition
zone.
Involvement of peripheral zone produces a lateral lobe;
involvement of central zone produces a middle lobe.
Effects:
Urethra - the prostatic urethra is elongated but not
narrowed anatomically.
Bladder - muscular hypertrophy, trabeculations,
sacculations and diverticula formation.
Veins - compression of prostatic venous plexus causes
congestion, called the vesical piles leading to
hematuria.
Clinical features:
Lower urinary tract symptoms (LUTS) or prostatism.
Lower urinary tract symptoms
Obstructive
Irritative
Hesitancy
Poor flow
Intermittent stream
Dribbling
Sensation of poor bladder emptying
Episodes of near retention
Frequency earliest symptom

Nocturia
Urgency
Urge incontinence
Enuresis
Investigation:
Digital rectal examination.
Serum PSA (prostate specific antigen) level.
Transrectal ultrasound scanning (TRUS) - indicated if
serum PSA > 4 nmol/lit.
Uroflowmetry.
Management:
Medical: hormone that mediates prostate enlargement
is dihydrotestosterone which is formed within the
prostate from serum testosterone.
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771
i. Finasteride - a competitive 5- reductase inhibitor

that converts testosterone to dihydrotestosterone.
ii. 1 blockers - terazosin/prazosin relaxes smooth muscle
of bladder neck (drug of choice in cardiac patients).
Surgery: Prostatectomy.
Types of surgery:
1. Transurethral resection of prostate (TURP) - most
commonly employed method.
Complications - water intoxication leading to CCF,
hyponatremia, hemolysis, confusion.
Prevention - use of isotonic glycerin for performing the
resection and isotonic saline for postoperative irrigation
may prevent the development of complications.
Management - water restriction.
2. Freyers suprapubic transvesical prostatectomy.
3. Millins retropubic prostatectomy.
4. Youngs perineal prostatectomy.
Note: Prostatectomy for BHP does not confer
protection against prostatic carcinoma.
Transurethral microwave thermotherapy (TUMT): May
be comparably effective to TURP.
Prostatic Carcinoma
Pathology:
Most commonly adenocarcinoma.
Most commonly arises from peripheral zone, i.e. in
posterior lobe.
Biologic behavior is affected by histological grade
(Gleason score).
Gleason grades: The dominant and secondary
glandular histologic patterns are scored from 1 (well
differentiated) to 5 (undifferentiated) and summed to
give total score of 2-10 for each tumor.
Clinical feature:
Commonly asymptomatic.
Most patients present with advanced or metastatic
disease at the time of diagnosis.
Symptom - dysuria, difficulty in voiding, urinary
frequency, complete urinary retention, pelvic pain or
bone pain, hematuria.
Metastasis:
Direct extension - upwards to seminal vesicles and
bladder floor.
772
Lymphatic spread - to obturator node, then to internal

iliac nodes. Others - common iliac, presacral and paraaortic nodes.
Hematogenous spread - most common cause of bone
metastasis. Bony metastases are very unlikely unless
the PSA exceeds 20 ng/ml (Pelvic bones> lumbar
vertebrae> thoracic vertebrae> ribs).
It produces both osteoblastic and osteolytic lesions.
Note: Vertebral involvement is due to the presence of
valveless communication with Batsons periprostatic
venous plexus.
Investigation:
Tumor markers
i. Acid phosphatase.
ii. Prostate specific antigen> 10 ng/ml is suggestive and>
35 ng/ml is diagnostic. But PSA is non-specific, as
it is also increased in BHP, prostatitis and prostatic
infarction.
Digital rectal examination.
TRUS - most accurate method for staging of local
disease. It is used in screening programme. It is most
useful for taking guided biopsy.
Biopsy - indication for biopsy is a PSA exceeding 4
ng/ml.
Bone scan - indicated when PSA > 20 ng/ml.
Management:
Early disease (T1 and T2):
Radical prostatectomy with pelvic node dissection in
patients < 65 years.
Radical radiotherapy.
In patients> 70 years - conservative management.
Advanced disease:
1. Androgen deprivation by means of:
i. Bilateral orchidectomy (total or subcapsular) and
adrenalectomy.
ii. Inhibition of pituitary gonadotropin and/or ACTH
production by estrogen, progesterone,
hypophysectomy, LHRH analogues (leuprolide or
buserelin).
iii. Inhibition of androgen synthesis by the testis and
adrenals (medical castration) by aminoglutethimide.
iv. Inhibition of binding of androgen to its receptor
protein by cyproterone, flutamide, bicalutamide.
Oncology
773
2. Chemotherapy - for hormone-unresponsive disease

and used for palliation.
TESTIS
Testicular Tumor
Testicular tumors are primarily germ cell tumors (GCT)
arising from primordial germ cells.
Classification:
1. Seminoma (50%) - most common between ages
35-45 years.
2. Non-seminoma (50%) - they include:
i. Embryonal cell Ca
Occurs in young
ii. Teratoma
adults (20-30 years)
iii. Choriocarcinoma
iv. Endodermal sinus (yolk sac) tumor - most common
in children < 3 years (infantile embryonal carcinoma)
Note: Lymphoma is most common in men over age 60
years.
Risk factors:
1. Cryptorchidism (incidence 1-5%) - orchidopexy before
puberty does not reduce the chance of GCT.
2. Other abnormalities in urogenital development, such
as testicular atrophy or intersex states.
3. Testicular feminization syndromes.
4. Klinefelters syndrome is associated with mediastinal
germ cell tumor.
Etiology: Disease is associated with a characteristic
cytogenetic defect, isochromosome 12p.
Clinical feature:
Painless testicular mass is the classic initial sign.
Other symptoms include testicular discomfort, clotted
hydrocele (in 10% cases).
Spread:
Seminomas tend to spread via lymphatics to paraaortic lymph nodes. It tends to spread in a contiguous
manner.
Blood-borne metastasis to lung and other viscera are
rare.
Non-seminomas tend to metastasize early to
retroperitoneal lymph nodes and lungs.
774
Histology: Seminomas are similar to dysgerminomas of

ovary. They are monomorphic (i.e. tumor with one
histological pattern).
Diagnosis:
Ultrasound of the scrotum - is very accurate in
determining whether any mass is intratesticular
(probably malignant) or extra-testicular (probably
benign).
Serum markers - -fetoprotein, -human chorionic
gonadotrophin, and lactate dehydrogenase. hCG may
be elevated in either seminoma or non-seminoma, but
AFP is elevated only in non-seminoma.
Excision biopsy.
CT scan and MRI - most useful to detect abdominal
and intrathoracic secondaries.
Staging:
Stage I: Disease is limited to the testis, epididymis, or
spermatic cord.
Stage II: Involves retroperitoneal nodes.
Stage III: Disease outside the retroperitoneum.
Stage IV: Pulmonary or hepatic metastasis.
Treatment:
For stages I and II seminoma, inguinal orchidectomy
followed by retroperitoneal radiation therapy to 25003000 cGy is effective.
For stages I and II non-seminoma germ cell tumors,
inguinal orchidectomy followed by retroperitoneal lymph
node dissection is effective.
For patients of either histology with bulky nodes or
stage III disease, chemotherapy is given. Cisplatin,
etoposide and bleomycin given every 21 day for four
cycles is the standard therapy.
Extragonadal Germ-cell Tumors
Sites:
The mediastinum - most common extragonadal site.
Retroperitoneum.
Pineal gland.
Treatment: Good response to chemotherapy.
SOFT TISSUE SARCOMAS

Site:
Lower extremities - most common site.
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775
Retroperitoneum.
Head and neck.
Features:
They are very aggressive and rapidly spreading.
They are not radiosensitive.
They spread via hematogenous route, most commonly
to the lungs.
Risk factors:
1. Previous irradiation.
2. Immunosuppression (congenital or acquired).
3. Exposure to chemical carcinogens such as polycyclic
hydrocarbons, asbestos, and dioxin.
4. Kaposis sarcoma is associated with human herpes virus
8 infection.
5. Germ line mutations in the p53 gene (Li-Fraumeni
syndrome), are at increased risk for these and other
malignancies. Those who have survived congenital
retinoblastoma (germ line mutations in the Rb gene)
are at risk of developing osteosarcomas.
Spread:
Hematogenous route is most common and most
common site of metastasis is the lungs.
Some sarcomas may spread via lymphatic route. They
are:
i. Rhabdomyosarcoma,
ii. Angiosarcoma,
iii. Clear cell sarcoma,
iv. Epithelial sarcoma,
v. Fibrosarcoma,
vi. Malignant fibrous histiocytoma,
vii. Synovial sarcoma.
Clinical feature: A common presentation is with an
asymptomatic mass. Local symptoms may be related to
pressure, traction, or entrapment of nerves.
Treatment: Radical excision with documented histologically
negative margins is the treatment of choice.
Prognosis:
Most important prognostic factors are the histologic
grade (synonymous with stage) and size of the tumor.
Sarcomas in lower extremities have the worst prognosis.
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Liposarcoma:
Most common soft tissue sarcoma.
Most common site is retroperitoneum.
Fibrosarcoma: They arise from fibroblasts.
Fibrohistiocytic tumors:
Fibrous histiocytoma - benign in nature; contains
numerous blood vessels and hemosiderin deposition
- sclerosing hemangioma.
Dermatofibrosarcoma protuberans - intermediate grade;
characterized by fibroblastic cells arrayed in a storiform
pattern.
Malignant fibrous histiocytoma.
Rhabdomyosarcoma:
Most common childhood sarcoma.
They arise from striated muscles.
In children most common type is embryonal (overall
most common type is pleomorphic).
Most common site is head and neck region.
CHILDHOOD MALIGNANCY
Classification
Benign:
Hemangiomas are the most common tumors (overall)
in infancy.
Astrocytomas are most common solid benign tumors
- overall most common solid tumor.
Malignant:
Leukemias (especially acute lymphoblastic leukemia)
are the most common malignant neoplasm in
childhood.
Embryonal malignancies 1. Neuroblastoma - most common solid tumor
(malignant).
2. Retinoblastoma - most common ocular tumor.
3. Wilms tumor.
4. Ewings sarcoma.
5. Medulloblastoma - most common malignant brain
tumor.
Rhabdomyosarcoma - most common childhood
sarcoma.
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777
Neuroblastoma
Age: They usually appear before 5 years of age (most
commonly 2 years).
Origin: They arise from primitive neuroblast (neural crest
origin).
Site:
1. Abdominal (most common) - adrenals (most common);
paravertebral sympathetic ganglia.
2. Posterior mediastinum.
3. Cervical area.
Inheritance: Some cases are inherited as autosomal
dominant trait.
Clinical feature:
Abdominal mass is the most common presentation
(it is the most common cause of abdominal mass in
children).
Others - weight loss, failure to thrive, hepatomegaly
(but no splenomegaly).
Increased catecholamine production from adrenals
causes mild hypertension (less frequent than
pheochromocytoma), flushing, sweating, irritability,
tachycardia and headaches.
Increased production of VIP causes watery diarrhea
and hypokalemia.
Due to bone metastasis fever, bone pain, orbital
proptosis.
Unusual presentations - acute cerebellar ataxia
characterized by opsomyoclonus and chaotic nystagmus (dancing eye syndrome); paraplegia (dumb-bell
tumor).
Metastasis: Distant spread occurs very early, through blood
stream mainly to bones of orbit (most common cause of
orbital metastasis), skull, ribs and long bones.
Diagnosis:
X-ray shows stippled calcification.
Increased urinary levels of catecholamines and their
metabolites VMA and HVA.
Bone scan shows lytic bone lesions in skull, ribs and
long bones.
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CT scan, MRI, MIBG scan.

Biopsy is confirmatory. Histology shows Homer-Wright
pseudorosettes.
Note: Horner-Wright rosettes are seen in medulloblastoma.
Staging:
Evans staging.
Special stage IVs - disease similar to stage I and II
with distant metastasis to liver/skin or bone marrow
but without radiographic evidence of bony metastasis.
Treatment:
Surgery - is the mainstay of treatment for localized
disease (stage I and II).
Second look surgery after chemotherapy for disease
confined to one side of midline. Chemo/radiotherapy
- for advanced disease.
Overall cure rate is 30-35 percent.
Prognosis:
Prognosis depends on Stage - I, II and IVs have excellent
prognosis.
Good prognostic factors:
i. Age < 1 year.
ii. Hypoploidy, triploidy.
iii. Opsoclonus.
iv. VIP production.
v. Trk A gene expression.
Bad prognostic factors:
i. Age > 1 year.
ii. Diploidy.
iii. Deletion of chromosome 1p.
iv. Amplification of N-MYC gene.
Retinoblastoma
Retinoblastomas are the most common ocular tumor in
childhood.
Origin: From the outer nuclear layer of retina.
Inheritance: It occurs in two forms
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Retinoblastoma
Characteristic
Hereditary
Sporadic
Origin
Laterality
Median age
Inheritance
Multifocal
Usually bilateral
14 months
Autosomal dominant with
complete penetrance
Osteosarcoma, soft
tissue sarcoma
Unifocal
Always unilateral
23 months
Other tumors
Chromosomal defect involved is mutation (usually

deletion) of RB1 gene located on chromosome 13q. Cancer
results when both the RB genes are mutant (loss of
heterozygosity).
Clinical feature:
Median age of presentation is 18 months.
90 percent cases occur before the age of 5 years.
Bilateral in 25-30 percent cases.
Presentations:
Leukocoria or amaurotic cats eye reflex (white
pupillary reflex) - most common presentation.
Strabismus, secondary glaucoma (may cause
buphthalmos), cataract, poor vision, painful eye.
Metastasis:
Most common route through optic nerve to CNS (most
common site).
Metastasis to brain may produce intracranial
calcification.
Diagnosis:
X-ray orbit shows intraorbital calcification, erosion and
widening of optic foramina.
X-ray skull shows intracranial calcification.
Optic nerve biopsy to detect metastasis.
Histopathology - Flexner-Wintersteiner rosettes,
flurettes.
Staging: Reese-Ellsworth staging.
Treatment:
Enucleation with a long piece of optic nerve is the
treatment of choice for large tumors involving more
than half of the globe.
For small lesions - chemoreduction is the treatment
of choice. Vincristine is the drug of choice.
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Other therapies - radiotherapy, cryotherapy, laser

treatment.
Note: Tumors that may regress spontaneously are
neuroblastoma, retinoblastoma and melanoma.
Rhabdomyosarcoma
Most common primary orbital malignant tumor in
children.
Most common soft tissue malignancy of childhood.
Origin: It arises from extraocular muscles.
Clinical feature: Rapidly progressive proptosis of sudden
onset in a child aged between 7-8 years.
Diagnosis: MRI is the investigation of choice.
Treatment:
Local radiotherapy followed by chemotherapy.
Enucleation in radiotherapy resistant tumor.
NEOPLASMS OF EAR
AND NOSE
Acoustic Neurofibroma
It is the most common cerebellopontine angle tumor.
Nature: Benign, encapsulated, extremely slow growing
tumor.
Origin: From neurilemmal sheath (schwan cells) of the
vestibular division of VIII cranial nerve (superior vestibular
nerve). May arise from any nerve except optic and olfactory
nerve.
Clinical feature:
Commonly occurs between 40 and 60 years.
Unilateral sensorineural deafness (earliest feature) with
tinnitus.
Other nerves involved are 5th, 7th, 9th, 10th. 5th nerve
is involved earliest producing loss of corneal reflex.
Diagnosis: MRI with gadolinium contrast.
Treatment: Surgery is the treatment of choice.
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781
Differential diagnosis: Mnires disease, other CP angle

tumors, e.g. meningioma, cholesteatoma, arachnoid cyst.
NEOPLASMS OF THE PARANASAL SINUSES
Benign
Osteoma: Most commonly involves the frontal sinus.
Malignant
Most commonly involves maxillary sinus.
Carcinoma of Maxillary Sinus
Most commonly squamous cell carcinoma.
Clinical feature: Nasal obstruction, blood stained nasal
discharge, pain, lacrimation.
Classification: Ohngren classification.
Metastasis: Lymph nodes involved are submandibular and
upper deep cervical nodes.
Diagnosis:
X-ray (OM view) shows erosion and destruction of bony
antral wall with soft tissue shadow.
CT scan is the best.
Treatment: Combination of surgery and radiotherapy for
all stages.
Ethmoidal Sinus Carcinoma
In wood workers - adenocarcinoma.
In nickel workers - squamous cell carcinoma (most
common type).
TUMORS OF THE NASOPHARYNX
Nasopharyngeal Angiofibroma
Origin: Posterior part of nasal cavity close to sphenopalatine
foramen.
Clinical feature:
Occurs in the age group 10-20 years.
Profuse and recurrent epistaxis.
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Nasal obstruction.
Conductive deafness due to secretory otitis media.
Mass in the nasopharynx - pink, fleshy.
Diagnosis:
CT scan with enhancement - best.
Biopsy is contraindicated due to chance of bleeding.
Treatment:
Surgical excision is the treatment of choice.
Approaches to surgery - transpalatal, lateral rhinotomy,
infratemporal.
May require blood transfusion.
Note: Most common cause of recurrent epistaxis in a young
male is nasopharyngeal angiofibroma; whereas in a young
female is hematopoietic disorder.
Nasopharyngeal Carcinoma
Etiology: Associated with E-B virus infection.
Site: Fossa of Rosenmuller in the lateral wall of
nasopharynx.
Type: Squamous cell carcinoma.
Clinical feature:
Occurs in 5th to 7th decade.
Cervical lymphadenopathy is the most common
manifestation.
Trotters triad: palatal fixation, conductive deafness,
facial pain.
Diagnosis:
CT scan.
Biopsy is confirmatory.
Treatment: Radiotherapy is the treatment of choice.
CARCINOMA OF HYPOPHARYNX
Most common type is squamous cell carcinoma.
Pyriform Fossa Tumor
Pyriform fossa is the most common site for malignancy
in the hypopharynx.
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783
Clinical feature: Palpable lymph nodes in the neck - most

common presentation.
Treatment:
Early stages - radiotherapy.
Growth limited to pyriform fossa total laryngectomy
and partial pharyngectomy.
Growth extending to postcricoid region - total laryngopharyngectomy with mucocutaneous flap (deltopectoral).
Postcricoid Carcinoma
Risk factors - Plummer-Vinson syndrome.
BREAST TUMORS
BENIGN CONDITIONS
Fibroadenosis
It is due to aberration of normal development and
involution (ANDI).
It is also called - fibrocystic disease, chronic mastitis,
mastopathy.
Pathology:
1. Cyst formation - one cyst may become large and
clinically palpable called bluedome cyst of Bloodgood.
2. Stromal fibrosis.
3. Glandular proliferation (adenosis).
4. Epithelial hyperplasia (epitheliosis).
5. Papillomatosis.
Clinical feature:
Breast lump and pain,
Usually bilateral, situated in the upper outer quadrant.
Changes are cyclical - both lumpiness and pain increase
before menstruation. It subsides during pregnancy,
lactation and after menopause.
Risk of malignancy:
Risk is high with atypical hyperplasia, epitheliosis.
Adenosis carries no risk of malignancy.
Treatment: Conservative - evening primrose oil, danazol,
LHRH analogs, antiestrogen (tamoxifen).
784
Breast Cyst
Breast cysts occur most commonly in the last decade of
reproductive life.
Cause: Non-integrated involution of stroma and epithelium.
Feature: Often multiple, may be bilateral and mimic
malignancy.
Diagnosis: Confirmed by aspiration and/or USG.
Treatment:
Simple aspiration.
Local excision in case of recurrence or if aspirated fluid
is blood stained.
Fibroadenoma
Most common benign tumor of the breast.
Pathology: Hyperplasia of a single lobule of breast. It is
well capsulated and can be enucleated through a
cosmetically appropriate incision.
Clinical feature:
Occurs between 15 and 25 years.
Smooth, firm, non-tender, well-localized swelling which
moves freely in the breast tissue (breast mouse).
A giant fibroadenoma is > 5 cm in diameter and occurs
during puberty.
X-ray: Popcorn calcification.
Phylloides Tumor (Cystosarcoma Phylloides/
Serocystic Disease of Brodie)
They are not simply giant fibroadenomas.
They may be benign (85%), locally invasive or frankly
malignant.
Occurs over 40 years of age.
Pathology: They show cystic spaces with leaf-like projections;
may produce skin ulceration due to pressure necrosis.
Treatment:
Benign type
Enucleation in very young women.
Wide local excision.
Malignant type - simple mastectomy.
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785
Duct Papilloma
Most common cause of bloody discharge from nipple.
Feature:
Usually single, arising from a single lactiferous duct.
Single papilloma is not premalignant. But multiple
papillomas may be premalignant.
Treatment: Microdochectomy or removal of papilloma and
involved duct.
CARCINOMA OF THE BREAST
Prevalence
It is the most common malignancy in women
worldwide. But in India, it is second to cervical
carcinoma.
Prevalence in India is 21.2/lac.
Etiology
1. Geography - more common in white women and in
high socioeconomic status.
2. Age - rare below 20 years. Mean age in India is 42
years.
3. Genetic - more common in women with a family
history. Mutation of tumor suppressor genes BRCA1,
BRCA2 and p53 impart greater risk (BRCA1 >
BRCA2).
BRCA1 gene is located on the long arm of chromosome
17. The BRCA-1 syndrome includes an increased risk
of colon and ovarian cancer in women and prostate
cancer in men.
BRCA2 gene is located on the long arm of chromosome
11. Mutations are associated with an increased risk
of breast cancer in men and women. Sporadic breast
cancers show many genetic alterations including over
expression of HER-2/neu, p53 mutations and loss of
heterozygosity at other loci.
4. Other risk factors :
i. Nulliparity and increased age at first pregnancy.
ii. Breast Ca in a first degree relative.
iii. Breast Ca in contralateral breast.
iv. Obesity, smoking and alcohol intake.
v. Gynecomastia in male breast.
786
vi. Early menarche and late menopause.

vii. Women who received therapeutic radiation before age
30.
viii. Females on non-vegetarian diet have greater risk.
Types
1. Ductal carcinoma - most common variant.
2. Lobular carcinoma - commonly multifocal and/or
bilateral.
3. Colloid carcinoma.
4. Medullary carcinoma.
5. Tubular carcinoma.
6. Inflammatory carcinoma - most malignant (mastitis
carcinomatosa).
7. In situ carcinoma - preinvasive cancer.
Scirrhous Carcinoma
The invasive ductal carcinoma is of scirrhous type because
it is very hard in consistency.
The cut section shows the following features:
i. Cuts with a gritty sensation.
ii. Cut surface is concave.
iii. Areas of hemorrhage and necrosis.
Pagets Disease of the Nipple
It is the superficial manifestation of an underlying breast
cancer.
It presents as an eczema-like condition of the nipple
and areola.
In case of doubt, the nipple eczema should be biopsied.
Treatment - mastectomy and biopsy.
Spread
1. Local spread
2. Lymphatic metastasis primarily to the axillary and
internal mammary nodes. Involvement of lymph node
is a marker of metastatic potential of the tumor.
3. Hematogenous spread to
Bones - most common; lumbar vertebrae> femur>
thoracic vertebrae> rib > skull. They are osteolytic
lesions and may produce hypercalcemia. May also
be osteosclerotic.
Liver, lungs, brain, adrenals and ovaries.
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787
Clinical feature:
Most common site is the upper, outer quadrant (60%).
Skin manifestations Peau d orange due to obstruction of cutaneous
lymphatics and edema.
Dimpling of skin - due to infiltration of ligament
of Cooper.
Cancer-en-cuirasse - skin over the chest wall and
breast is infiltrated with cancer nodules giving rise
to the appearance of an armor coat.
Lymphatic manifestations 1. Peau d orange.
2. Late edema of the arm - complication of breast
ca treatment.
3. Elephantiasis chirurgens.
4. Brawny edema of arm.
5. Lymphangiosarcoma - develops many years after
mastectomy, especially in those who have received
radiotherapy.
Staging
TNM staging of breast cancer
Tumor size
Node involvement
T1 - 2 cm
N1 mobile
M0 no metastasis
ipsilateral axillary nodes
Metastasis
T2 2-5 cm
N2 fixed
M1 distant metastasis
ipsilateral axillary nodes
T3 - > 5 cm
T4 any size
involving skin
or chest wall
Investigations
Mammography:
Signs of malignancy on mammography
i. Microcalcification.
ii. Irregular soft tissue shadow.
iii. Spiculations.
False negative results are most commonly due to
dense breast.
It is the best screening procedure.
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FNAC: It is least invasive and very accurate.

Triple assessment: Consists of clinical assessment,
radiological imaging and tissue sample taken for
cytological or histological analysis.
Sentinel node biopsy.
Estrogen receptor study:
In ER positive status - prognosis is good; hormone
therapy including tamoxifen is more beneficial, response
to treatment is better.
Estrogen receptor study is done on tumor tissues.
Screening: Self examination of breast is the best
approach.
Mammography is the best investigation. Mammography
combined with clinical breast examination increases the
sensitivity.
Management
Surgery:
1. Total (simple) mastectomy.
2. Total mastectomy with axillary clearance.
3. Halsted radical mastectomy: Structures retained are
axillary vein, Bells nerve (nerve to serratus anterior)
and cephalic vein (mnemonic - ABC).
4. Modified radical (Patey) mastectomy: Structures
removed are - Entire breast, overlying skin, all fat, fascia
and lymph nodes of axilla and pectoralis minor muscle.
Structures retained are - Pectoralis major, nerve to
serratus anterior and latissimus dorsi, axillary vein.
5. Conservative breast surgery: Wide excision with
lumpectomy - removing the tumor plus a rim of at
least 1 cm of normal breast tissue.
Quadrantectomy - when done with axillary dissection
and radiotherapy is called QUART. It is the best
conservative procedure.
Indications of conservative surgery:
Tumor < 4 cm in size (T1N0M0).
Negative axillary nodes.
Breast of adequate size.
Radiotherapy:
Indications of radiotherapy:
1. After conservative surgery to prevent recurrence.
It is given when there are four or more positive
axillary lymph nodes.
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789
2. Patients with higher risk of relapse such as invasive

carcinoma, extensive in situ carcinoma, patients
< 35 years old, multifocal disease.
3. In bone secondaries, to palliate pain and swelling.
4. Inflammatory carcinoma of breast.
5. Atrophic scirrhous carcinoma - as a curative
method.
Hormone therapy:
Hormone therapy includes:
1. Tamoxifen.
2. LHRH agonists (medical oophorectomy).
3. Oral aromatase inhibitors (letrozole or anastrazole)
for postmenopausal women.
4. Progesterone receptor antagonists.
5. Surgery - ablation of ovary, adrenals or pituitary.
6. Androgens.
7. Aminoglutethimide - medical adrenalectomy.
Indication of hormone therapy:
Tamoxifen adjuvant therapy is used for pre- or
postmenopausal women with tumors expressing
estrogen receptors whose nodes are positive or whose
nodes are negative but with large tumors or poor
prognostic features.
Chemotherapy:
Indication for chemotherapy:
1. Premenopausal women with positive lymph nodes.
2. Pre- and postmenopausal women with negative
lymph nodes but with large tumors or poor
prognostic features.
3. Postmenopausal women with positive lymph nodes
whose tumors do not express estrogen receptors.
Chemotherapy includes: CMF (cyclophosphamide,
methotrexate and 5-fluorouracil) and CAF
(cyclophosphamide, doxorubicin, 5-fluorouracil)
Breast reconstruction:
Types 1. Silicon gel implant.
2. Expandable saline prosthesis with prior tissue expansion.
3. If there is less skin or after radiotherapy - contralateral
transverses abdominis muscle (TRAM) flap or latissimus
dorsi musculocutaneous (LD) flap.
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Therapies for breast cancer
Type
Therapy
Ductal carcinoma
in situ
Operative invasive
breast cancer
Wide excision with breast radiation therapy
Locally advanced
disease
Metastatic disease
Modified radical mastectomy or lumpectomy

followed by breast radiation therapy. Axillary
dissection may be replaced with sentinel node
biopsy. Adjuvant combination chemotherapy
and tamoxifen adjuvant therapy is used for
women with above mentioned criteria
Neoadjuvant chemotherapy that includes an
anthracycline (CAF) followed by surgery plus
breast radiation therapy
Tamoxifen for estrogen receptor-positive
tumors, and combination chemotherapy for
receptor-negative tumors. Selective aromatase
inhibitor such as letrozole or anastrazole.
Bisphosphonates reduce skeletal complications
and may promote antitumor effects of other
therapy. Radiation therapy is useful for
palliation of symptoms
Prognosis:
1. Spread to axillary nodes - most important prognostic
factor.
2. Age - younger age worsens prognosis.
3. Sex - carcinoma of male breast has worse prognosis.
4. Type - intraductal Ca has the best prognosis,
inflammatory Ca has the worst prognosis.
5. Estrogen and progesterone receptor positive - good
prognosis.
6. Other poor prognostic factors include over expression
of HER-2/neu and C-MYC, mutations in p53, high
growth fraction, and aneuploidy.
Male Breast Carcinoma
Etiology: Gynaecomastia and excess estrogen.
Type: Commonly infiltrating ductal carcinoma.
Treatment: Bilateral orchidectomy and tamoxifen.
Prognosis: Depends upon stage of the disease. Worse
prognosis than carcinoma of female breast.
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791
GYNECOLOGICAL CANCER
UTERINE TUMORS
Fibroid Uterus
This is the most common benign tumor in women.
Pathology:
Anatomy:
The tumor is enclosed in a pseudocapsule separated
by loose areolar tissue.
The central part is least vascular and most likely to
undergo degeneration, whereas calcification is
common at the periphery.
Growth: It is an estrogen-dependant tumor as evidenced
by 1. Growth is increased by pregnancy and OCP.
2. Rare before 20 years of age.
3. Progesterone, GnRH cause shrinkage of the tumor.
Overall rate of growth is slow.
Types:
1. Interstitial or intramural - most common type; initially
all fibroids are intramural to start with. Intramural type
has the maximum malignant potential.
2. Subserous - a pedunculated subserous fibroid is called
the wandering or parasitic fibroid and most likely
to undergo torsion.
3. Submucous - least common type; but with maximum
symptoms.
Secondary changes:
1. Degeneration - most common change.
a. Hyaline degeneration - most common type.
b. Cystic degeneration.
c. Fatty degeneration.
Note: The above three changes occur in the central
area, and is of no significance; may cause atrophy
of fibroid.
d. Calcareous degeneration - most common change
in subserous type. Calcium carbonate and calcium
phosphate are deposited in the peripheral area along
the blood vessels. It occurs in old patients.
Calcification is called womb stone. Diagnosis is
by X-ray.
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2.
3.
4.
5.
6.
7.
8.
e. Red degeneration (carneous degeneration) - most

commonly occurs during third trimester of
pregnancy and puerperium. It is an aseptic process,
may be due to thrombosis of veins. It presents as
acute abdomen; and blood leukocyte count and
ESR are elevated.
Necrosis.
Infection.
Vascular changes.
Sarcomatous change - rarest complication. Incidence
is 0.5 percent.
Others - hemorrhage, polycythemia.
Torsion - of a pedunculated subserous fibroid.
Inversion - of uterus due to fundal myoma.
Clinical feature:
Most cases are asymptomatic.
Patient profile - age between 30 and 40 years (rare
before 20 years), nulliparous or with one child
secondary infertility.
Symptomsi. Menstrual disorders - menorrhagia (most common
symptom), metrorrhagia, polymenorrhea and
congestive (secondary) dysmenorrhea.
Menorrhagia is due to obstruction of uterine
contractility, increased vascularity, endometrial
hyperplasia and enlarged cavity.
ii. Infertility - most common with submucous myoma.
iii. Pain - fibroids are painless. Acute pain suggests torsion/
hemorrhage/red degeneration.
iv. Abdominal lump with sense of heaviness in lower
abdomen.
v. Pressure symptoms - retention of urine (premenstrually) in posterior wall fibroids. Hydroureter/
hydronephrosis may occur in broad ligament fibroid.
Investigation:
1. USG - is the investigation of choice. Well-defined tumor,
hypoechoic with cystic spaces if degeneration has
occurred.
2. Hysterosalpingogram and hysteroscopy - for submucous
fibroid.
3. Laparoscopy - if uterine size < 12 weeks and associated
with pain and infertility.
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793
4. Dilatation and curettage.

5. IVU for broad-ligament fibroid.
Treatment:
No treatment is required for fibroids < 12 weeks of
age. Periodic observation is done every 6 months.
Medical management
1. Progesterone
2. Androgen
3. Danazol
4. GnRH analogues
5. RU 486 (mifepristone)
Surgery 1. Myomectomy - for patients in reproductive age
group desirous of having a child.
Types Vaginal - in submucous fibroid.
Hysteroscopic - in submucous fibroid.
Laparoscopic - with myolysis (laser or cautery).
2. Hysterectomy is the operation of choice.
Indications - Age> 40 years who have completed
their families.
Procedure Vaginal route may be used in fibroids < 14
weeks size.
Otherwise abdominal operation is done.
Removal of the ovaries (bilateral oophorectomy)
is done in postmenopausal women.
Uterine Sarcoma
Incidence:
It comprises 4.5 percent of all malignant uterine
tumors.
Only 0.5 percent fibroids undergo sarcomatous change.
Type:
Most commonly intramural type.
Most common histological type is spindle-cell tumor
(leiomyosarcoma).
Spread: Via bloodstream to the lungs and kidneys.
Treatment: Total hysterectomy with bilateral oophorectomy
followed by radiotherapy.
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Uterine Polyps
Mucous polyp:
Most common type.
Treatment is by uterine curettage with removal of the
polyp.
Fibroid polyp: Most commonly a submucous fibroid
associated with chronic inversion of uterus (the two can
be differentiated by sound test).
DISEASES OF ENDOMETRIUM
Endometriosis
Endometriosis is the presence of endometrial tissue in
ectopic sites.
Sites:
1. Abdominal- ovary is the most common site; fallopian
tube.
2. Remote - pleura, lungs.
3. Extra-abdominal- umbilicus.
4. Stump endometriosis occurs in tubes (after tubectomy),
cervix (after amputation), vulva.
Etiology:
1. Retrograde menstruation - most common cause.
2. Coelomic metaplasia - in women with Mllerian
agenesis.
3. Direct spread.
Risk factors: Late marriage and small family size.
Pathology:
The ectopic endometrium is under the control of ovarian
hormones and proliferative changes are constantly
evident.
Chocolate cyst - occurs in ovary; attains size of 3-5
cm.
Powder burn deposits in utero-sacral ligament and
the pouch of Douglas.
Clinical feature: Patient profile - age between 30 and 45
years; often nulliparous.
Symptoms1. Dysmenorrhea - most common symptom.
2. Dyspareunia.
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795
3. Pelvic and abdominal pain that worsens during menses.

4. Menorrhagia.
5. Infertility - due to associated tubal or ovarian
dysfunction (commonly anovulation).
Diagnosis:
Confirmation of diagnosis is by double puncture
laparoscopy or laparotomy - gold standard.
Serum marker - CA 125.
Treatment:
Expectant treatment - Indications - unmarried or young
married women.
Hormones used are 1. OCP.
2. Progesterone - medroxyprogesterone acetate
(MOPA).
3. Danazol- androgen agonist. It produces endometrial
atrophy (pseudomenopause).
Gestrinone.
4. GnRH analogues like leuprolide, buserelin, nafarelin
are the drugs of choice. They produce medical
castration. Nafarelin can be given intranasally.
Surgery Indication - infertile patients with advanced
endometriosis.
Conservative - diathermy or laser vaporization.
Radical - hysterectomy with bilateral salpingooophorectomy.
For pain relief - LUNA (laser uterosacral nerve
ablation).
Adenomyosis
Pathology: There is diffuse, symmetrical enlargement of
uterus. But unlike fibroids, there is no capsule.
Clinical feature:
Patient profile - age> 40 years; parous.
Symptom - menorrhagia is the most common
symptom, dysmenorrhea.
Sign - hypogastric mass (of < 14 weeks size) and
symmetrical enlargement of uterus.
Treatment: Total hysterectomy is the method of choice.
796
Endometrial Carcinoma
Risk factors:
1. Early menarche and late menopause.
2. Nulliparity.
3. Corpus cancer syndrome - associated obesity,
hypertension and diabetes.
4. Dysfunctional uterine bleeding.
5. Infertility.
6. Unopposed estrogen stimulation
i. Granulosa cell tumor.
ii. Polycystic ovarian disease.
iii. Tamoxifen therapy.
iv. Hormone replacement therapy.
7. Exposure to radiation.
8. Positive family history.
Smoking decreases estrogen level and OCPs increase
progesterone levels and are thereby protective.
Pathology:
Most common type is adenocarcinoma.
Serous and clear cell carcinomas have poor prognosis.
Adenocarcinoma may be preceded by endometrial
hyperplasia. Progression to endometrial carcinoma in
women with atypical hyperplasia is 23 percent as
compared to 1.6 percent in women with no atypia.
Spread:
Lymphatic spread - most common route; spreads to
the pelvic and/or para-aortic nodes.
Vagina - vault metastasis is common after hysterectomy.
Suburethral metastasis to vulva.
Staging:
Stage Ia
Stage Ib
Stage Ic
Stage IIa
Stage IIb
Stage IIIa
Tumor limited to the endometrium.

Invasion < 1/2 myometrium (< 8 cm).
Invasion> 1/2 myometrium (> 8 cm).
Endocervical gland involvement.
Cervical stromal involvement.
Invades serosa and/or adnexa and/or positive
peritoneal cytology.
Stage IIIb Vaginal metastasis.
Stage IIIc Metastasis to pelvic and/or paraaortic lymph
nodes.
Stage IVa Involves bladder and/or bowel mucosa.
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797
Stage IVb Distant metastasis including intra-abdominal

and/or inguinal lymph nodes.
Clinical feature:
Patient profile - postmenopausal, nulliparous.
Symptom - postmenopausal bleeding is the most
common symptom; watery and offensive vaginal
discharge.
Diagnosis: Fractional curettage with Novak or Kevorkian
curet.
Treatment:
Surgery - total abdominal hysterectomy plus bilateral
salpingo-oophorectomy (Wertheims hysterectomy),
peritoneal washing, omental biopsy and node sampling
is the basic procedure for all stages. It serves both as
a staging procedure and treatment.
Endometrial hyperplasia without atypia - progestin and
follow-up endometrial biopsy every 3- 6 months.
Endometrial hyperplasia with atypia - hysterectomy.
Stage Ia surgery alone.
Stage Ib surgery followed by radiotherapy.
Stage II radiotherapy followed by surgery.
Stage III intracavitary radiotherapy.
Stage IV palliative radiotherapy.
Choriocarcinoma
Predisposing lesion:
Hydatidiform mole is present in 50 percent cases.
It is related to abortion (most common), term pregnancy
(associated with high risk) or ectopic pregnancy.
Spread: Vascular erosion takes place early and hence
distant metastasis occurs rapidly. Most common sites are
lungs (may cause hemoptysis), brain, liver, kidneys.
Diagnosis:
Serum marker - hCG.
Chest X-ray - cannon ball shadow in lung.
Treatment:
Chemotherapy is the mainstay of treatment.
Methotrexate is the drug of choice (MAC regimen
contains methotrexate, actinomycin and chlorambucil).
798
When there is spread to liver (abnormal liver function),

drug of choice is actinomycin D.
Prognosis: Excellent.
NEOPLASMS OF VULVA
Vulval Ulcer
1. Lipschutz ulcer - affects the labia minora and introitus.
2. Crohns disease.
3. Behets disease.
Vulval Cyst
Bartholins cyst:
Cause inflammation.
Pathology swelling of the labia majora.
Clinical feature dyspareunia.
Treatment marsupialization; surgical excision and
biopsy if > 40 years of age.
Cyst of the canal of Nuck:
Canal of Nuck is the remnant of processus vaginalis.
It occupies anterior part of labia majora.
Sebaceous cyst.
Vulval Dystrophy
Lichen sclerosis - is a benign lesion; histopathology
shows blunting or loss of rete pegs.
Hypertrophic dystrophy - is premalignant.
Vulval Intraepithelial Neoplasia (VIN)
Risk factors:
Leukoplakia of vulva.
Condyloma accuminata (HPV 6 and 11)
Type: Squamous cell carcinoma is the most common type.
Clinical feature: Pruritus.
Diagnosis: Biopsy.
Toludine blue followed by washing with acetic acid stains
the area blue and helps in colonoscopy and biopsy.
Treatment: CO2 LASER vaporization.
Oncology
799
Pagets Disease of Vulva
Also called leucoplakia of vulva.

It arises from sweat glands.
Clinical feature - color of the vulva becomes white.
Treatment - simple vulvectomy.
Vulval Carcinoma
It comprises of 1-4 percent of all genital malignancies.
Most commonly squamous cell carcinoma.
It is associated with increased chance of squamous
cell carcinoma of cervix.
Clinical feature:
It is unusual in younger age group.
Pruritus in a post-menopausal woman.
Spread: It spreads to superficial inguinal lymph nodes.
Treatment:
Early stages - surgery (uni/bilateral vulvectomy with
uni/bilateral inguinofemoral lymphadenectomy).
Late stages - radiotherapy or chemotherapy.
NEOPLASMS OF VAGINA
Vaginal Cyst
Gartners duct cyst:
Gartners duct is the remnant of mesonephric (Wolffian)
duct.
It lies on anterolateral wall of the vagina.
Vaginal Carcinoma
Most commonly squamous cell type.
Clinical feature:
Patient profile - occurs in the age group of 50-70 years.
Symptom - watery discharge; post-coital bleeding.
Stage: Stage III denotes involvement of pelvic wall.
Treatment:
Radiotherapy is the most commonly used method.
Surgery.
800
Clear cell adenocarcinoma: It occurs in adolescent girls

who were exposed to diethylstilbesterol during intrauterine
life.
Sarcoma botryoides:
It is seen in children < 5 years of age.
It is characterized by rapid spread.
Treatment - surgical excision followed by chemotherapy.
NEOPLASMS OF CERVIX
Cervical Intraepithelial Neoplasia (CIN)
CIN I mild dysplasia - involves basal 1/3rd.
CIN II moderate dysplasia - involves basal 2/3rd.
CIN III severe dysplasia - involves whole thickness
(carcinoma in situ).
Chance of progression of severe dysplasia to invasive
cancer is 10 percent. It takes 5-10 years.
Chance of progression of moderate dysplasia to invasive
cancer is 5 percent.
Risk factors:
1. Early coitus before the age of 18 years.
2. Early pregnancy before the age of 20 years.
3. Multiple sex partners.
4. STDs including Chlamydia infection.
5. HPV 16, 18 and 31 (HPV 6 and 11 produce benign
lesions) - most important risk factor.
6. HSV 2 infection.
7. Smoking.
Diagnosis:
Screening with PAP test:
Indication Age> 18 years who are sexually active.
All women above the age of 35 years.
Specimen Cervical scraping using Ayres spatula from whole
of the squamo-cutaneous junction. Vaginal pool
aspiration from posterior fornix.
Inference - abnormal PAP smear indicates
i. CIN or invasive malignancy.
ii. Inflammatory changes caused by - HPV, HSV
or trichomonus.
Oncology
801
Colposcopy: It is done for accurate determination of

the affected area. If colposcopy is not available,
Schillers iodine is applied.
Cone biopsy: is diagnostic.
Treatment:
CIN I and II LASER ablation.
CIN III and CIS
i. Cryocauterisation - (side effect is watery
discharge).
ii. Cold knife/laser conisation is the treatment of
choice. (Side effect - bleeding, cervical stenosis
and incompetence).
iii. Total hysterectomy with or without ovary removal
- for those who have completed their families.
Cervical Carcinoma
It is the most common carcinoma in women in
developing countries.
Ratio of breast Ca : Cervical Ca = 1 : 3.
Type: Squamous cell carcinoma is the most common type
(80%).
Staging:
Procedure: Examinations include - inspection, palpation,
colposcopy, endocervical curettage, hysteroscopy,
cystoscopy, proctoscopy, intravenous urogram, X-rays of
chest and skeleton.
FIGO staging for cervical carcinoma
Stages
Description
Stage 0
Stage I
Ia1
Carcinoma in situ or CIN III.

Carcinoma confined to cervix.
Stromal invasion < 3 mm in depth and extension <7
mm.
Stromal invasion > 3 but <5 mm in depth and extension
<7 mm.
Clinically visible lesion <4 cm.
Clinically visible lesion > 4 cm.
Carcinoma invades beyond the uterus, but not to the
pelvic wall or to the lower third of vagina.
No obvious parametrial involvement.
Obvious parametrial involvement.
Ia2
Ib1
Ib2
Stage II
IIa
IIb
Contd...
802
Contd...
Stages
Description
Stage III
Carcinoma extending to the pelvic wall; involves the

lower third of vagina; hydronephrosis or nonfunctioning
kidney are included.
Tumor involves the lower third of vagina, with no
extension to the pelvic wall.
Extension to the pelvic wall or hydronephrosis or
nonfunctioning kidney.
Carcinoma extending beyond the true pelvis, or involving
(biopsy proved) the mucosa of the bladder or rectum.
Spread to adjacent organs (bladder or rectum or both).
Spread to distant organs.
IIIa
IIIb
Stage IV
IVa
IVb
Diagnosis:
Early (CIS, Ia, Ib):
Symptom - bleeding per vaginum (earliest symptom),
post-coital bleeding, intermenstrual bleeding, and
excessive white discharge.
Investigation - colposcopy directed biopsy or direct
biopsy of a gross lesion. In case of suspected
microinvasion, a cone biopsy of the cervix is indicated
to detect the depth of invasion. Cold knife cone biopsy
is most accurate.
Advanced:
Patient profile - multiparous, premenopausal, in the
younger reproductive age group.
Symptom - irregular vaginal bleeding, offensive vaginal
discharge, pelvic pain, bladder and rectal symptoms,
anemia, uremia (may present with altered sensorium
and hiccup - signifies bilateral ureter invasion).
Most common cause of death is renal failure.
Investigation:
Screening - (Down staging) by PAP cytology.
Tumor marker SCC antigen.
Treatment:
Early stagesStage Ia1 (microinvasive) - simple hysterectomy or
conisation.
Stage Ia2 - radical hysterectomy and pelvic
lymphadenectomy.
Stage Ib, IIa Radical hysterectomy and pelvic lymphadenectomy or
primary radiotherapy with external beam radiation and
brachytherapy.
Oncology
803
Adjuvant therapy for early stages - patients with

extracervical extension (pelvic node involvement,
parametrial extension) are treated with concurrent
pelvic radiotherapy and cisplatin based chemotherapy.
Brachytherapy
Radioactive substances used is radium sulphate.
Irradiation is done at 2 points Point A - 2 cm cephalic and 2 cm lateral to the external
os and corresponds to the point of crossing of uterine
artery and ureter.
Point B-2 cm cephalic and 5 cm lateral to external
os and is the site of obturator gland.
Relatively advanced
Stage IIb - radiotherapy.
Late disease Stage IIIa - radiotherapy or chemotherapy (cisplatin).
Stage IIIb - radiotherapy.
Recurrent disease - pelvic exenteration.
NEOPLASMS OF OVARY
Functional Cysts (Non-neoplastic)
Follicular cyst:
Most common functional cyst.
Usually multiple and small; associated with cystic
glandular hyperplasia.
Lutein cyst:
It arises from theca lutein cells or glandular lutein cells.
Cause - increased hCG as occurs in H. mole.
Diagnosis - functional cysts are < 7 cm in diameter.
Treatment - nothing; undergoes spontaneous regression.
Benign Neoplasm
Feature of benign tumors is intact capsule.
Mucinous cyst adenoma:
Tumors are bilateral in 10 percent cases.
Potentially malignant.
Pathology Gross - largest benign tumor of ovary.
Microscopic - honey-comb appearance.
804
Serous cyst adenoma:

Most common ovarian tumor.
They arise from totipotent surface epithelium.
Bilateral in 30 percent cases.
Chance of malignancy is highest (30%).
Dermoid cyst:
They are bilateral in 15-20 percent cases.
There is two fold increase in incidence during pregnancy.
Pathology Gross - contains predominantly sebaceous material
and hair (Rokitansky protuberans).
Microscopic -lined by stratified squamous
epithelium.
Struma ovary - a rare type of dermoid containing
thyroid tissue; may cause hyperthyroidism.
Clinical feature of benign tumors:
Age - late child bearing age.
Parity - no correlation.
Symptom - may be asymptomatic; lump in abdomen
which grows in months.
Meigs syndrome: Ascites, right sided hydrothorax and
fibroma of ovary (or Brener, thecoma and granulosa cell
tumor).
Diagnosis:
Ultrasonography.
CA 125 level < 35 U/ml indicates benign tumor.
Complications:
1. Torsion of the pedicle - most common complication.
Most common with mucinous cyst adenoma and
teratoma. It is due to hemodynamic cause.
2. Hemorrhage.
3. Infection.
4. Rupture.
5. Pseudomyxoma peritonei - mucinous ascites associated
with mucinous cyst adenoma.
Note: It is also seen in mucocele of appendix and
gallbladder and intestinal malignancy.
6. Malignancy - rarest complication. Most common with
serous cyst adenoma especially of papillary variety;
least common with dermoid.
Oncology
805
Treatment:
Age < 40 years - conservative surgery - ovarian
cystectomy or ovariotomy.
Age > 40 years - total hysterectomy with bilateral
salpingo-oophorectomy.
Parovarian cyst: These are small, glistening cyst over the
serosa of fallopian tube.
Ovarian Carcinoma
Classification:
Primarya. Epithelial tumors (90%) - most commonly
adenocarcinoma; mostly serous type.
Types- Serous (50%), mucinous (25%), endometrioid
(15%), clear cell (5%), and Brenners tumors (1 %,
derived from urothelial or transitional epithelium).
b. Non-epithelial tumorsGerm cell tumors - most common below the age of
20 years.
Sex cord stromal tumors.
Secondary a. Typical.
b. Atypical- Krukenbergs tumor.
Genetics: Mutations in BRCA-1 and BRCA-2 (BRCA-1
> BRCA 2) predispose women to both breast and ovarian
cancer.
Pathology:
Malignant tumors consist of 1/3rd tumors in ovary.
They are bilateral in 1/3rd cases. Incidence of malignant
ovarian tumors in adolescence is 10 percent.
One feature of malignancy is ruptured capsule.
Psammoma bodies are found in 30 percent cases of
serous adenocarcinoma. Walthard cell rests are seen
in Brenners tumors.
Clinical feature:
Patient profile - postmenopausal, nulliparous.
Symptom - abdominal pain (most common symptom),
bloating, urinary symptoms, and weight gain indicative
of disease spread beyond the true pelvis. Other
symptoms include dyspepsia, loss of appetite.
806
Brenners tumors may produce ascites and hydrothorax

(pseudo Meigs syndrome).
Diagnosis:
Culdocentesis.
Tumor marker CA 125 > 65 U/ml (normal < 35 U/
ml) in about 80 percent cases.
Ultrasonography.
Surgical staging:
Procedure: Total abdominal hysterectomy, bilateral
salpingo-oophorectomy, partial omentectomy, pelvic and
para-aortic lymph node sampling, and peritoneal
washings.
Staging for ovarian carcinoma
Stage
Description
Stage I
Ia
Growth limited to the ovaries.

Limited to one ovary; no ascites; no tumor on external
surface; capsule intact.
Limited to both ovaries, no ascites; no tumor on
external surface; capsule intact.
Ia or Ib with tumor on external surface or ruptured
capsule or ascites containing malignant cells or positive
Growth involves one or both ovaries with pelvic
extension.
Extension to the uterus and/or tubes.
Extension to other pelvic tissues.
IIa or IIb with tumor on external surface or ruptured
capsule or ascites containing malignant cells or positive
Peritoneal implants outside the pelvis and/or
retroperitoneal or inguinal nodes; superficial liver
metastasis; extension to small bowel or omentum.
Microscopic seeding on abdominal peritoneal surfaces.
Abdominal implants 2 cm; nodes negative.
Abdominal implants> 2 cm and/or positive retroperitoneal or inguinal nodes.
Distant metastasis - pleural effusion; parenchymal liver
metastasis.
Ib
Ic
Stage II
IIa
IIb
IIc
Stage III
IIIa
IIIb
IIIc
Stage IV
Treatment:
Surgery - total abdominal hysterectomy, bilateral
salpingo-oophorectomy, lymphadenectomy and
omentectomy. Cytoreductive surgery improves response
to chemotherapy and prolongs survival in women with
advanced disease.
Chemotherapy -chemotherapy is most useful in ovarian
carcinoma among the genital malignancies.
Oncology
807
Stage I with good histology - surgery alone.

Stage II and stage I with poor histology - surgery
followed by single agent cisplatin or in combination
with paclitaxel.
Advanced stages - surgery followed by paclitaxel,
followed by carboplatin (or cisplatin).
Germ Cell Tumors
Dysgerminoma:
They are similar to the seminoma of testis.
They are associated with gonadal dysgenesis or
androgen insensitivity syndrome or true
hermaphroditism.
Feature - they do not secrete any hormone but produce
placental alkaline phosphatase.
Commonly occur in the younger age group (< 20 years)
- most common type of ovarian tumor in this age group.
They are unilateral and highly radiosensitive.
Endodermal sinus or yolk sac tumor:
They are composed of endodermal yolk sac.
This tumors produce fetoprotein.
Polyembryoma: They are the least radiosensitive germ cell
tumors.
Embryonal carcinoma:
Occurs in prepubertal girls.
They elaborate both fetoprotein and hCG.
Choriocarcinoma (non-gestational):
They elaborate hCG.
Treatment - surgery followed by chemotherapy.
Gonadoblastoma: They produce intrapelvic calcifications
visible on X-ray.
Sex Cord Stromal Tumors
Estrogen producing tumors (feminizing):
Granulosa cell tumors.
Thecomas.
Androgen producing tumors (masculizing):
Androblastoma or arrhenoblastoma or Sertoli-Leydig
cell tumors.
808
Gynandroblastoma.
Hilus cell tumors.
Granulosa cell tumors:
Predominantly unilateral.
Call-Exner bodies are pathognomonic.
They produce estrogen - increased chance of
endometrium hyperplasia and endometrial carcinoma;
also breast carcinoma. Also produce inhibin.
Clinical feature - precocious puberty, post-menopausal
bleeding.
They are potentially malignant tumors.
Spread to the opposite ovary.
Thecomas: They have greater chance of endometrial
carcinoma than granulosa cell tumors.
Androblastomas:
They produce androgens and produce virilization.
Removal of tumor reverses virilizing symptoms except
voice change.
Hilus cell tumors:
They arise from Leydigs cells.
Characteristically Reinkes crystals are seen.
Secondary Tumors of Ovary
Secondary tumors of ovary arise due to metastases from
GI tract (pylorus, colon, and rarely small gut), gallbladder,
breast and endometrial carcinoma. Least chance of
metastasis is from the cervix.
Krukenbergs tumor (atypical):
Primary sites are stomach (most common), colon,
breast.
Cause - retrograde lymphatic spread.
Features Always bilateral.
Capsule remains intact - ovaries maintain their shape.
with solid waxy consistency.
Histology - Signet ring appearance.
CARCINOMA OF FALLOPIAN TUBE
Least common malignancy in female genital tract.
Pathology: Most commonly adenocarcinoma.
Oncology
809
Clinical feature:
Patient profile - postmenopausal and nulliparous.
Symptoms - postmenopausal bleeding, intermittent
watery discharge.
BONE TUMORS
BENIGN TUMORS
Ivory Osteoma
Site: Most commonly the bones of skull and face.
Sometimes, it may protrude into one of the sinuses most
commonly the frontal sinuses.
Clinical feature: Asymptomatic; visible swelling.
Association: multiple osteomas outside paranasal sinuses
are associated with polyposis coli (Gardners syndrome).
X-ray: increased density of bone (osteosclerotic).
Osteoid Osteoma
This is the most common benign bone tumor.
Site: Osteoma occurs in the diaphysis of long bones. Most
commonly affected bone is the tibia.
Pathology: A radiolucent nidus (composed of partially
mineralized osteoid trabeculae) surrounded by dense
sclerotic bone.
Clinical feature:Nagging pain worse at night and relieved
by salicylates.
X-ray: Translucent nidus surrounded by dense zone of
sclerosis.
Osteoblastoma
They histologically resemble osteoid osteoma.
Commonly affect the spine and lower limbs.
Chondroblastoma
They are cartilage forming tumors.
Site: Affect the epiphysis of long bones. Bones around
the knee are most commonly affected.
810
Age: Usually affects the immature skeleton; most common

in second decade.
Pathology: Cystic swelling with dense calcification.
X-ray: Lytic lesion surrounded by a zone of sclerosis.
Calcification within the tumor give rise to mottled
appearance.
Hemangioma
Site: Affect the vertebrae (most commonly lumbar) and
skull.
Clinical feature: Pain and features of cord compression;
local gigantism.
X-ray: Loss of horizontal striatations and prominence of
vertical striatations of the affected vertebral body.
CT scan: Multiple dots in vertebral bodies may produce
the polka-dot sign.
Adamantinoma
Site: Most commonly the jaw (but most common tumor
affecting the jaw is squamous cell Ca).
X-ray: Honey comb appearance.
Chordoma
Nature: Locally malignant, sometimes actually malignant.
Origin: From ectopic cellular remnants of the notochord.
Site: Most commonly the sacrum and cervical spine.
Pathology: Chordomas show stellate or polygonal cells with
vacuolated cytoplasm (physaliphorous).
Radiology: Bone destruction is the only hallmark feature
of chordoma.
Giant Cell Tumor (Osteoclastoma)
Nature: 1/3rd benign, 1/3rd locally malignant, 1/3rd frankly
malignant.
Site: Located at the epiphysis of long bones. Most
commonly affect the bones around the knee.
Oncology
811
Pathology: Characterized by undifferentiated spindle cells

interspersed with multinucleated giant cells that resemble
osteoclasts.
Clinical feature:
Age 20-40 years.
Symptom swelling and vague pain.
On palpation egg shell crackling is characteristic.
X-ray: Solitary lytic lesion situated eccentrically with
expansion of overlying cortex. May produce soap bubble
appearance.
Treatment:
Surgery excision of the tumor is the treatment of
choice.
i. Excision only the fibula, lower end of ulna.
ii. Excision with reconstruction for femur and tibia
turn-o-plasty; for radius-fibular grafting.
Curettage with or without supplementary procedures
like cryotherapy, bone cement.
Radiotherapy for GCT affecting the vertebrae.
MALIGNANT TUMORS
Osteosarcoma
They are the most common primary malignant bone
tumors after multiple myeloma.
Etiology:
Primary osteosarcoma occurs in young age group
(15-25 years).
Secondary osteosarcoma occurs in older age group
(> 45 years).
Premalignant lesions are:
i. Pagets disease of bone.
ii. Diaphyseal aclasis.
iii. Enchondromatosis.
iv. Fibrous dysplasia.
v. Multiple osteochondroma.
vi. Post-irradiation.
Site: Osteosarcomas occur in the metaphysis of long bones,
most commonly at the lower end of femur.
812
Type:
Osteoblastic type.
Chondroid type.
Fibroblastic type highly malignant.
Osteolytic type more malignant than osteoblastic
type.
Telangiectatic type.
Clinical feature: Pain is the first symptom followed by
swelling.
Spread: Blood-borne metastasis to lungs (most common).
X-ray:
i. New bone formation.
ii. Periosteal reaction.
iii. Codmans triangle due to subperiosteal new bone
formation.
iv. Sun-ray appearance due to new bone formation
along the blood vessels within the tumor growing
centrifugally.
Treatment:
Local control amputation is the mainstay of
treatment.
Chemotherapy.
Parosteal Osteosarcoma
Origin: They arise in the region of periosteum.
Features:
i. Slow growing.
ii. Seen in adults (> 45 years).
iii. Diagnosis by X-ray.
iv. Prognosis better.
Ewings Sarcoma
Site: Ewings sarcomas occur in the diaphysis of long
bones, most commonly the femur. They may have
multicentric origin.
Pathology:
Gross characteristically involve a large area, even
the entire medullary cavity. The tumor ruptures through
the cortex early and tumor tissue extends into the
adjoining soft-tissues.
Oncology
813
Microscopic glycogen filled cytoplasm stained by PAS

are characteristic of sarcoma cells.
Tissue marker: CD99
Clinical feature:
Age of presentation 5 to 15 years.
Presents with pain and swelling.
Genetics: Most commonly associated with t 11:22.
Spread: They are highly malignant; blood-borne metastasis
to lungs and other sites.
X-ray: Onion-peel appearance.
Treatment:
They are highly radiosensitive.
Treatment is radiotherapy + chemotherapy.
Chondrosarcoma
Age: 30-60 years.
Site: Flat bones of pelvis, upper end of femur and humerus.
X-ray: Mottled calcification within the tumor.
Treatment: Local ablation + radiotherapy.
Synovial Sarcoma
Site: Most commonly occurs around the knee.
Cytogenetic marker: t(x; 18)
Spread: Via lymphatics.
Treatment: Lymph node excision.
Secondaries in Bone
Source:
Lungs in males most common.
Breast in females most common.
Others prostate, kidneys, thyroid, urinary bladder.
Type:
Osteolytic secondaries from kidneys and breast.
Features hypercalcemia.
Diagnosis X-ray.
Osteoblastic secondaries from prostatic Ca.
Features increased alkaline phosphatase,
hypocalcemia.
Diagnosis radionuclide scanning.
814
Site:
Most commonly affect the vertebra.
Bone secondaries are uncommon below the elbow and
knee.
Clinical feature: Pain is the most common symptom.
Diagnosis: CT scan is more reliable.
Note: Multiple myeloma produces cold spots on bone
scan.
Treatment: Radiation therapy.
Note: Surgical staging of bone tumors is done by Enneking
system.
TUMOR LIKE CONDITIONS OF BONE
Osteochondroma
They are the most common tumors of bone.
Site: Metaphysis of long bones, usually around the knee.
The tumors migrate to diaphysis as normal metaphyseal
growth occurs.
Clinical feature:
They occur in adolescents.
Symptom painless swelling.
Multiple cartilaginous exostoses (diaphyseal aclasis)
constitute an uncommon disorder inherited in an
autosomal dominant fashion.
May turn to chondrosarcoma.
Enchondroma (Chondroma)
Site: Most commonly involve the small bones of hands
and feet. They are the most common tumor of hand.
Associations:
i. Olliers disease or enchondromatosis non-hereditary;
characterized by multiple enchondromas.
ii. Maffuccis syndrome hereditary; characterized by
multiple enchondromas and cavernous hemangiomas.
Bone Cysts
Simple Bone Cyst
Occurs in children and adolescents.
Most commonly affect the diaphysis of long bones
mainly the upper end of humerus and upper end of
femur.
Produce solitary lytic lesion in bone.
Oncology
815
Aneurysmal Bone Cyst

Feature: Blood-filled space enclosed in a shell, ballooning
up the overlying cortex.
Site: Ends of long bones, usually the humerus; also the
vertebrae.
X-ray: Radiolucent area with expansion of overlying bone
(expansile lytic lesion).
Treatment: Curettage and bone grafting.
Fibrous Dysplasia
Monostotic fibrous dysplasia usually affects the long
bones, may produce solitary lytic lesion.
Polyostotic fibrous dysplasia + precocious puberty +
caf au lait spots in girls is known as McCune Albright
syndrome.
Pathological fracture occurring in femoral neck in
polyostotic fibrous dysplasia may produce shepherds
crook deformity.
Miscellaneous
Melorheostosis: cortical thickening resembling wax
dripping down one side of a candle (Melting Candle
Wax syndrome).
Langerhans cell histiocytosis: May produce of collapse
of a vertebral body (Vertebra Plana) and map-like
radiolucent area in skull (Geographic Skull).
12
DERMATOLOGY
ANATOMY
Skin is the largest organ in the body.
Epidermis
Layers:
Stratum corneum most superficial layer. It is
underdeveloped in preterm infants for 2-3 weeks.
Stratum lucidum.
Stratum granulosum.
Stratum spinosum (prickle cell layer) prickle cells are
keratinocytes linked by desmosomes. This layer provides
mechanical strength to the skin.
Stratum basalae or stratum germinatum deepest
layer, mitotic activities are more intense here.
Cells in epidermis:
Melanocytes dendritic cells in the basal layer.
Langerhans cells antigen-presenting cells, derived
from bone-marrow and found in the prickle cell layer.
Merkels cells slow adapting mechanoreceptors found
in prickle cell layer.
Epidermal proliferation time:
Or skin doubling time is 4 weeks.
Dermis
Layers:
Papillary layer.
Reticular layer composed of collagen fibers.
Components:
Collagen type I and III.
Elastin and proteoglycans.
Glands
Apocrine glands: sweat glands in axillae and groin,
mammary gland.
Dermatology
817
Holocrine glands: sebaceous gland.

Eccrine (merocrine) glands: sweat glands on palms
and soles.
Modified sweat gland: ceruminous glands and ciliary
glands.
Modified sebaceous glands: Meibomian glands.
PATHOLOGICAL TERMS
Hyperkeratosis: Increased thickening of stratum
corneum.
Parakeratosis: presence of immature nucleated cells in
stratum corneum.
Dyskeratosis: premature keratinization of epidermal cells.
Acanthosis: increased thickness of the prickle cell layer
due to stimulation of basal layer.
Acantholysis: loss of cohesion between epidermal cells,
seen in all types of pemphigus.
Grenz zone: clear zone between the epidermis and
dermal lesions.
Hydropic degeneration of basal cells: vacuolization of
basal cells seen in LE, dermatomyositis, early lichen
planus.
Foam cells: lipid-laden macrophages containing dead
lepra bacilli.
Spongiosis: accumulation of fluid between epidermal
cells, seen in acute eczema.
Types of Skin Lesions
Flat lesions:
Macule: < 2 cm, colored.
Patch: > 2 cm, colored.
Purpura: Extravasation of RBCs in the skin, blanches
on pressure.
Telangiectasia: Permanent dilatation of superficial
vessels.
Elevated lesions:
Papule: < 1 cm, solid.
Nodule: 1-5 cm, solid.
Tumor: > 5 cm, solid.
Plaque: > 1 cm, flat topped.
Vesicle: < 1 cm, fluid-filled.
Bullae: > 1 cm, fluid-filled.
Pustule: Vesicle filled with leukocytes.
818
DIAGNOSTIC TECHNIQUES
Tzanck Smear
Most commonly used in the diagnosis of herpes virus
infection shows multinucleated giant cells.
Also used in pemphigus shows acantholysis.
Woods Lamp
Generates 360 nm UV rays (black).
Use:
i. Coral red color erythrasma.
ii. Pale blue pseudomonas wounds.
iii. Yellow color tinea capitis.
iv. Pinkish red porphyria cutanea tarda (urine).
v. Others tinea versicolor pale yellow.
vi. Ash leaf spots.
Patch Test
Skin hypersensitivity test (delayed type).
Readings are made after 48 hours.
Use: In the diagnosis of contact dermatitis.
COMMON SKIN DISORDERS

ECZEMA OR DERMATITIS
Atopic Dermatitis
Infantile pattern: involves face, neck, extensor surfaces
and groin.
Childhood pattern: involves flexural skin, particularly
in the antecubital fossa and popliteal fossa.
Dennie morgan fold.
Diagnosis:
By clinical examination of skin.
Biopsy is best.
Contact Dermatitis
Delayed type of hypersensitivity mediated by memory
T cells.
Dermatology
819
Most common metal causing contact dermatitis in

nickel.
Most common site affected is hand.
Most common cause of air-borne contact dermatitis
perthenium.
Most common cause of contact dermatitis in Indian
women detergent.
Barloque dermatitis due to cosmetics.
Diagnosis: Patch test.
Hand Eczema
Caused by chronic exposure to water and detergent.
Clinical feature:
Dryness and cracking of the skin of hands with variable
erythema and edema.
Diagnosis: Scratch test with latex extract.
Nummular Eczema
Characterized by circular or oval coin-like lesion.
Most common sites are trunk and extensor surfaces
of extremities (pretibial skin and dorsum of hands).
Most commonly affects men in middle age group.
Lichen Simplex Chronicus
End stage of various eczematous disorders,
characterized by lichenification (thickening) of skin due
to chronic scratching and rubbing.
Most common sites nuchal region, dorsum of feet
and ankles.
Asteatotic Eczema
Also called the winter-itch.
Seen in elderly people in dry season.
Characterized by fine cracks like that on china or
porcelain over the anterior surface of legs.
Stasis Dermatitis
Due to venous incompetence and chronic edema.
Site over the medial aspect of the ankle.
820
Seborrheic Dermatitis
Most common location is the scalp.
In adults, it is seen in patients with Parkinsons disease,
CVA and HIV infection.
PAPULOSQUAMOUS DISORDERS
Psoriasis
Characterized by erythematous, sharply demarcated
papules and rounded plaques, covered by silvery micaceous
scales. The lesions are pruritic.
Pathology:
There is increase in epidermal proliferation rate (skin
doubling time reduced to 4 days).
Thickness is increased from normal 3-4 cells to 1215 cells. Stratum corneum is parakeratotic and
contains microabscesses of neutrophils (Munro
microabscess).
Types:
1. Stable plaque most common type.
Sites extensor aspects of elbows, knees, gluteal cleft
and the scalp.
2. Eruptive or guttate psoriasis most common in children
and young adults.
Involves the trunk, may follow a streptococcal URTI.
3. Erythrodermic psoriasis.
4. Pustular psoriasis
This follows an exacerbating episodes, e.g. infection,
withdrawal of steroids, etc.
Most commonly occurs on palms and soles. May be
generalized.
5. Inverse psoriasis
Non-scaly, red lesions in flexural areas, e.g.
inframammary region (compare the normal type).
Etiology:
1. Idiopathic may have positive family history.
2. External factors infection, stress.
3. Drugs antimalarials, beta blockers, lithium.
Clinical feature:
Pruritus.
Dermatology
821
Auspitz sign removal of scales causes pinpoint

bleeding.
Koebner or isomorphic phenomenon development
of lesions in traumatic skin.
Nail involvement punctuate pitting (thimble pitting),
onycholysis, subungual hyperkeratosis, oil drop sign
(yellow discoloration).
Psoriatic arthropathy seen in 5-10 percent cases, most
commonly involves the small bones in hands; sacroilitis.
X-ray bone: shows opera glass hand, pencil in cup
appearance of hands.
Treatment:
Topical therapy glucocorticoids, vitamin D analogue
(calcipitriol).
Phototherapy UVB radiation. Combination of UVA
radiation and oral/topical psoralen (PUVA) is known
as photochemotherapy.
Methotrexate is used in erythrodermic psoriasis,
pustular psoriasis and psoriatic arthritis.
Retinoids are used in pustular psoriasis (drug of choice
in this condition).
Lichen Planus
This is characterized by pruritic, polygonal, flat-topped,
violaceous papules.
Sites: Wrists, shins, lower back and genitalia.
Etiology: Drugs, chronic graft-versus-host disease, chronic
viral hepatitis (hepatitis C).
Pathology:
Subepidermal lymphocyte infiltration.
Degeneration of the basal cell layer.
Increased thickness of the stratum granulosum.
Civatte bodies are seen.
There is hyperpigmentation of the residual skin.
Clinical feature:
Intense itching.
Wickhams striae gray lines on lesions.
Oral mucosa white net-like eruption.
Scalp scarring alopecia.
822
Nail subungual hyperkeratosis, dystrophy of nail,

pterygeum, onychorrhexis, anychia.
Koebners phenomenon see above.
Course: Spontaneous remission occurs in most cases.
Treatment: Topical glucocorticoids.
For systemic disease systemic steroids.
Pityriasis Rosea
Etiology unknown.
This is characterized by annular lesions of 2-6 cm
diameter (the herald patch) followed by smaller annular
or popular lesions, predominantly on the trunk along
the cleavage lines.
Lesions are erythematous with fine branny scales.
Rarely involves the palms and soles (c.f. secondary
syphilis).
Common in young adults and in women.
Course usually self-limiting.
Lesions on the back are parallel to the ribs giving a
Christmas tree appearance.
Pityriasis Rubra Pilaris
Clinical feature: Orange-red perifollicular papules.
Site:
Generalized, first involves the face and scalp.
Characteristically, islands of normal skin are spared
skip lesions.
Others wax like keratoderma.
Seen in: middle aged and elderly.
Diagnosis: Skin biopsy.
Treatment: Isotretinoin, methotrexate.
Pityriasis
Cause
Lesion
P. alba
P. rosea
Unknown
Hypopigmented
macule with
scaling
Unknown
P. orbiculare (fungus)
Herald patch Hypo/hyperpigmented
followed by
macule with scaling
generalized
erythematous
P. versicolor
(Contd...)
Dermatology
823
(Contd...)
P. alba
Site
Face
Age group Children

Treatment Self-limiting
P. rosea
P. versicolor
lesion with
scaling (papulosquamous)
Trunk
Trunk, shoulders, arms,
neck
Young adults Young adults
and women
Self-limiting
Selenium sulfide
shampoo
CUTANEOUS INFECTIONS
Impetigo
Most common skin infection in children.
a. Non-bullous impetigo:
Causative organism Streptococcus pyogenes,
Features superficial skin infection with honey colored
crusted papules.
Complication acute glomerulonephritis.
In rugby players, it can spread to teammates scrum
pox.
b. Bullous impetigo:
Causative organism coagulase positive group II
Clinical feature tense, clear bullae.
Ecthyma
Variant of impetigo.
Occurs in lower extremities.
Causes punched-out ulcers.
Erysipelas
Causative organism Streptococcus pyogenes (most
common), Staphylococcus aureus (very rare).
Predisposing lesions chronic lymphedema.
Dermatophytosis and Fungal Infections
Please see the chapter of Infectious Diseases.
824
Warts
Please see the chapter of Virology.
ACNE
Acne Vulgaris
Characterized by papulopustular/nodulocystic rash.
Site:
Most commonly on the face.
Others back and chest.
Etiology:
Overproduction of sebum and blockage of hair follicular
orifice.
Secondary infection of pilosebaceous gland with fungus
(P. orbiculare) or bacteria (propionibacterium acne).
Clinical feature:
Occurs in teenagers and young adults.
Comedones are the hallmark of acne vulgaris.
Treatment:
Oral tetracycline or erythromycin.
Topical retinoic acid (for nodulocystic acne), benzoyl
peroxide, salicylic acid.
Acne Rosacea
Occurs in adults, most commonly in women.
Predisposing factors: History of flushing associated with
heat, emotional stimuli, alcohol, hot drinks or spicy foods.
Site: Most commonly the central face. This does not affect
the trunk.
Clinical feature: Erythema, telangiectasia, superficial
pustules, but no comedones.
Complication:
Nose connective tissue overgrowth. Rhinophyma is
due to sebaceous gland hypertrophy.
Eye keratitis, uveitis, chalazion.
Treatment: Oral tetracycline, topical metronidazole.
Dermatology
825
SKIN MANIFESTATIONS OF
INTERNAL DISEASES
Reiters Disease
Psoriasis plus arthritis most commonly involves the
DIP.
Other features oral ulcers, conjunctivitis, uveitis and/
or urethritis, circinate balanitis.
Skin lesion keratoderma blenorrhagica.
Erythroderma (Exfoliative Dermatitis)
Majority of the skin surface is erythematous.
Etiology:
1. Primary cutaneous disorders
i. Psoriasis most common cause.
ii. Dermatitis atopic, contact, stasis, seborrheic.
iii. Pityriasis rubra pliaris.
2. Drugs exfoliative dermatitis.
3. Systemic diseases
i. Cutaneous T cell lymphoma.
ii. Lymphoma.
4. Idiopathic.
Clinical feature: Erythema, edema and scale in skin; fever,
lymphadenopathy.
Figurate Skin Lesions
Erythema gyratum repens: due to underlying
malignancy.
Erythema migrans: Lyme disease.
Erythema marginatum: rheumatic fever.
ALOPECIA
Normal hair growth:
Phases
Anagen = growing phase.
Telagen = resting phase.
Catagen = involution phase.
Etiology:
a. Non-scarring alopecia
1. Alopecia areata autoimmune disease, exclamation
mark hair.
826
2. Androgenetic alopecia.
3. Tinea capitis most commonly due to trichophyton
tonsurans.
4. Lupus erythematous may involve the entire scalp
or may be limited to frontal scalp. Characterized by
multiple short hairs (lupus hair).
5. Secondary syphilis poorly circumscribed alopecia
with moth-eaten appearance.
6. Others hypo/hyperthyroidism, HIV infection.
7. Telogen effluvium following major stress (usually
after 3 months).
Treatment:
Alopecia areata minoxidil.
Androgenetic alopecia topical minoxidil
isotretinoin, finasteride, cyproterone acetate.
Testosterone is contraindicated.
b. Scarring/cicatrical alopecia (pseudopelade)
1. Cutaneous lupus (also SLE).
2. Lichen planus.
3. Linear scleroderma (morphea).
4. DLE.
5. Sarcoidosis.
Telogen effuvium:
Diffuse hair loss occuring 2-3 months after a precipitating
stimulus like infections, childbirth, surgery, hemorrage or
emotional stress.
HYPOPIGMENTATION
Oculocutaneous Albinism
Most commonly due to mutations in the tyrosine gene
or P gene.
Ocular manifestations decreased visual acuity,
nystagmus, photophobia, monocular vision.
Vitiligo
1. Vogt-Koyanagi-Harada syndrome:
Vitiligo, aseptic meningitis, uveitis, tinnitus, hearing loss
and/or dysacousis.
2. Scleroderma.
3. Melanoma associated leukoderma.
Treatment: Psoralen A is used in the treatment of vitiligo.
Dermatology
827
Piebaldism
Autosomal dominant inheritance.
Causes:
1. Hirschprungs disease.
2. Waardenburgs syndrome: congenital sensorineural
deafness, dystopia canthorum, heterochromic iris, broad
nasal root.
Tuberous Sclerosis
Features:
1. Ash leaf shaped spots hypopigmented patch present
at birth, usually multiple, diagnosed by Woods lamp.
2. Adenoma sebaceum (multiple angiofibromas of face).
3. Ungual and gingivial fibrosis (Koenons).
4. Fibrous plaques of the forehead.
5. Connective tissue nevi (Shagreen patches) seen
mainly in the lumbosacral region.
6. Others seizures, metal retardation, CNS and retinal
hamartomas, renal angiomyolipomas, renal cyst,
cardiac rhabdomyomas.
HYPERPIGMENTATION
LOCALIZED
Seborrheic Keratitis
Sign of Leser-Trelat.
Acanthosis nigricans
May be a reflection of internal malignancy, most
commonly of the GI tract.
Seen in flexural areas axillae, neck, groin, anogenital.
Benign type seen in childhood or puberty, associated
with obesity and diabetes.
Lentigens
1. Peutz-Jeghers syndrome: autosomal dominant.
i. Lentigens around the nose and mouth
ii. Multiple benign polyps in GI tract
iii. Ovarian tumor.
iv. Increased chance of malignancy of GI tract.
828
2. LEOPARD syndrome:
1. Lentigens.
2. ECG abnormalities.
3. Ocular hypertelorism.
4. Primary conduction defects.
5. Abnormal genitalia (cryptorchidism, hypospadias).
6. Retardation of growth.
7. Deafness (sensorineural).
Nevi
1. LAMB syndrome:
i. Lentigens.
ii. Atrial myxoma.
iii. Mucocutaneous myxoma.
iv. Blue nevi.
2. NAME syndrome:
i. Nevi.
ii. Atrial myxoma.
iii. Mysoid nerurofibroma.
iv. Ephelides (freckles).
Caf au lait Spots
i.
ii.
iii.
iv.
v.
Neurofibromatosis.
Albrights syndrome.
Watson syndrome (pulmonary stenosis).
LEOPARD syndrome.
Ataxia telangiectasia.
Dyskeratosis Congenita
Atrophic reticulated hyperpigmentation on the neck,
thighs and trunk.
Others nail dystrophy, pancytopenia, leucoplakia of
oral and anal mucosa.
DIFFUSE
Endocrinopathies
Addisons disease.
Nelsons syndrome.
Cushings disease.
Graves disease.
Dermatology
829
Metabolic
Porphyria cutanea tarda.
Hemochromatosis.
Autoimmune
Biliary cirrhosis.
Scleroderma.
POEMS syndrome (polyneuropathy, organomegaly,
endocrinopathy, M-protein and skin changes).
VESICLES/BULLAE
Autoimmune
Immunological skin diseases
Site
Bullae
Pemphigus
Pemphigoid
Superficial
(intraepidermal)
Flaccid
Deep (subepidermal) Subepidermal
Age
40-60 years
Sensation Painless
Location Buccal
mucosa
most common
Course
Bleed easily
with little
tendency to
heal
Acantho- Positive
lysis
Nikolskys Positive
sign
Association
Immuno IgG deposits

fluoresc- in epidermis
ence
study
Treatment Systemic
steroids
Tense
Dermatitis
herpetiformis
Papulovesicular
lesion
60-80 years
Painless
Lower extremities
most common
Extremely itchy
Elbow, knees,
buttocks
Rupture is late and

heals rapidly
Tendency for
grouping
Negative
Negative
Negative
Negative
Lymphoma
Gluten sensitive
enteropathy,
HLA B8
IgG against basement IgA deposit in
membrane
dermoepidermal
junction
Systemic
steroids
Dapsone
Pemphigus Vulgaris
This is due to IgG type antibody aginst intracellular
substance (desmoglein a glycoprotein) causing suprabasal
splitting.
830
Infections
Staphylococcal Scalded Skin Syndrome (SSSS)
Also termed as Ritters disease in neonates and toxic
epidermal necrolysis in adults.
Causative organism: Staphylococcus aureus phage group
II.
Pathology: Infection is extracutaneous (conjunctivitis, otitis
media, pharyngitis, etc.) and the cutaneous lesions are
sterile.
Clinical feature: Flaccid bullae and exfoliation of superficial
epidermis. There is no mucosal involvement or systemic
features (c.f. TEN).
Mediator: Staphylococcal exfoliative toxin.
Bullous Impetigo
In comparision to SSSS the skin lesions are the site
of infection, more localized, presents with honey-colored
crusts.
Toxic Epidermal Necrolysis (TEN)
Cause:
Drugs (most common) phenytoin.
Infections.
Clinical feature: Widespread bullae with erythema and
sloughing. Oral mucosa frequently involved. Systemic
features are frequent and associated with high mortality.
Diagnosis:
SSSS and TEN are differentiated by punch biopsy with
frozen section.
SSSS involves stratum corneum.
TEN involves stratum basale/germinatum.
Erythema Multiforme
Cause:
1. Herpes simplex virus most common cause.
2. Drugs sulfonamides.
3. Internal malignancy
4. Inflammatory bowel disease.
5. UV light.
Dermatology
831
Clinical feature:
Target or iris lesions.
Vesicles and bullae.
Most commonly seen on palms, hands, soles, extensor
forearms (most commonly the face and upper limbs).
Hemorrhagic crust on the lips.
Examples:
Steven-Johnson syndrome.
Toxic epidermal necrolysis.
Metabolic
Diabetes Mellitus
i.
ii.
iii.
iv.
Necrobiosis lipoidica diabeticorum.

Granuloma annulare.
Diabetic dermopathy (Binkleys spots).
Diabetic bullae occur in the extremities.
Porphyria Cutanea Tarda

Most commonly on the sun-exposed skin of face and
hands.
EXANTHEMS
First disease measles.

Second disease scarlet fever.
Third disease rubella.
Fourth disease Dukes disease (scarlantinella).
Fifth disease erythema infectiosum.
Sixth disease roseola infantum.
Scarlatiniform scarlet fever, TSS, Kawasakis diease.
Morbilliform measles, rubella, erythema infectiosum.
Erythema Infectiosum
Cause: Human parvovirus B19.
Clinical feature:
Slapped cheek appearance.
Occurs in children 3-12 years of old.
Rash waxes and wanes over 3 weeks.
May cause aplastic crisis.
Roseola Infantum
Cause: HHV-6B.
832
Clinical feature:
Common in children < 3 years of age.
Maculopapular rash appears after fever subsides.
Resolve within 2 days.
Spares the face.
URTICARIA AND ANGIOEDEMA
Type I hypersensitivity mediated by histamine.
Types:
i. Dermographism triple response to minor strokes on
the skin.
ii. Solar urticaria.
iii. Cold urticaria.
iv. Cholinergic urticaria.
Angioedema (Quinckes Disease)
Subcutaneous edema most commonly involving eyelids,
lips, tongue, larynx and GI tract.
PAPULONODULAR LESIONS
FLESH COLORED
Rheumatoid Nodules
Seen around pressure points especially the elbows.
Cause:
Rheumatoid arthritis.
Stills disease.
Rheumatic fever.
Neurofibroma
Soft papules and nodules, exhibit button hole sign.
Lisch Nodules
Yellow borwn spots in the iris, best seen by slit-lamp
examination.
PINK LESIONS
Primary systemic amyloidosis.
Dermatology
833
YELLOW LESIONS
i.
ii.
iii.
iv.
v.
Hyperlipidemia (xanthomas).
Gout (Tophi).
Diabetes (necrobiosis lipoidica) over the front of legs.
Pseudoxanthoma elasticum.
Torres syndrome (sebaceous tumors).
Pseudoxanthoma Elasticum
Pathology: Deposition of calcium on the elastic fibers of
the skin, eye and blood vessels.
Site: Flexural areas (neck, axillae, antecubital fossa and
inguinal area).
Clinical feature:
Plucked chicken appearance of skin.
Eye calcium deposition in Bruchs membrane leads
to angioid streaks and choroiditis.
Others angina, hypertension, gastrointestinal bleeding
and claudication.
RED LESIONS
Angiokeratomas
Multiple angiokeratomas are seen in Fabrys disease
(lysosomal storage disease).
Panniculitis
Inflammation of fat.
Erythema Nodosum
Cause: infections (streptococci most common, TB)
Drugs: sulfonamides.
Systemic: sarcoidosis, ulcerative colitis.
Site: most commonly on the shin.
Clinical feature: red tender nodules that develop blue color
as they resolve.
Erythema Induratum
Cause: Idiopathic.
Most common site is calf.
PCR analysis show M. tuberculosis complex DNA.
834
Weber-Christian Disease
Arthritis, fever and inflammation of visceral fat.
Others
1 Antitrypsin Deficiency, lupus profundus.
RED-BROWN LESIONS
Lupus Vulgaris
Most common form of cutaneous TB.
Seen in previously sensitized individuals. There is often
underlying TB elsewhere, usually in the lungs and lymph
nodes.
Site: Most commonly in the head and neck area.
Features:
Apple jelly nodules.
Healed lesions present central scarring.
Match stick test positive.
Diagnosis: Biopsy.
Sweets Syndrome
Painful papules/nodules on head, neck and upper
extremities.
Others fever, neutropenia, dense dermal infiltrate of
neutrophils.
Association: acute nonlymphocytic leukemia.
Treatment: steroids.
Mastocytosis (Urticaria Pigmentosa)
Clinical feature: Dariers sign. Multiple hyperpigmented
macular lesions which urticrate on scratching.
BLUE LESIONS
Mafuccis Syndrome
Associated with dyschondroplasia and osteochondromas.
Kasabach-Merritt Syndrome
Large single hemangioma + platelet consumption.
CUTANEOUS METASTASIS
In men, from lungs, colon, melanoma and oral cavity.
In women, from breast, colon and lungs.
Dermatology
835
PURPURA
Extravasation of RBC in dermis; does not blanch on
pressure. When 3 mm, it is called purpura (< 3 mm
petechiae).
Non-palpable
1.
2.
3.
4.
Thrombocytopenia (ITP, TTP).

Scurvy.
DIC.
Monoclonal cryoglobulinemia.
Palpable
1. Vasculitis
Leukocytoclastic vasculitis (LCV) or allergic vasculitis
most common cause. This includes H-S purpura,
drug induced vasculitis, mixed cryoglobulinemia.
2. Amyloidosis.
3. Acute meningococcemia.
4. Ecthyma gangrenosum pseudomonas bacteremia.
5. Rocky mountain spotted fever.
CUTANEOUS MANIFESTATION
OF INTERNAL MALIGNANCY
1. Acanthosis nigricans most commonly associated with
adenocarcinoma of stomach, breast Ca.
2. Erythema gyratum repens Ca bronchus.
3. Thrombophlebitis migrans Ca pancreas.
4. Bullous pemphigoid.
5. Bowens disease intraepidermal Ca.
6. Pyoderma gangrenosum leukemia.
7. Bazex syndrome (paraneoplastic acrokeratosis).
8. Necrolytic migratory erythema.
PHOTOSENSITIVITY
UV-B Radiation
Wavelength 290-320 nm.
Most efficient to produce redness of human skin, hence
called the sunburn spectrum.
UV-A Radiation
836
PUVA is used in psoriasis, vitiligo, mycoses fungoides,

alopecia.
Visible Light
Note: In porphyria, there is sensitivity to both short
and long wavelengths.
MISCELLANEOUS
INFECTIONS
Toxic Shock Syndrome
Cause:
i. Staphylococcus producing TSS toxin1 or enterotoxin
B or C.
Most common clinical setting is menstruation.
ii. Streptococcus pyogenes producing pyrogenic exotoxin
A.
Clinical feature: Fever, macular red rash, hypotension,
multiorgan failure.
Erythrasma
Causative organism: Corynebacterium minutissinum.
Mycobacterial Skin Infection
Lupus vulgaris: most common form of cutaneous TB
(see above).
Scrofuloderma: results from direct extension of
infection from underlying tuberculosis focus, i.e. infected
lymph nodes, muscle or bones.
Tuberculous chancre: occurs in person with no previous
infection or immunity.
Tuberculosis verrucosa cutis (TVC): occurs in previously
infected individuals with a high degree of immunity.
Tuberculids: generalized symmetric exanthems in
tuberculous patients, possibly resulting from
hypersensitivity.
Swimming-pool granuloma: caused by atypical
mycobacterium M. marinum.
Buruli ulcer: caused by atypical mycobacterium M.
ulcerans.
Dermatology
837
Scabies
Causative organism: Itch mite Sarcoptes scabiei.
Incubation period: 2-3 weeks.
Pathology: The fertilized female makes the characteristic
skin burrow in stratum corneum.
Clinical feature:
Intense pruritus, worse at night and after a hot shower.
Burrows seen most commonly on interdigital webs,
flexor aspects of wrists.
Site: the face, scalp, neck, palms and soles are spared
except in children.
Nodular scabies affects the scrotum.
Norwegian scabies hyperinfestation with thousands
of mites, seen in steroid therapy, immunodeficiency
or AIDS.
Treatment:
Gamma-Benzene hemachloride (lindane) 1% solution
(side effects seizures and aplastic anemia).
5% permethrin cream drug of choice.
Benzyl benzoate.
Tetmosol.
Crotamiton.
Ivermectin.
Pediculosis
Cause: Lice (pediculus) infestation.
Types:
Head lice.
Body lice may produce hyperpigmentation and
thickening of skin (Vagabonds disease).
Pubic lice may produce blepharitis.
Treatment:
One percent permethrin cream drug of choice.
Crotamiton.
Hidradenitis Suppurativa
Infection of apocrine sweat glands (in axillae, groin).
Most commonly due to bacteroids.
Treatment: metronidazole.
838
INHERITED DISORDERS
Ichthyosis Vulgaris
Feature:
Scaly lesions involving the extensor surfaces of
extremities, palms and soles.
Peak age of onset 1-4 years.
Herlequine skin changes.
Severe form of icthyosis vulgaris is called crocodile skin.
Pathology: Granular layer is absent.
Sarcoidosis
Maculopapular rash, erythema nodosum, subcutaneous
nodules (Darrier-Roussy sarcoidosis).
Lupus pernio: involves the nose, cheeks, lips, ears,
fingers and knees.
Darriers Disease
Point mutation of 12q23 which codes for a calcium
ATPase pump.
Abnormal cell to cell adhesion (loss of desmosomes)
and aberrant epidermal keratinization (dyskeratosis).
Sturge-Weber Syndrome
Facial portwine stain.
Leptomeningeal angiomatosis (causing epilepsy and
mental retardation).
Cerebral angiomas leading to cortical atrophy.
Pheochromocytoma.
Eye glaucoma, megalocornea, choroidal hemangiomas.
X-ray skull tram track appearance.
Ataxia Telangiectasia
Autosomal recessive due to gene defect on chromosome
11q22/23.
Dermatology
839
Clinical feature:
Cerebellar ataxia (earliest sign at the age of 12-18
moths).
Mucocutaneous telangiectasia.
Risk development of respiratory infection and
malignancy.
Von-Hippel Lindau Syndrome
Autosomal dominant.
Features:
Facial or occipitocervical port-wine stain.
Bilateral retinal angiomatosis.
Cerebellar, medullary or spinal hemangioblastomas.
Renal cell carcinoma.
Pheochromocytoma.
Acrodermatitis enteropathica
Cause: Malabsorption of dietary zinc.
Clinical feature:
Periorificial and acral dermatitis.
Alopecia, intractable diarrhea, neurological symptoms,
variable combined immunodeficiency.
Primary Amyloidosis
Pinch purpura most common skin lesion.
Lichen (papular) amyloidosis most common site is
skin.
Epidermolysis bullosa
Genetic disorder. Due to mutation of genes for keratin
14 and 5, laminin or collagen VII.
The skin and related epithelial tissues break and blister
as result of a minor trauma.
MISCELLANEOUS
Nail Involvement
1. Beaus line any severe systemic illness.
2. Onycholysis psoriasis, thyrotoxicosis, tetracycline,
trauma.
840
3.
4.
5.
6.
Pitting psoriasis, alopecia areata, lichen planus.

Ridging lichen planus.
Koilonychia iron deficiency anemia, lichen planus.
Muehrcks nail severe hypoalbuminemia as in
nephrotic syndrome.
7. Blue nails Wilsons disease.
8. Brown nail - Addisons disease, arsenic poisoning.
9. Leuconychia liver disease.
10. Mees line arsenic poisoning.
LASER
Ruby LASER is selectively absorbed.
CO2 LASER has the minimum penetration.
Central clearing
Central scarring
Central crusting
Seen in
Diagnosis
Tinea corporis
Lupus vulgaris
Leishmaniasis
KOH smear
Biopsy
LD body demonstration
Others
Dhobis itch = T. cruris.
Fordyces spot is situated on the lips.
Crystalline miliaria is due to obstruction of sweat
glands.
13
GENETICS
GENETIC STRUCTURE
NUCLEOTIDES
Nucleotide = nitrogenous base + pentose sugar +
phosphate group.
Purine and Pyrimidine
These are heterogeneous bases containing nitrogen.

Purines adenine (A) and guanine (G).
Pyrimidines cytosine (C), thymine (T) and uracil (U).
Both DNA and RNA contain A, G and C.
RNA contains U, whereas DNA contains T.
Nucleoside
Nucleoside = purine/pyrimidine base + ribose or
deoxyribose sugar.
The pentose sugar is linked via a covalent -N-glycosidic
bond to N9 of a purine or to N1 of a pyrimidine base.
Nucleotide
Nucleotide = nucleoside + phosphate group.
The phosphate group is attached by an ester linkage
to the 5-OH of the pentose sugar.
The phosphate groups are responsible for the negative
charge of nucleotides and nucleic acids.
Nucleotides present in the free state in cells are
hypoxanthine and xanthine.
ATP is the most abundant free nucleotide in cells.
Minor or Unusual Bases
Minor or unusual bases are formed occasionally in some
species of DNA and RNA, e.g. some viral DNA and
t-RNA.
842
Base modifications include methylation, hydroxymethylation, acetylation, glycosylation or alternation of

the atoms in pyrimidine ring.
Functions
Energy: Nucleoside triphosphates (e.g. ATP and GTP) have
high group transfer potentials (Go = 7 kcal/mol.) and
serve as the major biological transducer of free energy.
Second messenger:
cAMP and cGMP act as second messengers.
ATP
cAMP
Adenyl cyclase
5AMP
Phosphodiesterase
cGMP mediates NO induced muscle relaxation.

Biosynthetic pathways:
UDP-glucose is the glucosyl donor for biosynthesis of
glycogen and disaccharides.
UDP-glucuronic acid serves as glycosidic acid donor
for conjugation reaction of bilirubin and various drugs.
Coenzymes: Many coenzymes, e.g. NAD, NADP, FAD,
CoA are derivatives of nucleotides.
Others
Nucleosides, nucleotides absorb UV light at a wavelength
close to 260 nm (at pH 7) due to the conjugated double
bonds present in heterocyclic bases.
The 5-phosphoryl group of a nucleotide can esterify
a second alcohol functional group (-OH) forming a diester.
The 35 phosphoidiester bond forms backbone of
polynucleotides such as RNA and DNA.
PURINE AND PYRIMIDINE

Dietary nucleotides are not directly utilized in the body.
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DE NOVO SYNTHESIS OF PURINES

Sources of various atoms in purine ring:
Site
Liver is the major site of purine biosynthesis.
Synthesis
First step:
The major determinant of overall purine synthesis is

the concentration of PRPP.
PRPP is also involved in pyrimidine synthesis and
salvage pathways.
Second step:
This is the committed step in purine biosynthesis.

IMP production: The following reactions form inosine
monophosphate (IMP) which is the parent nucleotide for
formation of both AMP and GMP.
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Formation of diphosphate and triphosphate: Nucleotide

monophosphates (NMP) are converted to diphosphates
by non-specific kinases.
E.g.
Adenylate kinase activity is high in liver and muscles.
Nucleotide diphosphates are converted to triphosphates
by specific kinases.
Clinical Implication
Purine synthesis requires tetrahydrofolate which is formed
from dihydrofolate by dihydrofolate reductase.
1. Methotrexate blocks DHF reductase and blocks purine
synthesis.
2. Sulfonamides are structural analogues of PABA that
competitively inhibit bacterial synthesis of folic acid.
Thus, sulfa drugs also block purine synthesis in bacteria
(but not in human beings).
SALVAGE PATHWAY FOR PURINE SYNTHESIS
PRPP acts as a ribose 5-P donor.
3 types of reactions:
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PYRIMIDINE SYNTHESIS
Source
PRPP donates ribose 5-P group.
Glutamine, aspartate and CO2 donate the C and N
atoms (not glycine, c.f. purines).
Reactions
Step 1:
This is the regulatory step in pyrimidine synthesis in

mammalian cells.
Carbamoyl phosphate synthase
Location
Pathway
CPS I
CPS II
Mitochondria
Urea cycle
Cytosol
Pyrimidine synthesis
Step 4:
Formation of orotic acid by dihydrofolate dehydrogenase
which is the only mitochondrial enzyme involved in
pyrimidine synthesis. All other enzymes are cytosolic.
Step 5 and 6:
Orotic acid is converted to OMP and UMP by orotate
phosphoribosyl transferase and orotidylic acid
decarboxylase, respectively. Deficiency of any of these two
enzymes cause orotic aciduria.
OMP is the parent nucleotide for UMP, CMP, TMP.
Thymidylate synthetase converts dUMP to TMP. This
is blocked by 5-FU.
PURINE CATABOLISM
Purines are converted to uric acid and excreted in urine.
846
Allopurinol inhibits xanthine oxidase and decreases the

production of uric acid.
Uric acid is relatively insoluble and hence excess
production results in gout.
PYRIMIDINE CATABOLISM
Pyrimidine -alanine, CO 2 , NH 3 and -aminoisobutyrate.
These metabolites are highly water soluble and hence
excess production does not lead to any problem.
DISORDERS OF PURINE METABOLISM
Lesch-Nyhan Syndrome
This is due to complete deficiency of HGPRTase. There
is overproduction of purines and gout.
Others self-mutilation, involuntary movements,
mental retardation.
von Gierkes Disease
Due to deficiency of glucose 6-phosphatase, there is
increased production of PRPP precursor ribose 5-P (via
HMP shunt) increased purine production and
hyperuricemia.
Adenosine Deaminase Deficiency
This causes severe combined immunodeficiency involving
both T cells and B cells dysfunction.
Purine Nucleoside Phosphorylase Deficiency
This results in dysfunction of T cells but no apparent effect
on B cell function.
Gout
Please see the chapter of Metabolism.
DISORDERS OF PYRIMIDINE METABOLISM
Orotic Aciduria
Due to deficiency of orotate phosphoribosyl transferase
or orotidylic acid decarboxylase.
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Features: Abnormal growth, megaloblastic anemia,

increased orotate excretion in urine.
Treatment: Feeding a diet rich in uridine results in
improvement of anemia and decreases excretion of orotate
in urine.
DNA STRUCTURE AND

REPLICATION
DNA STRUCTURE
DNA contains 4 nucleotides namely deoxyadenylate,
deoxyguanylate, deoxycytidylate and thymidylate. These
nucleotides are interconnected by 35 phosphodiester
bridges to form a single strand. Each single strand has
one 5 end and one 3 end. Thus, DNA strands posses
polarity.
Note: Enzymes that hydrolyse phosphodiester bonds are
called the nucleases. Endonucleases can cleave any bond
within the chain and exonucleases can cleave only the
terminal bonds.
Double Helix
DNA exists in a double helix form in which two chains
are coiled around a common axis in an antiparallel manner.
The common form of DNA double helix is right handed.
DNA double helix exists in 6 forms (A to E and Z).
The B form is usually found under physiological conditions
(low salt, high degree of hydration). The B form has the
following structure:
i. Right handed helix
ii. Ten residues per 360o turn of the helix
iii. The planes of bases are perpendicular to the common
axis.
This resembles a twisted ladder (as described originally
by Watson and Crick).
Note: Z DNA has left handed helix.
848
Base Pairing
The bases of one strand are linked to the complementary
bases of the other strand by hydrogen bonds. There are
two H-bonds between A and T (A=T) and three H-bonds
between G and C (GC). For this reason, G-C rich regions
are more thermostable.
Bases are also stacked according to their hydrophilicity.
Hydrophobic bases are stacked inside and hydrophilic bases
outside.
These hydrogen bonds plus the hydrophobic interactions
between stacked bases stabilize the structure of the double
helix.
The spatial relationship between the two strands creates
a major and a minor groove.
Note: Actinomycin D exerts its cytotoxic effect by
intercalating into the narrow groove, thus interfering with
RNA and DNA synthesis.
Chargaffs Rule
In a DNA molecule the concentration of A equals that
of T (A=T) while the concentration of G equals that of
C (G=C).
In other words A+G = T+C.
Separation of Two Strands
The two strands of a DNA double helix can be separated
by increasing the temperature or decreasing the salt
concentration. This is called denaturation.
With denaturation, there is increase in optical
absorbance called hyperchromacity of denaturation.
Note: Formamide is used in recombinant DNA experiments.
It destabilizes the H-bonding and decreases the melting
temperature of DNA (Tm).
Supercoils
In bacteria, bacteriophage and many DNA viruses, DNA
molecules exist in a closed circular form. When such DNA
molecules are twisted on its own axis, supercoils are formed.
Positive supercoils are clockwise twists of a right-handed
DNA (over wound). Negative supercoils are anticlockwise
twists of a right-handed DNA (under wound).
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Supercoils are also formed during strand separation

prior to DNA replication (see below).
The enzymes responsible for such winding and
unwinding are called topoisomerases.
DNA ORGANIZATION
In eukaryotes, the linear DNAs are organized in variable
forms to ultimately build the chromatin. Each chromatin
consists of:
i. Double stranded DNA molecules,
ii. Small basic proteins called histones,
iii. Non-histone proteins (which include enzymes involved
in replication such as DNA topoisomerase), and
iv. A small amount of RNA.
Histones
Histones are small basic proteins that are positively charged
and forms ionic bonds with the negatively charged DNA.
DNA molecules wind around histone proteins to form
nucleosomes.
There are five types of histone proteins:
H1 it binds to the DNA chain between nucleosome
beads (the linker DNA).
H2 and H2B are lysine rich, found in the nucleosome
core.
H3 and H4 are arginine rich, also found in the core.
The four core histones are subject to five types of
covalent modifications
1. ADP-ribosylation,
2. Covalent linkage to ubiquitin,
3. Phosphorylation,
4. Acetylation and
5. Methylation.
Roles of modified histones:
i. Acetylation of H3 and H4 activation and inactivation
of gene transcription.
ii. ADP-ribosylation is associated with DNA repair.
Nucleofilament
Nucleosomes linked by linker DNA form a polynucleosome
which assumes the shape of a coil. This is called
nucleofilament or 30 nm fiber.
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Chromatins
There are regions in chromatin which are transcriptionally
active (euchromatin) or inactive (heterochromatin).
Euchromatin: On EM, these regions appear uncondensed.
DNA in these regions contain large base chain that are
sensitive to digestion by nuclease such as DNase I.
Heterochromatin: On EM, they appear as densely packed
regions. Constitutive heterochromatins are always inactive
and are found near the centromere and telomere regions.
Facultative heterochromatins are active in certain
conditions (e. g. X chromosomes in female).
During metaphase, two identical chromatids are
connected by centromere to form a chromosome. The
centromere is an A-T rich region and provides anchorage
for mitotic spindles.
Telomere
Ends of each chromatid contain a T-G rich repeat sequence
called the telomere. Telomere regulates the number of cell
division and it is shortened after DNA replication. Critical
shortening of telomeres are linked to cellular aging and
death.
Telomerase is a reverse transcriptase that synthesize
telomeres and thus prevent cellular damage.
Cells containing telomerase (hence, do not undergo
aging and death) are germ cells, cancer cells, and
hematopoietic cells.
Cells that do not contain telomerase (hence undergo
cellular aging and death) are somatic cells.
DNA REPLICATION
Replication is the process of forming two DNA
molecules from two strands of a DNA.
Replication is semiconservative in nature.
Steps
Origin of replication: In prokaryotes, DNA replication
is started with binding of a ori-binding protein (the O
protein) at a site on the dsDNA called the origin of
replication (ori) which results in local denaturation and
unwinding of an adjacent A + T rich region of DNA.
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851
In eukaryotes, replication starts at several sites along

the DNA helix, which are composed of short sequences
of A + T base pairs. This is referred to consensus
sequence.
Unwinding of DNA: The two strands of DNA are
separated by an enzyme called the DNA helicase. The
separated strands are kept apart by binding of specific
proteins called the single-stranded DNA binding proteins
(SSB).
Formation of replication fork: A replication fork consists
of four components that form in the following sequence:
1. The DNA helicase unwinds a short segment of the
parental duplex DNA.
2. DNA primase initiates synthesis of a short piece
of RNA that is essential as a primer of DNA
synthesis (RNA primer).
3. DNA polymerase initiates nascent, daughter strand
synthesis.
4. SSBs bind to ssDNA and prevent premature
reannealing of ssDNA to dsDNA.
Chain elongation: The DNA polymerase enzymes
elongate a new DNA strand by adding
deoxyribonucleotides to the 3 end of the growing chain.
Thus DNA polymerase only synthesizes DNA in the
5 3 direction.
On the leading strand, DNA is synthesized
continuously whereas in the lagging strand DNA is
synthesized in short fragments called the Okazaki
fragments (in 3 5 direction).
The complex of SSBs, primase and helicase on
the lagging strand is called primosome.
Different types of DNA polymerase
E. coli
Mammalian
Function
I
II
Gap filling and synthesis of lagging strand

DNA proofreading and repair
DNA repair
Mitochondrial DNA synthesis
Processive, leading strand synthesis
III
Proofreading: The DNA polymerase II has 3 5

exonuclease activity. As the nascent strand is
synthesized, it removes the RNA primer hydrolytically
and it removes the RNA primer hydrolytically and
replaces it with proper deoxyribonucleotide.
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The DNA ligase then seals the Okazaki fragments to

form a continuous strand.
Note: After replication of the mitochondrial DNA, the
small piece of RNA remains as an integral part of the
closed circular DNA structure.
Supercoils: As the two strands of parent DNA unwind,
positive supercoils are formed. These are removed by
enzymes called topoisomerase.
Topoisomerase I acts on a single strand, it has
both nuclease (strand-coiling) and ligase (strand-sealing)
activities. It does not require ATP.
Topoisomerase II it acts on both strands
simultaneously.
Note: DNA gyrase a topoisomerase II can introduce
negative supercoils into resting circular DNA in
prokaryotes. This is the target of antimicrobial agents
called quinolones.
Summary of enzyme actions
DNA helicase
Topoisomerase
DNA primase
DNA ligase
Processive unwinding of DNA

Relieves supercoils (unwinding)
Synthesis of RNA primer
Nicking of gaps between fragments of a strand
and Okazaki fragments
Note: The whole process of DNA replication takes about

9 hours in a typical cell.
DNA REPAIR
The DNA is damaged as a result of copying errors or by
a number of environmental factors like heat, radiation
etc. this damage is repaired by four mechanisms:
Mismatch Repair
Cause: error in replication.
Repair:
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Example: Faulty mismatch repair has been linked to

HNPCC.
Base Excision Repair
Cause: Base alteration either spontaneously or induced
by chemicals.
Repair:
Nucleotide Excision Repair

Cause: Spontaneous, chemical or UV ray induced,
smoking.
Repair:
Example: UV rays induce formation of thymine dimmers.

This is repaired by nucleotide excision repair. Faulty process
has been linked to cause xeroderma pigmentosa. Most
common cause for this is deficiency of the enzyme UVspecific endonuclease.
Double-Strand Break Repair
Cause: Ionizing radiation, chemicals, free radicals.
Repair: By a complex of protein called Ku and an enzyme
called the DNA-dependant protein kinase (DNA-PK).
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DNA repair
Type
Specific enzyme
Disorder
Mismatch repair
Base-excision repair
Nucleotide excision
repair
Double strand break
repair
GATC endonuclease
N-glycosylase
UV-specific
endonuclease
DNA-PK
HNPCC
Xeroderma
pigmentosa
HUMAN GENOME
The haploid genome of each human cell consists 3
109 base pairs of DNA, subdivided in 23 chromosomes.
Much (about 90%) of this is transcriptionally inactive.
The transcriptionally active DNA is called the genes.
There are about 30,000 genes in humans. The portions
of genes that are coded by RNA polymerase (see below)
are called exons. These are intervened by non-coding
regions called introns.
Repeat Sequence
In human DNA, at least 20-30 percent of the genome
consists of repetitive sequences. Repeat sequence DNA is
classified as moderately repetitive and highly repetitive.
Moderately repetitive sequences (long and short) can
transpose themselves in and out of the genome, hence
called transposons or jumping DNA.
For example Alu family is a transposon that may
be linked to neurofibromatosis.
Processed Genes
Processed genes are those which contain DNA sequence
identical to the mRNA. This results from transposons by
the action of a reverse transcriptase.
Pseudogenes
Pseudogenes are processed genes that contain nonsense
codons that preclude their expression.
Microsatellite Repeat Sequence
Microsatellite repeat sequences consist of 2-6 base pairs
repeated up to 50 times. Expansion of these sequences
results in diseases.
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For example trinucleotide repeat expansion has been

linked to Fragile X syndrome (CGG repeat), Huntingtons
chorea (CAG repeat), Myotonic dystrophy (CTG repeat),
Spinobulbar muscular atrophy (CAG repeat) and Kennedys
syndrome (CAG repeat).
RNA STRUCTURE AND

TRANSCRIPTION
Differences with DNA
DNA vs RNA
Sugar
Pyrimidine bases
Strand
Alkali lability
DNA
RNA
Deoxyribose
G and T
Double
Absent
Ribose
G and U
Single
Present
TYPES AND STRUCTURE OF RNA

Messenger RNA (mRNA)
Most heterogenous RNA in terms of size and stability.
Special character:
i. The 5 terminal of mRNA is capped by a 7 methyl
guanosine triphosphate. The cap facilitates initiation
of translation and helps stabilize the mRNA.
ii. Most mRNAs (except for histones and some interferons)
have a poly tail at their 3 terminal. The tail helps
stabilize the mRNA and facilitates their exit from
nucleus.
Function: mRNA carries the genetic information from DNA
to the protein-synthesis machinery.
Transfer RNA (tRNA)
They are smaller than rRNA and mRNA.
There are at least 20 tRNAs in every cells, one (or
more) for each 20 amino acids.
Special character:
i. tRNAs form extensive secondary structure that resemble
a clover leaf.
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ii. tRNAs contain many unusual and modified bases, e.g.

the TC arm contains thymidine which is unusual in
RNA.
Function: tRNAs act as a carrier of amino acids for protein
synthesis.
Ribosomal RNA (rRNA)
They are the largest and most abundant (80 percent)
RNA in the cell.
rRNAs bind ribosomes and form a complex which acts
as the site for protein synthesis.
Small Stable RNA (snRNA)
They are present both in nucleus and in cytoplasm.
They are involved in RNA processing.
TRANSCRIPTION
Synthesis of RNA from DNA is called transcription.
The strand of a dsDNA that is transcribed into a RNA
(hence having the complementary structure) is called the
template strand.
The other strand is called the coding strand because
it has structure identical to the RNA.
STEPS
Initiation
Enzyme:
RNA polymerase.
It is a multi subunit enzyme responsible for initiation,
chain elongation and termination of RNA synthesis.
Structure:
RNAP consists of a core that contains 2, 1 and
1 subunits. is thought to be the catalytic enzyme.
It also contains two zinc molecules.
The core is associated with a sigma () factor that
enables the enzyme to recognize promoter regions on
DNA. In some bacteria, another rho () factor is
responsible for termination.
Types:
RNAP I synthesizes the precursor of large rRNAs in
the nucleolus.
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RNAP II synthesizes precursor of mRNAs, snRNA

and some viral RNA (in virus). It is blocked by amanitin.
RNAP III produces the small RNAs including tRNAs,
small ss rRNA and some snRNA.
DNA vs RNA polymerase
Primer
Endo/exonuclease activity
Proofreading
RNAP
DNAP
Not needed
Absent
Absent
Needed
Present
Present
Events: Initiation of transcription involves the binding of

RNAP to a promoter region on template strand of DNA.
Recognition of promoter region:
i. Pribnow box 10 nucleotide upstream of the promoter
region is a 6 nucleotide-pair AT rich sequence
(5-TATAAT-3), also called TATA box or open complex.
In eukaryotes, similar sequence called Hogness box
is found 25 nucleotide upstream.
ii. In prokaryotes, 35 nucleotide upstream is another 8
nucleotide-pair sequence (5-TGTTGACA-3) called the
closed complex.
iii. In eukaryotes, 70 nucleotides upstream is a sequence
called the CAAT box (5-GGCCAATC-3).
Elongation
After binding of the RNAP, there is local unwinding of
the dsDNA. RNAP then starts synthesizing new RNA in
5 3 direction. As it pushes along the two strands of
DNA, supercoils are formed. These supercoils are removed
by topoisomerase.
Termination
-dependant termination is seen in E. coli.
-independent termination is seen in eukaryotes.
At a specific sequence on DNA (palindrome) the
nascent RNA posses a series of G and C bases forming
a hairpin loop followed by a stretch of nucleotide rich
in A and U. Following this termination occurs.
Note: Rifampicin binds to the subunit of bacterial RNAP
and interferes with transcription.
Dactinomycin binds to DNA template and interferes
with movement of RNAP along the DNA.
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Post-transcriptional Modification
It is seen in both prokaryotes and eukaryotes tRNA, rRNA
and eukaryote mRNA (but not prokaryote mRNA).
rRNA all rRNAs except 5S rRNA are formed from
a large (45S) precursor that is processed in the nucleolus.
5S rRNA is synthesized by RNAP III separately.
tRNA tRNAs are also synthesized in larger precursor
that are trimmed. Other modifications include:
i. Base modification including methylation,
reduction, deamination and rearranged glycosidic
bonds.
ii. Addition of a CCA sequence to the 3 end.
mRNA mRNAs are synthesized in a large heterogeneous precursor called the hnRNA. Modifications
include:
i. 5 capping by addition of a 7 methyl guanosine
triphosphate.
ii. Addition of poly-A tail to the 3 end.
iii. Splicing the introns (non-coding regions) are
removed and the exons are spliced together. This
occurs in the nucleus and mediated by snRNA.
Note: SLE results from formation of autoantibodies against
snRNPs (small nuclear ribonucleoproteins).
Ribozymes
Certain RNAs contain catalytic activities, e.g. transesterification reactions concerned with RNA metabolism
(splicing and endoribonuclease). These are called
ribozymes.
Some rRNAs perform peptidyl transferase activity.
RNA Editing
Certain mRNAs are modified by a process called RNA
processing.
For example RNA editing is responsible for formation
of apo B100 and apo B48 in the intestine both of which
are formed from a protein of apo B gene.
PROTEIN SYNTHESIS
Codons
Codons are combination of 3 nucleotide bases that code
for a specific amino acid.
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There are 43 = 64 codons among which 3 (UAG, UGA

and UAA) do not code for any amino acid and are called
nonsense (stop or termination) codon. The remaining 61
codons code for 20 amino acids.
AUG, which codes for methionine, serves as the
initiator codon in mammalian cells.
Characteristics of Genetic Code
1. Specificity or unambiguity a specific codon codes
for only a specific amino acid.
2. Degeneracy or redundancy more than one codon
can code for the same amino acid.
3. Universality.
4. Nonoverlapping.
5. Nonpunctured.
TRANSLATION
Translation is the process of synthesizing a polypeptide
chain based on the information on mRNA.
Site
The ribosome-mRNA complex in the cytosol. A single
mRNA can be translated by many ribosomes
simultaneously in mammals forming a polysome.
Polysomes attached to rough ER synthesize integral
membrane proteins and proteins to be exported out of
the cell. Free polysomes synthesize proteins retained within
the cell.
STEPS
Initiation
Initiation of translation involves binding of ribosome, mRNA
and other factor (initiation factor). Mechanism by which
ribosome recognizes the correct reading frame on mRNA
include:
i. Initiation codon AUG on mRNA binds to methioninetRNA and serves as the initiation codon.
ii. Shine-Dalgorno sequence it is a 7-nucleotide sequence
(5-UAGGAGG-3) 6-10 bases upstream of AUG that
is recognized by ribosome in E.coli.
iii. Kozak consensus sequence is the sequence that
surrounds AUG (5-GCCAGCCAUGG-3).
860
Elongation
i. Binding of aminoacyl tRNA to A site on 50S ribosome
tRNA reads the codon on mRNA (by anticodon arm)
and carries the amino acid specific for that codon.
The recognition and binding of specific amino acid
to the 3 end of corresponding tRNA is carried out by
enzyme called aminoacyl-tRNA synthetase that is
responsible for fidelity of protein synthesis. The charged
tRNA binds to the A (aminoacyl or the acceptor) site
on 50S ribosome. Elongation factors (EF) are involved
in this process.
ii. Peptide bond formation the amino group of the new
aminoacyl-tRNA on A site carries out nucleophilic
attack on the carbonyl group of the peptidyl-tRNA on
P site (peptidyl or polypeptide site). This is catalyzed
by a peptidyl transferase that is a component of 28S
rRNA. This rRNA acts as a ribozyme.
iii. Translocation: upon removal of peptidyl moiety from
tRNA on P site, the discharged tRNA dissociates from
P site. The ribosome complex moves upon the mRNA
from 5 3 end and the newly formed peptidyl-tRNA
shifts from A site to now empty P site (translocation).
Energy required for formation of a peptide bond:
2 ATP and 2 GTP molecules are hydrolysed to ADP
and GDP, respectively. Thus four high-energy phosphate
bonds are hydrolysed to form a peptide bond.
Termination
When a nonsense codon reaches the A site, a releasing
factor (RF) recognizes it and releases the protein and tRNA
from the P site by hydrolysis. Ribosome is dissociated from
the mRNA at the same time.
Post-translational Modification
Many proteins are synthesized as larger proteins that are
cleaved either in endoplasmic reticulum or in Golgi
apparatus or in secretory vesicles (e.g. insulin). Zymogens
are inactive precursors of secreted enzymes (e.g. digestive
proteases) that are activated through cleavage once they
reach their site of action (e.g. small intestine).
Other covalent modifications:
i. Phosphorylation e.g. synthesis of glycogen.
ii. Glycosylation producing glycoproteins.
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iii. Hydroxylation e.g. hydroxylation of proline and lysine

in the endoplasmic reticulum for the formation of
collagen.
iv. Others binding of biotin to carboxylase enzymes, etc.
Applied
Mechanisms of action of some antibiotics:
1. Streptomycin binds to 30S ribosome and distorts
its structure, interfere with the initiation of protein
synthesis.
2. Tetracycline interacts with small ribosomal subunits
and blocks access of the aminoacyl-tRNA to the A
site.
3. Chloramphenicol blocks peptidyl transferase and
inhibits peptide bond formation.
4. Erythromycin and clindamycin bind irreversibly to
50S ribosome and inhibit translocation.
5. Diphtheria toxin inactivates the eukaryotic elongation
factor, eEF2, thus preventing translocation.
6. Puromycin bears a structural similarity to aminoacyltRNA and becomes incorporated into the growing
peptide chain, thus causing inhibition of further
elongation in both prokaryotes and eukaryotes.
Wobble Phenomenon
Base at the 5 end of the anticodon on tRNA is not as
spatially defined as the other two bases. Movement of
this first base of anticodon allows non-traditional base
pairing with the 3 base of the codon (the last base of
the codon). This is known as Wobble and it may be the
explanation for the degeneracy of genetic code.
GENETIC DISORDERS
Total number of genes in human body is 30,000.
MUTATION
These are sudden heritable changes in the DNA.
Point mutation
Substitution of a single base by a different base.
i. Missense mutation when the substitution of base
results in an altered amino acid synthesis. E.g. sickle
cell anemia.
862
ii. Nonsense mutation when a codon is replaced by

a stop codon resulting in termination of translocation,
e.g. globin chain in Hb.
Frameshift mutation
Insertion or deletion of new base pairs.
For example
i. Single base deletion at the ABO locus is responsible
for the O allele.
ii. Three-base deletion is seen in cystic fibrosis.
Trinucleotide repeat mutations
For example Fragile X syndrome, Huntingtons chorea,
Myotonic dystrophy, Friedrichs ataxia.
Note: When a mutation results in no functional gene
product it is called a null mutation.
Mutation causes gain or loss of function. Gain of
function usually results in autosomal dominant (AD)
disorders, whereas loss of function usually results in
autosomal recessive (AR) disorders.
MENDELIAN (SINGLE GENE) DISORDERS
Autosomal Dominant Disorders
Most commonly occurring Mendelian disorder.
Manifest in heterozygous state.
Examples:
a. Neurological
1. Huntingtons chorea
2. Neurofibromatosis
3. Tuberous sclerosis
b. Renal
4. Polycystic kidney disease
c. GI tract
5. Familial polyposis coli
d. Blood
6. Hereditary spherocytosis
7. Von Willebrand disease
e. Skeletal
8. Marfans syndrome, Ehler-Danlos syndrome
9. Osteogenesis imperfecta
10. Achondroplasia
f. Metabolic
11. Familial hypercholesterolemia
g. ENT
12. Otospongiosis
h. Eye
13. Retinoblastoma
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Autosomal Recessive Disorders

Largest group of Mendelian disorders.
Manifest in homozygous state.
Autosomal recessive genes are located on chromosome
22, so that males and females are equally affected.
Examples:
a. Metabolic
1. Cystic fibrosis
2. Phenylketonuria
3. Galactosemia
4. Homocystinuria, alkaptonuria
5. Lysosomal storage diseases (except type II)
6. 1-antitrypsin deficiency
7. Lipid storage disorders (except Fabrys disease)
8. Wilson disease
9. Glycogen storage diseases
10. Hemochromatosis
b. Hematological
11. Sickle cell disease
12. Thalassemia
c. Endocrine
13. Congenital adrenal hyperplasia
d. Skeletal
14. Ehler-Danlos syndrome (some variants)
e. Neural
15. Friedrichs ataxia
f. Skin
16. Albinism.
X-linked Recessive Disorders
Heterozygous females are carriers. Homozygous females
and males are affected.
Examples:
a. Muscular
1. Duchenne muscular dystrophy,
b. Blood
2. Hemophilia A and B,
3. Chronic granulomatous disease,
4. G6PD deficiency,
c. Immunological
5. Agammaglobulinemia
6. Wiskott-Aldrich syndrome
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d. Metabolic
7. Diabetes insipidus
8. Lesch-Nyhan syndrome
9. Fabrys disease
10. Hunters disease
e. Neurons
11. Fragile X syndrome
f. Eye
12. Color blindness
X-Linked Dominant Disorders
1.
2.
3.
4.
Vitamin D resistant rickets

Orofacio-digital syndrome
Incontinentia pigmenti
Alports syndrome (most variants)
CHROMOSOMAL ABNORMALITIES
Autosomal Disorders
1.
2.
3.
4.
Trisomy 21 Downs syndrome.

Trisomy 18 Edwards syndrome.
Trisomy 13 Pataus syndrome.
Partial monosomy deletion of
i. Short arm of chromosome 5(5p) Cri-du-chat
syndrome.
ii. Long arm of chromosome 13(13q) Retinoblastoma.
iii. Short arm of chromosome 11(11p13) WAGR
syndrome.
iv. Long arm of chromosome 15 (15p) Prader-Willi
syndrome.
Note: p (for petit) = short arm; q = long arm.
Note:
Trisomy is the most common chromosomal
abnormality seen in spontaneous abortions (most
common is trisomy 16).
Autosomal monosomies are incompatible to life, and
fetuses are always aborted.
Most trisomies are maternal in origin; the incidence
increases with maternal age.
Autosomal imbalance is always associated with mental
retardation.
Deletions are diagnosed by FISH (fluorescence in situ
hybridization).
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865
Sex-linked Disorders
1. Monosomy (45 X) Turners syndrome,
2. Trisomy (47 XXY) Klinefelters syndrome.
Note: Sex linked monosomies (45 X) are usually
incompatible to fetal survival and results in abortions
(except Turners syndrome in which only 1% of affected
fetuses survive).
DOWNS SYNDROME
This is the most common chromosomal abnormality
seen clinically.
Incidence 1 per 700 newborns.
Etiology
Trisomy 21 due to non-disjunction of chromosomes
during meiotic division.
The extra autosome is maternal in origin (95%) and
the incidence of Downs syndrome increases with maternal
age.
Translocation of long arm of chromosome 21 to
chromosome 14 (t 14:21 or Robertsonian translocation)
and chromosome 22 results in Downs syndrome in
babies born to mothers under the age of 30 years.
Note: Balanced translocation 21:21 carries 100 percent
risk of developing Downs syndrome.
Translocation 14:21 carries a risk of only 15 percent
(carrier mother) and 1 percent (carrier father).
Clinical Feature
Mental retardation (IQ between 25-50) most common
cause.
Facies: Flat facies with upward slant of the eyes and
epicanthal folds, small nose with flat nasal bridge, oblique
palpebral fissure, facial grimace on crying.
Mouth: Short palate, small teeth, furrowed protruding
tongue.
Skull: Small (brachycephaly) with flat occiput, ears are
small and dysplastic and low set.
866
Extremities: hand clinodactyly (hypoplasia of middle

phalanx with a single flexion crease of the 5th finger),
simian crease; foot increased gap between the first and
second toes.
Musculoskeletal: Hypotonia, short stature.
Eye: Brushfield spots (whitish speckling on the iris).
Skin: Dermatoglyphics.
Hematological: Transient myeloproliferative syndrome.
Congenital Anomalies
CVS (most common) 40 percent. Most common
cause of death in infants. These include ASD, VSD
and PDA.
GI tract umbilical hernia, duodenal atresia,
Hirschsprungs disease, annular pancreas.
Skeletal absent 12th rib.
Complications
1. Lower respiratory tract infection most common cause
of death in older children.
2. Juvenile type of CML, AML, ALL.
3. Early onset Alzheimers disease.
Prenatal Diagnosis
1. Chorion villus sampling at 10-12 weeks.
Indication previous history of child with Downs
syndrome, maternal age above 35 years, patients with
balanced translocation.
2. Amniocentesis at 14-16 weeks for chromosomal
studies.
3. Maternal serum alpha-fetoprotein between 16-18
weeks. It is low in Downs syndrome.
4. Triple test at 16-18 weeks. This consists of maternal
AFP, hCG and unconjugated estriol (UE)3. In Downs
syndrome, MAFP and UE3 levels are decreased,
whereas hCG level is increased.
5. USG increased nuchal thickness in first trimester,
decreased length of femur and humerus.
6. Decreased levels of PAPPA.
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867
EDWARD AND PATAU SYNDROMES

Patau syndrome
Edward syndrome
Etiology
Skull
Trisomy 13
Microcephaly
Face
Microphthalmia, cleft
lip and palate
Polydactyly
Trisomy 18
Micrognathia, prominent
occiput
Low set ears
Hand
Overlapping fingers
Common to both mental retardation, CVS and renal defects,

Rocker-bottom foot.
CHROMOSOME 22q11 DELETION

Chromosome 22q11 deletion
DiGeorge syndrome
Velocardiofacial syndrome
Thymic hypoplasia
impaired T cell immunity
Parathyroid hypoplasia
hypocalcemia.
Congenital heart disease,

abnormalities of palate, facial
dysmorphism and developmental
delay.
DELETION OF 15q
Deletion of 15q
Prader-Willi syndrome
Angelmans syndrome
Deletion of chromosome 15q

derived from father
(p for paternal)
Features mental retardation,
short stature, hypotonia,
obesity, small hands and feet,
hypogonadism.
Deletion of chromosome 15q

derived from mother
Features mental retardation,
ataxia,
seizures, inappropriate laughter
(happy puppet syndrome).
Note: The above two syndromes are results of genomic

imprinting.
TRIPLET REPEAT MUTATIONS
Fragile X Syndrome
X-linked recessive.
Cause: mutation of FMR 1 gene.
Clinical feature:
Mental retardation (second most common cause after
Downs syndrome),
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Long face with large mandible, large ears and large

testicles (not large nose).
MUTATIONS IN MITOCHONDRIAL GENE
Maternal inheritance.
For example Laber hereditary optic neuropathy,
Kearns-Sayre syndrome.
MOLECULAR DIAGNOSIS OF GENETIC
DISORDERS
a. Recombinant DNA Technology
Restriction endonucleases are enzymes that recognize a
specific short sequence on double stranded DNA and cleave
the DNA at that site.
b. Blot Transfer
1. Southern blot for visualization of specific DNA
fragment.
2. Northern blot for visualization of specific tRNA.
3. Western blot for proteins.
Note: DNA fragments are separated by pulsed gel
electrophoresis and detected by their effects on
photographic films called autoradiograph.
c. Polymerase Chain Reaction
Enzymatic (heat-stable DNA polymerase) process for
amplification of DNA sequence.
Steps:
1. Heat denaturation of DNA strands.
2. Annealing of the primers to their complementary
sequence.
3. Extension of annealed primers with DNA polymerase.
Note: PCR can also be done on RNA templates. In
that case, at first a cDNA is reverse transcribed from
mRNA a process called RT-PCR.
d. Gene Mapping
For diagnosis of chromosomal anomalies.
1. Somatic cell hybridization.
2. In situ hybridization,
Genetics
869
3. Fluorescence in situ hybridization (FISH),

4. Deletion of restriction fragment length polymorphism
(RFLP) by chromosome walking technique for segments
> 50-100 kb.
e. Karyotyping
A karyotype is a photographic representation of a stained
metaphase spread in which the chromosome are arranged
in order of decreasing length.
Technique of staining:
i. G-banding (Giemsa stain) most common.
ii. Q-banding (Quinacrine banding)
iii. C-banding (Constitutive banding)
iv. R-banding (Reverse G banding).
Cells used in karyotyping are:
a. Prenatal amniocytes and chorionic villi.
b. Adults lymphocytes, fibroblasts.
DISORDERS OF DNA REPAIR
Inheritance
Ataxia Telangiectasia
Genetics:
Mutation of ATM gene on chromosome 11q leads to
defective DNA repair and increased chromosomal breakage
by UV rays.
Clinical Feature:
Presents in the first decade of life.
Cerebellar ataxia, oculocutaneous telangiectasia,
combined immunodeficiency (mainly IgA and IgG2, also
IgE and CMI) due to thymic hypoplasia recurrent
pulmonary infections.
Increased chance of malignancy mainly
lymphoreticular lymphoma, acute leukemia (T cell type).
Those heterogeneous for ATM shows increased risk of breast
Ca.
Endocrine IDDM and insulin resistance.
Premature aging.
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Diagnosis:
Persistent high levels of alpha fetoprotein and CEA.
Treatment:
Transfer factor therapy, fetal thymus transplants.
Xeroderma Pigmentosa
Pathogenesis:
UV rays causes DNA damage by formation of thymine
dimmers. Three enzymes are involved in the nucleotide
excision repair of such DNA viz. UV-specific endonuclease,
DNA polymerase I and DNA ligase. Defect in any of these
enzymes may give rise to xeroderma pigmentosa, the first
one is most common.
Clinical Feature:
Skin marked sensitivity to sunlight with subsequent
development of skin cancer.
Neurological mental retardation, deafness, seizures,
ataxia.
Diagnosis:
Cells cultured from patients show low activity for the
nucleotide excision repair process.
CONTIGUOUS GENE SYNDROME
Microdeletions of a single chromosome may result in
various clinical features due to a variety of rearrangements.
For example different deletions of the p arm of X
chromosome may produce ichthyosis, Kallmann
syndrome, ocular albinism, mental retardation,
chondrodysplasia punctata and short stature.
Other examples DiGeorge syndrome and Prader-Willi
syndrome.
14
NUTRITION
NUTRIENTS
Macronutrients: are those required in amounts > 100

mg/day.
Micronutrients (trace elements): are those required in
amount <100 mg/day.
MACRONUTRIENTS
PROTEIN
Amino Acids
Classification:
1. Glycine simplest amino acid.
2. Branched chain amino acids valine, leucine,
isoleucine.
3. Sulfur containing amino acids cysteine, methionine.
4. Acidic amino acids aspartic acid, glutamic acid.
5. Basic amino acids arginine, lysine, histidine.
6. Aromatic amino acids histidine, phenylalanine,
tyrosine, tryptophan.
7. Imino acid proline.
Note:
Histidine has dissociation constant 6.0 that is closest
to physiological pH.
Substitution of Ile or Leu for Val does not alter the
hemoglobin chain (all are branched chain amino acids).
Aromatic amino acids absorb UV light.
At isoelectric pH, an amino acid bears no net charge.
Nutritionally essential amino acids:
1. Arginine
Nutritionally semiessential
2. Histidine
3. Isoleucine
4. Lysine
5. Leucine
6. Methionine
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7.
8.
9.
10.
Phenylalanine
Threonine
Tryptophan
Valine
Naturally occurring amino acids: Hydroxyproline and

hydroxylysine (because they do not take part in protein
synthesis).
Synthesis of Nutritionally
Non-essential Amino Acids
1. Cysteine from methionine and serine.
2. Tyrosine from phenylalanine by phenylalanine
hydroxylase.
3. Proline and hydroxyproline from glutamate.
4. -alanine is formed from carnosine, cytosine and
anserine.
Note:
Hydroxylysine and hydroxyproline are components of
collagen.
Hydroxylation of proline and lysine requires hydroxylase
enzymes which, in addition, require molecular O2,
ascorbic acid (vitamin C), Fe++ and -ketoglutarate.
Metabolism of Amino Acids
Metabolism of Nitrogen in Amino Acids
All nitrogen is ultimately converted to urea in the liver.
Steps:
1. Transamination: removes the amino group of amino
acids.
Enzyme transaminase which requires vitamin B6.

Ultimately all -amino acids are converted to
glutamate.
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873
2. Glutamate has two fates

i. Oxidative deamination by glutamate dehydrogenase
in liver.
ii. Conversion to glutamine by glutamine synthase in

brain.
Note: In the brain, major mechanism for detoxification
of ammonia is glutamine formation.
Glutamine is again converted to glutamate with
the release of NH3 in kidneys by glutaminase.
In the brain, glutamate is produced from ketoglutarate.
3. NH3 transport:
From gut as alanine.
From musles as alanine.
From kidneys as alanine.
Branched chain amino acid (valine) transports NH3
from gut to muscles in feeding state and to the
brain in fasting state.
4. Urea formation in liver:
Main reaction
First step of urea cycle is
874
Final step
Note: The two N atoms of urea are derived from NH3

(from glutamate) and aspartate.
Fumerate is formed as a byproduct.
Catabolism of Carbon Skeleton of Amino Acids
They are ultimately converted to glycogen (glycogenic amino
acids), fat (ketogenic amino acids, e.g. leucine) or both
(e.g. phenylalanine).
-ketoacids are formed from all amino acids by
predominantly transamination reaction (which removes N
atoms see above) and enter the TCA cycle to produce
energy or converted to glycogen and fat.
Note:
Oxaloacetate is converted to glucose by the process
called neoglucogenesis.
Acetyl CoA is the precursor of fat.
Conversion of Amino Acids
to Specialized Products
Conversion of amino acids to specialized products
Glycine
1. Glycine conjugates-glycocholic acid

and hippuric acid,
2. Creatine,
3. Heme,
4. Purines.
(Contd...)
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875
(Contd...)
-alanine
1. Coenzyme A,
2. Carnosine*.
Serine
1. Sphingosine,
2. Purines and pyrimidines.
L-cysteine Taurine (produces taurocholic acid).
Histidine
Histamine by decarboxylation.
L-arginine Precursor of NO.
Tryptophan Serotonin# by hydroxylation.
Tyrosine
1. Melanin by tyrosine hydroxylase.
2. Hormones
i. Epinephrine and norepinephrine,
ii. Thyroxine and triiodothyronine.
Methionine 1. Creatine (also involves glycine and arginine),
2. Choline.
Note: S-adenosyl methionine acts
as methyl group donor.
Glutamate GABA by decarboxylation.
Ornithine
Spermidin and spermin.
* Carnosine is present in skeletal muscles but not in cardiac muscle.
# Fate of serotonin:
i. Catabolized by MAO to 5-hydroxyindole acetic acid (5-HIAA)
which is excreted in urine.
ii. Converted to melatonin in the pineal gland.
FAT
Essential Fatty Acids
1. Dienoic Linoleic acid most essential.
2. Trienoic Linolenic acid (most important in first 6
months of life).
3. Tetraenoic arachidonic acid.
Note:
Monoenoic FA oleic acid is the most abundant FA in
natural fats.
Eicosanoids are 20C FA (e.g. PGs, LTs) derived from
arachidonic acid.
Triglycerides (esters of glycerol and FA) are the main
storage forms of FA.
Phospholipids
1. Sphingomyelins in the nervous system.
Sphingosine (alcohol) + FA = ceramide.
Ceramide + PO4 + choline = sphingomyelin.
876
2. Cardiolipin in mitochondrial membrane.

3. Lecithins (phosphatidylcholine) most abundant
phospholipids in cell membrane.
4. Dipalmitoyl lecithin is surfactant.
5. Cephalin (phosphatidylethanolamine).
6. Plasmalogens.
Glycolipids
1. Cerebrosides ceramide + galactose/glucose.
2. Gangliosides ceramide + galactose + glucose +
sialic acid (neuraminic acid).
Fatty Acid Biosynthesis
This occurs in the cytosol mainly in liver, kidneys, lungs
and adipose tissue.
Precursor:
Acetyl CoA.
Acetyl CoA is formed from pyruvate by pyruvate
dehydrogenase in the mitochondria. It condenses with
oxaloacetate to form citrate which translocates to cytosol
via the tricarboxylase transporter where it undergoes
cleavage to acetyl CoA and oxaloacetate by ATP-citrate
lyase.
Cofactors:
i. Energy is derived from NADPH (produced by pentose
phosphate pathway).
ii. Biotin.
iii. Mn++.
Enzymes:
FA synthase complex is a multi-enzyme complex containing
7 enzymes.
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877
Rate Limiting Step:

First step is the formation of malonyl CoA from acetyl
CoA by acetyl CoA carboxylase which is the rate limiting
enzyme.
Regulation:
Insulin stimulates lipogenesis by dephophorylation of acetylCoA carboxylase.
FA Chain Elongation:
Occurs in the endoplasmic reticulum.
Ultimate Product:
Free palmitate.
Fatty Acid Oxidation (Ketogenesis)
-oxidation of FA takes place in the mitochondria.
Steps:
1. Formation of acyl-CoA in the cytosol.
2. Acyl group of acyl-CoA transfers acyl group to carnitine

to form acylcarnitine which is transported across the
inner mitochondrial membrane to mitochondria where
it regenerates acyl-CoA.
Note: Carnitine is synthesized from lysine and
methionine.
3. -oxidation: Cleavage of chain between (2) and
(3) carbons to produce acetyl CoA.
Example:
Note: In case of odd chain FA, the last product is 3C

molecule propionyl CoA which is the only glucogenic
part of a FA.
878
Energy:
A total of 129 mol ATP are produced per mole of
palmitate.
Ketogenesis:
Ketone bodies are acetone, acetoacetate and 3hydroxy butyrate (most abundant ketoacid).
Ketoacids are produced from acetyl CoA in liver when
there is excessive -oxidation of FA to form excess acetylCoA, e.g. in diabetes.
HMG-CoA is produced as an intermediate.
Liver produces acetoacetate but cannot utilize it. Ketone
bodies serve as fuels for extrahepatic tissues (e.g. for
brain during starvation). This involves the reaction
acetoacetate + succinyl CoA succinate +
acetoacetyl CoA.
Cholesterol Synthesis and Metabolism
Precursor: Acetyl CoA.
Main reaction: The main reaction is the conversion of HMGCoA to mevalonate by HMG-CoA reductase which is the
rate limiting enzyme.
Energy: Is derived from NADPH.
Intermediates: Sequlene, lanosterol.
Transport: Cholesterol is transported as LDL in blood.
Role: Cholesterol is the precursor of steroids, sex hormones,
bile acids and vitamin D.
Bile Acid Production
Rate-limiting enzyme is 7- hydroxylase.
CARBOHYDRATE
Classification
1. Monosaccharides
i. Aldose, e.g. glucose (contains CHO group).
ii. Ketose, e.g. fructose (contains =CO group).
Note: Aldose-ketose isomerism is catalyzed by
isomerase.
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879
2. Disaccharides maltose (glucose + glucose), sucrose

(glucose + fructose), lactose (glucose + galactose).
3. Oligosaccharides, e.g. maltotriose.
4. Polysaccharides, e.g. starch and dextrins.
Note: Reducing sugars are maltose, trehalose, glucose
and lactose.
Products
Glycosides: Non-carbohydrate part of glycoside is called
aglycone.
Aminosugars (hexosamines): For example, glucosamine is
a constituent of hyaluronic acid; galactosamine is a
constituent of chondroitin.
Polysaccharides:
Glycogen storage polysaccharide in body.
Inulin used to measure GFR. It is a fructosan.
Cellulose main bulk of diet. It is not metabolized
in our body due to absence of (1-4) hydrolase.
Glycosaminoglycans (mucopolysaccharides): Contain
amino sugars and uronic acid. When attached to a protein,
it is called proteoglycans, e.g. hyaluronic acid, chondroitin
sulfate and heparin (heteropolysaccharides).
Glycolysis
Site: Cytosol.
Special Points:
Glycolysis involves 4 kinases Hexokinase,
phosphofructokinase, phophoglycerate kinase and
pyruvate kinase.
Hexokinase is the first committed step in glycolysis.
Enolase is inhibited by fluoride.
In RBCs, 2,3 DPG is produced from glyceraldehyde
3-phosphate.
Phosphofructokinase is the rate-limiting enzyme.
Conversion of pyruvate to acetyl CoA by pyruvate
dehydrogenase requires thiamine.
Energy 38 molecules of ATP in aerobic glycolysis;
2 molecules in anaerobic glycolysis.
880
Glycogen Metabolism
Site: In liver and muscles.
Reaction:
Regulation:
This is mediated by cAMP.
Glucagon and epinephrine stimulates phosphorylase
and inhibits glycogen synthase.
Insulin stimulates glycogen synthase and inhibits
phosphorylase.
Note: Glucose 6 phosphatase is present in liver and
kidney but not in muscle. So muscle does not add
glucose to blood.
Neoglucogenesis
Site: Liver and kidney.
Substrate: Glucogenic amino acids, lactate, proprionate
and glycerol.
Enzymes:
Four enzymes are exclusive for neoglucogenesis. They are:
1. Glucose 6 phosphatase,
2. Fructose 1,6 bisphosphatase,
3. Pyruvate carboxylase,
4. Phosphophenolpyruvate carboxykinase.
Pentose Phosphate Pathway
This occurs in liver, adipose tissue, adrenal cortex, thyroid,
RBC, testis and lactating mammary gland.
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881
Role:
Production of:
i. NADPH which is the energy source for fatty acid
and cholesterol synthesis.
ii. Ribose sugars which are components of nucleotides.
NADPH is also required for glutathione peroxidase in
RBCs.
Enzyme:
Glucose 6-phosphate dehydrogenase catalyzes conversion
of glucose 6-phosphate to 6-phosphogluconate with
production of NADPH.
Transketolase involved in HMP shunt requires thiamin
for action.
Intermediates:
Xylulose 5-phosphate, glyceraldehydes 3-phosphate,
sedoheptulose 7-phosphate.
Uronic Acid Pathway
Site: In liver.
Conversion of glucose to glucuronic acid, ascorbic acid
and pentose sugars.
UDP-glucuronate is involved in metabolism (glucuronide
conjugation) of steroid hormones, bilirubin and certain
drugs (e.g. sulphonamides).
Reaction:
Fructose Metabolism
Synthesis:
Metabolism:
882
Note: Glucose produces sorbitol by aldose reductase which

is responsible for cataract in diabetes.
Galactose Metabolism
VITAMINS
Fat-soluble vitamins vitamins A, D, E and K.
Water-soluble vitamins vitamins B complex and C.
Thiamin (Vitamin B1)
Role:
Thiamin diphosphate (TPP) is a coenzyme for the following
reactions
1. Oxidative decarboxylation of -ketoacids.
Examples:
2. Transketolase reaction which transfers 2C unit of

a ketose to the aldehyde carbon of an aldose sugar
(in pentose phosphate pathway).
Note: Erythrocyte Transketolase activity is used as a
measure of thiamin deficiency.
Riboflavin (Vitamin B2)
Active riboflavin is FMN or FAD.
Role: They serve as prosthetic groups of oxidoreductase
enzymes.
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883
Niacin (Vitamin B3)

Active niacin is NAD+ and NADP+.
Role: Same as riboflavin.
Pantothenic Acid (Vitamin B5)
Active pantothenic acid is coenzyme A and acyl carrier
protein.
Pantoic acid + -alanine Pantothenic acid.
Pantothenic acid + thioethanolamine + adenine +
ribose 3-PO4 + pyrophosphate Coenzyme A.
Vitamin B6
These are pyridoxine, pyridoxal and pyridoxamine.
Active B6 is pyridoxal phosphate.
Role: Pyridoxal phosphate is coenzyme for following
reactions
1. Transamination,
2. Decarboxylation (e.g. dopamine decarboxylase),
3. Threonine aldolase activity.
Note: Vitamin B 6 is used in the treatment of
homocystinuria.
Biotin
Biotin is a coenzyme of carboxylase enzymes:
1. Pyruvate carboxylase in neoglucogenesis,
2. Propionyl CoA carboxylase in neoglucogenesis,
3. Acetyl CoA carboxylase in FA synthesis.
Cobalamin (Vitamin B12)
It is the extrinsic factor.
Structure: Cobalamin contains corrin ring (made up of
ribose sugars) and cobalt ion.
Absorption:
Occurs in the terminal ileum.
This requires the binding with the intrinsic factor which
is secreted by the parietal cells of gastric mucosa.
Transport: By transcobalamin.
884
Role:
Active vitamin B12
i. Deoxyadenosylcobalamin is coenzyme for conversion
of methylmalonyl CoA to succinyl CoA.
ii. Methylcobalamin is coenzyme for conversion of
homocysteine to methionine and methyltetrahydrofolate to tetrahydrofolate.
Folate
Total serum folic acid is 2-20 mg/ml.
Active folate is tetrahydrofolate.
Note: Folate reductase is inhibited by methotrexate and

trimethoprim.
The gene responsible for folic acid transport is located on
Ch. 21.
Role:
Tetrahydrofolate is the carrier of activated 1C units.
Serine is the major source of one carbon unit.
Role in metabolism of glycine (also vitamin B6).
Metabolism: Figlu, a catabolite of histidine, transfers its
formamino group to tetrahydrofolate. In folate deficiency
Figlu is excreted in urine after oral challenge with histidine.
Ascorbic acid (Vitamin C)
Roles:
1. It is a reducing agent. It can reduce cytochrome a and
c.
2. In collagen synthesis, it is required for hydroxylation
of proline and lysine.
3. It increases the absorption of iron from intestine.
4. It is an antioxidant.
Vitamin A
-carotene is provitamin A.
Active vitamin A is retinol and its derivatives retinal
and retinoic acid.
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885
Role:
1. Retinal is a component of visual pigment rhodopsin.
Rhodopsin contains opsin and 11-cis retinal which is
converted to all-trans-retinal on exposure to light.
2. Retinoic acid participates in glycoprotein synthesis
important in growth.
3. Immunity it maintains the integrity of epithelial tissues.
4. carotene is an antioxidant.
5. Spermatogenesis.
Note: Vitamin A is useful in cancer therapy.
Vitamin D
Synthesis:
Note:
25 (OH) D3 is the major form in circulation and major
storage form in liver.
1, 25 (OH)2 D3 or calcitriol is the most potent form.
Role: Calcitriol stimulates intestinal absorption of calcium
and phosphate.
Note: Vitamin A and vitamin D also act as hormones.
Tocopherol (Vitamin E)
Absorption: Fat absorption promotes vitamin E absorption.
Role: It is the most potent natural antioxidant (prevents
rancidity of fat), antisterility factor.
Vitamin K
K1 phytonadione.
K3 menadione.
Vitamin K is synthesized by bacteria in the intestine.
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Absorption: It depends on fat absorption.

Role: Posttranslational modification (carboxylation of
glutamate) of coagulation factors II, VII, IX and X.
MICRONUTRIENTS
Trace elements are required in amount < 100 mg/day.
Roles
1. Magnesium cofactor of kinase (e.g. pyruvate kinase).
2. Manganese cofactor of mitochondrial superoxide
dismutase.
3. Molybdenum constituent of oxidase enzymes (e.g.
xanthine oxidase).
4. Selenium constituent of glutathione peroxidase.
5. Zinc cofactor of carbonic anhydrase,
carboxypeptidase, alkaline phosphatase, lactate
dehydrogenase, also plays role in insulin secretion.
6. Copper cofactor of oxidases.
7. Chromium potentiates the action of insulin.
Dietary Fibers
These are cellulose, hemicellulose, pectin, lignin, gums
and pentosans.
Role: High fiber diet reduces the risk of
1. Diverticulosis,
2. Colonic cancer,
3. Cardiovascular disease,
Mechanism: They retain water in colon and delay stomach
emptying. They also delay passage of food through gut
and thus increase transit time.
DIETARY SOURCES
PROTEIN
Animal proteins contain all the essential amino acids.
Milk and egg proteins are biologically complete.
Nutrition
887
Cereals
They are deficient in lysine (limiting amino acid) and
threonine.
a. Rice: protein content 6-9 percent. Rice protein is richer
in lysine than other cereals, hence considered to be
of better quality.
Milling: deprives rice of thiamin, riboflavin and protein.
Parboiling: means partial cooking in steam. It is better
than milling.
b. Wheat: limiting amino acids are lysine and threonine
(see above).
c. Maize: deficient in tryptophan and lysine. Maize
contains excess leucine which interferes with conversion
of tryptophan to niacin pellagragenic.
Pulses
Pulses are deficient in methionine and rich in lysine. For
this reason, cereals and pulses are given together in a
balanced diet.
Soyabeans contain 40 percent protein (maximum).
Millets
Ragi is the richest vegetable source of calcium.
Milk
Human milk contains 1.1 gm protein, 3.3 gm of
fat and 7.4 gm of carbohydrate (lactose) per 100 gm.
Minerals rich in calcium (2.8%), poor in iron (nil).
Vitamins rich in all vitamins except vitamin C and
K.
Ratio of casein to albumin in human milk is 1:1.
Energy value 15 C/ounce (65 C/100 gm).
Cow milk contains less carbohydrate but more protein
and fat than human milk.
Energy value of cow milk 67 C/100 gm.
Egg
It is the reference protein because NPU of egg is 100.

Egg contains maximum cholesterol (250 mg/egg).
Egg contains all vitamins except vitamin C.
Energy 70 C/egg.
Raw egg in rich in avidin which binds biotin and causes
deficiency.
888
Meat
Meat yields maximum calories.
Dietary sources
Nutrients
Source
Fat
Linoleic acid
Linolenic acid
Arachidonic acid
Saturated FA
Safflower oil, corn oil and sunflower oil.

Soyabean oil.
Meat, egg, milk.
Coconut oil, palm oil
Vitamin
Vitamin A
Vitamin E
Vitamin D
Vitamin K
Niacin
Folate
Vitamin B 1
Vitamin B 12
Vitamin C
Minerals
Calcium
Iron
Iodine
Green leafy vegetables.

Vegetable oils which are rich in polyunsaturated
FA are rich in vitamin E (e.g. germ oil). Others
egg yolk, butter.
Halibut liver oil (maximum), milk, egg, fish fat.
Green leafy vegetables; cows milk is a rich
source.
Raw rice is a rich source.100 gm meat gives
6.8 mg niacin. 1 cup of coffee gives 1 mg of
niacin. Niacin is produced from tryptophan in
body. 60 mg tryptophan produces 1 mg of
niacin.
Overcooking destroys folate.
Whole wheat.
Liver, meat, fish, eggs and milk. It is not found
in vegetable foods.
Germinating pulses; alma or Indian gooseberry
is a rich source.Highest concentration of vitamin
C is found in adrenal cortex.
Best source is milk. 1 liter of cows milk provides
1200 mg of calcium. Ragi, sitaphal contain good
amounts of calcium.
Heme iron is better absorbed than non-heme
iron. Foods rich in heme iron are liver, mutton,
and fish. Jaggery is a rich source of iron.
Sea foods (sea fish and salts), cord liver oil.
Note:
Sodium - Human body contains 100 gm of sodium.
Potassium - Human body contains 250 gm of
potassium.
Iodine - Human body contains 50 mg of iodine.
Nutrition
889
RECOMMENDED DAILY ALLOWANCE

Daily requirement
Protein
Vitamin A
Thiamin
Vitamin C
Calcium
Iodine
Adults 1.0 gm/kg per day,

13-15 years 1.33 gm/kg or 62 gm/day for girls.
Adults 600 mcg (2000 IU),
Infants (0-12 moths) 350 mcg,
Children (1-6 years) 400 mcg.
0.5 mg/1000 kcal of energy intake.
60 mg.
400-500 mg for adults.
150 mcg.
Pregnancy and Lactation

Calcium - + 600 mg (= 1000 mg/day) in the second
half of pregnancy.
Iron 40 mg (3.5 mg should be absorbed).
Vitamin D 10 mcg (400 IU).
Folate 400 mcg.
Protein - + 15 gm/day in pregnancy and + 25 gm/
day in lactation.
ENERGY REQUIREMENT
Protein should supply 15-20 percent of total energy.
Fat should supply 20-30 percent of total energy.
Carbohydrate should supply 50-70 percent of total
energy.
Energy requirement
Infants (< 1 year)
110-120 C/kg
Children
1-3 years
4-6 years
1200 C/day
1700 C/day
Adults
Moderate worker
Severe worker
Pregnancy
Lactation
2900 C/day in males, 2200 C/day in females

3800 C/day in males, 2950 C/day in females
+ 300 C/day (= 2500 C/day)
+ 550-700 C/day (= 2900 C/day)
MALNUTRITION
PROTEIN ENERGY MALNUTRITION (PEM)
It is defined as combined deficiency of protein and calorie.
890
Incidence
1-2 percent in preschool age children (< 6 years).
Classification
Gomezs classification or weight for age classification:
According to IAP, weight for age should be:
90-110 percent - normal.
75-89 percent - grade I malnutrition (mild).
60-74 percent - grade II malnutrition (moderate).
< 60 percent - grade III malnutrition (severe).
80 percent cases of PEM are intermediate, i.e. grade
I and II.
Note: The normal reference child is the 50th centile of
Boston standards.
McLarens classification or height for age classification.
Waterlows (height for age and weight for height)
classification:
Low height for age ratio indicates chronic malnutrition.
Low weight for height ratio indicates acute
malnutrition.
Note:
Severity of malnutrition is assessed by weight for
height.
Duration of malnutrition is assessed by height for
age.
Mid-arm circumference:
This is measured by Shakirs tape.
Markings on Shakirs tape
Green - > 13.5 cm normal.
Yellow 12.5-13.5 cm mild to moderate malnutrition.
Red - < 12.5 cm severe malnutrition.
Mid-arm circumference is best measure of nutrition at
a village level.
Note: Reference standard for classification of PEM is 80
percent of 50th percentile of NCHS standards (median).
Clinical Feature
Marasmus is defined as < 60 percent weight for age
without edema.
Nutrition
891
Kwashiorkor is defined as 60-80 percent weight for age

with edema.
Marasmaric-Kwashiorkor is defined as < 60 percent
weight for age with edema.
Essential criteria for Kwashiorkor:
1. Growth retardation,
2. Psychomotor changes,
3. Edema of the dependent parts.
Features
Marasmus
Kwashiorkor
Weigh for age

Edema
Mental changes
Muscle wasting
< 60%
Nil
Quiet and apathetic
Prominent (hallmark of Marasmus)
Severe loss of sub
cutaneous fat
Good
Present
Negative
Negative
60-80%
Present
Irritable and lethargic
Non-prominent (due
to edema)
None
Fat wasting
Appetite
Diarrhea
Skin changes
Hair changes
Liver
Biochemical:
i. Serum albumin
ii. Urinary urea/gm
of creatinine
iii. Hydroxyproline/
creatinine ratio
iv. Plasma/amino
acid ratio
Normal
Poor
Present
Flaky paint dermatosis
Hypopigmented, flag
sign
Fatty infiltration
Normal or decreased Decreased

Normal or decreased Decreased
Decreased
Decreased
Normal
Decreased
Others:
Oxidation reaction is decreased in malnutrition.
Secretory IgA level is decreased recurrent infection,
diarrhea.
Prognosis
Bad prognostic factors include:
1. Hypothermia,
2. Hypoglycemia,
3. Dyselectrolytemia,
4. Diarrhea and dehydration,
5. Congestive cardiac failure,
6. Infection.
892
Treatment
Therapeutic diet should provide 150 C/kg/day for
moderately malnourished and 200 C/kg/day for severely
malnourished children.
FAT MALNUTRITION
1. Phrenoderma or toad skin is caused by deficiency
of essential fatty acids.
2. Congestive heart disease HDL is protective whereas
LDL and VLDL are atherogenic.
VITAMIN DEFICIENCIES
Vitamin A Deficiency
Clinical feature:
a. Ocular
1. Night blindness
2. Conjunctival xerosis
3. Bitots spot
4. Corneal xerosis
5. Keratomalacia
b. Extraocular
1. Respiratory infection
2. Rarely hydrocephalus.
Prevalence criteria:
1. Night blindness > 1 percent.
2. Bitots spot > 0.5 percent.
3. Corneal ulcer > 0.05 percent.
4. Decreased serum retinal > 5 percent of population.
Management:
a. Prophylaxis
Age < 1 year 100000 IU vitamin A in oil orally
between 6 month and 1 year.
Age 1-6 years 200000 IU vitamin A in oil orally
every 6 month.
b. Therapeutic
100000 IU orally or 50000 IU IM for infants
< 1 year and weight < 8 kg.
200000 IU orally or 100000 IU IM for others on
days 0, 1 and 14.
Nutrition
893
Prevention: Food fortification (dalda) with vitamin A

(medium term intervention).
Vitamin B1
Causes of deficiency:
1. Consumption of polished (milled) rice.
2. Cooking above 100oC (destroyed by heat).
3. Alcohol consumption and food faddists.
4. Congestive heart failure due to decreased intake or
increased excretion by diuretics.
5. Malnutrition.
Clinical feature:
1. Beriberi
a. Dry beriberi affects the nervous system.
b. Wet beriberi affects the CVS.
Features:
i. Peripheral vasodilatation increased cardiac output
and increased peripheral venous pressure.
ii. Retention of water and sodium edema.
iii. Biventricular myocardial failure.
2. Peripheral neuropathy.
3. Central neuropathy
i. Wernickes encephalopathy (cerebral beriberi)
vomiting, nystagmus, uni/bilateral ophthalmoplegia,
fever, ataxia and progressive mental deterioration.
ii. Korsakoffs psychosis retrograde amnesia,
impaired ability to learn and confabulation.
Vitamin B2 (Riboflavin)
Cause: Riboflavin antagonist galactoflavin.
Clinical feature: Angular stomatitis, glossitis, cheilosis,
nasolabial dysbacea, seborrheic dermatitis, normocytic
normochromic anemia, corneal vascularization.
Niacin (Vitamin B3)
Cause: Subsiding only on maize and jowar.
Clinical feature: Niacin deficiency causes pellagra
characterized by the triad of dermatitis, dementia and
diarrhea. Other features are paresthesia, polyneuritis, and
psychosis.
894
Pyridoxine (Vitamin B6)

Drugs causing deficiency:
1. Isoniazid,
2. Cycloserine,
3. Penicillamine,
4. Carbonyl reagents.
Clinical feature: Hypochromic microcytic anemia,
peripheral neuritis, convulsions in infants.
Pyridoxine responsive diseases:
1. Homocystinuria,
2. Xanthurenic aciduria,
3. Cystathionuria,
4. Oxaluria.
Biotin
Cause: Prolonged consumption of new egg white (due to
avidin).
Clinical feature: Depression, hallucinations, dermatitis,
muscle pain, nausea.
Cobalamin (Vitamin B12)
Cause:
1. Atrophic gastritis pernicious anemia.
2. Malabsorption blind loop syndrome, tropical sprue,
Crohns disease, intestinal TB.
Clinical feature:
Macrocytic normochromic anemia,
Demyelination of the lateral and posterior columns in
spinal cord.
Others homocystinuria, methyl malonic aciduria.
Note:
B vitamins causing dermatitis niacin, biotin,
pyridoxine.
B vitamins causing neurological symptoms thiamin,
niacin, pyridoxine, cobalamin.
Vitamin C
Vitamin C deficiency causes scurvy.
Nutrition
895
Pathology: Defective hydroxylation of proline and lysine

defective collagen synthesis endothelial disintegrity
bleeding.
Clinical feature: Scurvy develops 3-4 months after depletion
of vitamin C store.
In
adults:
Perifollicular hyperkeratotic papule,
Perifollicular hemorrhage,
Non-palpable purpura on the back of lower extremities,
Hemorrhage into joints, gum bleeding, splinter
hemorrhage in nail beds.
In infants:
Hemorrhage under the periosteum of long bones causes
painful swelling infant is reluctant to move and
assumes frog position. This may be mistaken for
paralysis (pseudoparalysis).
Elevation of rib margins (scorubutic rosary) due to
epiphyseal separation.
Bleeding from the gum and skin.
Retrobulbar, subarachnoid and intracerebral
hemorrhage (not perifollicular hemorrhage c.f. adults).
Others: normocytic normochromic anemia, jaundice.
Investigation:
1. Buffy coat estimation.
2. X-ray shows a dense line at metaphysis- epiphyseal
junction, bone thickening (woody leg), metaphyseal
lucency (Trummenfeld zone), pencil-thin cortex
(Wimbergers sign), Pelrkan spurs.
Vitamin E
Clinical feature:
Hemolytic anemia in premature infants.
Others ataxia, areflexia, decreased position and
vibration senses.
Vitamin K
Causes:
1. Fat malabsorption,
2. Prolonged oral antibiotic therapy,
3. Breastfeeding.
Clinical feature: Hemorrhagic disease in newborns.
896
VITAMIN EXCESS
Hypervitaminosis A
This causes injury to the lysosomes.
Cause: Consumption of polar bear liver.
Clinical feature: Bone and joint pain, anorexia, hair loss,
increased ICT, hepatosplenomegaly, pruritus, weight loss.
Vitamin K Excess
Clinical feature: Jaundice (unconjugated hyperbilirubinemia) in newborn due to hemolysis.
TRACE ELEMENT DEFICIENCY
Zinc
Features: Growth retardation, alopecia, dermatitis,
diarrhea, defective cell-mediated immunity, microcytic
anemia, hepatosplenomegaly, hyposmia, hypogonadism.
Acrodermatitis enteropathica: Autosomal recessive disorder
of Zn absorption.
Clinical feature: Hyperkeratosis, parakeratosis,
acrodermatitis, alopecia.
Selenium
Selenium deficiency causes cardiomyopathy (Keshans
disease).
Copper
Wilsons disease, Menkes kinky hair syndrome.
Fluorine
Recommended level of fluorine in drinking water =
0.5-0.8 mg/liter.
Deficiency causes dental sclerosis.
Excess of fluorine causes fluorosis.
Features of fluorosis:
1. Dental fluorosis earliest sign, mottling of the enamel.
2. Skeletal fluorosis causes osteosclerosis. May cause genu
valgum and osteoporosis.
Nutrition
897
X-ray shows:
i. Spine increased density, calcification of posterior
longitudinal ligament.
ii. Pelvis calcification of ischio-pubic and sacro-pubic
ligaments.
iii. Extremities interosseous membrane calcification.
Prevention: Defluoridation of water by Nalgonda technique.
OBESITY
Obesity is the most prevalent form of malnutrition.
DEFINITION
Assessment Criteria
1. Body mass index (BMI) Quetelets index:
BMI = weight (in kg)/height2 (in meter).
Normal range 18.5-24.99 kg/m2.
Overweight > 27 kg/m2.
Obesity > 30 kg/m2.
2. Ponderal index:
It is defined as height (in cm)/cube root of body
weight (in kg).
3. Broca index:
Height (in cm) 100.
4. Corpulence index:
Actual weight/desirable weight.
It should not exceed 1.2.
5. Skin fold thickness: most commonly used method.
PATHOGENESIS
Congenital disorders with obesity
Features
Prader-Willi
syndrome
Laurence-MoonBiedl syndrome
Stature
Cranio-facial
abnormalities
Limbs
Eye
Common features
Short
Characteristic
Normal
Normal
Small hands and feet

Polydactyly
Normal
Retinitis pigmentosa
Obesity, hypogonadism
and mental retardation.
898
Pickwickians Syndrome
Obesity, hypoventilation (hypoxia and hypercapnia),
polycythemia, pulmonary hypertension (may lead to right
heart failure) and daytime somnolence.
Other Syndromes Associated with Obesity
1.
2.
3.
4.
Froehlichs syndrome,
Ahlstroms syndrome,
Cohens syndrome,
Carpenters syndrome.
EFFECTS OF OBESITY
There is increased chance of
1. CVS hypertension and atherosclerosis (decreased HDL
and increased LDL levels). Increased risk of sudden
death.
2. Type II diabetes.
3. Cancer Endometrial and postmenopausal breast
carcinoma in females, colorectal and prostatic
carcinoma in males.
4. Gallbladder stone.
5. Joint osteoarthritis and gout (hyperuricemia).
6. Endocrine insulin resistance, decreased level of GH
and testosterone.
7. Pulmonary sleep apnea and RHF.
MANAGEMENT
a. Diet and behavior therapy.
b. Drugs
1. Amphetamines,
2. Noradrenergic agents diethylpropion, mazindol.
3. Serotonergic agents fenfluramine.
4. Noradrenergic/serotonergic agent sibutramine.
c. Surgery intestinal bypass.
Nutrition
899
TOTAL PARENTERAL
NUTRITION
Indications
1.
2.
3.
4.
Postoperative ileus.
Extensive bowel resection.
Fistulas enterocolic and enterocutaneous.
Extensive Crohns disease.
Route
Best route subclavian vein.
Others jugular and femoral veins.
Complications
a. Immediate (within 48 hours)
1. Hyperglycemia.
2. Hypokalemia, hypomagnesemia, hypophosphatemia.
3. Azotemia.
b. First 2 weeks hyperosmolar dehydration (HONC).
c. Late
1. Hepatic steatosis most common complication.
2. Cholestatic liver disease.
3. Hypercalcemia negative calcium balance.
4. Osteopenia.
5. Mineral deficiency Zn.
Note: Calory to N2 value ratio in TPN = 2000 kcal : 13
gm N2 (i.e. 150:1).
FOOD ASSESSMENT
QUALITY OF PROTEIN
1. Biological value: Biological value of a food is the percent
of absorbed nitrogen retained in the body.
2. Net Protein Utilization (NPU): NPU is the percent of

nitrogen in food retained in the body.
900
Also NPU = digestibility coefficient biological value/

100.
Note:
NPU is of more practical use.
NPU of Indian diets = 50-80 (average 65).
NPU of egg is 100 and of milk is 75.
3. Protein efficiency ratio: Weight increase (in grams)/gram
of protein consumed.
15 GENERAL PATHOLOGY
CELL INJURY, ADAPTATION
AND DEATH
Etiology
Hypoxia is the most common cause of cell injury.
TYPES WITH MECHANISM
Hypoxic Injury
Pathology:
Reperfusion Injury
Restoration of blood flow to ischemic but viable tissues
paradoxically exacerbate the damage. This is seen in
myocardial and cerebral infarctions.
Free Radical Injury
Free radicals are substances with a single unpaired electron
in an outer orbit.
Production:
Redox reaction in the body:
Fenton reaction Fe++ ion donates free electron to
produce free radicals.
Fe++ + H2O Fe+++ + OH + OH
This may also occur with Cu++.
902
Effects:
i. Lipid peroxidation of membrane.
ii. DNA fragmentation single strand break of DNA by
reacting with thymine.
iii. Cross-linking of proteins.
Antioxidants:
i. Superoxide dismutase.
ii. Glutathione peroxidase.
iii. Catalase (in peroxisomes) degradation of H2O2.
iv. Vitamin A, E, C and beta caroteine scavenger
molecules.
v. Transferring, ferritin and ceruloplasmin.
SUBCELLULAR CHANGES
IN RESPONSE TO INJURY
Lysosomal Catabolism
Lysosomes contain hydrolytic enzymes that catalyse
extracellular (heterophagy) or intracellular (autophagy)
particles by combining with vacuoles containing those
particles to form secondary lysosome or phagolysosome.
Chdiak-Higashi syndrome is due to defective
phagolysosome formation.
Indigestible particles remain within cells as residual
bodies such as lipofuscin pigment granules.
Hypertrophy of Smooth Endoplasmic Reticulum
This occurs in liver in response to prolonged use of
barbiturates.
Mitochondrial Changes
i. Size megamitochondria is seen in hepatocytes in
alcoholic liver disease.
ii. Number increased in hypertrophy and decreased in
atrophy.
iii. Oncocytoma in salivary glands, thyroid and kidneys
consist of cells containing abnormal large
mitochondria.
iv. Mitochondrial myopathies.
General Pathology
903
Cytoskeletal Changes
For example in Kartageners syndrome there is sterility due
to sperm immobility and recurrent respiratory infections
due to immobile cilia (immotile cilia syndrome).
Heat Shock Proteins (Chaperones)
They play important roles in normal cellular protein

housekeeping.
They are involved in protein folding.
Diseases caused by misfolded proteins are amyloidosis,
Alzheimers disease, prion diseases.
INTRACELLULAR ACCUMULATIONS
Fatty Change
Most common substance to accumulate in cells is fat

(triglyceride).
Most common site for fat to accumulate is liver and
heart.
Most common cause of fatty liver is alcoholic liver
disease.
Fatty change in heart is caused by prolonged anemia,
diphtheric myocarditis.
Note: Fat in tissue can be demonstrated by Sudan
dyes, Oil red O and osmic acid.
Cholesterol
Foam cells: Foam cells are macrophages filled with lipid
particles (cholesterol and cholesteryl esters).
Xanthoma: Xanthomas are clusters of foam cells in
subepithelial connective tissue of skin or tendons seen in
familial hyperlipidemic syndromes.
Proteins
Russell bodies: Intracellular accumulation of newly
synthesized immunoglobulins in the rough endoplasmic
reticulum of plasma cells seen in multiple myeloma.
Mallory bodies or alcoholic hyaline: Intracytoplasmic
accumulation composed of prekeratin intermediate
filaments found in the liver cells in chronic alcoholism.
904
Neurofibrillary tangles: Found in the brain in Alzheimers

disease.
Glycogen
In diabetes and glycogen storage diseases, glycogen is
accumulated in cells (see glycogen storage diseases).
Glycogen is stained with PAS.
Pigments
Most common exogenous pigment to accumulate is carbon.
Lipofuscin or wear and tear pigment:
This is an indicator of free radical injury and lipid
peroxidation. This is also seen in atrophy.
This is seen in heart (most common), liver and brain.
When apparent in tissues grossly, it is called brown
atrophy.
This occurs in severe malnutrition (maximum), aging,
and cancer cachexia.
Hemosiderin or aggregates of ferritin:
Diagnosis by Prussian blue stain, iron appears as
golden-yellow pigment.
For example brown induration of the lungs as a result
of small hemorrhages in mitral stenosis and left
ventricular failure.
Microscopically, they show heart failure cells which
are hemosiderin-laden alveolar macrophages.
PATHOLOGICAL CALCIFICATION
Dystrophic Calcification
This is the deposition of Ca++ in dead or dying tissues.
For example atheromas in advanced atherosclerosis,
aneurysms, valve cusps in aging or damaged valves (e.g.
rheumatic fever).
Pathogenesis:
Initiation occurs in the mitochondria of dead or dying
cells.
Propagation depends on the concentration of Ca++
and PO43 and collagen.
General Pathology
905
Metastatic Calcification
This occurs in normal tissues in conditions of

hypercalcemia.
Cause:
i. Hyperparathyroidism.
ii. Destruction of bone (e.g. Pagets disease of bone).
iii. Vitamin D intoxication.
iv. Sarcoidosis.
v. Renal failure.
Sites: Vessels (Monkeberg medial sclerosis), kidneys, lungs
(most common) and gastric mucosa.
Note: Heterotropic calcification is seen in ankylosing
spondylitis, Forrestiers disease.
REVERSIBILITY OF CELL INJURY
REVERSIBLE CELL INJURY
Mechanism
i. Plasma membrane alterations such as blebbing,
blunting and distortion of microvilli.
ii. Mitochondrial swelling.
iii. Dilatation of endoplasmic reticulum.
iv. Nuclear disaggregation of granular and fibrillary
elements.
Morphology
Reversible changes are also called degeneration.
1. Cellular swelling (hydropic change or vacuolar
degeneration) due to intracellular accumulation of
Na+ and water.
2. Hyaline change
Examples:
i. Hyaline degeneration of voluntary muscles, also
called Zenkers degeneration, occurs in the rectus
abdominis muscle in typhoid fever.
ii. Mallorys hyaline in hepatocytes in alcoholic liver
disease.
iii. Corpora amylacea in prostate in elderly, in brain
and spinal cord in old age, in old infarcts in the
lungs.
906
3. Mucoid change
Example: Catarrhal inflammation, cystic fibrosis of the
pancreas.
IRREVERSIBLE CELL INJURY
This is also called necrosis.
Pathogenesis
Etiology:
i. Enzymatic digestion of cells.
ii. Protein denaturation.
Mechanism:
i. Extensive damage to the cell membrane.
ii. Swelling of lysosomes.
iii. Vacuolization of mitochondria.
iv. Accumulation of amorphous calcium-rich densities in
mitochondrial matrix earliest ultrastructural change.
Morphology
Increased eosinophilia, decreased basophilia.
Cytoplasm: becomes vacuolated and appears moth-eaten,
dystrophic calcification.
Nucleus:
Karyolysis fading of basophilia of chromatin.
Pyknosis nuclear shrinkage.
Karyorrhexis fragmentation of nucleus.
Types
1. Coagulative necrosis: most common type.
Cause hypoxia (most common), infections.
Characterized by preservation of the basic structural
outline of the coagulated cells.
Mechanism denaturation of structural and
enzyme proteins.
Site occurs in all tissues except the brain. Most
common in heart (myocardial infarction), kidneys
and spleen.
2. Liquefactive necrosis:
Cause infections, ischemia of CNS.
Mechanism degradation of tissues by powerful
hydrolytic enzymes.
Site brain.
General Pathology
907
Note: gangrene is a type of ischemic coagulative necrosis

with a liquefactive component.
3. Casseous necrosis:
This occurs in the center of tubercular infection.
Morphology grossly, center looks cheesy (hence
the name). Microscopically, the center contains
structureless granular debris surrounded by
epithelioid cells, giant cells (of Langerhans or foreign
body type) and lymphocytes.
4. Fat necrosis:
Cause
i. Acute pancreatitis involves the omentum and
retroperitoneal fat.
ii. Trauma most commonly to the breast.
5. Fibrinoid necrosis:
Examples
i. Immunological tissue injury (autoimmune
diseases, Arthrus reaction) polyarteritis nodosa.
ii. Arterioles in malignant hypertension.
iii. Peptic ulcer.
iv. Aschoffs nodules in rheumatic fever.
CELLULAR ADAPTATION
Atrophy
Decrease in size of the cells by loss of cell substances.
Cause:
i. Decreased workload (e.g. immobilization of limbs
following a fracture).
ii. Loss of innervation.
iii. Diminished blood supply.
iv. Inadequate nutrition.
v. Loss of endocrine function.
vi. Physiological e.g. loss of hormone stimulation in
menopause.
Hypertrophy
Increase in size of the cells.
Example: hypertrophy of uterus in pregnancy, cardiac
enlargement in hypertension.
908
Hyperplasia
Increase in the number of cells.
Example:
i. Hyperplasia of female breast in puberty and following
childbirth.
ii. Compensatory hyperplasia after resection of the liver,
etc.
iii. Skin warts.
iv. Endometrial hyperplasia after menopause.
Metaplasia
Reversible change of one adult cell type to the other.
Example: Barretts esophagus, where the normal squamous
epithelium of the esophagus is replaced by columnar
epithelium.
APOPTOSIS
Apoptosis is the programmed cell death.
Pathology
i. Shrinkage of cell with dilatation of endoplasmic
reticulum.
ii. Formation of cytoplasmic buds and apoptotic bodies
(membrane bound vesicles of cytosol and organelles).
iii. Chromatin condensation.
iv. Karyorrhexis internucleosomal DNA fragmentation.
Histology of apoptotic cells: Round or oval mass of intensely
eosinophilic cytoplasm with dense nuclear chromatin
fragments.
Features
i. Does not show the features of inflammation.
ii. Very rapid process considerable changes may occur
before it is evident in histology.
Regulation
Inhibitors BCL-2, BCL-XL.

Promoters BAX, BAD, p53.
CD 95 is a mediator of apoptosis.
General Pathology
909
Differentiation with Necrotic Cells

By Agarose gel electrophoresis which shows
DNA laddering in apoptosis apoptotic cells contain
phosphatidyl serine in the outer membrane which can
be identified by Annexin V a marker.
Smear formation in necrosis.
Examples of Apoptosis
Endometrium after menstruation.

Breasts after weaning.
Tumor cell necrosis.
Pathological atrophy after duct obstruction.
Councilman bodies in viral hepatitis.
CELLULAR AGING
Changes
Irregular nuclei, pleomorphic vacuolated mitochondria.

Decrease in the number of endoplasmic reticulum.
Distorted Golgi apparatus.
Accumulation of lipofuscin, abnormally folded proteins
and advanced glycosylation end products.
Mechanism
i. Incomplete replication of chromosome ends (telomer
shortening).
ii. Clock genes.
Other theories wear-and-tear theory, free radical injury.
Progeria or Accelerated Aging
Seen in Werners syndrome, cockayne syndrome, ataxia
telangiectasia.
INFLAMMATION
Signs of Inflammation
According to Celsus:
i. Rubor (redness),
ii. Tumor (swelling),
910
iii. Calor (heat),

iv. Dolor (pain),
v. Also functio laesa.
ACUTE INFLAMMATION
VASCULAR EVENTS
a. Changes in Vascular Caliber and Flow
i. Transient vasoconstriction.
ii. Persistent progressive vasodilatation results in
redness and warmth.
iii. Increased hydrostatic pressure transudation of
fluid increased blood viscosity slowing of
blood flow and stasis.
iv. Margination of neutrophils to the vascular
endothelial surface emigration to extravascular
space.
Clinical implication the triple response:
1. Red line due to capillary dilatation (relaxation of
precapillary sphincter mediated by histamine).
2. Wheal due to transudation (histamine release).
3. Flare due to arteriolar dilatation (axonal reflex).
b. Increased Vascular Permeability
This causes the protein-rich fluid to exudate into interstitium
decreased plasma oncotic pressure and increased
interstitial pressure more fluid goes out of circulation
edema.
Mechanism:
i. Endothelial cell contraction reversible and short lived,
also called immediate transient response. This occurs
only in the post-capillary venules.
Mediators histamine, bradykinin, leukotriens.
ii. Endothelial cell retraction due to structural
reorganization of endothelial cytoskeleton. It develops
4-6 hours after injury and persists for 24 hours or more.
Mediators cytokines (TNF, IL-1).
General Pathology
911
iii. Direct endothelial injury causes endothelial cell

necrosis and detachment (as in burns, infections). This
process begins immediately after injury and lasts for
hours (immediate sustained response). This also causes
delayed prolonged leakage.
iv. Leukocyte mediated injury late response.
v. Others increased transcytosis in venules, leakage from
new capillaries.
CELLULAR EVENTS
a. Extravasation of Leukocytes, Predominantly
the Polymorphonuclear Cells
Stages:
i. Margination and rolling mediated by selectins E and
P on endothelial cells and Sialyl Lewis X on leukocytes.
ii. Adhesion and transmigration adhesion is mediated
by immunoglobulin superfamily on endothelial cells
(ICAM-1 and VCAM-1), cytokines (TNF and IL-1) and
integrins on endothelial cell surfaces (CD 18 LAF-1
and Mac-1 for ICAM and VLA4 for VCAM).
Transmigration is mediated by PECAM-1 or CD 31.
Note: The process of immigration of leukocytes through
the basement membrane into the extravascular space
is called diapedesis. This occurs in venules.
b. Chemotaxis and Activation
Mediators:
C5a, leukotrien B4, IL-8 ( chemokine), soluble bacterial
products (peptides and N-formylmethionine), kallikrein.
c. Phagocytosis
This was described by Metchinkoff.
Stages:
i. Opsonisation
Mediators IgG (Fc portion) and C3b, collectins.
ii. Engulfment.
iii. Degranulation of neutrophilic enzymes.
iv. Killing and degradation of the invading organisms
by oxygen bursts.
912

Adhesion molecules
On endothelial cells
On leukocytes
Role
Selectin P and E
VCAM-1 (Ig)
ICAM-1 (Ig)
Sialyl-Lewis X
VLA-4 integrin
CD11/CD18 integrins
(LFA-1, Mac 1)
CD 31 (PECAM 1)
Rolling
Adhesion
Adhesion
CD 31 (PECAM 1)
Transmigration
MEDIATORS OF ACUTE INFLAMMATION

Amines
i. Histamine it is liberated from the mast cells; causes
arteriolar dilatation and mediates immediate transient
response.
Other actions of histamine:
Increases gastric acid secretion.
Associated with arousal and blood pressure.
ii. Serotonin from platelets mediates transient
vasoconstriction following injury.
Substance P
Mediates pain.
Plasma Proteases
Hageman factor (factor XII): plays central roles in four
systems
i. Intrinsic coagulation pathway.
ii. Kinin system formation of bradykinin from high
molecular weight kininogen (HMWK).
Action of bradykinin: It increases vascular permeability,
causes arteriolar dilatation, bronchial smooth muscle
contraction and pain.
iii. Fibrinolytic system.
iv. Complement system two pathways
Classic pathway triggered by fixation of C1 to
antigen-antibody complex.
Alternate pathway triggered by bacterial endotoxin,
polysaccharides or IgA. This involves distinct set of serum
proteins (properdin, factor B and D).
Both the pathways lead to formation of the enzyme
C3 convertase, which subsequently carry on the chain.
Thus, C3 plays the central role in complement system.
General Pathology
913
Actions:
a. C3a and C5a (anaphylatoxins) cause increased
histamine release from the mast cells increased
vascular permeability and vasodilatation.
b. C5a chemotaxis.
c. C3b opsonisation.
Platelet Activating Factor (PAF)
Source: Endothelium, blood cells, by the action of
phospholipase A2.
Action: Vasoconstriction (most important), bronchoconstriction and platelet aggregation.
Cytokines
Source: Activated lymphocytes and macrophages.
Action:
i. Lymphocyte proliferation activated by IL-2, inhibited
by TGF.
ii. Innate immunity/acute inflammatory response TNF
and IL-1.
iii. Cell mediated immunity IFN- and IL-12 activate
macrophages.
Arachidonic Acid Metabolites
914
Nitric Oxide
Source endothelium.
Action vasodilatation.
Lysosomal Constituents
Acid proteases.
Neutral proteases elastase, collagenase and
cathepsin.
Antiproteases 2 macroglobulin, 1 antitrypsin.
Summary of Effects of Mediators

1. Vasodilatation PGI2, NO, PGD2, PGE2, PGF2.
2. Increased vascular permeability vasoactive amines,
C3a and C5a, bradykinin, LTC4/D4/E4, PAF.
3. Chemokines C5a, LTB4, IL-8.
4. Fever IL-1, IL-6, TNF.
5. Pain bradykinin, substance P.
6. Vasoconstriction TXA2, LTC4/D4/E4, PAF.
7. Bronchoconstriction leukotriens (most powerful),
vasoactive amines, bradykinin.
8. Cell lysis C5-C9.
OUTCOME OF ACUTE INFLAMMATION
1. Resolution.
2. Scarring and fibrosis.
3. Progression to chronic inflammation.
Note:
Other roles of prostaglandin:
PGE1 (misoprostol) cytoprotective, used in NSAID
induced gastritis.
PGE1 (alprostadil) used to keep patency of ductus
arteriosus (which is normally maintained by PGE2 and
PGI2).
PGE2 (dinoprostone), PGE1 (misoprostol), 15 methyl
PGF2 (carboprost) all cause increased uterine
contraction and are used for second trimester MTP.
CHRONIC INFLAMMATION
Etiology
1. Viral infections.
2. Certain bacterial infections like TB.
General Pathology
915
3. Prolonged exposure to toxic agents, e.g. silicosis.

4. Autoimmune disorders, e.g. rheumatoid arthritis.
Features
1. Mononuclear cell (macrophage, lymphocyte, plasma
cells) infiltration.
2. Tissue destruction.
3. Repair, involving new vessel proliferation (angiogenesis)
and fibrosis.
Note: Major activator of macrophages is IFN secreted
by TH1 cells.
Granuloma
This is a collection of activated macrophages called the
epithelioid cells (because they look like squamous cells on
LM) and rimmed at the periphery by lymphoid cells.
Etiology:
a. Bacterial tuberculosis (soft granuloma), syphilis,
leprosy, actinomycosis, bartonella (cat scratch disease),
yersinia.
b. Parasitic schistosomiasis.
c. Fungal histoplasma.
d. Foreign body foreign body granuloma.
e. Sarcoidosis.
f. Metals berylliosis.
Note: Caseous necrosis is produced by TB, syphilis,
histoplasma and coccidioidomycosis.
TB can also produce non-caseating granuloma.
Giant Cells
They are condensations of 20 or more macrophages.
Feature: Abundant cytoplasm with multiple nuclei arranged
in specific fashion.
Types:
1. Foreign body type seen in infective granulomas like
TB, leprosy.
2. Langerhans type seen in TB, sarcoidosis.
3. Tuton type seen in xanthomas.
4. Tumor type seen in ca liver, soft tissue sarcoma.
Note: Durck granuloma is seen in brain.
916
Morphology
1. Serous inflammation effusions, e.g. blisters.
2. Fibrinous inflammation, e.g. fibrinous pericarditis.
3. Suppurative inflammation
Pus is a collection of neutrophils, necrotic cells and
edema fluid.
Abscess is localized collection of pus. Abscesses
typically have a central necrotic zone, rimmed by
neutrophils and surrounded by dilated vessels and
fibroblasts.
4. Ulceration.
HEALING
Regeneration
When healing occurs by proliferation of parenchymal cells
and usually results in complete restoration of the original
tissue, it is called regeneration.
Repair
When healing takes place by proliferation of connective
tissue elements resulting in fibrosis and scarring, it is called
repair.
REGENERATION
Cell Cycle
Most cells are in resting or G0 phase.

Most important stage of regulation of cell cycle is G0
phase.
Largest stages G1 and S phases.
Shortest stage M phase.
Cell cycle is regulated by cyclins in association with
cyclin dependant kinases (please see the chapter of
Oncology).
Cell Types
Labile cells:
Continuously dividing cells, e.g. hematopoietic cells in
the bone marrow, surface epithelium.
General Pathology
917
Stable cells:
Quiescent normally but capable of dividing in response
to injury, e.g. parenchyma of solid organs (liver,
spleen, kidneys), endothelial cells of blood vessels,
fibroblasts and smooth muscle cells (mesenchymal).
Permanent cells: For example neurons and cardiac muscle
cells.
Mediators
Polypeptide growth factors induce proliferation by

affecting the expression of protooncogenes.
Mechanism by tissue kinase pathway.
EXTRACELLULAR MATRIX
Types
1. Interstitial matrix: in between cells.
Constituents fibrillar and nonfibrillar collagens,
proteoglycans, glycoproteins (most commonly
fibronectin).
2. Basement membrane: under epithelium overlying
mesenchymal cells.
Constituents nonfibrillar collagen (type IV),
glycoproteins (laminin).
Note: Degradation of collagen and other ECM proteins
is achieved by metalloproteinases (MMP).
Role
1.
2.
3.
4.
5.
6.
Mechanical support for cell anchorage.

Determination of cell orientation.
Control of cell growth.
Maintenance of tissue renewal.
Establishment of tissue microenvironment.
Storage and presentation of regulatory molecules.
Components
a. Fibrous structural proteins confer tensile strength and
recoil.
i. Collagen triple helix structure. Two types fibrillar
(types I, III and V), non-fibrillar (type IV).
ii. Elastin and fibrillin elastic fibers that help in recoil.
918
b. Water hydrated gels permit resilience and lubrication

(as in cartilages).
For example proteoglycans (dermatan and heparan
sulfate), hyaluronan.
c. Adhesive glycoproteins and integrins connect the
matrix elements one to another and to cells.
For example fibronectin (major component of
interstitial ECM), laminin (major component of
basement membrane). They mediate differentiation, motility, attachment, spread and migration.
Note: Integrins are adhesive proteins. They bind to
the ECM via RGD (Arg-Gly-Asp) motifs.
REPAIR
Stages
1. Formation of new blood vessels (angiogenesis).
2. Fibrosis (scar formation)
Emigration and proliferation of fibroblasts
(within 24 hours) into the site of injury
from adjacent mesenchymal tissues
Formation of granulation tissue (in 3-5 days)

characterized by proliferation of fibroblast and
new thin-walled, delicate capillaries in loose ECM
As healing progresses, the number of proliferating

fibroblasts and new vessels decrease, with increase in
deposition of ECM. Collagen is synthesized from fibroblasts.
3. Scar remodeling degradation of collagens and outer

ECM components by metaloproteins which are
dependant on zinc.
WOUND HEALING
Healing by First Intention
Healing of a clean, uninfected surgical incision

approximated by sutures.
In this type, epithelial regeneration predominates over
fibrosis.
Events:
24 hours neutrophils at wound margin.
24-48 hours migration and proliferation of epithelial
cells from both margins and deposition of basement
membrane.
General Pathology
919
By day 3 neutrophils replaced by macrophages.

Granulation tissue progressively invades incision space.
Collagens appear.
By day 5 neovascularization at its peak as granulation
tissue fills the gap.
Note: Collagen content reaches maximum during the
3rd week.
Healing by Second Intention

There is extensive in growth of granulation tissue from the
wound margin, followed in time by accumulation of ECM
and scarring.
Secondary healing shows the phenomenon of wound
contraction. This occurs due to the presence of
myofibroblasts.
Wound strength: Wound strength increases rapidly and
becomes 70-80 percent of normal by 3 moths, but usually
does not return to preinjury strength.
BONE GROWTH
Stages
Osteoblasts osteoclasts (bone resorption)
Osteocytes
Osteoid (type I collagen) nonmineralized, forms the

bone matrix.
| In the presence of osteo calcin and osteonectin
Mineralized with Ca-hydroxyapatite and Ca-phosphate
(constitutes 65-70% of bone weight)
Note:
Osteocalcin level is increased in serum during bone
growth and its measurement serves as a sensitive and
specific marker of osteoblastic activity.
Bone cells are mesenchymal in origin.
Enzymes
Osteoblast alkaline phosphatase.

Osteoclast acid hydrolase, collagenase and acid
phosphatase.
920
FLUID AND ELECTROLYTES

WATER BALANCE
60 percent of body weight is water.
Distribution
Note: TBW is measured using D2O.

Plasma Osmolality
Normal plasma osmolality is 275-290 mosmol/kg.

Major ECF particles are Na+, Cl- and HCO3-. They
exert 80 percent of plasma osmolality.
Major ICF particles are K+, organic phosphate esters
(ATP, creatine phosphate and phospholipids). They exert
20 percent of plasma osmolality.
Major ions
ECF
Major cation
Major anion
Na , Ca
Cl -
ICF
++
K+, Mg ++
PO43 -, proteins
Sodium Pump
3 Na+ are actively pumped out of cell in exchange

of 2 K+ by the Na+-K+ ATPase (coupling ratio 3:2).
It is activated at 4oC.
Hypocalcemia inhibits this pump.
Water Intake
Exogenous = 2-3 liters/day.

Endogenous due to oxidation of food = 500 ml/
day.
Water intake is regulated by osmoreceptors situated
in anterolateral nucleus of hypothalamus.
General Pathology
921
Water Output
Insensible loss through the lungs and skin = 500 ml/

day.
Water lost in sweat = 600-1000 ml/24 hours.
Through urine = 1500 ml/24 hours.
GI tract 9 liter of fluid enters the GI tract daily
2 liter by ingestion and 7 liter by excretion. 98 percent
is reabsorbed and water lost in feces is 100-200 ml/
day.
Water Reabsorption
Normally, 60-70 percent of filtered water is reabsorbed
in the proximal convoluted tubule (both in the presence
and absence of ADH).
Major regulator is AVP which acts on V2 receptors on
the basolateral membrane of principal cells (P cells) in
the collecting duct to increase water reabsorption.
HYPOVOLEMIA
Etiology
a. Renal
1. Diabetes insipidus.
2. Diuretics.
b. Extrarenal
1. GI tract vomiting, diarrhea.
2. Hemorrhage.
Pathophysiology
Hypovolemia ECF volume contraction decreased
plasma volume, hypotension
Activation of baroreceptors in carotid body and aortic

arch
Increased sympathetic tone
Decreased GFR by preferential afferent arteriolar

contraction and increased Na+ reabsorption in PCT
Increased Na+ reabsorption also occur in the collecting

duct mediated by increased production of aldosterone and
AVP and decreased production of ANP.
Clinical Feature
Weakness and intense thirst.
922
Diagnosis
Prerenal azotemia increased BUN:creatine ratio to

20 : 1 (normal is 10 : 1).
Increased hematocrit, decreased urine output with
increased specific gravity.
Treatment
Isotonic saline (0.9% NaCl or 154 mmol/liter on Na+).
WATER INTOXICATION
Etiology
i. Over ingestion of 5% glucose (hypotonic) solution.
ii. Colorectal washouts with plain water instead of saline.
iii. Excessive uptake of water (and glycine) from irrigation
fluid during TURP.
iv. Syndrome of inappropriate ADH secretion.
Clinical Feature
Drowsiness, weakness, convulsions and coma.
Treatment
Water restriction.
SODIUM BALANCE
Total body Na+ is 5000 mmol (58 meq/kg) of which

47 percent is in the bones (maximum).
Normal Na+ concentration in plasma = 135-145
mmol/liter.
Daily intake 1 mmol/kg.
REGULATION
Na+ Reabsorption
More than 99% of GFR is reabsorbed from
i. PCT (2/3rd of GFR) passively.
ii. Thick AsLH by apical Na+-K+-Cl - cotransporter.
iii. DCT thiazide sensitive Na+- Cl --cotransporter.
iv. Cortical and medullary collecting ducts.
Chief regulation is by aldosterone which acts on Na+Cl -cotransporter in the DCT to retain Na+ and enhance
excretion of K+.
General Pathology
923
During postoperative period there is increased

aldosterone activity for the first 48 hours, which leads to
Na+ retention and excess Cl - excretion.
HYPONATREMIA
Etiology
1. Hypoosmolal hyponatremia
a. Primary Na + loss (secondary water gain)
decreased ECF volume.
i. Vomiting, diarrhea
ii. Renal osmotic diuresis, Addisons disease
b. Primary water gain (secondary Na+ loss) increased
ECF volume.
i. Polydypsia
ii. SIADH
iii. Glucocorticoid deficiency
iv. Hypothyroidism
c. Primary Na+ gain
i. Heart failure
ii. Cirrhosis
iii. Nephrotic syndrome
2. Pseudohyponatremia
a. Isotonic hyperlipidemia, hyperproteinemia, postTURP
b. Hypertonic hyperglycemia
Clinical Feature
Primarily neurological symptoms confusion and
restlessness, seizures, delirium.
Muscle cramp and weakness, periodic paralysis,
Circulatory failure.
HYPERNATREMIA
Etiology
Most common cause is renal water loss due to diabetes
insipidus.
Pathophysiology
Due to increased tonicity, water comes out of cells
decreased ICF and increased ECF volume hypertension
and increased ICT.
924
Clinical Feature
Altered mental status, weakness, irritability, convulsions
and coma.
Polyuria and thirst.
Muscle twitching.
Due to extracellular volume expansion skin turgor is
not decreased and frontanells not depressed in children.
POTASSIUM
98 percent K+ is in ICF. of body K+ is in the skeletal
muscles.
Normal K+ concentration 3.5-5 mmol/liter.
K+ is the most important ion to maintain resting
membrane potential.
Daily K+ requirement is 150 mEq.
Regulation
K+ reabsorption 90 percent of filtered K+ is reabsorbed
in
i. PCT passively along with Na+ and water.
ii. Thick AsLH by Na+- K+- Cl - cotransport.
K+ is secreted by the principal cells in DCT and
collecting duct in exchange of Na+.
In metabolic acidosis, more K+ comes out of cells in
exchange of H+ hyperkalemia.
In metabolic alkalosis hypokalemia.
In acidosis, increased H+ present at DCT decreases
K+ secretion and thereby decrease K+ excretion.
HYPOKALEMIA
Etiology
a. Redistribution into cells:
1. Metabolic alkalosis
2. Insulin increased activity of Na+- K+ ATPase
3. Total parenteral nutrition
4. Aldosterone, -adrenergic stimulation
b. Increased loss:
1. Diarrhea
General Pathology
925
2. Renal
i. Proximal RTA
ii. Bartters syndrome
iii. Conns disease (primary hyperall are
aldosteronism)
associated with
iv. Congenital adrenal hyperplasia
hypertension
v. Cushings syndrome
vi. Liddles syndrome
c. Pseudohypokalemia:
Leukocytosis (AML).
d. Drugs: Amphotericin B, carbenicillin, gentamicin,
diuretics, degraded tetracyclines, steroids.
Clinical Feature
Muscle weakness, decreased reflexes, abdominal
distension due to paralytic ileus, increased risk of
rhabdomyolysis.
Rapid, slow, gasping breathing (hypoventilation).
ECG:
Hypokalemia prolongs ventricular repolarization (QT
prolongation) with prominent U wave - actually there
is QU prolongation.
Flattening or inversion of T wave, ST depression,
prolongation of PR, decreased voltage and widening
of QRS.
Hypokalemia may precipitate digitalis toxicity.
Treatment
Without alkalosis 40 mmol KCl in 1 liter of 5%
glucose, or 0.9% saline.
Note: Maximum K+ content in Darrows solution
36 mEq/liter.
HYPERKALEMIA
Etiology
Renal failure
Addisons disease (aldosterone deficiency)
Acidosis
Crush syndrome
926
Drugs captopril, digitalis, scoline, beta blockers

Pseudohyperkalemia leukocytosis, thrombocytosis,
hemolysis.
Clinical Feature
Weakness, flaccid paralysis, hypoventilation, metabolic
acidosis.
ECG:
Cardiac toxicity is the most serious effect of
hyperkalemia.
Plasma K+ > 7 meq/L = starts with tall T wave
(Tenting of T wave), prolonged PR and QRS.
K+ > 8.5 meq/L = absent P wave, broad QRS
complex, sine- wave pattern, ventricular fibrillation or
asystole.
Treatment
Ca-gluconate decreases membrane excitability.
Insulin shifts K+ into cells.
IV NaHCO3 shifts K+ into cells.
OTHER IONS
Serum Ca++ = 2.2-2.5 mmol/liter.

Serum Mg++(intracellular) = 0.7-0.9 mmol/liter.
Serum Cl = 95-105 mmol/liter.
Serum HCO3 = 25-30 mmol/liter.
ACID-BASE BALANCE
Normal arterial pH = 7.35-7.45.
Henderson-Hasselbalch Equation
pH depends on bicarbonate:carbonic acid (PCO2) ratio.
Normal value = 20:1.
Decrease in the ratio causes a decrease in pH (acidosis)
vice versa.
Measurement
PaCO2 = 40 mmHg.
PaO2 = 100 mmHg.
Standard HCO3 = 22-25 mmol/liter.
General Pathology
927
Response to change in pH
Primary response
Secondary response
Respiratory alkalosis Decreased PaCO 2
(hyperventilation)
Respiratory acidosis Increased PaCO2
(hypoventilation)
Metabolic alkalosis
Increased HCO3Metabolic acidosis
Decreased HCO3-
Decreased HCO 3 in
plasma (increased
HCO 3 excretion)
Increased HCO 3
Increased PaCO 2
(hypoventilation)
Decreased PaCO2
(hyperventilation)
Kussmaul breathing.
Anion Gap
This represents the undetermined or unmeasured anions
in blood.
This constitutes mainly of proteins.
This is represented by = (Na++ K+)(HCO3 +Cl)
Normal value = 10-12 mmol/liter.
METABOLIC ACIDOSIS
Etiology
A. With increased anion gap:
1. Lactic acidosis see below.
2. Ketoacidosis alcohol, diabetes, starvation.
3. Toxins ethylene glycol, methanol, salicylates.
4. Renal failure.
B. Normal anion gap:
Hyperchloremic acidosis:
1. GI bicarbonate loss diarrhea (cholera),
ureterosigmoidostomy.
2. Renal
i. Hypokalemic type I and II renal tubular
acidosis.
ii. Hyperkalemic mineralocorticoid deficiency,
type IV RTA.
Note: Metabolic acidosis leads to hyperkalemia. But
lactic acidosis, diabetic ketoacidosis and RTA often
lowers K+ level in blood.
Causes of Lactic Acidosis
Type A Circulatory failure, cholera, CO poisoning.
Type B diabetes, alcohol, renal failure, phenformin
therapy.
928
Clinical Feature
Rapid, deep breathing Kussmaul breathing due to fall
in blood pH and stimulation of respiratory center.
Treatment
Adequate tissue perfusion O2 therapy.
Alkali therapy with NaHCO3.
Calculation for HCO3 requirement in metabolic acidosis:
1/2 body weight (desired HCO3 measured
HCO3)
= 1/2 body weight (25 measured HCO3)
Half of this quantity should be administered in 1/2
an hour.
METABOLIC ALKALOSIS
Etiology
1. Milk-Alkali syndrome (NaHCO3 ingestion).
2. Vomiting most commonly due to pyloric stenosis,
also duodenal obstruction.
3. Diuretics.
4. Cushings syndrome.
5. Bartters syndrome.
Clinical Feature
Cheyne-Strokes respiration with periods of apnea lasting
from 5-30 seconds.
Tetany Trousseaus sign.
Treatment
Without hypokalemia no treatment is required.
With hypokalemia IV fluid with 40 mmol/liter of KCl.
RESPIRATORY ACIDOSIS
Etiology
Hypoventilation due to:
1. Inadequate ventilation of anesthetized patient most
common cause.
2. Emphysema.
General Pathology
3. Muscular dystrophy.
4. Breathing 7% CO2.
5. Barbiturate poisoning.
Treatment
Mechanical ventilation when PCO2 > 50 mmHg.
RESPIRATORY ALKALOSIS
Most common type of acid-base disturbance.
Etiology
Hyperventilation due to:
1. High altitude.
2. Hyperpyrexia.
3. Lesion in hypothalamus.
4. Hysteria.
5. Salicylates.
Treatment
Insufflation of CO2.
929
SUPPLEMENT
FORENSIC AND
STATE MEDICINE
IMPORTANT SECTIONS IN IPC
Important sections in IPC
Section
Subject
S.
S.
S.
S.
S.
S.
S.
S.
S.
S.
S.
S.
S.
Medical examination of arrested person

McNaughten rule
Legal protection for doctors
Police inquest
Perjury
Punishment for murder
Criminal negligence
Dowry death
Abandoning of infants
Grievous injury
Definition of rape
Punishment for rape
Unnatural sexual offences
54, CrPC
84, IPC
88-93, IPC
174, CrPC
193, IPC
302, IPC
304A, IPC
304B, IPC
317, IPC
320, IPC
375, IPC
376, IPC
377, IPC
RULES
McNaughten rule, Durhams rule, Currens rule
responsibility of insane in criminal case.
Locards principle exchange principle.
Rule of nines by Alexander Wallace for the estimation
of the total body surface area burnt.
Rule of Haase age of the fetus. During the first five
months of pregnancy the square root of the length
gives the approximate age of the fetus in months, e.g.
a fetus of 16 cm is of 4 months age.
Puppes rule sequence of bullet shots.
Widmarks formula for estimation of alcohol in body.
Supplement
931
TEST AND FORMULA

Gustafsons method age of adults from teeth.
Pearsons formula, Trotter and Gleser formula stature
from long bones.
Dermal nitrate test for the detection of gun powder.
Harrison and Gilroy test for the detection of heavy
metals in gun powder.
Gettler test drowning.
Florence test, Barberios test, Acid phosphatase test
(best) for the detection of seminal fluid.
Hydrostatic test for livebirth.
Benzidine test, Teichmanns test, Takayama test for
the detection of blood stain.
Leucomalachite green test for blood stain or
peroxide.
Spectroscopic examination best for the detection of
blood stain.
Precipitin test for determination whether the blood
is from human or animals.
Absorption elution technique, mixed agglutination
technique, absorption inhibition technique for
determination of ABO blood group.
DNA fingerprinting best method for paternity
determination.
Marshs test, Reinschs test for arsenic.
Cavett test, Kozelka and Hine test, Gas chromatography
(best) for estimation of alcohol in blood.
Note:
Takayama test or haemochromogen crystal test for
detection of blood stain produces pink, feathery crystals.
Leucomalachite test produces peacock blue color.
Phenolphthalein test for blood stain produces pink color.
TOXICOLOGY
Pupil
Dilated in datura, barbiturate, alcohol poisoning.
Contracted in opium, organophosphorus, carbolic
acid poisoning.
Alternate dilatation and contraction is seen in aconite
poisoning.
932
Urine
Green color in carbolic acid poisoning.
Golden color in barbiturate poisoning.
Brown color in nitric acid poisoning.
Stomach
Leathery stomach in carbolic acid poisoning.
Velvety stomach in arsenic poisoning.
Brown color in sulphuric acid poisoning.
Lines
Aldrich-Mees line on fingernails in arsenic poisoning.
Blue line on gum in mercury poisoning.
Burtonian line (stippled blue line on gum) in chronic
lead poisoning.
Odor
Garlicky odor in phosphorus poisoning.

Odor of bitter almond in cyanide poisoning.
Odor of burnt rope in cannabis poisoning.
Odor of rotten eggs in H2S poisoning.
Antidotes
Universal antidote contains powdered animal charcoal
(or burnt toast) 2 parts; magnesium oxide one part;
tannic acid (or strong tea) one part.
Organophosphorus, carbamates poisoning atropine.
Organochlorine (Endrin) poisoning no antidote.
Oxalic acid poisoning calcium gluconate or lactate.
Arsenic freshly precipitated hydrated ferric oxide.
Mercury poisoning BAL, penicillamine.
Copper poisoning penicillamine.
Lead poisoning EDTA, BAL (in presence of renal
impairment).
Nitrates poisoning methylene blue.
Methyl alcohol poisoning ethyl alcohol.
Opioid poisoning nalorphine.
Paracetamol poisoning N-acetylcysteine.
Cocaine poisoning amyl nitrate.
Cyanide poisoning amyl nitrate plus sodium
thiosulphate.
Iron poisoning IM desferrioxamine or oral deferiprone.
Supplement
933
Note:
Dimercaprol or BAL contains two SH groups.
BAL is contraindicated in iron and cadmium poisoning.
EDTA is not used in mercury poisoning.
Hemodialysis is useful in poisoning by alcohol,
lithium, phenobarbital, salicylates and digitalis.
Preservatives
Rectified spirit is not used in cases of poisoning by
alcohol, acetic acid, phenol, phosphorus, paraldehyde.
Tisseues are preserved in 10 percent formalin. In
suspected cases of poisoning viscera should not be
preserved in formalin.
Blood 100 ml (minimum 10 ml) should be preserved.
Alcohol sodium fluoride 10mg/ml is used as
preservative.
Vitreous fluoride.
RADIOLOGY
RADIOLOGICAL APPEARANCES
Appearance
Air bronchogram
Bulls eye lesion
Butterfly or bats
wing pattern
Bulging fissure sign
Crescent sign
Cannon ball shadow
Egg shell calcification
Golden S sign
Karley lines
Popcorn calcification
Pallas sign, Humptons
Disease
Respiratory system
Consolidation, pulmonary edema, respiratory
distress syndrome
Granuloma
Pulmonary edema
Klebsiella pneumonia
Aspergilloma or fungus ball
Pulmonary metastasis
Silicosis, sarcoidosis, scleroderma, histoplasmosis, amyloidosis, treated lymphoma
Central bronchogenic carcinoma with right
upper lobe collapse
Left ventricular failure, mitral stenosis,
pneumoconiosis
Hamartoma
Pulmonary embolism
hump
Sail sign
Signet ring appearance
Steeple sign
Thumb sign
Tram track sign
Thymoma
Bronchiectasis
Croup
Acute epiglottitis
Bronchiectasis
Contd...
934
Contd...
Appearance
Disease
Water lily sign

Wave sign of Muvley
Hydatid disease
Thymus
Cardiovascular system
Couer en sabot
Fallots tetralogy
(boot shaped heart)
Egg on side appearance Transposition of great arteries (TGA)
Flask shaped heart
Pericardial effusion
Hilar dance sign
Atrial septal defect (ASD)
on fluoroscopy
Rib notching
Inferior rib notching
Coarctation of aorta, SVC/IVC obstruction,
pulmonary AV malformation, hyperparathyroidism, Balock-taussig shunt
Superior rib notching Connective tissue disorders RA, SLE,
scleroderma; hyperparathyroidism, Marfans
syndrome, polio.
Snowman heart or
Total anomalous pulmonary
figure of 8 heart
venous connection (TAPVC)
Apple core appearance

Birds beak tapering
of esophagus
Bulls eye lesion in
liver in USG
Central dot sign
Chain of lakes
appearance on ERCP
Claw sign
Coffee bean sign
Corkscrew esophagus
Double bubble sign
Frostbergs inverted
3 sign
Gasless abdomen
Mercedes Benz sign
String sign of Kantor
Stem pipe colon
(ahaustral)
Thumb printing
Triple bubble sign
Absent clavicle
Anterior beaking of
vertebrae
Bare orbit sign
Bamboo spine,
squaring of vertebra
Beheaded Scotty dog
Abdomen
Carcinoma colon
Achalasia cardia
Candidiasis
Carolis disease
Chronic pancreatitis
Intususseption
Sigmoid volvulus
Diffuse esophageal spasm
Duodenal atresia
Carcinoma head of pancreas
Acute pancreatitis
Radiolucent gallstone with gas within it
Crohns disease
Ulcerative colitis
Ischemic colitis
Jejunal atresia
Skeletal system
Cleidocranial dysplasia
Type I MPS (Hurlers anteroinferior),
type IV MPS (Morquios central)
Neurofibromatosis
Ankylosing spondylitis
Spondylolisthesis
Contd...
Supplement
935
Contd...
Appearance
Disease
Bone within bone

appearance
Champagne glass
pelvis, trident hand
Heel pad sign
Iliac horns
Ivory vertebra
IV disc calcification
Loosers zone
(pseudofracture)
Molten candle wax
appearance
Scotty dog with collar
Rugger jersey spine
Soap bubble
appearance
Sun-ray appearance,
Codmans triangle
Vertebral plana
Osteopetrosis
Achondroplasia
Acromegaly
Nail patella syndrome
Lymphoma
Alkaptonuria
Osteomalacia
Meloreosteosis (Leris disease)
Spondylolysis
Osteopetrosis, renal osteodystrophy
Giant cell tumor of bone
Osteosarcoma
Eosinophilic granuloma
Genitourinary system
Adder head/Cobra
Ureterocele
head appearance on IVU
Flower vase
Horseshoe kidney
appearance on IVU
Golf hole ureter
TB urinary bladder
on cystoscopy
Nephrocalcinosis
Hyperparathyroidism, medullary sponge
kidney, renal tubular acidosis, chronic
glomerulonephritis, hypercalcemia
Rim sign in
Severe hydronephrosis
nephrogram
Spider leg appearance
Polycystic kidney
on IVU
Thimble bladder
TB urinary bladder
Basal ganglia
calcification
Head, Neck and CNS

Idiopathic, hypoparathyroidism, Fahrs
syndrome, Cockayne syndrome, CO, Pb
poisoning, toxoplasmosis
Raised ICT
Copper beaten
appearance of skull
Geographic skull
Hair-on-end
appearance of skull
Snow-driven appearance
Suprasellar calcification
Tram track calcification
Histiocytosis X
Thalassemia, sickle cell anemia
Pindborg tumor
Craniopharyngioma
Sturge-Weber syndrome
936
VIEWS IN X-RAY
Chest X-ray
Lung apex lordotic view, AP (apical view).
Left atrial enlargement right anterior oblique view
with barium in esophagus.
Pneumothorax PA view in full expiration.
Pleural effusion lateral decubitus view.
Tracheal bifurcation PA view.
Abdomen
Hiatal disorders barium meal in Trendelenburgs
position.
Pneumoperitoneum left lateral decubitus with
horizontal beam.
Skull and PNS
Basal skull view (submento-vertical) structures seen
are sphenoid, posterior ethmoid and maxillary sinuses;
mandible along with coronoid and condyloid processes;
zygoma and zygomatic arch.
Caldwell-Luc view structures seen are superior orbital
fissure; frontal, ethmoid and maxillary sinuses; foramen
rotundum; lamina papyracea and superior margin of
orbit.
Stenvers view structures seen are internal auditory
meatus, mastoid air cells.
CONTRAST AGENTS
Barium studies barium sulphate.
Tracheoesophageal fistula, esophageal atresia
dianosil (water soluble, non-ionic).
Oral cholecystography iopaonic acid (telepaque).
Bronchography dianosil.
IV cholangiography biligraffin.
Liver scan isotope used technetium, contrast used
I131 rose Bengal.
IVU urograffin.
RADIOISOTOPES
Ventriculography technetium.
Myocardial perfusion thallium 201 (produces cold
spot) and Tc99 pyrophosphate (produces hot spot).
Supplement
937
Liver scan technetium.

Pancreatic scan selenium 75.
Neuroectodermal tumors (NET) somatostatin receptor
scintigraphy.
Renal imaging for parenchyma (anatomical imaging)
Tc99DMSA; for perfusion (functional imaging)
Tc99DTPA.
Thyroid scan anatomical imaging I131 (half life
2-8 days); functional imaging I123 (half life 13 hours).
Parathyroid scanning Thallium-Tc99 substraction
scanning, sestamibi scanning.
Bone scan MDP Tc99 methylene diphosphate.
GI bleeding Tc99 RBC (can detect as low as 0.1 ml/
min of bleeding as compared to 0.5 ml/min by
angiography).
Ectopic gastric mucosa (e.g. in Meckels diverticulum)
Tc99 pertechnetate scanning.
ANATOMY OF LIMBS
Front of Arm
Muscles
1. Coracobrachialis
2. Biceps brachii
3. Brachialis
Nerve supply: Musculocutaneous nerve.
Action:
i. Flexion of arm coracobrachialis.
ii. Biceps is supinator (screwing movement).
iii. Brachialis flexion of forearm at elbow.
Musculocutaneous Nerve
Origin: Lateral cord of brachial plexus.
Root value: C 5, 6, 7.
Course: It continues as the lateral cutaneous nerve of
forearm to supply the skin on the lateral surface of forearm
from elbow to wrist.
Applied: Injury to musculocutaneous nerve produces
i. Loss of flexion at elbow and supination of forearm
(see muscle actions above).
ii. Loss of sensation on the lateral surface of forearm.
938
Cubital Fossa
Boundary:
Laterally, medial border of brachioradialis.
Medially, lateral border of pronator teres.
Back of Arm
Triceps
Origin: Arises from three heads:
i. Long head from infraglenoid tubercle of scapula.
ii. Lateral head from the lateral lip of spiral groove.
iii. Medial head from shaft of humerus below the spiral
groove.
Nerve supply: Radial nerve (usually supplies from axilla).
Applied: In radial nerve injury in the spiral groove, the
long and lateral heads of triceps escape paralysis.
Front of Forearm
Muscles
Superficial muscles: From medial to lateral:
1. Pronator teres
2. Flexor carpi radialis
3. Palmaris longus
4. Flexor digitorum superficialis
5. Flexor carpi ulnaris.
Nerve supply: All the muscles are supplied by median nerve
except the flexor carpi ulnaris which is supplied by ulnar
nerve.
Deep muscles:
1. Flexor digitorum profundus
2. Flexor pollicis longus
3. Pronator quadratus
Nerve supply: All are supplied by anterior interosseous
branch of median nerve (C8, T1) except medial half of
FDP which is supplied by ulnar nerve.
Back of Forearm
Muscles
Special actions:
1. Anconeus screwing movement.
Supplement
939
2. Extensor digitorum extension of IP, MP and wrist

joints.
Nerve supply: All extensor muscles are supplied by posterior
interosseous branch of radial nerve.
Hand
Muscles
Thenar eminence abductor pollicis brevis, flexor
pollicis brevis, opponens pollicis.
Hypothenar eminence abductor digiti minimi, flexor
digiti minimi, opponens digiti minimi.
Intrinsic muscles
1. Interossi
i. Palmar adductors of fingers (Palmar adductors
PAD).
ii. Dorsal abductors of fingers (Dorsal abductors
DAB).
In addition they produce flexion of MCP joints
and extension of IP joints.
2. Lumbricals produce flexion of MCP joints and
extension of IP joints.
Nerve supply:
Motor all the muscles of hand are supplied by ulnar
nerve except five three thenar muscles and first and
second lumbricals which are supplied by median nerve.
Sensory
Palm medial 1 and 1/2 fingers by ulnar nerve; lateral
3 and 1/2 fingers by median nerve.
Dorsum medial 2 and 1/2 fingers by ulnar nerve;
lateral 2 and 1/2 fingers by radial nerve.
Distal digits on dorsum the index, middle and lateral
half of ring finger are supplied by median nerve.
INFERIOR EXTREMITY
Femoral triangle:
Muscles in femoral triangle form the floor of the triangle.
From medial to lateral these are:
1. Adductor longus
2. Pectineus
3. Psoas major
4. Iliacus
940
Front of Thigh
Muscles:
1. Sartorius
2. Quadriceps femoris which include:
i. Rectus femoris
ii. Vastus medialis
iii. Vastus intermedius
iv. Vastus lateralis
Nerve supply: Femoral nerve.
Medial Side of Thigh (Adductor Compartment)
Muscles:
1. Adductor longus
2. Adductor brevis
3. Adductor magnus
4. Gracilis
5. Pectineus
Nerve supply: Obturator nerve.
Gluteal Region
Muscles
Action
Nerve supply
Gluteus maximus
Chief extensor of hip
Gluteus medius
Gluteus minimus
Tensor fascia lata
Piriformis
Gemelli
Obturator internus
Abductors and medial

rotators of thigh. TFL
is extensor of knee
Lateral rotators of thigh
Inferior gluteal
nerve
Superior gluteal
nerve
Obturator externus
Quadratus femoris
Lateral rotator of thigh

Back of Thigh
Hamstring Muscles
They are:
1. Semimembranosus
2. Semitendinosus
3. Long head of biceps femoris
4. Ischial head of adductor magnus
Nerve to obturator
internus
Obturator nerve
Nerve to quadratus
femoris
Supplement
941
Origin: All arise from the ischial tuberosity.

Nerve supply: Tibial nerve.
Action: Flexors of knee and extensors of hip.
Front of Leg
Extensor Retinaculum
Structures passing below extensor retinaculum:
1. Tibialis anterior
2. Extensor hallucis longus
3. Anterior tibial artery
4. Anterior tibial vein
5. Deep peroneal nerve
6. Extensor digitorum longus
7. Peroneus tertius
Nerve supply: Deep peroneal nerve.
Back of Leg
Superficial Muscles
1. Gastrocnemius
2. Soleus
3. Plantaris
Nerve supply: All are supplied by tibial nerve.
Deep Muscles
1. Popliteus (intracapsual origin). Action lateral rotation
of femur (unlocking).
2. Flexor digitorum longus
3. Flexor hallucis longus
4. Tibialis posterior tendon passes behind medial
malleolus.
Nerve supply: All are supplied by tibial nerve.
Flexor Retinaculum
Structures passing deep to flexor retinaculum:
1. Tibialis anterior
2. Flexor digitorum longus
3. Posterior tibial artery and vein
942
4. Tibial nerve
5. Flexor hallucis longus
Mnemonic Tom Dick AN Harry
Nerves
Lumbar Plexus
Lies in the posterior part of the substance of psoas
major muscle.
Formed by anterior primary rami of L1 to L5 spinal
nerves.
Branches:
L1
i. Ilioinguinal nerve supplies the skin at root of the
penis. It enters the inguinal canal through the interval
betweens external and internal oblique muscles and
leaves the canal through superficial ring. It may be
injured during hernia operation.
ii. Iliohypogastric nerve may be injured during
appendicectomy.
L1 and L2 genitofemoral nerve.
i. Femoral branch supplies the skin over femoral
triangle.
ii. Genital branch supplies cremaster muscle in male
and sensory to the round ligament and labia majus
in female.
L2 and L3 lateral cutaneous nerve of thigh.
Applied may cause paresthesia melalgia.
L 2,3,4
i. Doral division femoral nerve (longest branch).
ii. Ventral division obturator nerve.
L4,5 (ventral rami) lumbosacral trunk. Takes part
in the formation of sacral plexus.
Femoral nerve:
Muscular to anterior compartment muscles.
Cutaneous
i. Anterior division intermediate and medial cutaneous
nerve of thigh.
ii. Posterior division saphenous nerve.
Saphenous nerve: It accompanies great saphenous vein
and supplies the skin on the medial side of leg and foot
upto the ball of great toe.
Supplement
943
Obturator nerve: It supplies the muscles of adductor

compartment and obturator externus. Posterior division
supplies the knee joint.
Sacral Plexus
Formed by: Lumbosacral trunk and ventral rami of S1
to S3 spinal nerves.
Branches:
L4,5 and S1
i. Ventral division nerve to quadraturs femoris.
ii. Dorsal division superior gluteal nerve.
L5 and S1,2
i. Ventral division nerve to obturator internus.
ii. Dorsal division inferior gluteal nerve.
L4,5 and S1,2 (sciatic nerve)
i. Ventral division tibial nerve (also contains fibers
from S3).
ii. Dorsal division common peroneal nerve.
S2,3,4 ventral division pudendal nerve.
Tibial nerve:
It is the larger terminal branch of sciatic nerve.
It supplies all muscles of back of thigh and back of
leg.
Cutaneous branch sural nerve (most common nerve
used for nerve grafting).
Common peroneal nerve:
It is the smaller terminal branch of sciatic nerve.
It winds round the neck of fibula (where it can be
palpated) and divides into superficial and deep peroneal
nerves.
It crosses the popliteal fossa in a superficial plane.
Branches
i. At back of thigh only to short head of biceps
femoris.
ii. All muscles of the anterior compartment of leg by
deep peroneal nerve (injury to which produces foot
drop).
Arteries
Femora l Artery
It is the continuation of external iliac artery.
944
It begins behind the inguinal ligament at the midinguinal

point (mid point between anterior superior iliac spine
and pubic ramus).
In the femoral sheath, it occupies the lateral
compartment along with femoral branch of
genitofemoral nerve.
It pierces the adductor magnus and continues as the
popliteal artery in the popliteal fossa.
Branches:
Superficial
i. Superficial external pudendal
ii. Superficial circumflex iliac
iii. Superficial epigastric
All these arteries pierce the cribriform fascia.
Deep
i. Deep external pudendal
ii. Profunda femoris artery longest branch. It supplies
all three compartments of thigh.
Branches medial circumflex femoral chief arterial
supply to the head of femur; lateral circumflex femoral;
perforating branches main supply to back of thigh.
Popliteal Artery
It is the continuation of the femoral artery.
It begins at the opening in the adductor magnus (hiatus
magnus).
It is the deepest structure at the popliteal fossa.
It forms the anastomosis around knee joint by
i. Genicular branches medial (superior and inferior)
and lateral (superior and inferior).
ii. Descending genicular branch on medial side.
iii. Tibial recurrent branches (anterior and posterior) on
lateral side.
It ends at the lower border of popliteus dividing into
anterior and posterior tibial branches.
Anterior Tibial Artery
It is the smaller terminal branch of popliteal artery.
It is the main arterial supply to the anterior
compartment of leg.
It continues as the dorsalis pedis artery which is the
main supply to the dorsum of foot.
Supplement
945
Posterior Tibial Artery

It is the larger terminal branch of popliteal artery.
It supplies the back and lateral compartment of leg
through peroneal artery.
It supplies the sole through lateral and medial plantar
arteries.
MISCELLANEOUS ANATOMY
Nerve Supply of Neck
All muscles of
Palate: Supplied by cranial part of accessory nerve
except tensor veli palati which is supplied by mandibular
nerve.
Tongue: Supplied by hypoglossal nerve except
palatoglossas which is supplied by cranial accessory
nerve.
Pharynx: Supplied by cranial accessory nerve except
stylopharyngeus which is supplied by glossopharyngeal
nerve.
Larynx: Supplied by recurrent laryngeal nerve except
cricothyroid which is supplied by external laryngeal
branch of superficial laryngeal nerve.
Development
Pharyngeal/Branchial Arches
Derivatives of skeletal elements:
Cartilage of first arch Meckels cartilage.
Derivatives
i. Malleus and incus
ii. Anterior malleolar ligament and spenomandibular
ligament
iii. Bones of face including maxilla, mandible.
Cartilage of second arch Reicherts cartilage.
Derivatives
i. Stapes
ii. Styloid process
iii. Styloid ligament
iv. Smaller cornu and superior part of hyoid bone.
Cartilage of third arch greater cornu and lower part
of body of hyoid bone.
Fourth and sixth arches cartilages of larynx.
946
Nerves and Muscles

First arch mandibular nerve (pre-trematic) and chorda
tympani nerve (post-trematic).
Second arch facial nerve.
Third arch glossopharyngeal nerve and
stylopharyngeus muscle.
Fourth and sixth arch superior laryngeal and recurrent
laryngeal nerves; muscles of pharynx and larynx.
Ectodermal Clefts
External acoustic meatus from first cleft.
Pinna from hillocks on first cleft.
Second to sixth clefts the space bounded by
overhanging second arch and third, fourth and sixth
arches is known as cervical sinus, persistence of which
results in branchial sinus.
Endodermal Pouches
First pouch ventral part forms the tongue; dorsal
part forms tubotympanic recess which forms middle
ear and E. tube.
Second pouch palatine tonsil (lateral part).
Third pouch inferior parathyroid and thymus.
Fourth pouch superior parathyroid glands.
Thyroid Gland
Develops from thyroglossal duct.
C cells (parafollicualar cells) are derived from caudal
pharyngeal complex or ultimobranchial body.
Reflexes
Reflex
Deep reflexes
Ankle jerk
Knee jerk
Biceps jerk
Triceps jerk
Radial jerk
Jaw jerk
Inverse supinator jerk
Superficial reflexes
Plantar reflex
Abdominal reflex
Cremasteric reflex
Root value
S1, 2
L2, 3, 4
C5, 6
C7, 8
C6
Pons
C5, 6
S1, 2
T7 to T11
L1
Supplement
947
SURGERY
RETENTION OF URINE
Acute Retention
Etiology:
Male bladder outlet obstruction, urethral stricture.
Female retroverted gravid uterus, urethral stenosis,
cystitis and multiple sclerosis.
In male child meatal ulcer with scabbing.
Chronic Retention
Painless
Risk of upper urinary tract dilatation.
Men with chronic retention due to BOO need
prostatectomy.
Neuropathic Bladder
Cause: Spinal injury.
Effects of spinal injury:
i. Spinal shock detrusor is paralysed, the bladder
distends and there is overflow incontinence.
ii. Lesion above T10 micturition reflexes present but
disconnected with higher centers resulting in detrusorsphincter dissynergia.
iii. Damage to S2,3,4 and cauda equina lesion
micturition reflex is lost (detrusor areflexia) resulting
in atonic or autonomous bladder.
Treatment: Clean intermittent self catheterization (CISC).
URINARY INCONTINENCE
Nerve Supply to Bladder and Urethra
Higher center for micturition is in brain which sends
inhibitory impulses to spinal centers.
Parasympathetic:
Originates from S2, 3, 4.
Action detrusor contractility (voiding) through the release
of ACh. They also carry the sensory impulse.
948
Sympathetic:
Originates from T10 to L2.
Postganglionic fibers are adrenergic.
adrenergic fibers innervate bladder to cause relaxation.
adrenergic fibers innervate urethra to cause contraction.
Thus sympathetic system is involved in storage of urine.
Somatic:
To the striated muscles of urethra through pudendal nerve
(S2, 3, 4).
Note: oxybutynin and tolterodine are anticholinergic drugs
used in urge incontinence.
Urodynamic Study
Normal values:
Intravesical pressure < 15 cm H2O.
Voiding pressure < 60 cm H2O (in men) and <
40 cm H2O (in women).
Flow rate 15-25 ml/sec.
Classification of Incontinence
1. Stress incontinence due to urethral hypermobility or
sphincter weakness.
2. Urge incontinence due to idiopathic detrusor instability
or neurogenic bladder.
3. Overflow incontinence due to spinal shock or
autonomic bladder.
4. Continuous or true incontinence due to ectopic ureter
(paradoxical incontinence), genitourinary fistula.
Incontinence in Men
Etiology:
i. Chronic retention with overflow incontinence most
common type. Causes are benign hyperplasia of
prostate, prostatic ca, urethral stricture, hypertrophy
of bladder neck in young age group.
ii. Urge incontinence seen in 50 percent cases of BOO.
Also seen in neurogenic bladder due to diabetic
neuropathy, multiple sclerosis, Parkinsons disease and
stroke.
Supplement
949
Diagnosis of BOO:
Urodynamic study shows
Voiding pressure > 90 cm H2O.
Urinary flow rate < 10 ml/sec.
Management of BOO:
Conservative
Indications mild symptoms, i.e. flow rate > 10
ml/sec, good emptying (residual volume <100 ml).
Drugs adrenergic blockers (prazosin, tamsulosin)
they decrease tone of the bladder neck.
5 reductase inhibitors (finasteride) inhibit
conversion of testosterone to dihydrotestosterone
and cause shrinkage of BHP.
Operative
Indications severe symptoms with low flow rate
(<12 ml/sec). Other indications acute retention,
chronic retention (with residual volume > 250 ml,
increase in BUN, hydroureter), hemorrhage, signs
of prostatism, complications of BOO like stone,
UTI, diverticulum.
Method prostatectomy.
i. Transurethral resection of prostate (TURP)
ii. Retropubic
iii. Transvesical.
Complications
Local bacteremia, hemorrhage, perforation.
General water intoxication and hyponatremia (in TURP).
Prevention by using isotonic glycine.
Note: Preliminary vasectomy is no longer performed.
Incontinence in Women
Genuine Stress Incontinence
Most common in elderly female.
Etiology: Anterior vaginal wall relaxation due to prolapse
most common cause.
Clinical feature: Seen in multiparous women with history
of difficult labor (h/o forceps delivery).
In young women epispadias may be present.
Symptoms leakage of urine during stress (e.g. coughing).
Symptoms may change with menstrual cycle.
950
Diagnosis:
i. Bonneys test.
ii. Urodynamic study uroflowmetry and cystometry
reveal no abnormality.
Treatment: surgery
i. Cystourethroplasty (Kellys) most commonly
employed.
ii. Cystourethropexy (Marshall-Marchetti-Krants MKK).
iii. Burch culposuspension best.
Urge Incontinence
Cause:
i. Idiopathic detrusor instability
ii. Neurogenic bladder
Symptom: Urgency, frequency, nocturia may be present.
Diagnosis: Urodynamic study is confirmatory. It shows
increased flow rate with urge to pass urine at low bladder
filling.
Treatment:
Drugs mainstay of treatment.
Anticholinergic drugs (propantheline) for frequency.
Muscle relaxant (oxybutynin) for urgency.
TCAs (imipramine) for nocturia.
DDAVP for enuresis.
Surgery denervation of bladder.
Clam enterocystoplasty to increase capacity.
Urinary diversion ileal conduit.
Continuous (true) Incontinence
Without any urge to pass urine vesicovaginal fistula.
With urge to pass urine ureterovaginal fistula.
Vesicovaginal Fistula
Most common type of genitourinary fistula.
Cause:
i. Obstetrical most common in developing countries
(India). Obstructed labor with ischemia of bladder
base is the cause. It takes 3-5 days to develop
following delivery.
ii. Gynecological operations most common cause in
developed countries.
Supplement
951
Clinical feature:
Patient profile young primiparous with h/o difficult labor
or instrumental delivery. Continuous escape of urine per
vagina with no urge to pass urine.
Diagnosis:
Three swab test confirmatory. Also differentiates from
ureterovaginal and urethrovaginal fistula.
Treatment:
Surgery local repair by flap splitting method.
Time 3-6 months following delivery.
Postoperative care daily bladder wash with lotio
acriflavine.
Uretero-vaginal Fistula
Etiology: Abdominal or pelvic surgery most common
cause.
Site: Most commonly at the distal uterine artery in cardinal
ligament.
Clinical feature: Continuous incontinence with urge to pass
urine and can pass urine normally.
Diagnosis: Chromocystoscopy, IVU.
Note: Other types of fistulae:
Ureterovaginal patient is continent but urine dribbles
through vagina during micturition.
Vesicouterine cyclical hematuria.
URINARY BLADDER
Ectopia Vesicae (Extrophy of the Bladder)
Etiology: Incomplete development of infraumbilical part
of anterior abdominal wall with incomplete development
of the anterior wall of urinary bladder due to delayed rupture
of the cloacal membrane.
Associated anomalies:
In male (more common) epispadias, bilateral inguinal
hernia, rudimentary prostate and seminal vesicle. Testes
are normal.
In female bifid clitoris.
In both separation of pubic bones.
Others umbilical hernia, visible ureterovesical efflux,
waddling gait.
952
Treatment:
In the first year of life iliac osteotomy, closure of bladder
and abdominal wall.
Later in life reconstruction of bladder neck and
sphincter followed by bladder augmentation or urinary
diversion by ureterosigmoid anastomosis.
Note: Complications of ureterosigmoidostomy:
i. Hyperchloremic acidosis
ii. Hypokalemia.
Diverticula
Types:
1. Congenital situated in the midline anterosuperiorly.
2. Pulsion diverticulum due to contracture of the bladder
neck (BOO).
Feature: The mouth of the diverticulum is situated above
and to the outer side of one ureteric orifice.
Cystitis
Causative organism: E. coli (most common).
Route: Most commonly ascending infection from urethra.
Tuberculous Cystitis
Due to descending infection from the kidneys.
Diagnosis: Retrograde cystography shows a contracted
thimble bladder.
Treatment: ATD.
Surgery ileocystoplasty or cecocystoplasty.
Interstitial Cystitis
Also called Hunners ulcer.
Bilharziasis
Causative organism: Schistosoma hematobium.
Clinical feature: Intermittent, painless terminal hematuria.
Cystoscopy: Sandy patches in bladder.
Complication: Increased chance of squamous cell Ca of
bladder.
Supplement
953
URETHRA
Congenital Anomalies of Male Urethra
Posterior Urethral Valve
Symmetrical folds of urothelium which act as flap valves
and cause obstruction in boys.
Site: Most commonly just distal (below) to verumontanum.
Pathology: Due to flap valve action, patient can not pass
urine but urethral catheter can be easily passed.
Clinical feature: Poor urinary flow since birth.
Association: VURD syndrome posterior urethral valve,
unilateral reflux, renal dysplasia.
Diagnosis: Micturating cystourethrogram (MCU).
Treatment: Endoscopic transurethral resection of valves.
Hypospadias
It is the most common congenital malformation of urethra.
Incidence 1 in 350 live births (cf. epispadias).
Pathology:
The external meatus opens on the undersurface of penis
or perineum.
The inferior aspect of prepuce is poorly developed
(hooded prepuce).
The absent structure distal to the ectopic opening is
represented by a fibrous cord which deforms the penis
downword (ventrally) it is called chordee.
The more distant the opening from the normal position,
the more pronounced is the bowing. Thus chordee is
maximum in perineal variety and least or absent in
glandular type.
Types:
1. Glandular most common type.
2. Coronal.
3. Penile or penoscrotal.
4. Perineal most severe. Testicular maldescent may be
present.
Treatment:
Glandular type requires no treatment except in case
of associated meatal stenosis for which a meatotomy
is performed.
954
For other types repair is done at 6-12 months of age.

Circumcision should not be done before repair.
Epispadias
Incidence in male is 1 in 30,000 livebirths.
Pathology: Opening on the dorsum (usually a vertical
slit) of the penis with upward curvature of penis.
Total epispadias usually occurs with ectopia vesicae.
Urethral Stricture
Cause:
i. Trauma most common cause.
ii. Post-gonococcal stricture most commonly involves
the bulbar urethra.
iii. Iatrogenic.
Diagnosis:
i. Retrograde urethrography mainstay of diagnosis.
ii. Micturating cystourethrography (done after 3-4
weeks).
iii. Endoscopy.
iv. USG.
Treatment: Intermittent dilatation.
PENIS
Phimosis
Physiological adhesion of foreskin and glans may persist
upto 6 years of age.
Balanitis xerotica obliterans may cuase phimosis in
adults.
Clinical feature: Ballooning of prepuce during micturition.
Treatment: Circumcision.
Indication
i. Recurrent attacks of balanitis in young boys.
ii. In adults to improve sexual function, tight frenulum,
balanitis, and sometimes prior to RT for Ca penis.
Paraphimosis
May produce gangrene.
Treatment: Injection hyaluronidase in NS, circumcision.
Supplement
955
Peyronies Disease
Hard plaques of fibrosis in the tunica of one or both
corpora cavernosa.
May be associated with Dupuytrens contracture and
retroperitoneal fibrosis.
Clinical feature: Affects men over 40 years of age. Pain
and curvature of penis on erection.
Treatment: May regress spontaneously. Nesbitts operation.
Carcinoma of Penis
Etiology: Circumcision soon after birth confers almost
complete immunity against ca penis. Later circumcision
does not prevent it. Risk factors for Ca penis are
i. Chronic balanoprosthitis
ii. Leucoplakia of the glans
iii. Genital warts
iv. Pagets disease of the penis (erythroplakia of Querat)
causes cancer of the substance of the penis.
Clinical feature:
Sixty percent have inguinal lymph node enlargement
at presentation. In half, this is due to sepsis.
Death may occur due to involvement of the femoral
or external iliac artery with torrential hemorrhage.
Treatment:
Radiotherapy Circumcision precedes treatment.
Surgery for large anaplastic growths, if there is
infiltration of the shaft and when radiotherapy fails.
Treatment of associated enlarged lymph nodes is
delayed until at least 3 weeks with antibiotic therapy.
Block dissection is indicated if there is persistent
enlargement.
SCROTUM
Fourniers Gangrene
Cause: Idiopathic.
APPENDICES
APPENDIX I: SELECTED REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
Human Anatomy BD Chaurasia 4th edn.

Review of Medical Physiology Ganong 22nd edn.
Harpers Biochemistry 27th edn.
Lippincotts Biochemistry 3rd edn.
Textbook of Microbiology R Ananthanarayanan 6th
edn.
Essentials of Medical Pharmacology KD Tripathi,
5th/6th edn.
The Essentials of Forensic Medicine and Toxicology
KS Narayan Reddy, 25th/26th edn.
Pathologic Basis of Disease Robbins, 7th edn.
Preventive and Social Medicine Park, 19th edn.
Essential Pediatrics OP Ghai 6th edn.
Harrisons Principles of Internal Medicine 15th/16th
edn.
Current Medical Diagnosis and Treatment 2007
edn.
Short Practice of Surgery Bailey and Love 23rd/
24th edn.
Schwartzs Surgery 7th edn.
Shaws Textbook of Gynecology 13th/14th edn.
Textbook of Gynecology DC Dutta 4th edn.
Textbook of Obstetrics DC Dutta 5th/6th edn.
Essential Orthopaedics J Maheswari 3rd edn.
Diseases of Ear, Nose and Throat PL Dhingra
4th edn.
Fundamentals of Ear, Nose and Throat and HeadNeck Diseases SK Dey 6th edn.
Parsons Diseases of the Eye 19th edn.
Essentials of Ophthalmology SK Basak 3rd edn.
Textbook of Radiology and Imaging David Sutton
7th ed.
958
APPENDIX II: LABORATORY VALUES

Constituent
Values
Hematology
Erythrocyte count
Adult male
Adult female
4.50-5.90 106/mm 3
4.00-5.20 106/mm 3
Total leukocyte count

Differential count
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
4.5-11.0 103/mm3
Platelet count
ESR
In females
In males
150-350 103/mm 3
40-70%
22-44%
4-11%
0-8%
0-3%
1-25 mm/h
0-17 mm/h
Hemoglobin electrophoresis
Hemoglobin A
Hemoglobin A2
Hemoglobin F
95-98%
1.5-3.5%
0-2.0%
Mean corpuscular hemoglobin (MCH)
26.0-34.0 pg/cell
Mean corpuscular hemoglobin
31.0-37.0 g/dl
concentration (MCHC)
Mean corpuscular volume (MCV)
78-100 fl
Reticulocyte count
Coagulation times
Activated clotting time
Bleeding time
Prothrombin time
Thrombin time
Partial thromboplastin time, activated
0.5-2.5%
Iron
Ferritin
Male
Female
30-160 g/dl
Folate
Vitamin B 12
Liver functions
3.1-17.5 ng/ml
>250 pg/ml
Albumin
Aminotransferases
Aspartate (AST, SGOT)
Alanine (ALT, SGPT)
3.5-5.5 g/dl
70-180 sec
2-9.5 min
11.1-13.1 sec
16-24 sec
22.1-35.1 sec
30-300 ng/ml
10-200 ng/ml
0-35 U/L
0-35 U/L
Contd...
Appendices
Contd...
Constituent
Values
Bilirubin
Total
Direct
Indirect
0.3-1.0 mg/dl
0.1-0.3 mg/dl
0.2-0.7 mg/dl
Alkaline phosphatase
Lactate dehydrogenase
30-120 U/L
100-190 U/L
Gamma glutamyltransferase
1-94 U/L
Arterial blood gas

HCO3
PCO 2
PO 2
pH
21-30 meq/L
35-45 mmHg
80-100 mmHg
7.38-7.44
Electrolytes
Calcium
Sodium
Potassium
Chloride
Phosphorus
9.0-10.5 mg/dl
136-145 meq/L
3.5-5.0 meq/L
98-106 meq/L
3.0-4.5 mg/dl
Renal functions
Urea nitrogen
Uric acid
Males
Females
Creatinine
Specific gravity of urine
10-20 mg/dl
2.5-8.0 mg/dl
1.5-6.0 mg/dl
<1.5 mg/dl
1.003-1.030
959
Index
A
Abdomen 936
Abdominal aortic aneurysm
250
Abdominal wall hernias 162
Aberrant renal vessels 339
Abetalipoproteinemia 453
ABLB or Fowlers test 40
Abnormal facial movements 17
Abnormal gait 17
Abnormal heart sounds 214
Abnormal IGS 261
Abnormal limb movements 18
ABO system 701
Absolute bone conduction test 39
Absorption 95, 106
Acanthamoeba infections 616
Acanthosis nigricans 827
Achalasia 91
Achondroplasia 456
Acid-base balance 926
Acidification of urine 311
Acne 824
rosacea 824
vulgaris 824
Acoustic neurofibroma 780
Acrodermatitis enteropathica
839
Acromegaly 395
Actinomyces 576
Actinomycetes 576
Actinomycosis 576
Actinomycotic mycetoma 577
Acute appendicitis 124
Acute arthritis 488
Acute bacterial meningitis 379
Acute complications of diabetes
421
Acute demyelinating
polyneuropathy 385
Acute eosinophilic pneumonia
195
Acute epidural (extradural)
hemorrhage 372
Acute fatty liver 80
Acute gastric dilatation 109
Acute inflammation 910,912,914
Acute intermittent porphyria 446
Acute intussusception 119

Acute ITP 692
Acute lymphangitis 257
Acute lymphoblastic leukemia
668
Acute mesenteric ischemia 117
Acute myeloid leukemia 664
Acute myocardial infarction 244
Acute nephritic syndrome 317
Acute pancreatitis 149
Acute pulmonary edema 224
Acute pyelonephritis 81,328
Acute renal failure 311
Acute respiratory distress
syndrome 207
Acute retention 947
Acute subdural hemorrhage 371
Acute viral hepatitis 129
Acyanotic with left to right shunt
226
Acyanotic without shunt 228
Adamantinoma 810
Addisons disease 415
Adductor compartment 940
Adenocarcinoma of colon 763
Adenomas 407,762
Adenomyosis 795
Adenosine deaminase deficiency
846
Adenovirus 591
ADH secretion 399
Adhesions and bands 119
Adies tonic pupil 29
Adolescent mortality and
morbidity 85
Adrenal cortical hormones 411
Adrenal medulla 416
Adult hypothyroidism 402
Adult T-cell lymphoma 675
Aeromonas hydrophila 542
African trypanosomiasis 624
After bone marrow
transplantation 495
After kidney transplantation 495
Agglutination test 262
Aggressive B-cell 674
Aggressive T-cell 675
AIDS 281
962
AIDS-related lymphomas 675

Albrights hereditary
osteodystrophy 466
Alcoholic liver disease 134
Aldosteronism 414
Alertness 23
Aleukemic leukemia 666
Alexia 20
Alkaptonuria 459
Alkaptonuric arthritis 308
Alkylating agents 721
Allergic angiitis 195
Allergic bronchopulmonary
mycosis 194
Alopecia 825
Alpha chain disease 683
Alphavirus 600
Alports syndrome 326,457
Alterations in ventilatory
function 166
Altitudinal hemianopia 32
Alzheimers disease 361
Amenorrhea 439
American trypanosomiasis 624
Amines 912
Amino acids 871, 872, 874
Amnesia 25
Amoebae 614
Amoebic liver abscess 142
Amoebic ulcer 114
Amyloidosis 287,326
Amyotrophic lateral sclerosis 365
Anaerobic bacilli 527
Anaerobic cocci 527
Anal canal 156
Anal fissure 157
Anal fistula 158
Anaphylaxis 269
Anaplasia 705
Anatomic factors 440
Androgen excess 415
Androgen insensitivity/testicular
feminization syndrome 440
Anemia 78, 644, 647
chronic disease 646
liver disease 647
pregnancy 78
renal disease 647
Anencephaly 348
Aneurysmal bone cyst 815
Angina pectoris 248
Anginal pain 2
Angiodysplasia 116
Angioedema 832
Angiokeratomas 833
Anion gap 927

Ankylosing spondylitis 297
Ann Arbor staging 678
Annular pancreas 149
Anomalous origin 232
Anomic aphasia 20
Ano-rectal abscess 158
Anorectal ring 156
Anosmia 36
Anoxic-ischemic
encephalopathy 384
Anterior tibial artery 944
Anthracis 518
Anthracosis 187
Anthrax 519
Antibiotics 723
Antibody 259
Antidiuretic hormone 398
Antidotes 932
Antigen and antibody 259
Antigen presenting cells 266
Antigen-antibody reaction 261
Antimetabolites 722
Antinuclear antibody 291
Antiphospholipid antibodies 291
Aortic aneurysm 250
Aortic dissection 252
Aortic regurgitation 237
Aortic stenosis 74,236
Aphasia 19
Aplastic anemia 659
Apolipoprotein 450
Apoptosis 908, 909
Apraxia 20
Apud cells 765
Arachidonic acid metabolites
913
Arboviruses 600
Argyll Robertson pupil 29
Arnold Chiari malformation 351
Arterial disorders 250
Arterial pulse 212
Arteries 943
Arteriovenous fistula 257
Arthritides 308
Arthritis in inflammatory bowel
diseases 307
Arthus reaction 271
Asbestosis 186
Ascending cholangitis 142
Ascites 66,138
Ascitic fluid 66
Ascorbic acid 884
Aseptic meningitis 380
Ashermans syndrome 441
Index
Aspergillosis 612
Assessment criteria 897
Asteatotic eczema 819
Asthma 174
Asymptomatic bacteriuria 81
Ataxia 16,365
Ataxia telangiectasia 838, 869
Atherosclerosis 244, 253
Athetosis 16
Atopic dermatitis 818
Atopy 270
Atrial fibrillation 219
Atrial flutter 220
Atrial myxoma 243
Atrial premature complexes 218
Atrial septal defect 226
Atrophy 907
Atypical mycobacteria 559
Atypical pneumonia 190
Audiometry 39
Auditory pathway 38
Autoimmune 829
gastritis 103
hemolytic anemia 653
polyglandular deficiency 466
Autonomic nervous system 390
Autosomal disorders 864
Autosomal dominant disorders
862
Autosomal recessive polycystic
kidney 332
AV conduction disturbances 217
AV malformation 361
AV nodal re-entry 220
Axillary vein thrombosis 256
B
Babesiosis 626
Bacillus 518
Back of arm 938
Back of forearm 938
Back of leg 941
Back of thigh 940
Back pain 3
Bacteria 282
Bacterial genetics 499
Bacterial morphology and
physiology 496
Bacterial vaginosis 488
Bacteriophage 583
Bagassosis 185
Balance and gait 16
Balantidium coli 626
Bald tongue 43
Balints syndrome 20
963
Barretts esophagus 91
Bartonella 550
Bartters syndrome 333
Basal cell carcinoma 729
Basal metabolic rate 393
Base excision repair 853
Base pairing 848
Basic electrical rhythm 96
Becker dystrophy 388
Behets syndrome 299
Bells palsy 367
Benign liver tumors 748
Benign neoplasms of lung 747
Benign nephrosclerosis 331
Benign prostatic hyperplasia 770
Benign tumors of kidney 344
Bernard-Soulier syndrome 693
Berylliosis 187
Bilateral diffuse polyposis 741
Bilateral facial nerve palsy 367
Bile 127
Bile acid production 878
Bilharziasis 952
Biliary atresia 143
Biliary cirrhosis 135
Bilirubin 59
Bilirubin metabolism 59
Biological therapy 725
Biology of aging 86
Biotin 883,894
Bites 495
Bladder and urethra 345
Bladder function 311
Blastomycosis 611
Blind loop syndrome 109
Blood 637
components 702
groups 701
level 448
picture 665
tissue flagellates 622
transfusion 701
Blot transfer 868
Blue lesions 834
Bone 814
cysts 814
growth 919
Bone diseases 470
Bone marrow 703
examination 704
transplantation 703
Bone metabolism 461
Bone tumors 809
Bordetella pertussis 544
Borrelia 571
964
Bourneville disease 378

Brachial plexus disease 5
Brain 373
abscess 381
tumors 373
Brain death 24
Brainstem evoked response
audiometry 41
Brainstem reflexes 23
Breast 66
cyst 784
milk jaundice 66
tumors 783
Breastfeeding 83
Breath holding spells 355
Breathing 45
Brocas aphasia (motor
aphasia) 19
Bronchial adenomas 747
Bronchial carcinoid 747
Bronchial cyst 748
Bronchiectasis 178
Bronchiolitis 181
Bronchoalveolar lavage 173
Bronchogenic carcinoma 744
Bronchogenic cyst 204
Bronchopulmonary dysplasia
209
Bronchopulmonary segments
164
Brown-Sequard syndrome 368
Brucella 546
Bruton disease 275
Budd-Chiari syndrome 136
Buergers disease 253,324
Bullous impetigo 830
Bundle branch block 216
Bunyaviridae 602
Burkitts lymphoma 675
C
Caf au lait spots 828
Calcitonin 462
Calcium 461
Cancer 709
cachexia 713
genetics 709
therapy 717
urinary bladder 768
Candidiasis 608
Capillary hemangioma 727
Capsule 497
Carbohydrate 878
Carbohydrate metabolism 461
Carcinogenesis 712
Carcinoid syndrome 767

Carcinoid tumor of appendix
126, 766
Carcinoma 409, 705
anal canal 765
biliary tree 751
breast 785
cheek 735
fallopian tube 808
gallbladder 751
hypopharynx 782
in situ 705
lip 737
liver 749
maxillary sinus 781
pancreas 152,172
penis 955
tongue 736
Cardiac arrest and sudden
cardiac death 52
Cardiac disease 74
Cardiac hypertrophy 216,240
Cardiac lesions 291
Cardiac tamponade 241
Cardiac tumors 242
Cardiomyopathy and
myocarditis 238
Cardiovascular system 212
Carolis disease 136
Carpal tunnel syndrome 391
Catecholamines 416
Cat-Scratch disease 550
Cavernous hemangioma 728
CBD strictures 148
Ceco-central scotoma 32
Celiac sprue 107
Cell cycle 708,916
Cell injury 901
Cell types 916
Cell wall 496
Cells 264
Cellular adaptation 907
Cellular aging 909
Cellular events 911
Cereals 887
Cerebellar disease 17
Cerebral ischemia infarction
358
Cerebrovascular diseases 358
Cereus 519
Cervical carcinoma 801
Cervical intraepithelial neoplasia
800
Cervix 434
Cestodes-tapeworm 633
Index
Chagas disease 624
Chance of malignancy 663
Chancroid 486
Changes in vascular caliber and
flow 910
Charcots joint 308
Chargaffs rule 848
Chediac-Higashi syndrome 278
Chemical carcinogens 712
Chemical control of breathing 44
Chemokines 269
Chemoreceptor 44
Chemotaxis and activation 911
Chemotherapy 720
Chest pain 2
Cheyne-Stokes breathing 45
Chiari malformation 350, 370
Chickenpox 585
Childhood malignancy 776
Chlamydiae 577
Chlamydial infection 488
Cholangiocarcinoma 751
Cholangitis 147
Cholecystitis 145
Cholecystokinin pancreazymin
97
Choledochal cyst 144
Choleric ulcer 114
Cholesterol 903
Cholesterol and mixed stones 144
Cholesterol synthesis and
metabolism 878
Cholesterosis/strawberry
gallbladder 147
Chondroblastoma 809,813
Chordoma 810
Chorea 15
Choriocarcinoma 797
Chromatins 850
Chromoblastomycosis 610
Chromosomal abnormality
660,864
Chromosomal mosaicism 442
Chromosomal sex 443
Chromosome 22q11 deletion 867
Chronic anovulation with
estrogen absent 443
Chronic anovulation with
estrogen present 442
Chronic constrictive pericarditis
242
Chronic gastritis (atrophic) 103
Chronic granulomatous disease
278
Chronic hepatitis 132
965
Chronic hyperplastic candidiasis

734
Chronic inflammation 914
Chronic ITP 692
Chronic loss of vision 34
Chronic lymphocytic leukemia
669
Chronic lymphocytic thyroiditis
410
Chronic myeloid leukemia 666
Chronic myelomonocytic
leukemia 661
Chronic myelopathies 370
Chronic obstructive pulmonary
diseases 176
Chronic pain syndrome 2
Chronic pancreatitis 151
Chronic PID 491
Chronic pyelonephritis 328
Chronic rejection 273
Chronic relapsing
polyneuropathy 386
Chronic renal failure 314
Chronic retention 947
Chronic rheumatic carditis 234
Chronic subdural hemorrhage
372
Churg-Strauss disease 300
Churg-Strauss syndrome 195
Ciliates 626
Circulating anticoagulants 700
Circus movement 220
Cirrhosis 137
Cirrhosis of liver 133
Cl. botulinum 524
Cl. difficile 525
Cl. perfringens 520
Cl. septicum 521
Cl. tetani 521
Clonorchis sinensis 633
Clostridium 519
Clubbing and hypertrophic
osteoarthropathy 48
Cluster headache 354
CMV infection in immunocompromised host 589
CMV mononucleosis 589
CO2 narcosis 171
CO2 transport 172
Coagulase negative
staphylococcus 506
Coagulation disorders in liver
disease 700
Coal workers pneumoconiosis
187
966
Coarctation of aorta 229

Cobalamin 883,894
Coccidioidomycosis 612
Cochlea 38
Codons 858
Collagen vascular disease 188
Colonic diverticulum 115
Color blindness 30
Color vision 30
Colostomy 123
Coma 23
Combination therapy 724
Common skin disorders 818
Common variable
immunodeficiency 275
Complement activation 263
Complement fixation test 262
Complex partial seizure 357
Conduction aphasia 19
Condyloma acuminata 489
Congenital anomaly 157
Congenital aortic stenosis 228
Congenital CMV infection 588
Congenital diaphragmatic
hernia 206
Congenital erythropoietic
porphyria 448
Congenital heart diseases 225
Congenital hypothyroidism 402
Congenital myopathies 388
Congenital PUJ obstruction 340
Congenital rubella 599
Congenital syphilis 568
Congenital toxoplasmosis 621
Conjugation 499
Contact dermatitis 818
Contact ulcer 741
Contiguous gene syndrome 870
Continuous (true) incontinence
950
Continuous murmur 216
Contrast agents 936
Conversion of amino acids 874
Coombs and gell classification
269
Copper 896
Cor pulmonale 237
Coronary revascularization 248
Corpus luteum 434
Cortical sensations 22
Corynebacterium 514
Corynebacterium diphtheriae 514
Cough 47
Coxsackie virus 594
Cranial nerves 366
Cranio-facial malformations 352

Craniopharyngioma 376, 397
Craniosynostosis 352
Cretinism 402
Creutzfeldt-Jacob disease 383
Crohns disease 112
Crossed hemiplegia 14
Croup 197
Cryptococcosis 611
Cryptogenic fibrosing alveolitis
183
Cryptomenorrhea 439
Cryptosporidiosis 626
Cubital fossa 938
Cushings syndrome 412
Cutaneous manifestation of
internal malignancy 835
Cutaneous metastasis 834
Cyanosis 48
Cyanotic with right to left shunt
230
Cystic fibrosis 180
Cystic glandular hyperplasia 437
Cystic medial necrosis 251
Cysticercus cellulose 634
Cystinosis 460
Cystinuria 460
Cystitis 952
Cystosarcoma phylloides 784
Cytokines 268,913
Cytomegalovirus 588
Cytoplasm 497
Cytoskeletal changes 903
D
Dandy-Walker malformation 351
Dandy-Walker syndrome 370
Darriers disease 838
De novo synthesis of purines 843
Dead space 167
Deep muscles 941
Deep mycosis 610
Deep vein thrombosis 255
Deformity 6
Delayed hypersensitivity 271
Delayed puberty 85
Deletion of 15q 867
Dementia 26
Dengue syndrome 601
Dentate/pectinate line 156
Denys-Drash syndrome 327
Dermatology 816
Dermatophytoses 606
Dermis 816
Descending tracts 11
Index
Desmoplasia 706
Diabetes insipidus 78,398
Diabetes mellitus 76,420,831
Diabetic foot ulcer 425
Diabetic ketoacidosis 421
Diabetic nephropathy 325,424
Diabetic neuropathy 424
Diabetic retinopathy 423
Dialysis 315
Diaphragm 205
Diaphragmatic paralysis 205
Diarrhea and food poisoning 483
Diastematomyelia 352
Diastolic murmur 215
Dietary fibers 886
Dietary sources 886
Diffuse alveolar hemorrhage
syndrome 188
Diffuse esophageal spasm 92
Diffuse hyperplastic goiter 404
Diffuse large B-cell lymphoma 674
Digeorge syndrome 277,466
Digestion 94, 95
Digestive enzymes 94
Digitalis 223
Digitalis toxicity 224
Dilated cardiomyopathy 238
Diphyllobothrium latum 635
Direct inguinal hernia 160
Disability 6
Disc prolapse 3
Disseminated intravascular
coagulation 699
Dissociated sensory loss 22
Distal RTA 334
Diverticula 952
Diverticular disease 114
Diverticulum of stomach 109
DNA organization 849
DNA repair 712, 852, 869
DNA replication 850
DNA structure and replication
847
DNA viruses 605
Double helix 847
Double-strand break repair 853
Downs syndrome 865
DPT vaccine 517
Dracunculiasis 627
Drainage 201
Dressing apraxia 20
Drug induced hyperthermia 8
Drug induced parkinsonism 364
Drug induced SLE 292
Dry heat 500
967
Duchenne muscular dystrophy

387
Duct papilloma 785
Duffy system 702
Duodenal atresia 105
Duodenal ulcer 99
Duodenum 99
Duplication of renal pelvis 339
DVT and pulmonary embolism
75
Dysfunction 264
Dysfunctional uterine bleeding
437
Dyskeratosis congenita 828
Dysmenorrhea 436
Dysphagia lusoria 89
Dysplasia 705
Dystrophic calcification 904
E
E. coli 528
Early diastolic 215
Early jaundice 62
Early systolic 215
Ebsteins anomaly 231
Echo virus 594
Echynococcus granulosus 634
Eclampsia 73
Ecthyma 823
Ectodermal clefts 946
Ectopia vesicae 951
Ectopic thyroid 401
Ectopic ureter 339
Eczema or dermatitis 818
Edema 49
Edward and Patau syndromes
867
Ehler-Danlos syndrome 456
Eisenmenger syndrome 75,231
ELISA 263
Elongation 857,860
Emphysema 177
Emphysema cholecystitis 146
Empty Sella syndrome 397
Empyema 203
Enchondroma (chondroma) 814
Endemic syphilis 571
Endocrine tumors of GI tract 765
Endocrine tumors of pancreas
753
Endocrinology and metabolism
393
Endocrinopathies 828
Endodermal pouches 946
Endometrial carcinoma 796
968
Endometrial changes 433

Endometriosis 794
Endometrium 794
Energy requirement 889
Entamoeba histolytica 614
Enteric fever 534
Enteric nervous system 96
Enteric strictures 119
Enterobacteriaceae 528
Enterocutaneous fistula 123
Enterovirus 591
Enzymes 919
Eosinophilia 643
Eosinophilic granuloma 684
Ependymomas 374
Epidemic typhus 575
Epidermis 816
Epidermolysis bullosa 839
Epidural abscess 369
Epidural masses 369
Epigastric hernia 163
Epiglottitis 197
Epilepsy 84,354
Epilepsy on pregnancy 84
Episodic disorders 17
Episodic weakness 18
Epispadias 954
Epstein-Barr virus 587
Erbs palsy 6
Erosive gastropathy 104
Erysipelas 823
Erythema induratum 833
Erythema infectiosum 831
Erythema multiforme 830
Erythema nodosum 833
Erythrasma 836
Erythroderma 825
Erythroid series 638
Erythroplakia 734
Erythropoiesis 638
Esophageal carcinoma 756
Esophageal rupture 89
Esophageal tumors 94
esophagitis 91
Esophagus 88, 92
Estrogen 430
Ethmoidal sinus carcinoma 781
Ethylene oxide gas 503
Evaluation of jaundice 61
Evans syndrome 653
Ewings sarcoma 812
Exanthems 831
Exfoliative cytology 716
Exfoliative dermatitis 825
Exomphalos 162
Extensor retinaculum 941

External hemorrhoids 157
Extracellular matrix 917
Extragonadal germ-cell tumors
774
Extranodal marginal zone
lymphoma 674
Extrapulmonary TB 553
Extrapyramidal disorders 363
Extravasation 911
Extrinsic innervation 96
Eye and vision 27
F
Fab classification 661
Facial nerve palsy 366
Factor IX deficiency
hemophilia B 697
Factor VIII 695
Factor VIII deficiency
hemophilia A 695
Factor XIII deficiency 697
Factors regulating hematopoiesis
637
Familial adenomatous polyposis
762
Familial hypercholesterolemia
452
Familial lipoprotein lipase
deficiency 452
Fanconis anemia 659
Fanconis syndrome 335
Farmers lung 185
Fasciola buski 633
Fasciola hepatica 633
Fat malnutrition 892
Fatty acid biosynthesis 876
Fatty acid oxidation 877
Fatty acids 875
Fatty change 903
Fatty liver 140
Febrile convulsion 354
Feltys syndrome 154
Female pseudohermaphroditism
congenital adrenal
hyperplasia 444
Femoral artery 943
Femoral canal 161
Femoral hernia 161
Femoral ring 161
Fever 7
Fever and hyperthermia 7
Fibroadenoma 784
Fibroadenosis 783
Fibroid uterus 791
Index
Fibromuscular dysplasia 253,330
Fibrous dysplasia 471,815
Figurate skin lesions 825
Filariasis 629
Filoviridae 604
Fimbriae 498
First heart sound 213
Fish eye disease 453
Fish tapeworm 635
Flaccidity 13
Flagella 497
Flagellates 622
Flavivirus 600
Flexor retinaculum 941
Floppy Baby syndrome 389
Flow cytometry 717
Fluid and electrolytes 920
Fluidity of blood 685
Fluorine 896
Focal nodular hyperplasia 749
Folate deficiency 649
Follicular carcinoma 408
Follicular lymphoma 673
Food assessment 899
Food poisoning 484,521
Forebrain abnormalities 352
Forensic and state medicine 930
Fourniers gangrene 955
Fourth heart sound 214
Fragile X syndrome 867
Fragilis 527
Francisella tularensis 550
Franklins disease 683
Free radical injury 901
Free-living amoebas 616
Friedreichs ataxia 365
Frontal lobe syndrome 25
Fructose metabolism 881
Functional cysts 803
Functional platelet disorders 692
Fungal infections 823
Fusobacterium fusiforme 527
G
G6PD deficiency 652
Galactose metabolism 882
Galactosemia 461
Gallbladder 143
Gallstone ileus 146
Gallstones 119,144
Gamma chain disease 683
Gas exchange 167
Gas gangrene 521
Gas transport 171
Gastric carcinoma 757
969
Gastric lymphoma 759

Gastric motility and emptying 98
Gastric polyp 757
Gastric secretion 98
Gastric stromal tumors 759
Gastric ulcer 100
Gastrin 96
Gastrinoma 754
Gastritis 103
Gastro-esophageal reflux disease
90
Gastrointestinal hormones 96
Gastrointestinal polyps 760
Gastrointestinal system 88
Gelles test 39
Gene mapping 868
Generalized absence seizure 356
Generalized seizures 355
Generalized tonic-clonic seizure
355
Genes regulating apoptosis 712
Genetic code 859
Genetic disorders 861
Genetic materials 499
Genetic structure 841
Genetics 180,745,841
Genetics in colorectal
carcinoma 122
Genital herpes 486
Genital ulcers 486
Genital ulcers at a glance 487
Genital warts 489
Genitourinary tumors 768
Genuine stress incontinence 949
Geographic tongue 43
Geriatric medicine 86
Germ cell tumors 807
Gerstmann syndrome 20,384
Gestational diabetes 76
Gestational hypertension 74
GH excess 395
GH secretion 395
GI bleeding 58
GI function 54, 96
GI tract 81,94
Giant cell arteritis 302
Giant cell tumor 810
Giant cells 915
Giardiasis 625
Gigantism 395
Glands 816
Glandular fever 588
Glanzmanns thromboasthenia
693
970
Glasgow Coma Scale 372

Glaucoma 31
Gliomas 373
Global aphasia 19
Glomerular filtration rate 310
Glomerulopathies 317, 325
Glomus tumor 728
Glucagonoma 755
Glucocorticoids 411
Glucose tolerance 420
Gluteal region 940
Glycogen 904
Glycogen metabolism 880
Glycolipids 876
Glycolysis 879
Glycosuria in pregnancy 78
Goiter 403, 404
Gonadal dysgenesis 441
Gonococcus 513
Gonorrhea 485
Goodpastuers syndrome 188
Goodpastures disease 320
Gout 846
Gouty arthritis 449
Graft rejection 272
Graft-versus-host disease 274
Granuloma 915
Granuloma inguinale
(donovanosis) 487
Granulomatosis 195
Granulopoiesis 641
Graves disease 405
Group C B-hemolytic
streptococci 509
Group D (enterococcus) 509
Guillain-Barr syndrome 385
Gunthers disease 448
Gynecological cancer 791
H
H. ducreyi 543
H. influenzae meningitis
Haemoflagellates 622
Haemophilus influenzae
Hairy cell leukemia 670
Halogens 503
Hamartoma 748
Hamartomatous polyps
Hamstring muscles 940
Hand 939
Hand eczema 819
Hand-Schller-Christian
684
Hantavirus 602
Haptens 259
380
543
761
disease
Haptoglobin 651
Hartnups disease 460
Hashimotos thyroiditis 410
Head and neck tumors 733
Headache 3,353
Hearing 37
Heart block 218
Heart disease in pregnancy 74
Heart failure 222
Heart sound 213
Heart transplantation 274
Heat shock proteins 903
Heatstroke 9
Heavy chain disease 683
Helicobacter pylori 536
Helminths 627
Hemagglutination 594
Hemangioma 727,748,810
Hematological changes 70
Hematological disorders 290
Hematology 637
Hematopoiesis 637
Hematuria 68
Heme 59
Hemiballismus 15
Hemiplegia 14
Hemisection 368
Hemobilia 148
Hemochromatosis 446
Hemodialysis 315
Hemoglobin 638
Hemoglobinopathies 655
Hemolytic anemia 650
Hemolytic disease of newborn 62
Hemolytic uremic syndrome
325,694
Hemophilic arthropathy 308,696
Hemoptysis 48
Hemorrhagic disease of
newborn 698
Hemorrhagic disorders due to
platelets 691
Hemorrhoids 157
Hemostasis and disorders of
platelets 685
Henderson-Hasselbalch
equation 926
Henoch-Schnlein purpura 694
Hepatic adenomas 749
Hepatic artery ligation 148
Hepatic encephalopathy 139
Hepatic metastases 750
Hepatitis 129,133
Hepatocellular carcinoma 749
Hepatolenticular degeneration
141
Index
Hepatorenal syndrome 139
Hereditary diseases 326
Hereditary elliptocytosis 652
Hereditary fructose intolerance
461
Hereditary myopathies 387
Hereditary persistence of HBF 658
Hereditary spherocytosis 651
Hereditary tubular disorders 331
Hereditary/idiopathic
hypoparathyroidism 466
Heredity 708
Hernias 159
Herpes simplex 584
Herpes virus 584
Herpes zoster (Shingles) 586
Hiatus hernia 93
Hidradenitis suppurativa 837
High-grade astrocytoma 374
Hippus 29
Hirschsprungs disease 110
Histones 849
Histoplasmosis 612
HIV and acquired
immunodeficiency 279
Hodgkins lymphoma 676
Holo/pansystolic 215
Homocystinurias 458
Hormone therapy 724
Hormones 713
Horseshoe kidney 339
Human diseases 577
Human genome 854
Human herpes virus type 6 589
Human leukocyte antigen 266
Huntingtons disease 363
Hyaline membrane disease 208
Hyalinosis 323
Hydatid cyst 142
Hydatid disease 634
Hydrocephalus 349
Hydroxylase deficiency 444
Hymenolepsis nana 635
Hyper IGE-recurrent infection
278
Hyperacute rejection 272
Hyperbilirubinemia 128
Hypercalcemia 463, 464
Hypercalcemic nephropathy 329
Hypereosinophilic syndrome 196
Hyperfunction of adrenal cortex
412
Hyper-IGM syndrome 276
Hyperkalemia 216,925
Hyperkalemic distal RTA 334
971
Hyperlipoproteinemias 451
Hypernatremia 923
Hypernephroma 342
Hyperosmolar non-ketotic coma
423
Hyperostosis corticalis
generalisata 470, 471
Hyperparathyroidism 464
Hyperpigmentation 827
Hyperplasia 908
Hyperplastic polyps 760
Hyperplastic tuberculosis 113
Hyperprolactinemia 397
Hyperpyrexia 7
Hypersensitivity 269
Hypersensitivity pneumonitis/
extrinsic allergic alveolitis
184
Hypersplenism 154
Hypertension in pregnancy 71
Hypertensive vascular disease
248
Hypertonia 13
Hypertrophic cardiomyopathy
238
Hypertrophic osteoarthropathy
49
Hypertrophic pyloric stenosis 104
Hypertrophy 902,907
Hyperuricemia and gout 448
Hyperventilation 170
Hypervitaminosis A 896
Hypocalcemia 465
Hypofunction of adrenal cortex
415
Hypogeusia 37
Hypoglycemia 421,425
Hypoglycemic unawareness 426
Hypokalemia 217,924
Hypolipoproteinemia 453
Hypomagnesemia 469
Hyponatremia 923
Hypopigmentation 826
Hypopituitarism 395
hypoproliferative anemia 646
Hypospadias 953
Hypothermia 9
Hypothyroidism 401
Hypotonia 13
Hypoventilation 170
Hypovolemia 921
Hypoxemia 168
Hypoxemic-ischemic
encephalopathy 209
Hypoxia 168
Hypoxic injury 901
972
I
Ichthyosis vulgaris 838
Idiopathic myelofibrosis 663
Idiopathic pulmonary fibrosis 183
Idiopathic retroperitoneal
fibrosis 117
Idiopathic thrombocytopenic
purpura 691
Ileal atresia 105
Iliac aneurysm 251
Immune response 268
Immune system 259
Immunity 546,562
Immunodeficiency with
thymoma 277
Immunofluorescence 263
Immunohistology 717
Immunologic disorders 290
Immunologically mediated skin
disease 289
Imperforate anus 157
Impetigo 823
Inclusion bodies 582
Incontinence 948
Indian tick typhus 575
Indirect inguinal hernia 160
Indolent B-cell 673
Indolent myeloma 683
Indolent T-cell 675
Infantile spasms 357
Infective arthritis 306
Infective endocarditis 476
Inferior extremity 939
Infiltrative and metabolic
diseases 140
Inflammation 909
Inflammatory bowel disease 111
Inflammatory diarrhea 483
Inflammatory disorders 90
Influenza 594
Inguinal canal 159
Inguinal hernia 160
Inherited disorders 838
Inner ear 37
Insulin 418
Insulinoma 753
Interferon 582
Internal hemorrhoids 157
Interstitial cystitis 952
Interstitial lung diseases 182
Intestinal amoeba 614
Intestinal flagellates 625
Intestinal lymphangiectasia 108
Intestinal nematodes 628
Intestinal obstruction 118

Intestinal T-cell lymphoma 675
Intra-abdominal infections and
abscess 479
Intracellular accumulations 903
Intracerebral hemorrhage 360
Intracorpuscular hemolysis 650
Intracranial infections 379
Intradural masses 369
Intrahepatic cholestasis 80
Intramedullary masses 369
Intubation granuloma 741
Ions 926
Iron deficiency anemia 79,644
Irreversible cell injury 906
Ischemic ARF 312
Ischemic colitis 116
Ischemic heart disease 247
Isolated hematuria - IGA
nephropathy 324
Isolated hypogonadotropic
hypogonadism 443
Isolated IGA deficiency 276
Isospecificity 259
Isosporiasis 626
Isovaleric acidemia 460
Ivory osteoma 809
J
Janz syndrome 356
Japanese encephalitis 600
Jaundice 59, 64, 65, 80
JC virus 591
Jobs syndrome 278
Joints 305
Jugular venous pulse 212
Juvenile delinquency 86
Juvenile intestinal polyposis 761
Juvenile myoclonic seizures 356
Juvenile nephronophthisis 333
Juvenile rheumatoid arthritis 294
K
Karyotyping 869
Kasabach-Merritt syndrome 834
Kawasakis disease 303
Kearns-Sayre syndrome 384
Kelly-Seegmiller syndrome 449
Keratoacanthoma 731
Keratosis 741
Kernicterus 64
Ketogenesis 877
Kidney 329, 344
Kidney stones 335
Index
Kidney transplantation 274
Klebsiella 530
pneumonia 192
pneumoniae 530
Klinefelter syndrome 443
Klumpices palsy 6
Kussmauls breathing 46
Kyasanur-Forest disease 601
L
L. Braziliensis mucocutaneous
leishmaniasis 624
L. donovani kala-azar 623
L. tropica cutaneous
leishmaniasis 624
Laboratory tests 690
Laboratory values 958
Lactase deficiency 107
Lactic acidosis 927
Lambert-Eaton (L-E) syndrome
387
Langerhans cell histiocytosis or
histiocytosis X 684
Large bowel obstruction 119
Laryngitis 197
Laryngocele 741
Laryngotracheobronchitis 197
Larynx 197
Laser 840
Lateral aberrant thyroid 401
Lateral medullary syndrome 359
Lebers optic atrophy 384
Legionella pneumophila 547
Leiomyoma 759
Leiomyosarcoma 759
Leishmaniasis 622
Lentigens 827
Leptospira 572
Leptotrichia buccalis 527
Lesch-Nyhan syndrome 448,846
Lesion in frontal lobe 26
Letterer-Siwe disease 684
Leucoplakia 734
Leukemias 664
Leukocyte adhesion deficiency
277
Leydig cells 427
Lichen planus 821
Lichen simplex chronicus 819
Liddles syndrome 415
Light reflex 28
Limbs 937
Lipid and glycogen storage
diseases 454
Lipid transport 449
973
Lipodystrophy 327
Lipoid nephrosis 322
Lipoprotein lipase 450
Lipoprotein metabolism 449
Lisch nodules 832
Listeria monocytogenes 526
Liver 126
Lofflers syndrome 195
Loiasis 631
Lou Gehrig disease 365
Low-grade astrocytoma 373
Lumbar plexus 942
Lumbar puncture headache 3
Lung abscess 196
Lupus vulgaris 834
Lyme disease 572
Lymphangiosarcoma 258
Lymphatic disorders 257
Lymphedema precox 258
Lymphocytes 264,642
Lymphogranuloma venorum 487
Lymphoid leukemias 668
Lymphoma of the small bowel
760
Lymphomas 671
Lymphopoiesis 641
Lysogenic conversion 499
Lysosomal catabolism 902
Lysosomal constituents 914
Lysosomal storage diseases 453
M
M. pneumoniae 573
M. tuberculosis 551
Macroglossia 43
Macronutrients 871
Maduramycosis 577
Mafuccis syndrome 834
Magnesium metabolism 469
Major histocompatibility
complex 266
Malabsorption 106
Malaria 617
Malayi 631
Male breast carcinoma 790
Malignant carcinoma of larynx
742
Malignant hypertension 249
Malignant hyperthermia 8
Malignant lesions 729
Malignant melanoma 732
Malignant mesothelioma 748
Malignant nephrosclerosis 331
Malignant tumors 811
Malignant tumors of colon 763
974
Mallory-Weiss syndrome 90
Malnutrition 889
Mantle cell lymphoma 674
Maple syrup urine disease 460
Marcus-Gunn pupil 29
Marfans syndrome 457
Mastocytosis 834
Mayer-Rokitansky-KusterHauser syndrome 440
McCune Albright syndrome
85,471
Measles 597
Meckels diverticulum 114
Meconium aspiration syndrome
209
Meconium ileus 120
Medial medullary syndrome 359
Medial side of thigh 940
Mediastinal disorders 203
Mediastinal masses 203
Mediastinitis 205
Medico legal aspects 86
Medullary carcinoma 408
Medullary cystic disease 333
Medullary sponge kidney 332
Medullary syndromes 359
Medulloblastoma 374
Megacolon 110
Megaloblastic anemia 79,648
Melaninogenicus 527
Melitensis 546
Membrane transfer 460
Membrano (mesangio)
proliferative GN 324
Membranous glomerulopathy 323
Memory 25
Mendelian (single gene)
disorders 862
Mntriers disease 10,104
Meningiomas 375
Meningococcus 512
Menopause 438
Menorrhagia 435
Menstrual cycle 431
Menstruation 435, 439
Merrf syndrome 384
Mesenteric adenitis 116
Mesenteric cyst 116
Mesenteric disorders 116
Mesial temporal lobe epilepsy 357
Mesosomes 497
Messenger RNA 855
Metabolic acidosis 927
Metabolic alkalosis 928
Metabolic bone diseases 467
Metabolic changes 216

Metaplasia 705;908
Metastasis 707
Metastatic calcification 905
Metastatic tumors 243
Metastatic tumors of brain 377
Metropathia hemorrhagica 437
Metrorrhagia 435
Microangiopathic hemolytic
anemia 653
Microbiology 181
Micronutrients 886
Microsatellite repeat sequence
854
Microscopic polyangiitis 301
Mid diastolic 215
Mid/ejection systolic 215
Migraine 353
Migrating motor complex 96
Milk 887
Millets 887
Milroys disease 258
Mineralocorticoid 412
Minimal change disease 322
Minor or unusual bases 841
Minor salivary glands 740
Minutissimum 518
Miosis 30
Mismatch repair 852
Mitochondrial changes 902
Mitochondrial disorders 74,384
Mitral regurgitation 235
Mitral stenosis 74,235
Mitral valve prolapse 236
Mittelschmerzs syndrome 436
Moist heat 501
Molecular diagnosis of genetic
disorders 868
Molluscum contagiosum 584
Molluscum sebaceum 731
Monilial vaginitis 489
Monoclonal gammopathy of
unknown significance 683
Monocytes 643
Mononeuritis multiplex 301
Mononeuropathy 391
Mononeuropathy multiplex 391
Mononucleosis 588
Monoplegia 15
Moraxella (branhamella)
catarrhalis 527
Morbillivirus 597
Motility 519
Motility disorders 91
Motor neuron diseases 365
Index
975
Neoglucogenesis 880
Neonatal cholestatic jaundice 66
Neonatal hypoglycemia 425
Neonatal hypothermia 9
Neonatal jaundice 62
Neonatal seizure 354
Neonatal septicemia 474
Neonatal tetanus 524
Neoplasms
cervix 800
ear and nose 780
kidney 341
lung 744
ovary 803
paranasal sinuses 781
pleura 748
vagina 799
vulva 798
Neoplastic polyps 762
Neoplastic tumors 742
Nephrocalcinosis 338
Nephrolithiasis 335
Nephrons 309
Nephrotic syndrome 321
Nephrotoxic ARF 313
Nerve supply of neck 945
Nerve supply to bladder and
urethra 947
Nerves and muscles 946
Nervous system dysfunction 10
Neuroblastoma 777
Neurocutaneous syndromes 377
Neurofibroma 832
Neurofibromatosis 377
Neuroimaging 347
Neuroleptic malignant syndrome
9
Neurological channelopathies
389
Neurological disorders 290
Neuromuscular junction 386
N
Neuropathic bladder 947
Na+ reabsorption 922
Neuropathic joint disease 308
Naegleria fowleri 616
Neuropathic pain 1
Naevi 728
Neurotransmitter 1
Naevus flammens 728
Nezelof syndrome 277
Nail involvement 839
Niacin 883,893
Nitric oxide 914
Nasopharyngeal angiofibroma
Nitrogen in amino acids 872
781
Nasopharyngeal carcinoma 782 Nocardia 576
Nodular regenerative
Natural anticoagulants 687
hyperplasia 749
Necrotic cells 909
Nomenclature 705
Necrotizing enterocolitis 121
Non-ascent of kidney 339
Neisseria 512
Non-chemical control of
Nelsons syndrome 414
breathing 44
Nematodes 627
Movement disorders 15
MPS I (Hurlers disease) or
gargoylism 454
MPS II (Hunters disease) 454
Mu chain disease 683
Mucocele of gallbladder 147
Mucopolysaccharidosis 453
Mucormycosis 613
Mllerian agenesis 440
Multiple endocrine neoplasia 445
Multiple myeloma 680, 683
Multiple sclerosis 390
Mumps 596
Murmur 215
Muscle 387, 937
Muscle disorders 18
Musculocutaneous nerve 937
Mutation 861
Mutations in mitochondrial gene
868
Myasthenia gravis 386
Mycobacterial skin infection 836
Mycobacterium leprae 560
Mycology 605
Mycoplasma 573
Mycosis fungoides 675
Mycotic aneurysm 252
Mycotic mycetoma 610
Mydriasis 30
Myelodysplastic syndrome 660
Myeloid leukemias 664
Myeloperoxidase deficiency 278
Myelophthisic anemia 659
Myeloproliferative disorders 661
Myocardial ischemia 216
Myocarditis 240
Myoclonic seizure 356
Myoclonus 16
Myotonic dystrophy 388
976
Non-cirrhotic hepatic fibrosis 136

Non-cirrhotic portal fibrosis 136
Non-enterococcus group D 509
Non-gastritis epithelial cell injury
104
Non-Hodgkins lymphoma 671
Nonpolyposis syndrome 763
Non-sporing anaerobes 527
Non-tropical sprue 107
Noonan syndrome 441
Normal pressure hydrocephalus
362
Nosocomial infection 495
Nucleofilament 849
Nucleoside 841,853
Nucleus 497
Null cells 265
Nummular eczema 819
Nutrients 871
Nutritional and metabolic
diseases 384
Nystagmus 34
Osteochondroma 814
Osteoclastoma 810
Osteogenesis imperfecta 455
Osteoid osteoma 809
Osteomalacia 469
Osteopetrosis 471
Osteoporosis 467
Osteosarcoma 811
Ovarian carcinoma 805
Ovarian failure 441
Ovarian hormones 430
Ovaries and female genital tract
429
Ovary 808
Overt diabetes 77
Ovulation 434
Oxytocin 394
Pagets disease 470

nipple 786
vulva 799
Pain pathway 1
O
Pain physiology 1
O2 transport 171
Painful red eye 33
Obesity 897
Pancreas 148,418
Obstructive lung diseases 174
Pancreas transplantation 274
Occipital lobe 27
Pancreatic tumors 752
Ocular reflexes 28
Pancreatitis 149
Oculocutaneous albinism 826
Panhypopituitarism 443
Oculomotor (3rd nerve) palsy 368 Panniculitis 833
Olfactory cortex 36
Pantothenic acid 883
Olfactory pathways 35
Papillary carcinoma 407
Oligodendrogliomas 374
Papillary necrosis 328
Omphalocele 162
Papovavirus 590
Onchocerciasis 631
Papulonodular lesions 832
Oncogenic viruses 605
Papulosquamous disorders 820
Oogenesis 432
Paracoccidioidomycosis 612
Ophthalmoplegic migraine 354 Paragonimus westermani 633
Opportunistic infection 281
Paralytic ileus 121
Opportunistic systemic mycosis
Paramyxoviruses 596
612
Paraneoplastic syndromes 714
Opsonization 263
Paraphimosis 954
Oral and oropharyngeal cancer Paraplegia 14
733
Parasitology 614
Oral cavity 42
Parathyroid hormone 462
Oral mucosa 42
Paraumbilical hernia 162
Oral submucosal fibrosis 735
Parietal lobe 26
Organ donation 273
Parkinsons disease 363
Organ of corti 38
Parosteal osteosarcoma 812
Organ transplantation 272
Parotid gland tumors 738
Orotic aciduria 846
Paroxymal supraventricular
Orthomyxovirus 594
tachycardia 220
Osteoarthritis 305
Paroxysmal cold hemoglobinuria
Osteoblastoma 809
653
Index
Paroxysmal nocturnal
hemoglobinuria 654
Partial seizures 357
Parvovirus 589
Patch test 818
Patent ductus arteriosus 228
Paterson-Brown Kelly syndrome
93
Pathological terms 817
Pauciarticular 294
Pauci-immune GN 321
Pediatric disoders 104,208
Pediculosis 837
Pelvic abscess 480
Pelvic inflammatory disease 490
Pemphigus vulgaris 829
Pendreds syndrome 404
Penis 954
Pentose phosphate pathway 880
Peptic ulcer 101, 102
Pericardial effusion 241
Pericarditis 240
Pericardium 240
Perinatal varicella 586
Perinephric and renal abscess 482
Periodic paralysis 389
Peripheral neuropathy 384
Peristalsis 96
Peritoneal dialysis 316
Peritonitis 479
Petit-mal 356
Peutz-Jeghers syndrome 122
Peyronies disease 955
Phagocytosis 911
Pharyngeal/branchial arches 945
Phenols 503
Phenotypic sex 444
Phenylketonuria 457
Pheochromocytoma 416
Phimosis 954
Phospholipids 875
Phosphorus 461
Photosensitivity 835
Phylloides tumor 784
Picks disease 363
Pickwickians syndrome 898
Picornaviruses 591
Piebaldism 827
Piedra 608
Pigment stones 145
Pigmented lesions 42
Pill-induced gastritis 90
Pilocytic astrocytoma 373
Pink lesions 832
Pinta 571
977
Pituitary gland 393

Pityriasis (tinea) versicolor 608
Pityriasis rosea 822
Pityriasis rubra pilaris 822
Plague 549
Plasma cell disorders 679
Plasma osmolality 920
Plasma proteases 912
Plasmodium parasites 618
Platelet activating factor 913
Platelet membrane defect 693
Platelets 685
Pleural effusion 200
Pleural fluid examination 200
Plummer-Vinson syndrome 93
Pneumatosis cystoides
intestinalis 123
Pneumococcus 510
Pneumoconiosis 186
Pneumocystis
carinii 626
pneumonia 192
Pneumomediastinum 205
Pneumonia 189
Pneumothorax 202
Pneumovirus 596
Poems syndrome 683
Polio virus 591
Polyarteritis nodosa 299
Polyarticular 295
Polycystic kidney (adult) 331
Polycystic ovarian disease 442
Polycythemia vera 661
Polyglandular syndrome 415
Polymerase chain reaction 868
Polymorphs (neutrophils) 641
Polymyositis and dermatomyositis 296
Polyneuropathy 385
Polyposis syndromes 760
Popliteal aneurysm 251
Popliteal artery 944
Porcelain gallbladder 146
Porphyria cutanea tarda
447,831
Porphyrias 446
Port wine stain 728
Portal hypertension 137
Portal vein thrombosis 137
Portasystemic encephalopathy
139
Postcricoid carcinoma 783
Posterior tibial artery 945
Posterior urethral valve 953
Postnatally acquired rubella 599
978
Postprimary or secondary TB 552

Post-streptococcal GN 320
Post-transcriptional
modification 858
Post-translational modification
860
Postural hypotension 390
Potassium 924
Poxviruses 583
Precipitation test 261
Precocious puberty 85
Pre-eclampsia 71
Pre-excitation syndrome 220
Pregnancy and lactation 889
Pregnancy induced hypertension
71
Premalignant lesions 729
Premature ovarian failure 442
Premenopausal menorrhagia 437
Prenatal diagnosis 697
Pre-renal azotemia 312
Preservatives 933
Pretransplant testing 273
Primary amyloidosis 839
Primary brain tumors 373
Primary CNS lymphoma 375
Primary dementias 361
Primary hemostasis 686
Primary hyperparathyroidism
463
Primary immunodeficiencies 275
Primary peritonitis 479
Primary pulmonary
hypertension 199
Primary pulmonary
hypoventilation 170
Primary sclerosing cholangitis 148
Primary spontaneous
pneumothorax 202
Primary TB 552
Primary tumors 243
Prion diseases 383
Processed genes 854
Progeria 87,909
Progesterone 431
Progressive multifocal leukoencephalopathy 382
Progressive supranuclear palsy
363
Prolactin 396
Prolactinomas 443
Prolonged jaundice 66
Prolonged QT syndrome 221
Proptosis 34
Prosopagnosia 21
Prostate 770
Prostatic carcinoma 771
Protein 871
Protein energy malnutrition 889
Protein losing enteropathy 109
Protein synthesis 858
Proteins 903
Proteinuria 68
Proteus 530
Proto-oncogenes 709
Protozoa 281
Proximal RTA 334
Pseudoaneurysm 252
Pseudogenes 854
Pseudogout 306
Pseudohypertrophic muscular
dystrophy 387
Pseudohypoparathyroidism 466
Pseudomembranous colitis 114
Pseudomonas aeruginosa 542
Pseudotuberculosis 518
Pseudoxanthoma elasticum 833
Psoriasis 820
Psoriatic arthritis 307
Ptosis 34
Puberty and adolescence 84
Puberty menorrhagia 437
Pulmonary circulation 166
Pulmonary edema 46
pulmonary eosinophilia 195
Pulmonary function 43
Pulmonary hypertension 74
Pulmonary infections 189
Pulmonary infiltrates with
eosinophilia 194
Pulmonary stenosis 230
Pulmonary thromboembolism
197
Pulse-respiration ratio 8
Pulses 887
Pulse-temperature ratio 8
Pupillary defects 29
Pure red cell aplasia 660
Pure tone audiometry 40
Pure word deafness 20
Purine and pyrimidine 841
Purine catabolism 845
Purine metabolism 846
Purine nucleoside phosphorylase
deficiency 846
Pyogenic liver abscess 142
Pyonephrosis 329
Pyridoxine 894
Pyriform fossa tumor 782
Pyrimidine catabolism 846
Index
Pyrimidine metabolism 846
Pyrimidine synthesis 845
979
Renal tubular acidosis 333

Renal vein thrombosis 331
Renin secretion 311
Q
Reperfusion injury 901
Resistance 538
Q fever 575
Resistant ovary syndrome 442
Quinckes disease 832
Respiration 43
R
Respiratory acidosis 928
Respiratory alkalosis 929
Rabies 602
Respiratory distress syndrome
Radiation nephritis 329
208
Radioimmunoassay 263
Respiratory function 164
Radioisotopes 936
Respiratory quotient 393
Radiological appearance
Respiratory syncytial virus 596
346,933
Respiratory system 174
Ramsay Hunt syndrome 367
Restrictive cardiomyopathy 239
Rapidly progressive/crescentic
Reticular activating system 23
GN 319
Retina 27
Raynauds phenomenon 254
Retinoblastoma 778
Reactional states 563
Retroperitoneal fibrosis 117
Reactive arthritis 298
Retroperitoneal space 117
Recombinant dna technology
Retrosternal goiter 404
868
Retrovirus 605
Recommended daily allowance
Reversibility of cell injury 905
889
Reversibility of changes 425
Rectal carcinoma 765
Reversible cell injury 905
Rectal stricture 156
Reyes syndrome 140
Rectum 155
Rh system 701
Recurrent hernia 163
Recurrent jaundice of pregnancy Rhabdomyoma 243
Rhabdomyosarcoma 780
128
Rhabdovirus 602
Red blood cells 638
Rheumatic heart disease 232
Red cell indices 639
Rheumatoid arthritis 292
Red cell morphology 640
Rheumatoid nodules 832
Red urine 68
Rhinosporidiosis 611
Red-brown lesions 834
Rhythm 217
Reflexes 946
Riboflavin 882
Reflux nephropathy 341
Ribosomal RNA 856
Reinkes edema 741
Ribosomes 497
Reiters disease 825
Ribozymes 858
Reiters syndrome 298
Richters hernia 162
Relapsing fever 572
Rickets 467
Renal agenesis 339
Rickets and osteomalacia 467
Renal artery stenosis 330
Rickettsia 574
Renal azotemia 312
Rickettsial pox 575
Renal cell carcinoma 342
Riedels thyroiditis 409
Renal disease 81,449
Ring scotoma 32
Renal disorder 290
Rinnes test 39
Renal ectopia 339
RNA editing 858
Renal failure indices 313
RNA structure and transcription
Renal functions 68
855
Renal injuries 344
Renal osteodystrophy 314
RNA viruses 605
Renal system 309
Rocky mountain spotted fever
Renal transplant 316
575
Renal tuberculosis 329
Role of endothelium 685
980
Rosenthals syndrome 697

Roseola infantum 831
Rotavirus 604
Rubella 599
Runyons classification 559
Rupture of spleen 153
Rye classification 677
Shy-Drager syndrome 364

Sickle cell anemia 655
Sideroblastic anemia 647
Significant bacteriuria 493
Silicosis 186
Simple bone cyst 814
Sinus bradycardia 217
Sipple syndrome 445
S
Sjgrens syndrome 296
Skin
Sacral plexus 943
manifestations 825
Salivary gland neoplasm 738
pathogens 560
Salmonella gastroenteritis 536
tumors 727
Salmonella septicemia 536
Skin lesions 817
Salmonella species 536
Skull and PNS 936
Salvage pathway 844
SLE 83
Saphenous opening 161
Sleep apnea syndrome 206
Scabies 837
Sleeping sickness 624
Schistosomiasis 330,632
Sliding hernia 160
Schroeders disease 437
Slow viruses 604
Schwannomas 376
Small and large intestiene 110
Sciatica 4
Small gut adenocarcinoma 760
Scintillating scotoma 32
Small lymphocytic lymphoma 673
Scirrhous carcinoma 786
Small stable rna (SNRNA) 856
Scleroderma 92
Smell 35
Sclerosing peritonitis 480
Sodium balance 922
Screening for cancer 726
Sodium pump 920
Scrotum 955
Soft tissue sarcomas 774
Seborrheic dermatitis 820
Solitary rectal ulcer 156
Seborrheic keratitis 827
Somatostatin 98
Secretin 97
Somatostatinoma 755
Selenium 896
Specific immunity 275
Seligmanns disease 683
Spermatogenesis 427
Semen 428
Spigelian hernia 163
Sensory aphasia 19
Spina bifida 349
Sensory neuropathies 22
Spinal cord 368
Sensory system 21
compression 369
Sentinel pile 157
infarction 370
Sepsis and septic shock 472
trauma 369
Serocystic disease of Brodie 784
Spinal mascular atrophy 366,389
Seronegative arthritis 307
Spinal shock 368
Sertoli cells 426
Spinal stenosis 4
Serum sickness 271
Spinal tumors 4
Severe combined immunodeficiency 276
Spirochetes 565
Sex cord stromal tumors 807
Spleen 152,290
Sex-linked disorders 865
Splenectomy 154
Sexual differentiation 443
Splenic abscess 154,482
Sexual precocity 429
Splenic infarction 154
Sexually transmitted diseases 485 Splenomegaly 153
Sezary syndrome 675
Splenunculi (accessory spleen)
Shigella 531
153
Shock 51
Spontaneous bacterial
Short bowel syndrome 106
peritonitis 139,479
Shoulder pain 4
Spontaneous pneumothorax
Shwachmans disease 278
202
Index
Spontaneous rupture of spleen
153
Spores 498,520
Sporotrichosis 610
Sporozoa 617
Squamous cell carcinoma
(SCC) 730
Stages of iron deficiency 645
Staging of oral cancers 738
Stapedial reflex 41
Staphylococcal pneumonia 191
Staphylococcal scalded skin
syndrome 830
Staphylococcus 504
aureus 504
epidermidis 506
saprophyticus 506
Stasis dermatitis 819
Status epilepticus 356
Steele-Richardson-Olszewski
syndrome 363
Stein-Leventhal syndrome 442
Stills disease 294,475
Stomach and intestine 99
Stomach bed 99
Stone 335
Stones in CBD 147
Strangulated inguinal hernia 160
Strangulation 118
Strawberry/raspberry tongue 43
Streptococcal pneumonia 190
Streptococcus 507
agalactiae 508
equisimilis 509
pyogenes 507
Stress related mucosal injury 104
Stridor 47
Structural defect 53
Structure and function immune
system 264
Sturge-Weber syndrome 838
Subacute combined
degeneration 370
Subacute sclerosing
panencephalitis 383
Subacute thyroiditis 409
Subarachnoid hemorrhage 360
Subcellular changes in response
to injury 902
Subdural empyema 381
Submandibular gland tumors 740
Subphrenic abscess 481
Supercoils 848
Superficial muscles 941
Superficial mycosis 606
981
Superficial vein thrombosis 256

Superior mesenteric syndrome
120
Superior vena cava syndrome
726
Supportive care 725
Sweets syndrome 834
Syncope 10
Synovial sarcoma 813
Synthesis and metabolism 462
Syphilis 487,566
Syphilitic (leutic) aneurysm 252
Syringomyelia 351,370
Systemic infections 611
Systemic inflammatory response
syndrome 472
Systemic lupus erythematosus
289,327
Systemic sclerosis/scleroderma
295
Systolic murmur 215
T
T. pallidum 566
Tabes dorsalis 371
Tachyarrhythmias 218
Taeniasis solium 633
Takayasus arteritis 302
Tarsal tunnel syndrome 392
Taste buds 36
Taste modalities 37
Taste pathways 37
Telomere 850
Temporal arteritis 302
Temporal lobe 27
Temporal lobe epilepsy 357
Tension pneumothorax 203
Tertiary hyperparathyroidism
464
Tertiary peritonitis 480
Test and formula 931
Testicular agenesis 440
Testicular tumor 773
Testis 426, 428, 773
Tetanus 522
Tetralogy of Fallot 230
Thalassemia 656
Thiamin 882
Third heart sound (S3) 214
Thoracic outlet syndrome 4
Thromboangiitis obliterans 253
Thrombocytopenia 691
Thrombocytosis 663
Thromboembolism in pregnancy
75
982
Thrombosis 688
Thrombotic disorders 688
Thrombotic thrombocytopenic
purpura 693
Thymic hypoplasia 277
Thymoma 204
Thyroglossal cyst 401
Thyroglossal fistula 401
Thyroglossal tract 401
Thyroid gland 400,946
Thyroid hormones 400
Thyroiditis 409
Thyrotoxicosis 405,406
Thyrotoxicosis in pregnancy 81
TIC doulourux 366
Tietzes syndrome 308
Time period 84
Tinea nigra 608
Tinea or ring worm 606
Tissue nematodes 627
Tocopherol 885
Togavirus 600
Tone-Decay test 40
Tongue 43
Topoisomerase inhibitors 723
Torsades de pointes 221
Total body water 49
Total parenteral nutrition 899
Toxic epidermal necrolysis 830
Toxic myopathies 389
Toxic nodular goiter 406
Toxic shock syndrome 836
Toxicology 931
Toxoplasma gondii 621
Trace element deficiency 896
Tracheoesophageal fistula 88
Trachoma 577
Transfer RNA 855
Transformation 499
Transfusion reactions 702
Transient tachypnea of newborn
209
Transitional cell carcinoma 768
Transplant recipients 495
Transplant rejection 317
Transplants 272
Transposition of great vessels 231
Transverse myelitis 370
Traumatic injury 371
Traumatic paraplegia 14
Traumatic pneumothorax 203
Travelers diarrhea 484
Treacher-Collins syndrome 352
Trematodes-Flukes 632
Tremor 15
Treponema 565
Triceps 938
Trichobezoar 109
Trichomonas vaginalis 625
Trichomonas vaginitis 489
Tricuspid atresia 230
Tricuspid regurgitation 237
Trigeminal (5th nerve) palsy 366
Trigeminal neuralgia 366
Triplet repeat mutations 867
Tropical eosinophilia 195
Tropical pulmonary eosinophilia
631
Tropical sprue 107
Trypanosoma 624
Tubercular meningitis 380
Tuberculosis of genital tract 491
Tuberculous cystitis 952
Tuberculous ulcer 113
Tuberous sclerosis 378,827
Tubular adenomas 762
Tubular function 310
Tubulointerstitial disease 327
Tularemia 550
Tumor
bone 814
GI tract 756
large intestine 122,760
larynx 740
liver and biliary tract 748
lysis syndrome 726
markers 715
nasopharynx 781
rectum and anal canal 765
related emergencies 726
renal pelvis 344
small intestine 121,759
stomach and duodenum
109, 757
suppressor genes 711
Turners syndrome 441
Tympanometry 41
Typhoid ulcer 113
Tyrosine transaminase
deficiency 459
Tyrosinemia 459
Tyrosinosis 459
Tzanck smear 818
U
Ulcerative colitis 111
Ulcerative tuberculosis 113
Umbilical hernia 162
Ureaplasma urealyticum 574
Uremia 314
Index
983
Verrucous carcinoma 731

Vertigo 10
Vesicles/bullae 829
Vesicoureteric reflux 340
Vesicovaginal fistula 950
Vessel wall disorder 693
Vibrio 537
Vibrio cholerae 537
Villous adenoma 762
Vinca alkaloids 722
Vincents angina 572
Vipoma 755
Viral encephalitis 382
Viral hepatitis 80
Viridans streptococcus 509
Virology 579
Virulence 507
Virulence factors 518
Virus infections 582
Viruses 713
Visceral abscesses 482
Visceral pain 1
Visible light 836
Visual field 31
Visual field defects (scotoma)
31
V
Visual pathways 33
V. parahemolyticus 541
Vitamin
V. vulnificus 541
A deficiency 892
Vaccines 83
B1 882,893
Vaginal carcinoma 799
B12 894
Vaginal cyst 799
B12 deficiency 649
Valvular heart disease 235
B2 882,893
Varicose veins 254
B3 893
Variola and vaccinia 583
B5 883
Vascular anomalies 116
B6 883
Vascular diseases 244,253
C 884
Vascular disorders 197
D 461
Vascular events 910
deficiencies 892
Vascular injury to kidney 330
E 885
excess 896
Vascular malformations 727
K 885
Vascular permeability 910
K deficiency 698
Vasculitis syndromes 299
K excess 896
Vasopressin or ADH 394
Vitiligo 826
Veno-occlusive disease 137
Vocal cord polyps 741
Venous disorders 254
Vocal nodule (Singers nodule)
Ventilation and perfusion 167
740
Ventilator modes 210
Vomiting 54
Ventricular ectopics 218
von Buchems disease 471
Ventricular fibrillation (cardiac
von Gierkes disease 846
arrest) 222
Ventricular premature complexes von Hippel-Lindau syndrome
333,379
218
von Reckling-Hausens disease
Ventricular septal defect 227
377
Ventricular tachycardia 221
Ureteric stones 337
Ureterocele 339
Uretero-vaginal fistula 951
Urethra 953
Urethral stricture 954
Urethritis 486
Urge incontinence 950
Urinary bladder 951
Urinary bladder stone 337
Urinary cast 69
Urinary incontinence 947
Urinary tract infection 492
Urine 932, 947
Urine output 69
Urodynamic study 948
Uronic acid pathway 881
Urticaria and angioedema 832
Urticaria pigmentosa 834
Uterine polyps 794
Uterine sarcoma 793
Uterine tumors 791
Uti in pediatric age group 494
UV-A radiation 835
UV-B radiation 835
984
Von Willebrands disease 692

Vulval carcinoma 799
Vulval cyst 798
Vulval dystrophy 798
Vulval intraepithelial neoplasia
798
W
W. bancrofti 629
Wagner-Barker classification of
hypertensive retinopathy
249
Waldenstroms
macroglobulinemia 683
Wallenbergs syndrome 359
Warts 824
Water balance 920
Water clearance 311
Water intake 920
Water intoxication 922
Water output 921
Water reabsorption 921
Watery diarrhea 483
Weakness 11
Weber test 39
Weber-Christian disease 834
Wegeners granulomatosis
300,325
Weight 57
Weight gain 69
Weils disease 572
Weil-Felix reaction 531
Wermers syndrome 445
Wernickes aphasia 19
West nile fever 602
West syndrome 357

Whipples disease 108
White blood cells 641
White lesion 43
Williams syndrome 446
Wilms tumor 341
Wilson disease 141
Wiskott-Aldrich syndrome 276
Wobble phenomenon 861
Wolmans disease 452
Woods lamp 818
Wound healing 918
WPW syndrome 220
X
Xanthogranulomatous
pyelonephritis 328
Xeroderma pigmentosa 870
X-linked agammaglobulinemia
275
X-linked dominant disorders
864
X-linked recessive disorders 863
Y
Yaws 571
Yellow fever 600
Yellow lesions 833
Yersinia pestis 548
Z
Zenkers diverticulum 93
Zinc 896
Zollinger-Ellison syndrome 754

Pradip Kumar Das - A Systematic Review of Subjects For PG Medical Entrance Examinations

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A Systematic Review of

IPGME&R and SSKM Hospital

JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTD

Charis ne dhare thak ente,

x A Systematic Review of Subjects for PGMEE

Primary sensory afferents (A and C fibers)

Dorsal root ganglia in the vertebral foramina

Lateral spinothalamic tract

Somatic sensory area

2 A Systematic Review of Subjects for PGMEE

Myocardial infarction: Similar to angina but of more

4 A Systematic Review of Subjects for PGMEE

Multiple myeloma is the most common primary tumor

Scalenus anterior syndrome.

6 A Systematic Review of Subjects for PGMEE

Circadian rhythm: body temperature is maximum at 6

8 A Systematic Review of Subjects for PGMEE

Features: Increased temperature, muscle contraction

A Systematic Review of Subjects for PGMEE

Episodic attacks of:

A Systematic Review of Subjects for PGMEE

Lower motor neuron (LMN) Anterior horn cells and

Note: In Friedrichs ataxia, Babinskis sign is +ve (UMN

A Systematic Review of Subjects for PGMEE

Note: Lesion above C5 is fatal due to respiratory failure.

A Systematic Review of Subjects for PGMEE

Features: Hypotonia, pronator sign, milking sign, spooning

BALANCE AND GAIT

iii. Posterior column Multiple sclerosis, syringomyelia.

A Systematic Review of Subjects for PGMEE

2. Facial tics Gilles de la Tourette syndrome.

A Systematic Review of Subjects for PGMEE

Cause Lesion in arcuate fasciculus. Lesions of auditory

Crosses the midline and ascends as ventral or lateral

Project to ventral posterolateral

Ultimately project to the postcentral

A Systematic Review of Subjects for PGMEE

First synapse in the gracile and cuneate nuclei of medulla

Second order neurons cross midline and lie medial to

Synapse at VPL of thalamus

Third order neurons project to parietal cortex

Papillary reaction to light.

Note: Normal cerebral blood flow (CBF) is 75 ml/100 g/

A Systematic Review of Subjects for PGMEE

A Systematic Review of Subjects for PGMEE

EYE AND VISION

A Systematic Review of Subjects for PGMEE

A Systematic Review of Subjects for PGMEE

A Systematic Review of Subjects for PGMEE

Also seen in Optic neuritis, ischemic optic

Damage to Visual Pathways

Conjunctivitis most common cause

Sudden Visual Loss

A Systematic Review of Subjects for PGMEE

2 Congenital nystagmus Pendular or sinusoidal due

A Systematic Review of Subjects for PGMEE

Sweet Organic substances

A Systematic Review of Subjects for PGMEE

Medial geniculate body in the thalamus

A Systematic Review of Subjects for PGMEE

A Systematic Review of Subjects for PGMEE

iv. Others unconjugated hyperbilirubinemia,