Chiro Essentials

Boards Review
Part 1

3rd edition

J.R. La Rose

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 Chiro Essentials

Boards Review
Part 1

J.R. La Rose

Third Edition, 2011

All rights reserved. No part of this book may be

reproduced or transmitted in any form or by any
means including photocopies or utilized by any
information storage and retrieval system without
permission in writing from the authors, except for
brief quotations in a review.

DISCLAIMER

Care has been taken by the authors to confirm the accuracy of the information
presented. However, the authors and the publishers are not responsible for
errors of omission or for any consequences from application of the information in
this book and make no warranty, expressed or implied, with respect to the
completeness or accuracy of the content of the publication. The application of the
information contained in this book in a particular situation remains the sole
responsibility of the reader.

ISBN: 978-0-615-28610-5

Printed in the United States by:

Mira Digital Publishing
3800 Park Avenue
St. Louis, MO 63110
1-866-341-9588

Cover design by Jessie Tapia

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 Preface to the 3rd edition

This is the third edition of ChiroEssentials Boards Review part 1. Errors have
been corrected and there are additional drawings and new information. Public
Health has been deleted from the Microbiology section in keeping with the recent
NBCE® change in the scope of the subject. This review for NBCE® Part 1 has
been prepared with the sole purpose of helping chiropractic students to be better
prepared for the NBCE® Part 1. The information contained in this book highlights
the major facts and concepts commonly covered in the NBCE® Part 1. Although it
is recommended that you use this book as early as possible in conjunction with
your basic science courses, it is not intended to replace any lectures, lecturers or
the recommended textbooks. The material is organized in a systemic manner in
which relevant topics in General Anatomy, Spinal Anatomy, Physiology,
Pathology, Microbiology and Chemistry are covered. The information in this book
has been gleaned from a variety of sources including the basic medical science
textbooks such as Moore’s Clinically Oriented Anatomy, Guyton and Hall’s
Textbook of Physiology, Robbins and Cotran’s Pathological Basis of Disease, the
Lippincott Williams & Wilkins Board Review Series, the Elsevier Mosby Crash
Course series and Mosby’s Review Questions for the NBCE® examinations Parts
I and II. The material is presented in bullet format to facilitate easy learning and
rapid recall. Key words are highlighted to trigger recall. It is recommended that
you look up unfamiliar words and concepts. The use of the recommended
textbooks is highly encouraged to supplement this book if you need a more
detailed explanation of unfamiliar concepts. Where there are differences of
opinion on certain issues, I have used the recommended NBCE® textbooks and
have indicated the source with an asterix. The Rapid Review session added to
the 3rd edition had very favorable comments from many students and has been
expanded to cover many of the important areas. The author would also like to
express thanks to Jessie Tapia who did most of the drawings. Like the previous
edition, this is still a work in progress and will be revised on an annual basis.
Should you find errors or omissions, please do not hesitate to email me at
chiroessentials@gmail.com with a reference and the necessary amendments
will be made. As soon as possible after you take the examination, it is
recommended that you review the book to help us create an even better fourth
edition. Let me know what information should be revised, included or removed.

Jimi La Rose , MBBS, M Med

Professor
Palmer College of Chiropractic
Florida campus
2011

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 Table of Contents

1. General Anatomy
a. Introduction 9
b. Anatomical Triangles 11
c. Anatomical Spaces 14
d. Cardiovascular 19
e. Endocrine 27
f. Gastrointestinal 29
g. Musculoskeletal 35
h. Reproductive 46
i. Respiratory 50
j. Reticuloendothelial 54
k. Skin 58
l. Thoracic cage 59
m. Urinary 63

2. Spinal Anatomy
a. Vertebral Column 69
b. Spinal Joints 73
c. Back Muscles 75
d. Spinal Cord 76
e. Central Nervous System 80
f. Skull, Scalp and Face 92
g. Peripheral Nervous System 96
h. Autonomic Nervous System 100

3. Physiology
a. Cardiovascular 105
b. Endocrine 108
c. Gastrointestinal 112
d. Hematological 115
e. Immunological 117
f. Musculoskeletal 119
g. Neurophysiology 122
h. Renal 124
i. Reproductive 128
j. Respiratory 130

4. Pathology
a. General principles 135
b. Genetic disorders 137
c. Neoplasia 139
d. Cardiovascular 141
e. Endocrine 144
f. Gastrointestinal 147

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 g. Musculoskeletal 149
h. Nervous system 153
i. Nutritional 157
j. Renal 159
k. Respiratory 161
l. Sexually Transmitted Diseases 164
m. Skin diseases 166

5. Microbiology
a. History of Microbiology 169
b. General principles 170
c. Viral 172
d. Bacterial 175
e. Fungal 183
f. Parasitic 185
g. Tests for micro-organisms 189
h. Specificity and Sensitivity 191
i. Infection control 192
j. Epidemiological terms 192

6. Chemistry
a. General principles 195
b. Carbohydrate metabolism 197
c. Glycolysis 199
d. Gluconeogenesis 201
e. Krebs cycle 203
f. Oxidative Phosphorylation 206
g. Cori cycle 208
h. Pentose Phosphate Pathway 209
i. Glycogen metabolism 210
j. Fat metabolism 212
k. Protein metabolism 215
l. Purine metabolism 217
m. Vitamins and minerals 218
n. Pathways summary 221

7. Rapid Review 223

a. Classic presentations 225
b. Pathology 228
c. Microbiology 230
d. Chemistry 232

8. INDEX 235

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GENERAL ANATOMY

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INTRODUCTION

The anatomical position

In the anatomical position, the body is facing forwards, with the limbs fully extended and the palms
facing forwards.

Positions a body can lie

A body may be placed in the following positions:
 prone [facing downwards]
 supine [facing upwards]

Various regions of the body

 cephalic [head]
 caudal [tail]
 cervical [neck]
 thoracic [chest]
 abdominal [between chest and genitals]
 lumbar [lower back]
 sacral [over the sacrum]

Surfaces of limbs
 dorsal [back] or posterior
 ventral [front] or anterior

Various planes in the body

 horizontal-in line with the horizon [also known as transverse]
 vertical-at right angle to horizontal
 sagittal-from top-bottom plane separating left from right
 coronal-vertical plane separating the back from the front
 median-in the sagittal plane
 medial-close to the midline
 lateral-away from the midline

Coronal plane

Sagittal plane

Horizontal plane

Fig 1: Anatomical Position

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Anatomical terms related to movements
 flexion-bent towards the trunk
 extension-stretched out away from trunk
 adduction-brought towards midline
 abduction-moved away from midline
 supination-turned upwards
 pronation-turned downwards
 medial rotation-turned inwards
 lateral rotation-turned outwards
 ulnar deviation-bent towards ulnar side
 radial deviation-bent towards radial side

Meaning of the following anatomical terms

 proximal-closer to the origin of the limb
 distal-further away from the origin of the limb
 superficial-closer to the surface
 deep-further away from the surface
 cranial-towards the head
 caudal-towards the tail
 palmar-part of hand that holds
 plantar-part of foot that one stands on [sole]
 superior-located above
 inferior-located below

Histology introduction
Cells may be classified into the following groups:
o epithelial
o muscle-smooth, skeletal and cardiac
o nervous
o bone
o blood
o connective tissue
All of the above cell type can reproduce except cardiac and skeletal muscle and nervous tissue.
There are several types of epithelia:
 squamous
o simple: lining lymphatic and blood vessels, pleura and peritoneum
o stratified: skin, esophagus, lower half of the anal canal
 cuboidal
o Bowman’s capsule, convoluted tubules of the kidney, thyroid follicles
 columnar
o simple: lining of the gastrointestinal tract
o stratified: uterine tube
o pseudostratified: respiratory tract
 transitional
o ureter, urinary bladder and most of the urethra

Embryology introduction
nd
The body develops from an embryo which at the end of the 2 week has two layers [bilaminar] and at the
rd
end of the 3 week [Day 21] of gestation has three germinal layers [trilaminar]:
 the endoderm lies on the inside and gives rise to the following:
o epithelium of the respiratory, gastrointestinal and genitourinary tract
 the ectoderm lies on the outside and gives rise to the following:
o epidermis including hair
o retina and lens
o Central Nervous System, Peripheral Nervous System, pia and arachnoid mater
o adrenal medulla
 the mesoderm lies in the middle between the two and gives rise to the following:
o bones and muscles of the trunk and extremities
o cardiovascular system and most of the genitourinary system
o cartilage and muscle of the respiratory system
o adrenal cortex, dermis of the skin and dura mater of the spinal cord

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ANATOMICAL TRIANGLES

Suboccipital Triangle
 Boundaries: rectus capitis posterior major, obliquus capitis superior, obliquus capitis inferior
 Roof: deep fascia covered by semispinalis capitis
 Floor: posterior arch of C1 and posterior atlanto-occipital membrane
rd
 Contents: 3 part of vertebral artery, suboccipital nerve [CI] and suboccipital veins
 All of the muscles forming its boundaries are supplied by the dorsal ramus of C1

Obliquus capitis superior

Rectus capitis posterior major rd

3 part of vertebral artery

Obliquus capitis inferior

Fig 2: Suboccipital Triangle

Anterior Cervical Triangle
 Boundaries: anterior midline, inferior ramus of mandible and anterior border of SCM
 Roof: skin, superficial fascia and investing layer of deep cervical fascia
 Contents: carotid, submandibular, submental and muscular triangles

Anterior and posterior bellies of digastric

Superior belly of omohyoid

Sternocleidomastoid

Inferior belly of omohyoid

Trapezius

Fig 3: Cervical Triangles

Carotid Triangle
 Boundaries: SCM, posterior belly of digastric and superior belly of omohyoid
 Roof: skin, subcutaneous fascia and investing layer of deep cervical fascia
 Floor: hyoglossus, middle and inferior constrictor muscles
 Contents: CN XI, XII and the carotid sheath containing common carotid artery, external carotid
artery, internal carotid artery, internal jugular vein and CN X; lying anterior to the carotid
sheath are lymph nodes and the ansa cervicalis

Submandibular Triangle [aka digastric triangle]

 Boundaries: posterior and anterior bellies of digastric and inferior ramus of mandible
 Roof: skin, superficial fascia
 Floor: mylohyoid, hyoglossus and part of middle constrictor
 Contents: submandibular gland, nodes, facial vein and artery, hypoglossal and mylohyoid nerve

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 Submental Triangle [aka suprahyoid triangle]
 Boundaries: anterior bellies of both digastric and hyoid bone
 Roof: skin, subcutaneous fascia
 Floor: mylohyoid muscles
 Contents: submental lymph nodes and submental veins

Muscular Triangle
 Boundaries: sternocleidomastoid, superior belly of omohyoid and anterior midline of neck
 Roof: skin and superficial fascia
 Contents: sternohyoid, sternothyroid and thyrohyoid muscles, thyroid, trachea and larynx

Posterior Cervical Triangle

 It is subdivided by inferior belly of omohyoid into the occipital and supraclavicular triangles [2]
 Boundaries: sternocleidomastoid, trapezius and middle third of the clavicle [3]
 Roof: Skin, superficial fascia, platysma and investing layer of deep cervical fascia [4]
 Floor: splenius capitis, levator scapulae, scalenus posterior, medius and anterior [5]
 Contents:
o [6 vessels] subclavian artery, suprascapular, transverse cervical, occipital arteries, the
subclavian and external jugular veins
o [7 nerves] great auricular, lesser occipital, supraclavicular, transverse cervical nerves,
trunks of the brachial plexus and CN XI*
*Clinically Oriented Anatomy includes the phrenic nerve in the posterior cervical triangle

Triangle of Auscultation
 Boundaries: trapezius, latissimus dorsi and medial border of scapula
 Roof: skin and superficial fascia
 Floor: rhomboid major
 Contents: none

Lumbar Triangle [of Petit]

 Boundaries: latissimus dorsi, external oblique and iliac crest
 Roof: skin and superficial fascia
 Floor: transverses abdominis
 Contents: none

Trapezius

Triangle of Scapula
Auscultation

Latissimus dorsi

External oblique
Lumbar triangle

Iliac crest

Fig 4: Triangles of the Back

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Inguinal Triangle [of Hesselbach]
 Boundaries: rectus abdominis, inferior epigastric vessels and inguinal ligament
o Inguinal ligament is the infolding of the lower end of the aponeurosis of External oblique
and extends from the Anterior Superior Iliac Spine to the pubic tubercle
 Roof: skin and external oblique aponeurosis
 Floor: transversalis fascia
 Direct hernias pass through Hesselbach’s triangle
 Indirect hernias pass through the deep inguinal ring which is a defect in the transversalis fascia

Rectus abdominis

Deep Inguinal ring

Inguinal ligament

Inferior epigastric vessels

Fig 5: Inguinal Triangle

Femoral Triangle [of Scarpa]
 Boundaries: inguinal ligament, medial borders of sartorius and adductor longus*
 Roof: skin, superficial fascia and fascia lata
 Floor: iliopsoas, pectineus and adductor longus*
 Contents: femoral nerve, femoral artery, femoral vein and femoral canal
 The femoral artery, vein and canal lie inside the femoral sheath which is formed from the fascia
related to the transversalis and iliacus muscles
 The femoral nerve lies outside of the femoral sheath
*Gray’s Anatomy: The Anatomical Basic of Clinical Practice, 39th ed. p1421

Inguinal ligament
Iliopsoas

Femoral nerve and vessels Pectineus

Adductor longus

Sartorius

Fig 6: Femoral Triangle

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ANATOMICAL SPACES

Thoracic Outlet [aka Superior Thoracic Aperture]

st
 Boundaries: T1 vertebra [posterior], 1 ribs [lateral] and the manubrium of sternum [anterior]
 Roof: suprapleural membrane [Sibson’s fascia] which extends:
o from the tip of the transverse process of C7
st
o to the inner aspect of 1 rib
 Contents: trachea, esophagus, thoracic duct, brachiocephalic trunk, left common carotid and left
subclavian arteries, right and left brachiocephalic veins, right and left vagus nerves, phrenic nerves,
right and left sympathetic trunks, T1 of the brachial plexus and the sternohyoid, sternothyroid and
longus coli muscles

Brachial plexus

st T1
1 rib Subclavian artery

Manubrium

Fig 7: Thoracic Outlet

Axilla
 Boundaries: pectoralis major and minor [anterior], subscapularis, teres major and latissimus dorsi
[posterior], upper 4 ribs and serratus anterior [medial] and bicipital groove of the humerus [lateral]
 Roof:
o triangular interval bounded by:
 clavicle [anterior]
st
 1 rib [medial]
 scapula [posterior]
 Floor:
o skin
o superficial fascia
 Contents: axillary artery and branches, axillary vein and tributaries, cords of the brachial plexus and
six groups of lymph nodes:
o Anterior [pectoral]
o Posterior [subscapular]
o Infraclavicular
o Central
o Apical
o Lateral [along the axillary vein]

Quadrangular Space
 Boundaries:
o teres minor [superior]
o teres major [inferior]
long head of triceps [medial]
o humerus [lateral]
 Contents:
o axillary nerve
o posterior circumflex humeral artery and vein
 Roof: none
 Floor: none

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Triangular Space
 Boundaries: teres minor [superior], teres major [inferior], long head of triceps [lateral]
 Contents: circumflex scapular branch of the subscapular artery
 Roof: none
 Floor: none

Quadrangular space

Triangular space

Teres minor

Teres major
Long head of triceps

Fig 8: Quadrangular and Triangular Spaces

Cubital Fossa
 Boundaries: pronator teres [medial], brachioradialis [lateral], imaginary line between humeral
epicondyles [superior]
 Roof: skin, superficial fascia containing median cubital vein, deep fascia and the bicipital
aponeurosis
 Floor:
o brachialis [medial]
o supinator muscle [lateral]
 Contents from lateral to medial: radial nerve, tendon of biceps brachii, brachial artery [and its
terminal branches-radial and ulnar] and the median nerve

Brachialis

Brachial artery

Median nerve
Biceps tendon Imaginary line
Radial Nerve
Bicipital aponeurosis

Pronator teres
Brachioradialis

Figure 9: Cubital Fossa

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Anatomical Snuffbox
 Boundaries: tendons of abductor pollicis longus and extensor pollicis brevis [anterior] and tendon of
extensor pollicis longus [posterior]
 Roof: skin, superficial fascia with cephalic vein and superficial branch of the radial nerve
 Floor:
o styloid process of radius
o scaphoid
o trapezium
st
o base of the 1 metacarpus
 Contents: radial artery and tendons of extensor carpi radialis longus and brevis

Abductor pollicis longus

Extensor pollicis brevis

Extensor pollicis longus

F ig 10: A natomical Snuffbox

Carpal Tunnel
 Roof: flexor retinaculum-1” fibrous square attached to the following carpal bones:
o Scaphoid, Trapezium, Os hamate and Pisiform bones [STOP]
 Floor: carpal bones [trapezium, trapezoid, capitate and hamate]
 Contents: the median nerve, tendons of Flexor digitorum superficialis and profundus and tendon of
Flexor pollicis longus [Flexor carpi radialis lies in a separate compartment]
 NB: the superficial palmar branch of the median nerve passes over the retinaculum and therefore is
not compressed allowing for the sensation of the palm to be intact in carpal tunnel syndrome

Median nerve Flexor retinaculum

Flexor carpi radialis

Flexor digitorum
superficialis and
Flexor pollicis longus tendon profundus tendons

Fig 11: Carpal Tunnel

Guyon’s canal [aka ulnar tunnel]

 Floor: flexor retinaculum
 Roof: pisohamate ligament
 Medial border: pisiform
 Lateral border: hamate
 Contents: ulnar nerve and ulnar artery

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Inguinal Canal [of 2’s]
 Boundaries: external oblique aponeurosis and internal oblique [anterior] with the conjoint tendon
and transversalis fascia [posterior]
 Roof: arching fibers of internal oblique and transversus abdominis
 Floor: inguinal ligament and lacunar ligament medially
 Extent: between the deep and superficial inguinal rings
 Contents:
o ilioinguinal nerve
o spermatic cord in males
o round ligament of uterus in females
 Extent: from the deep ring [above a point midway between the ASIS and pubic tubercle] to the
superficial ring [medial to the pubic tubercle and above the pubic crest]

External Oblique
Internal Oblique
Spermatic cord
Transversus abdominis

Deep inguinal ring Superficial inguinal ring

Inguinal ligament

Fig 12: Inguinal Canal

Femoral Canal
 Boundaries: lacunar ligament [medial], inguinal ligament [anterior], femoral vein [lateral] and
pectineus and pectineal ligament [posteriorly]
 Roof: connective tissue
 Contents: lymph node [Cloquet or Rosenmuller], lymphatics and connective tissue

Femoral nerve Femoral artery, vein and canal

Fig 13: Femoral Canal

Adductor Canal [Subsartorial or Hunter’s canal]

 Boundaries:
o vastus medialis [anterolateral]
o sartorius [medial]
o adductor longus [posterior]
o magnus [posterior]
 Contents:
o femoral artery
o femoral vein
o saphenous nerve
o nerve to vastus medialis

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 Vastus medialis

Sartorius

Adductor longus

Adductor magnus

Fig 14: Adductor Canal

Popliteal Fossa
 Boundaries: biceps femoris [superolateral], semitendinosus and semimembranosus [superomedial],
lateral and medial heads of gastrocnemius [inferolateral and inferomedial]
 Roof: skin, superficial fascia with short saphenous vein and deep fascia
 Floor: lower end of femur, posterior aspect of knee joint, popliteus muscle and fascia
 Contents:
o tibial nerve
o popliteal vein and artery
o common peroneal [fibular] nerve
o nodes
o fat
o the artery is deepest, the tibial nerve is most superficial and the vein is in between

Gracilis

Semitendinosus

Popliteal vein Biceps femoris

Tibial nerve
Semimembranosus
Common Fibular nerve
Popliteal artery

Fig 15: Popliteal Fossa

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Tarsal Tunnel
 it lies behind the medial malleolus and under the flexor retinaculum
 Contents:
o Tibialis posterior tendon
o Flexor Digitorum longus tendon
o posterior tibial Artery, vein and Nerve
o Flexor Hallucis longus tendon
o [Tom, Dick ANd Harry] in that order from anterior to posterior

Tibialis posterior Flexor Hallucis longus

Flexor Digitorum longus
Posterior tibial Artery, vein and Nerve
Medial Malleolus Flexor retinaculum

Fig 16: Tarsal Tunnel

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CARDIOVASCULAR ANATOMY

Embryology
 the heart develops in the mesoderm in the cephalic region of the developing fetus at the third
week
 angioblastic tissue coalesce to form the right and left endocardial tubes which fuse to form the
primitive heart tube
 the primitive heart tube folds on itself and develops three dilations-atrial, ventricular and the
bulbus cordis
 the proximal end of the heart tube is formed by the sinus venosus
 the distal end is formed by the truncus arteriosus

Sinus venosus

Atrium
Truncus arteriosus
Endocardial tubes
Bulbus cordis

Ventricle

Truncus arteriosus

Fig 17: Embryology of Heart

th
 the atrial dilation is divided by a septum [septum primum] in the 5 week
 a hole appears in the upper part of the septum primum-ostium secundum
 another septum appear to the right of the septum primum called the septum secundum
o this septum is incomplete inferiorly remaining as the limbus of the fossa ovalis
 the ventricular dilation is divided by a septum which goes upwards towards the endocardial
cushions

Septum secundum Septum primum

Ostium secundum
Foramen ovale
Endocardial cushions

Interventricular septum

Right ventricle Left ventricle

Fig 18: Septal Development

20
 th th
 the truncus arteriosus is divided into two separate tubes-aortic and pulmonary in the 7 and 8
weeks
 the two tubes twist on each other to allow the pulmonary artery to lie anterior to the aorta initially
and then posterior
 there is a connection called the ductus arteriosus in the fetus that allows oxygenated blood to be
shunted from the left pulmonary artery to the arch of the aorta
 this ductus closes shortly after birth to form the ligamentum arteriosum
 the following congenital anomalies may occur:
o Ventricular Septal Defect: most common congenital heart disease]
o Atrial Septal Defect: most common is an ostium secundum defect
o Fallot’s tetralogy: most common congenital cyanotic heart disease
o Patent Foramen Ovale
o Persistent Ductus Arteriosus
 Fallot’s tetralogy:
o Pulmonary stenosis
o Ventricular Septal Defect
o Right Ventricular Hypertrophy
o Over-riding [dextroposition] of the aorta
 cyanosis is due to the mixing of arterial blood with deoxygenated blood and occurs in right to left
shunts
 the acyanotic congenital heart diseases include Atrial Septal Defect, Ventricular Septal Defect and
a Persistent Ductus Arteriosus and are all left to right shunts
 Persistent Ductus Arteriosus results from failure of the ductus arteriosus to close after birth

Surface markings of the heart

rd
 3 right costal cartilage 1 finger’s breath from the sternal edge
th
 6 right costal cartilage 1 finger’s breath from the sternal edge
nd
 2 left costal cartilage 1 finger’s breath from the sternal edge
th
 5 left intercostal space 7-9 cm from the midsternal line

Cardiac Chambers
 Right heart border is made up of the right atrium
 Inferior heart border is made up of the right ventricle
 Left heart border is made of the left ventricle and left auricle of left atrium

Right heart border Left heart border

Fig 19: Heart Borders

Right atrium
 it has two origins-from the sinus venosus and from the true atrium
 the rough part is derived from the true atrium
o the rough part of the atrium has the pectinate muscle bundles
 the smooth part is derived from the sinus venosus embryologically
 they are separated by a ridge called the crista terminalis

21
  the openings of the Superior Vena Cava [SVC] and Inferior Vena Cava [IVC] are located in the
superior and inferior aspects of the right atrium
 there is an oval depression [fossa ovale] on the interatrial septum
 this represents the location of the fetal foramen ovalis-the septum primum
 above the depression is a ridge called the limbus of the fossa ovalis
 this is the remnant of the septum secundum
 just above the opening of the tricuspid valve lies the orifice of the coronary sinus
 60-70% of myocardial venous blood drains into the heart via the coronary sinus

Left atrium
 it has the openings of the 4 pulmonary veins carrying oxygenated blood from the lungs
 like the right atrium, it has both rough and smooth parts reflecting its dual embryological origins

Right ventricle
 it has several large fleshy trabeculae carneae and papillary muscles
 there is a large fleshy piece called the septomarginal branch [aka moderator band] which carries
a major part of the right bundle branch
 the infundibulum is a smooth funnel-shaped inlet to the opening of the pulmonary valves

Left ventricle
 it has a thick muscular wall [three times that of the right ventricle] with trabeculae carneae
 the left ventricle is separated from the right ventricle by the interventricular septum
o the septum has a thin upper membranous part and a thicker lower muscular part

Surface Markings of heart valve sounds

nd
 2 right intercostal space 1.25 cm from the sternal border -Aortic
nd
 2 left intercostal space 1.25 cm away from the sternal border -Pulmonary
th
 4 left intercostal 1.25 cm away from the sternal border -Tricuspid
th
 5 left intercostal space 7-9 cm away from the midsternal line -Mitral

A P

M
N

Fig 20: Heart Valve Sounds

Heart Valves
There are 4 heart valves which allow blood flow from the following:
 from right atrium to right ventricle -Tricuspid [with anterior, posterior and septal leaflets]
 from right ventricle to pulmonary trunk -Pulmonary [with anterior, right and left posterior
semilunar valves-PAP]
 from left atrium to left ventricle -Mitral [with anterior and posterior leaflets]
 from left ventricle to ascending aorta -Aortic [with posterior, right/left anterior semilunar
valves-APA]
The valve leaflets are attached to papillary muscles by fibrous cords called the chorda tendinae.

22
Coronary Blood Supply
 the heart is supplied by two branches that arise from the ascending part of the aorta
o right coronary artery
o left coronary artery

The right coronary artery

 originates from the right aortic coronary sinus
 runs between right auricle and pulmonary trunk in the anterior atrioventricular sulcus
 its branches include:
o sinu-atrial
o right marginal
o posterior interventricular
o atrioventricular
 distributed to:
o right atrium
o right ventricle
o 30% of left atrium
o SA node [55% of the population]
o AV node [85% of the population]
o posterior 1/3 of the interventricular septum

The left coronary artery

 originates from the left aortic coronary sinus [posterior aortic sinus is non-coronary] and runs
between the left auricle and pulmonary trunk
 its branches are:
o circumflex
o anterior Interventricular [aka left anterior descending]
o left marginal
 distributed to:
o left ventricle
o 70% of left atrium
o anterior 2/3 of the interventricular septum

Circumflex artery

Right coronary artery Left anterior descending artery

Posterior Interventricular
artery
Right marginal artery

Fig 21: Coronary Arteries

Venous Drainage
 the coronary sinus drains 60-70% of the venous blood of the heart via the following veins:
o great cardiac vein [accompanies the left anterior descending artery]
o small cardiac vein [accompanies the right marginal artery]
o middle cardiac vein [accompanies the posterior interventricular artery]
o oblique cardiac vein
 the rest of the coronary venous blood drains via:
o the anterior cardiac vein which opens into the right atrium
o the smaller venae cordis minimi which are minute veins that drain into the other
chambers

23
 Coronary Sinus

Anterior cardiac veins Great cardiac vein

Middle cardiac vein

Small cardiac vein

Fig 22: Venous Drainage

Cardiac Conduction System

 made of specialized myocardial tissue [not nerves] with automatic rhythmicity
 The Sino-Atrial node is located in the upper right atrium near the opening of SVC
 The Atrio-Ventricular node is located in the posteroinferior part of the interatrial septum
 The Bundle of His is located in the membranous part of the interventricular septum
 Right and left bundle branches are located in the muscular part of the interventricular septum
 Bundle branches end as the subendocardial Purkinje fibers
 The SA node is innervated by cardiac plexuses with sympathetic fibers from T1-5 and
parasympathetic fibers from CN X

SA node Interatrial septum

AV node
Bundle of His

Purkinje fibers
Right bundle branch Left bundle branch

Fig 23: Conduction System

Cardiac Plexuses
 divided into two parts-deep and superficial
o the superficial plexus lies below the arch
o the deep lies behind the arch of the aorta
 superficial part receives fibers from:
o superior cervical sympathetic ganglion
o inferior cardiac branch of the vagus
 deep plexus receives contributions from the superior, middle and inferior cervical sympathetic
ganglia, the superior and inferior cardiac branches of the vagus and branches from the
recurrent laryngeal nerves from the vagus nerve

24
Branches of the thoracic aorta
 right and left coronary arteries [from the ascending aorta]
 brachiocephalic trunk [from the arch of aorta]
 left common carotid [from the arch of aorta]
 left subclavian artery [from the arch of aorta]
rd th
 3 to 11 posterior intercostals [from the descending part of thoracic aorta]
 bronchial [from the descending part of thoracic aorta]
 esophageal [from the descending part of thoracic aorta]

Branches of the abdominal aorta

 4 paired visceral arteries:
o inferior phrenic
o middle adrenal
o renal
o gonadal
st th
 4 paired parietal-1 to 4 lumbar arteries
 4 unpaired visceral:
o celiac trunk [at the level of T12]
o superior mesenteric [at the level of L1]
o inferior mesenteric [at the level of L3]
o median sacral [at the level of L4]
 aorta ends at L4 by bifurcating into:
o common iliac arteries which then divide into
o internal and external iliac arteries

Internal Iliac Artery

The internal iliac artery has 9 branches:
Some Inherit Money, Others Inherit Insanity, Usually. Isn’t Life Silly?
 anterior division [6 branches]:
o Superior vesical
o Inferior vesical
o Middle rectal
o Obturator
o Inferior gluteal
o Internal pudendal
o plus the Uterine and vaginal arteries in females
 posterior division [3 branches]:
o Iliolumbar
o Lateral sacral
o Superior gluteal

External Iliac Artery

 the external iliac artery has three branches [CID]:
o Cremasteric artery [only in males]
o Inferior epigastric artery
o Deep circumflex artery
 continues as the femoral artery beyond the inguinal ligament with the following branches:
o Superficial external pudendal
o Deep external pudendal
o Superficial circumflex iliac
o Deep femoral with its medial and lateral circumflex branches
 the femoral artery passes through the adductor canal to become the popliteal artery
 branches of the popliteal artery include:
o medial and lateral superior, middle, medial and lateral inferior genicular arteries
 the popliteal artery bifurcates into the posterior and anterior tibial arteries in the lower part of
the popliteal fossa
 the posterior tibial artery leaves the popliteal fossa
 it enters the posterior compartment of the leg
 it passes behind the medial malleolus to divide into:
o medial plantar artery
o lateral plantar artery

25
 External Iliac artery

Medial Circumflex Femoral artery

Femoral artery

Lateral Circumflex femoral artery

Popliteal artery

Posterior tibial artery

Peroneal artery

Anterior tibial artery

Dorsalis pedis artery

Fig 24: Arteries of the Lower Limb

 branches of the posterior tibial artery are:
o posterior medial malleolar
o muscular
o peroneal or fibular
o nutrient to the tibia
 the anterior tibial artery leaves the popliteal fossa
 passes above the interosseous membrane between the tibia and fibula
 then it enters the anterior leg compartment where it gives the following branches:
o recurrent genicular
o anterior medial
o lateral malleolar
 the anterior tibial artery continues in the foot as the dorsalis pedis artery
 the dorsalis pedis artery gives off a branch called the arcuate artery which supplies the dorsum of
the foot
st nd
 the dorsalis pedis artery passes through the space in between the 1 and 2 toes
 it joins the lateral plantar branch of the posterior tibial artery to form the plantar arch

26
Subclavian Artery
 the left subclavian artery comes off of the arch of the aorta
 the right subclavian artery comes off of the brachiocephalic trunk
st
 both pass over the 1 rib behind the Scalenus anterior muscle
 branches of the subclavian artery include:
o internal thoracic
o vertebral
o thyrocervical trunk with the following branches [SIT]:
 Suprascapular
 Inferior thyroid
 Transverse cervical
o costocervical trunk with the flowing branches:
 superior intercostal
 deep cervical
st
 beyond the outer border of 1 rib, the subclavian artery becomes the axillary artery which is
divided into three parts by pectoralis minor
 branches of the axillary artery include:
st
o 1 part [proximal to pectoralis minor]-superior thoracic artery
nd
o 2 part [beneath pectoralis minor]-thoraco-acromial and lateral thoracic arteries
rd
o 3 part [distal to pectoralis minor]-subscapular, posterior and anterior circumflex humeral
arteries

Superior thoracic artery

Thoraco-acromial artery
Anterior
circumflex
humeral
artery

Lateral thoracic artery

Subscapular artery

Figure 25: Axillary Artery

 the axillary artery becomes the brachial artery beyond the lower border of teres major
 its branches are:
o profunda brachial [accompanies the radial nerve]
o nutrient
o muscular
o superior and inferior ulnar collateral arteries
 the brachial artery terminates in the cubital fossa at the level of the neck of the radius by
bifurcating into the radial and ulnar arteries
 the branches of the radial artery include [RCMP]:
o Radial recurrent
o Carpal
o Muscular
o superficial Palmar arteries
 the branches of the ulnar artery are:
o anterior and posterior ulnar collateral
o common interosseous
o muscular
o anterior and posterior carpal
o deep palmar

27
  the radial and ulnar arteries form two arches in the palm:
o the superficial palmar arch is the continuation of the ulnar artery
 lies between the palmar aponeurosis and the digital flexor tendons
 it is completed by the superficial palmar branch of the radial artery
o the deep palmar arch is the continuation of the radial artery
 lies between the palmar interossei and the deep digital flexor tendons
 it lies proximal to the superficial palmar arch
 the common palmar digital arteries are derived from the arches and supply the fingers

Brachial artery

Superior ulnar collateral artery

Profunda brachii artery
Inferior ulnar collateral artery

Posterior ulnar collateral artery

Anterior interosseous artery

Radial artery

Ulnar artery

Deep palmar arch

Superficial palmar arch

Fig 26: Arterial Tree of the Upper Limb

Important neurovascular relations in the upper and lower limbs:

 the axillary nerve accompanies the posterior circumflex artery in the quadrangular space
 the brachial artery is accompanied by the median nerve in the arm
 the superior ulnar collateral artery accompanies the ulnar nerve behind the medial epicondyle
 the ulnar artery is accompanied by the ulnar nerve in the forearm
 the median nerve is accompanied by the anterior interosseous nerve in the forearm
 the superficial radial nerve is accompanied by the radial artery in the middle of the forearm
 the posterior interosseous nerve accompanies the posterior interosseous branch of the radial
nerve in the middle of the forearm
 the femoral nerve is accompanied by the femoral artery in the upper thigh
 the saphenous nerve accompanies the femoral artery in the mid-thigh
 the popliteal artery accompanies the tibial nerve in the popliteal fossa
 the posterior tibial nerve accompanies the posterior tibial artery in the posterior leg
compartment
 the anterior tibial artery accompanies the deep peroneal nerve in the anterior leg compartment

28
ENDOCRINE ANATOMY

Pituitary gland
 this gland is considered the master endocrine gland
 it has two parts [anterior and posterior] and two embryological origins [Rathke’s pouch and a
down growth of the hypothalamus respectively]
 it lies in the sella turcica found within the sphenoid bone below the optic chiasma
 it is covered by a fold of dura called the diaphragm sellae
 the anterior lobe is from Rathke’s pouch [stomodeal ectoderm] and produces Follicle Stimulating
Hormone [FSH], Luteinizing Hormone [LH], Adrenocorticotropin Hormone [ACTH], Thyroid
Stimulating Hormone [TSH], Prolactin [PRL] and Growth Hormone [GH]
 the above hormones are influenced by releasing factors from the hypothalamus [except
Prolactin which is influenced by Prolactin Inhibiting Factor-which is dopamine]
 the posterior lobe stores [does not produce] Oxytocin and Anti-Diuretic Hormone [ADH or
vasopressin], which are produced by the paraventricular and supraoptic nuclei of the
hypothalamus respectively
 supplied by the superior and inferior hypophyseal arteries from the Internal Carotid Artery

Thyroid gland
 this H-shaped endocrine gland is formed by two pear-shaped lobes linked by an isthmus
 it is derived from a down growth from the foramen cecum in the tongue
 it weighs 25 grams and lies in the anterior cervical triangle under the cover of SCM and the
infrahyoid muscles
 the thyroid is enclosed in a true fibrous capsule and an outer false capsule derived from the
pre-tracheal layer of deep cervical fascia
nd th
 the lobes lie under the lower end of SCM, the isthmus lie over the 2 to 4 tracheal rings
 it is supplied by the following arteries:
o superior thyroid artery from External Carotid Artery
o inferior thyroid artery from the thyrocervical trunk
o thyroidea ima which occurs in 3-10%
 its venous drainage is via the superior, middle and inferior thyroid veins [note that the middle
thyroid vein accompanies the inferior thyroid artery]
 the superior thyroid artery is accompanied by the external laryngeal branch of the superior
laryngeal nerve which innervates the cricothyroid muscle, the only muscle that tenses the vocal
cords
 the inferior thyroid artery is closely related to the recurrent laryngeal nerve which supplies the
rest of the intrinsic laryngeal muscles
 consists of cuboidal cell-lined follicles secrete thyroxin from which T3 is developed
 parafollicular cells are found in between the follicles
o these cells secrete calcitonin

Hyoid bone
Thyrohyoid membrane

Thyroid cartilage
Cricothyroid membrane
Cricoid cartilage
Pyramidal lobe

Isthmus Lateral lobe

Trachea

Fig 27: Thyroid Gland

29
Parathyroid glands
 there are usually two pairs of parathyroid glands
th
 the superior pair is derived from mesoderm in the 4 pharyngeal pouch
rd
 the inferior pair is derived from the 3 pharyngeal pouch
 supplied by the inferior thyroid artery
 each gland contains two types of cells-chief cells and oxyphils
 PTH is secreted by the chief cells in the parathyroid glands
 PTH takes calcium out of the bone and into the bloodstream

Pancreas
 the pancreas is both an endocrine and exocrine gland
 it is derived from ventral and dorsal endodermal buds from the foregut
 its endocrine secretions from the islets of Langerhans:
o beta cells [75%] -insulin
o alpha cells [20%] -glucagon
o delta cells [5%] -somatostatin
 the islets of Langerhans are embedded in between the pancreatic acini
 the pancreas weighs approximately 90 grams
 it has a large head, small uncinate process, a short neck, a wide body and a long tail
 it lies in the bed of the stomach with its head is in the C-shaped curve of the duodenum, its body
is draped across the IVC, aorta and the left kidney and its tail end lies in the hilum of the spleen
 its main pancreatic duct [of Wirsung] carries the exocrine juices from the tail, body and neck of
the pancreas
 the main pancreatic duct joins with the common bile duct to open into the ampulla of Vater in
the main duodenal papilla into the duodenum
 the opening of the main duct is guarded by a smooth muscle sphincter [of Oddi]
 the accessory pancreatic duct [of Santorini] drains the head and opens approximately 2 cm
above the main duodenal papilla via the minor duodenal papilla
 the difference in the drainage is due to the fact that the head is derived from the ventral
pancreatic bud and the rest of the pancreas comes from the dorsal pancreatic bud
 blood supply:
o superior pacreaticodudodenal artery [from the gastoduodenal artery of the celiac trunk]
o inferior pacreaticoduodenal artery [from the superior mesenteric artery]
o great pancreatic artery [from the splenic artery]

Adrenal Gland
 these are paired endocrine glands
 the adrenal gland is derived from two separate embryological origins:
o outer layer [cortex] from mesoderm
o inner layer [medulla] from the neuroectoderm [neural crest cells]
 the right one is triangular and smaller
 the left one is semilunar and larger
 its cortex has three structural zones with different hormones:
o zona Glomerulosa – Mineralocorticoids – Aldosterone [under Renin control]-Salt
o zona Fasciculata – Glucocorticoids [under ATCH control]-Sweet
o zone Reticularis – Sex hormones-Sex
o the deeper you go the sweeter the sex gets
 the medulla secretes norepinephrine under sympathetic control
 the adrenal medulla behaves like a sympathetic ganglion
 3 arteries supply the adrenal gland:
o superior adrenal artery from inferior phrenic artery
o middle adrenal artery from the abdominal aorta
o inferior adrenal artery from the renal artery
 the gland is drained by a single vein
 the left adrenal vein drains into the left renal vein
 the right adrenal vein drains into the Inferior Vena Cava

30
GASTRO-INTESTINAL ANATOMY

Embryology
 derived from endoderm
 3 parts:
o foregut [supplied by the celiac trunk]
 gives rises to the following:
 esophagus
 stomach
 proximal half of the duodenum-up to major duodenal papilla
o midgut [supplied by the superior mesenteric artery]
 gives rise to the following:
 distal half of duodenum
 small intestine
 proximal half of large intestine up to the proximal two thirds of
transverse colon
o hindgut [supplied by the inferior mesenteric artery]
 gives rise to the rest of the large intestine from the distal third of the transverse
colon to the proximal half of the anal canal

Foregut

Midgut

Hindgut

Fig 28: Gut Development

 Meckel’s diverticulum:
o this is an uncommon congenital anomaly
o it occurs in 2% of the population
o it is 2 inches long
o it is located 2 feet proximal to the ileocecal junction
o it may contain 2 types of ectopic tissue-gastric and pancreatic tissue
o it is found 2 times more common in males

Regional Topographical Anatomy of the abdomen

 can be divided into 4 quadrants-right and left upper and right and left lower quadrants
 9 regions with associated organs:
o epigastric-stomach, duodenum and pancreas
o right hypochondrium-liver and gallbladder
o left hypochondrium-spleen
o umbilical-small intestine
o right and left flanks-kidneys
o right Iliac fossa-appendix, right ovary and right uterine tube and cecum
o left Iliac fossa-left ovary, left uterine tube and sigmoid colon
o hypogastric [suprapubic]-bladder and uterus

31
  the dermatomes and underlying parietal peritoneum are innervated by the lower 6 thoracic and
st
the 1 lumbar spinal nerves:
o T7-xiphoid level
o T10-umbilical level
o L1-inguinal region

Anterior Abdominal Wall

 The anterior abdominal wall consists of 6 layers:
o skin
o subcutaneous tissue:
 the subcutaneous layer is further subdivided into 2 layers:
 fatty layer [Camper] which is continuous with the fatty subcutaneous
layer of the rest of the body
 membranous layer [Scarpa] only exists in the lower abdomen
o it extends as far as one finger’s breath below the inguinal
ligament where is it attached to the fascia lata of the thigh
o it extends medially and inferiorly to continue with Colles fascia
in the scrotum and Buck’s fascia around the penis
o it is attached to the base of the urogenital diaphragm
o muscles:
 in the regions lateral to the linea semilunaris [the lateral edge of the rectus
sheath] there are three muscles:
 external oblique
 internal oblique
 transversus abdominis
 in the region medial to the linea semilunaris, there are three different structures:
 anterior layer of the rectus sheath
 rectus abdominis muscle
 posterior layer of the rectus sheath
o transversalis fascia
o extraperitoneal fat
o parietal peritoneum
 The anterior abdominal wall is innervated by the lower 5 intercostal nerves [T7-11], the subcostal
nerve [T12], the iliohypogastric and ilioinguinal nerves [L1]

Rectus sheath
 The rectus sheath is formed in the following ways:
o above the arcuate line:
 the anterior layer consists of the external oblique aponeurosis and the anterior
layer of the internal oblique aponeurosis
 the posterior layer is made up of the posterior layer of the aponeurosis of the
internal oblique and the aponeurosis of transversus abdominis
o below the arcuate line:
 the anterior layer consists of the aponeurosis of the external oblique, internal
oblique and transversus abdominis
 the posterior layer below the arcuate line is deficient and is covered only by
transversalis fascia
o the arcuate line is located posterior to the rectus muscle midway between the
umbilicus and the symphysis
 Contents of the rectus sheath
o rectus abdominis muscle
o pyramidalis muscle [absent in 15% of the population]
o superior and inferior epigastric arteries and veins which lie below the rectus muscle

Peritoneum
 the peritoneum is the inner lining of the abdominal cavity
 it has two parts: parietal and visceral
o the parietal layer is sensitive to pain and is innervated by the lower intercostal and
subcostal nerves like the anterior abdominal wall
o the visceral layer is not sensitive to pain but sensitive to distension
 the abdominal cavity is divided into two compartments: greater and lesser sacs

32
  the lesser sac lies behind the stomach and opens into the greater sac via the epiploeic
foramen of Winslow
 most of the intra-abdominal organs are covered completely by peritoneum
 those that are only covered anteriorly by peritoneum are referred to as retroperitoneal
 retroperitoneal structures [AC DC PARK AID]: ascending colon, descending colon, pancreas,
nd th
adrenals, rectum [lower 2/3], kidneys, aorta, IVC, duodenum [2 to 4 parts]

Stomach
 J-shaped sac lined by columnar epithelium and covered by three layers of smooth muscle-outer
longitudinal, inner circular and innermost oblique
 the stomach has 2 notches-cardiac and angular
 there are 2 curvatures-lesser and greater
 there are 2 attached omenta-greater and lesser
 it is guarded by 2 sphincters-lower esophageal and pyloric
 it contains 2 main types of cells-chief cells producing pepsinogen and parietal [oxyntic] cells
which produce hydrochloric acid and Intrinsic Factor
 it is supplied by the following direct or indirect braches of the celiac trunk:
o left gastric [from the celiac trunk]
o right gastric [from the common hepatic or from the proper hepatic artery]
o left gastro-epiploic and short gastric [from the splenic artery]
o right gastro-epiploic [from the gastro-duodenal branch of the common hepatic artery]
Cardia
Short gastric arteries

Left gastric artery

Common hepatic artery

Fundus

Gastroduodenal artery
Left gastro-
epiploic
artery

Pylorus Anrtrum
Right gastric artery

Right gastro-epiploic artery

Fig 29: Blood Supply of the Stomach

Duodenum
 10-inch C-shaped tube surrounding the head of the pancreas
 it has 4 parts:
st
o 1 [2” long] – superior part
nd
o 2 [3” long] – descending part
rd
o 3 [4” long] – horizontal part
th
o 4 [1” long] – ascending part
 the upper half [above the major duodenal papilla] is supplied by superior pancreatico-duodenal
artery [from gastro-duodenal branch of the common hepatic artery from celiac trunk]
 the lower half by the inferior pancreatico-duodenal artery [the first branch of the superior
mesenteric artery]
 the common bile duct of the biliary tree opens into the second part of the duodenum
 the superior mesenteric vein and artery pass over the third part of the duodenum
 the fourth part is continuous with the jejunum at the duodeno-jejunal junction
 this junction is fixed and is held in place by the suspensory ligament [of Treitz] which is attached
to the right crus of the diaphragm
 the first inch of the first part of the duodenum is intraperitoneal
 the rest of the duodenum is retroperitoneal

33
 Aorta

Spleen

Right kidney
Left kidney
Duodenum

IVC Stomach
Pancreas

Fig 30: Relations of the pancreas

Biliary Tree
 the biliary tree is made up of the following:
o right and left hepatic ducts join to form the common hepatic duct
o the cystic duct of the gallbladder joins with the common hepatic duct to form the
common bile duct
o the triangle between the cystic duct, common hepatic duct and the liver is known as
Callot’s triangle and it contains the cystic artery
o the common bile duct travels in the free edge of the lesser omentum along with the
proper hepatic artery and the portal vein
o the common bile duct passes through the head of the pancreas and is joined by the
main pancreatic duct to open into the second part of the duodenum
o the opening into the duodenum is guarded by the smooth muscle sphincter of Oddi
 the gallbladder is a 50 cc bile-containing sac lying just beneath the liver
o it lies in a fossa in the liver between the right and quadrate lobes
o it has the following parts:
 fundus
 body
 neck
 cystic duct with the spiral valve [of Heister]

Right hepatic duct

Left hepatic duct
Cystic duct

Common hepatic duct

Main pancreatic duct

Common Bile Duct

Figure 31: Biliary tree

34
Small intestine
 the small intestine lies between the duodenum and the large intestine
 it is subdivided into proximal and distal parts:
o proximal part of the small intestine-jejunum [8’ long] occupies the upper left part of the
abdomen, is thicker, wider and more vascular
o the distal part of the small intestine-ileum [12’ long] occupies the lower right part of the
abdomen and is thinner, narrower and less vascular
 the mesentery of the jejunum has large translucent [less fat] windows with few large vascular
arcades with longer and fewer vasa recta
 the mesentery of the ileum has small opaque [more fat] windows, numerous smaller arcades
and numerous short vasa recta
 the ileum has numerous lymphoid aggregates called Peyer’s patches [Gut Associated
Lymphoid Tissue]
 the Superior Mesenteric Artery supplies all of the small intestine and the large intestine up to
the proximal two thirds of the transverse colon

Small versus Large Intestine

 large intestine has haustra, teniae coli, appendices epiploica and a larger diameter
 small intestine has no haustra, teniae coli or appendices epiploica

Colon
 subdivided into the cecum [3” long], ascending [5” long], transverse [20” long], descending [10”
long] and sigmoid [15” long]
 the appendix is an approximately 4” long out-pouching from the posteromedial aspect of the
cecum where the teniae coli meet and it is suspended by the mesoappendix
 it is located in the following areas:
o behind cecum [65%]
o in pelvis [30%]
o either retro-ileal or pre-ileal [5%]
 it is supplied by the appendicular artery [branch of the ileocecal branch of the SMA]
 its base is located at McBurney’s point-2/3 along a line from the umbilicus to the ASIS

Retro-ileal
Pre-ileal

Retrocecal [65%]

Pelvic [30%]

Fig 32: Location of the Appendix

 the large intestine is derived from both the midgut and the hindgut and therefore is supplied by both
the Superior Mesenteric and Inferior Mesenteric arteries
 there is a watershed area at the junction of the proximal two thirds and distal third transverse
colon due to the end of the mid gut and the beginning of the hind gut
 a watershed area is where the blood supply may be compromised during hypovolemic shock
 lymphatics of the colon drain first to pericolic, then to paracolic to mesenteric to para-aortic
nodes which lie close to the aorta
 the sigmoid continues as the rectum

35
 Transverse colon

Descending colon
Ascending colon

Cecum

Sigmoid colon

Fig 33: Large Intestine

Rectum
 the rectum is 5 inches long and lies in the curve of the sacrum
 it not exactly straight but has three curves-two left and one right
 the lower part of the rectum is dilated-ampulla
 the upper third is covered by pelvic peritoneum on the anterior and lateral sides
 the middle third is covered by peritoneum only on the anterior aspect
 the lower third has no peritoneum covering and is considered retroperitoneal
 it is supplied by the superior rectal branch of the Inferior Mesenteric Artery
 it is derived from the hind gut
 it drains to the inferior mesenteric nodes
 the rectum continues as the anal canal once it passes through the pelvic diaphragm

Anal Canal
 it is approximately 1½ inches long
 it is derived from two embryological origins-endoderm and ectoderm
 the junction between the two embryological origins is the pectineal line
 the columns of Morgagni are longitudinal folds in the anal mucosa above the pectineal line
 the columns are connected inferiorly by mucosal folds called the valves of Ball
 the anal glands open behind these valves
 the anal canal is directed posteriorly and inferiorly
 it is guarded by two sphincters:
o internal circular sphincter which is made up of smooth muscle
o external sphincter [skeletal muscle] which has three parts
 deep
 superficial
 submucosal
 the external sphincter is supplied by the inferior rectal branch of the pudendal nerve

Pectineal line
 the pectinate line is an important line separating the upper anal half from the lower half:
 the upper half is derived from the hind gut [endoderm] and is insensitive to pain
 the blood supply to the upper half is from the inferior mesenteric artery
 the lymphatics from the upper half drain into the inferior mesenteric nodes
 the lower half is derived from ectoderm and sensitive to pain
 the blood supply to the lower half is from the inferior rectal branch of the internal pudendal
artery which is a branch of the anterior division of the internal iliac artery
 the lymphatics from the lower half drain into the lateral group of superficial inguinal nodes in
the groin

36
MUSCULOSKELETAL ANATOMY

Classification of Bones
Bones may be classified according to their shape or method of ossification.
 long -femur, phalanges
 short -carpals and tarsals
 flat -ribs, frontal, parietal and temporal skull bones
 irregular -vertebra
 sesamoid -intratendinous [pisiform and patella]
 intra-cartilaginous ossification -all long bones EXCEPT the clavicle
 intra-membranous ossification -clavicle, flat skull bones and axial skeleton
st
NB. The clavicle is the 1 bone to begin ossification and the last to completely ossify

Classification of Joints
Joints may be classified according to their movements, axes of movement or structure

Movement:
 Synarthrosis [Immobile] Fibrous joint
 Amphiarthrosis [Slightly mobile] Cartilaginous joint
 Diarthrosis [Mobile] Synovial joint

Axis of movement: applies to the freely mobile joints:

 uniaxial [one plane]-flexion/extension
 biaxial [two planes]-flexion/extension and internal/external rotation
 multiaxial [more than two planes]-flexion/extension, abduction/adduction and
internal/external rotation and/or circumduction

Structure: Fibrous, Cartilaginous or Synovial

Fibrous:
 Synostosis [sutural]
 Syndesmosis [interosseous membrane]
 Gomphosis [tooth and tooth socket in the gum]

Periosteum

Fibrous sutural joint

Fig 34: Fibrous Joint

Cartilaginous:
 Synchondrosis [primary cartilaginous] growing ends of long bones
 Symphysis [secondary cartilaginous] IVD, pubic symphysis, manubriosternal joint

Fibrocartilage
disc

Synchondrosis

Fig 35: Cartilaginous Joints

37
Synovial:
 Synovial [diarthrosis] interphalangeal joints

Synovial membrane
Fibrous capsule
Hyaline cartilage

Joint cavity

Fig 36: Synovial Joint

Mixed
 synovial/fibrous-sacroiliac joint which becomes a synostosis as a person gets older

Types of synovial joints:

 planar [gliding] zygapophyseal, acromio-clavicular
 ginglymus [hinge] humero-ulnar
 trochoid [pivot] medial atlanto-axial, proximal radio-ulnar
 condylar [ellipsoid] metacarpophalangeal
st
 sellar [saddle] 1 carpo-metacarpal
 spheroidal [ball and socket] hip and shoulder

Remember all midline joints are secondary cartilaginous joints EXCEPT the following:
 the median atlanto-axial [atlantodental] joint which is a trochoid synovial joint

Synovial Joint Structures

 the articular surfaces of all synovial joints are covered by hyaline cartilage
o EXCEPT the temporomandibular, sternoclavicular and acromioclavicular joints
 which are covered by fibrocartilage [each of these also have complete or partial
intra-articular discs]
 the synovial membrane lines the interior of the fibrous joint capsule and the non-articular
surfaces of the nearby bones
 the synovium is made up of plump cells derived from mesoderm:
o Type A synoviocytes which are macrophagic cells
o Type B synoviocytes secretes synovial fluid which contains hyaluronic acid and
glycoproteins

Innervation of joints
This follows Hilton’s law:
 the nerve which innervates a muscle that acts on a joint, will supply the joint and an area of skin
over the joint

Bone histology
 Bone is made up of:
o central Haversian canals
o concentric lamella
o bone matrix

38
  central Haversian canals with blood vessels
o the canals are connect by Volkmann’s canals
 supplying nutrients and removing waste
 concentric lamellae surround the Haversian canals
o the lamellae are comprised of lacunae which the osteocytes
o the lacunae are connected by canaliculi which contain thin cytoplasmic strands
 allowing the osteocytes to communicate with each other
 bone matrix-calcified intercellular material comprised of
o osteoblasts synthesize the matrix [build bone] and later become osteocytes
o osteoclasts reabsorb and remodel bone tissue [clears bone away]

Cartilage Histology
 cartilage has an outer layer called the perichondrium in which are found the chondroblasts and
blood vessels
 mainly comprised of [95%] extracellular matrix of gylcosaminoglycans and proteogylcans and few
chondrocytes [5%] in lacunae
 chondrocytes arise from chrondroblasts cells
 cartilage has no blood vessels or nerves
o damaged cartilage shows very limited ability to regenerate
 there are 3 types of cartilage:
o Hyaline: most abundant, consisting mainly of Type II collagen fibers covers joint
o Elastic: contains Type II collagen fibers and elastin; found in the larynx
o Fibrocartilage: dense compact Type I collagen fibers; found in intra-articular discs

Classification of muscle
 muscle consists mainly of contractile fibers
 muscle can be classified according to the histological types:
o smooth
 no cross striation [hence smooth]
 spindle-shaped cell
 central nucleus
 involuntary
o skeletal
 cross striations
 elongated peripheral nucleus
 voluntary control
o cardiac
 cross striations
 branches
 intercalated discs
 central nucleus
 involuntary control
 individual muscle fibers are surrounded by delicate connective tissue called the endomysium
 a bundle [fascicle] of fibers is in turn surrounded by more connective tissue called the perimysium
 the epimysium is the dense connective tissue surrounds the entire muscle which is made up of
several bundles or fascicles
 skeletal muscle may be further classified according to the shape into the following groups:
o fusiform
 thick in the middle and tapered at each end: biceps brachii, gastrocnemius
o parallel
 uniform width with parallel fascicles: rectus abdominis and sartorius
o triangular
 fan-shaped with a broad origin and narrow insertion: pectoralis major
o pennate
 feather-shaped
 unipennate: palmar interossei
 bipennate: rectus femoris and dorsal interossei
 multipennate: deltoid
o circular
 forms rings around certain body openings: orbicularis oculi and anal sphincter

39
SPECIFIC JOINT ANATOMY

Temporomandibular Joint
 Type Atypical synovial
 Classification Compound hinge and gliding joint [articular surfaces are covered by fibrocartilage
instead of hyaline like most other synovial joints]
fibrocartilage is more resistant to damage and can regenerate
Intra-articular disc separates an upper [above the disc] from a lower [below the
disc] compartment
Protraction and retraction [gliding] occurs in the upper compartment
Elevation and depression [hinge] occurs in the lower compartment
 Bones involved Condyle of the mandible, mandibular fossa and articular eminence of the
temporal bone
 Range of motion Elevation, depression, protraction, retraction and side to side
 Muscles acting Elevation-temporalis, masseter, medial pterygoid
Depression [5 cm]-gravity, mylohyoid, digastric, lateral pterygoid
Protraction [1 cm]-lateral pterygoid, anterior part of temporalis, superficial fibers
of masseter
Retraction-posterior part of temporalis and deep part of masseter
Side to Side [1 cm]-pterygoids acting alternately
The superior part of the lateral pterygoid muscle is partially inserted into the
anterior portion of the intra-articular disc
 Innervation Auriculotemporal, deep temporal and masseteric branches of CN V3

Mandibular fossa Articular eminence

Intra-articular disc

Condyle of mandible

Fig 37: Temporomandibular Joint

Shoulder [glenohumeral] Joint

 Type Synovial
 Classification Ball and socket [spheroidal]
 Bones involved Glenoid fossa [deepened by labrum glenoidale] and head of humerus
 Range of motion Flexion, extension, internal rotation, external rotation, adduction and
abduction
 Muscles acting Flexion-pectoralis major, anterior fibers of deltoid
Extension-latissimus dorsi, teres major, posterior fibers of deltoid
Internal Rotation- subscapularis, pectoralis major, teres major and latissimus
dorsi, anterior fibers of deltoid
External Rotation-posterior part of deltoid, infraspinatus, teres minor
Adduction-pectoralis major, teres major and minor, latissimus dorsi,
subscapularis, coracobrachialis
o o
Abduction-initiated by supraspinatus-0 to15 and completed by deltoid-15 to 90
 Innervation Axillary and suprascapular nerves

40
Sternoclavicular Joint
 Type Synovial with an intra-articular disc
 Classification Saddle [sellar] type but behaves as a ball and socket [articular surfaces are
covered with fibrocartilage unlike other synovial joints which are covered by
hyaline cartilage]
 Bones involved Manubrium of sternum and the medial head of the clavicle
 Range of motion Elevation, depression, protraction, retraction and circumduction
 Muscles acting Elevation-sternocleidomastoid and trapezius
Depression-pectoralis minor, subclavius
Protraction-pectoralis minor
Retraction-trapezius
Circumduction-combination of the above
 Innervation Medial branch of the supraclavicular nerves [C3]

Elbow Joint
 Type Synovial
 Classification Hinge [ginglymus]
 Bones involved Lower end of humerus and the head of the radius and trochlea of the ulna
 Range of motion Flexion and extension
 Muscles acting Flexion-biceps brachii, brachialis, brachioradialis
Extension-triceps and anconeus
 Innervation Radial and musculocutaneous nerves

Proximal and Distal Radio-ulnar Joints

 Type Synovial
 Classification Pivot [trochoid]
 Bones involved Head of radius and radial notch of the ulna [proximal]
Head of ulna and distal end of radius [distal]
 Range of motion Supination and pronation
 Muscles acting Supination-biceps brachii and supinator
Pronation-pronator teres and pronator quadratus
 Innervation Median, ulnar and radial nerves

Wrist Joint
 Type Synovial
 Classification Condyloid [ellipsoid]
 Bones involved Distal end of radius, scaphoid and lunate bones
 Range of motion Flexion, extension, adduction, abduction and circumduction
 Muscles acting Flexion-flexor carpi radialis and ulnaris, flexors of fingers
Extension-extensor radialis longus and brevis, extensor ulnaris, extensors of the
fingers
Adduction [ulnar deviation]-flexor and extensor carpi ulnaris
Abduction [radial deviation]-flexor and extensor carpi radialis
 Innervation Radial, median and ulnar nerves

Triquetrum
Scaphoid
Lunate

Radius Ulna

Fig 38: Wrist Joint-dorsal view

41
 st
1 Carpometacarpal Joint
 Type Synovial
 Classification Saddle [sellar]
st
 Bones involved Trapezium and 1 metacarpal bones
 Range of motion Flexion and extension
Abduction and adduction
Opposition [approximating the tips of the thumb and the little finger]
 Muscles acting Flexion-flexor pollicis longus and brevis
Extension-extensor pollicis longus and brevis
Abduction-abductor pollicis longus and brevis
Adduction-adductor pollicis
Opposition-Opponens pollicis
 Innervation Radial and median nerves

Metacarpophalangeal Joint
 Type Synovial
 Classification Condyloid [ellipsoid]
 Bones involved Head of metacarpal and base of proximal phalanx
 Range of motion Flexion and extension
Adduction and abduction
Circumduction
 Muscles acting Flexion-flexor digitorum superficialis and profundus and lumbricals
Extension-extensor digitorum
Adduction-palmar interossei [PAd]
Abduction-dorsal interossei [DAb]
Circumduction-combination of the above
 Innervation Median, ulnar and radial nerves

Interphalangeal Joint
 Type Synovial
 Classification Hinge [ginglymus]
 Bones involved Proximal and middle, and between the middle and distal phalanges
 Range of motion Flexion and extension
 Muscles acting Flexion-flexor digitorum superficialis and profundus
Extension-extensor digitorum, lumbricals and interossei
 Innervation Median, ulnar and radial nerves

Hip Joint
 Type Synovial
 Classification Ball and socket [spheroidal]
 Bones involved Acetabulum of os coxae [hip bone] and the head of the femur
 Range of motion Flexion and extension
Adduction and abduction
Internal and external rotation
Rotation
Circumduction
 Muscles acting Flexion-iliopsoas, rectus femoris and sartorius
Extension-gluteus maximus, semimembranosus, semitendinosus and hamstring
part of adductor magnus
Abduction-gluteus medius, minimus and tensor fasciae latae
Adduction-adductor longus, brevis and adductor part of adductor magnus,
gracilis, pectineus and lower part of gluteus maximus
Internal Rotation-gluteus medius and minimus
External Rotation-gluteus maximus, psoas, piriformis, the gemelli, obturator
interns and externus, quadratus femoris
Circumduction-a combination of the above
 Innervation Femoral, obturator and nerve to quadratus femoris

42
 Head of femur
Acetabular fossa
Joint capsule

Round ligament of the

head of the femur

Fig 39: Hip Joint

There are four ligaments of the hip joint:

 one intra-articular ligament:
o round ligament of the head of the femur from the transverse acetabular ligament and
the rim of the nearby acetabular notch to the fovea centralis of the femur
o contains the central foveolar artery in children [absent in the adult]
 three extra-articular ligaments:
o iliofemoral ligament from the anterior inferior iliac spine to the root of the femoral neck
 prevents hyperextension
o pubofemoral ligament from the superior pubic ramus to lower part of the capsule
 prevents hyper-abduction
o ischiofemoral ligament from the ischium to the posterior part of the capsule
 prevents hyperextension

Knee Joint
 Type Synovial
 Classification Modified hinge [ginglymus]
 Bones involved Lower end of the femur and the upper end of the tibia
 Range of motion Flexion, extension and rotation
 Muscles acting Flexion-biceps femoris, semitendinosus, semimembranosus, gastrocnemius,
sartorius, gracilis
Extension-quadriceps femoris
Medial rotation-popliteus
 Innervation Femoral, tibial and common peroneal nerves

Posterior cruciate ligament

Lateral collateral ligament

Medial collateral ligament

Lateral meniscus

Medial meniscus
Anterior cruciate ligament

Fig 40: Knee Joint

43
  there are two intra-articular ligaments:
o anterior cruciate ligament
 originates from the anterior part of the intercondylar ridge
 inserted into the posterior side of the medial aspect of the lateral condyle of
the femur; prevents anterior movement of tibia on the femur
o posterior cruciate ligament
 originates from the posterior part of the intercondylar ridge
 inserted into the anterior part of the lateral aspect of the medial condyle of
the femur; prevents posterior movement of tibia on the femur
 there are two extra-articular ligaments:
o medial collateral
 thick broad ligament from femur to tibia
 attached to the medial meniscus; prevents abduction stress
o lateral collateral
 thin narrow ligament from femur to head of fibula; prevents adduction stress
 there are two intra-articular discs:
o medial meniscus
 semilunar fibrocartilaginous disc attached to the medial collateral ligament
and to the intercondylar ridge
o lateral meniscus
 nearly circular
 attached to the intercondylar ridge
 not attached to the lateral collateral ligament

Patellar ligament Anterior cruciate ligament

Medial meniscus
Lateral meniscus

Lateral Medial collateral ligament

collateral
ligament

Posterior cruciate ligament

Fig 41: Intra-articular Ligaments of Knee Joint

Ankle Joint
 Type Synovial
 Classification Hinge [ginglymus]
 Bones involved Lower end of the tibia and fibula and the talus
 Range of motion Flexion [dorsiflexion] and extension [plantar flexion]
 Muscles acting Flexion-tibialis anterior, extensor hallucis longus and extensor digitorum
longus
Extension-gastrocnemius, soleus, plantaris and tibialis posterior
Inversion and eversion do not occur at the ankle [tibiotalar] joint but in the
subtalar joint
 Innervation Tibial and deep peroneal nerves

44
IMPORTANT MUSCLES

Sternocleidomastoid
Origin Mastoid process and lateral third of superior nuchal line
Insertion Manubrium of sternum and medial third of the clavicle
Innervation Spinal part of CN XI [motor] and ventral rami of C2, C3 [proprioception]
Action Tilts the head towards the shoulder on the same side and rotates the head to the
opposite side

Trapezius
Origin Medial third of superior nuchal line, external occipital protuberance, ligamentum
nuchae, spinous processes of C7 and all thoracic vertebrae
Insertion Lateral third of clavicle, acromion and spine of scapula
Innervation Spinal part of CN XI [motor] and branches of C3 and C4 [proprioception]
Action Shrugs the shoulder, retracts and rotates the scapula

Latissimus dorsi
Origin Thoracolumbar fascia, spinous processes of the lower thoracic and lumbar
vertebrae
Insertion Floor of the bicipital groove
Innervation Thoracodorsal nerve [C6, 7, 8]
Action Adducts, extends and medially rotates the arm

Levator scapulae
Origin Transverse processes of C1 and C2
Posterior tubercles of the transverse processes of C3 and C4
Insertion From the superior angle to the root of the spine of the scapula
Innervation Dorsal scapular nerve [C5]
Action Elevates the scapula

Scalenus anterior
Origin Anterior tubercles of the transverse processes of C3, 4, 5 and 6
Insertion Scalene tubercle on the upper inner aspect of the first rib
Innervation Anterior rami of C4, 5 and 6
Action Ipsilateral lateral flexion of the neck

Scalenus medius
Origin Posterior tubercles of the transverse processes of C2 to C6
st
Insertion Upper aspect of the 1 rib between groove for the subclavian artery and the tubercle
Innervation Anterior rami of C3 to C7
Action Ipsilateral lateral flexion of the neck

Serratus anterior
Origin Lateral aspects of the upper 8 ribs
Insertion Along the medial aspect of the inferior surface of the scapula
Innervation Long Thoracic Nerve [C5, 6 and 7]
Action Draws the scapula forwards and rotates the scapula

Deltoid
Origin Lateral third of clavicle, acromion and spine of the scapula
Insertion Deltoid tubercle of the humerus
Innervation Axillary nerve [C5 and C6]
o o
Action Abducts the arm [15 to 90 ], anterior fibers flex and medially rotates the arm
Posterior fibers extend and laterally rotate arm

Pectoralis major
Origin Sternum, upper 6 costal cartilages and medial half of clavicle
Insertion Lateral lip of the bicipital groove
Innervation Medial and lateral pectoral nerves [C5, 6, 7 and C8, T1]
Action Adducts, flex and medially rotates the arm; it also extends the flexed arm

45
Supraspinatus
Origin Supraspinous fossa of the scapula
Insertion Superior facet of the greater tuberosity of the humerus
Innervation Suprascapular nerve [C5 and C6]
o
Action Initiates abduction [0-15 ] of the arm

Infraspinatus
Origin Infraspinous fossa of the scapula
Insertion Middle facet of greater tuberosity of the humerus [just below supraspinatus insertion]
Innervation Suprascapular nerve [C5 and C6]
Action Externally rotates the humerus

Teres major
Origin Oval depression on the lateral aspect of the dorsum of the scapula above the inferior
angle
Insertion Medial lip of the bicipital groove
Innervation Lower subscapular nerve [C5 and 6]
Action Extends, adducts and medially rotates the arm

Teres minor
Origin Middle third of the lateral border of scapula
Insertion Inferior facet of greater tuberosity of humerus [just below infraspinatus insertion]
Innervation Axillary nerve [C5 and C6]
Action Externally rotates the arm

Subscapularis
Origin medial two-thirds of the ventral aspect of the scapula
Insertion Lesser tuberosity of the humerus
Innervation Upper and lower subscapular nerves [C5 and C6]
Action Internally rotates and adducts the arm

Biceps brachii
Origin Coracoid process [short head] and the supraglenoid tubercle [long head]
Insertion Posterior border of the radial tuberosity of the radius
Innervation Musculocutaneous nerve [C5, 6, 7]
Action Flexes and supinates the elbow

Triceps
Origin Infraglenoid tubercle [long head], lateral upper and medial lower parts of the humerus
Insertion Olecranon of the ulna
Innervation Radial nerve [C7 and C8]
Action Extends the forearm and adducts the arm

Brachioradialis
Origin Upper two-thirds of the lateral supracondylar ridge of humerus
Insertion Base of the styloid process of the radius
Innervation Radial nerve [C6 and C7]
Action Flexes the forearm

Pronator teres
Origin Medial epicondyle of the humerus and medial border of the coronoid process of ulna
Insertion Upper part of the radius
Innervation Median nerve [C6 and 7] which passes between the humeral and ulnar heads
Action Pronates the forearm and flexes the elbow

Psoas major
Origin Bodies, intervertebral discs and transverse processes of L1-5
Insertion Lesser trochanter of the femur
Innervation L2, 3 and 4 from the lumbar plexus
Action Flexes the thigh and trunk

46
Gluteus maximus
Origin Ilium, sacrum, coccyx and sacrotuberous ligament
Insertion Gluteal tuberosity of the femur [25%] and iliotibial band [75%]
Innervation Inferior Gluteal nerve [L5, S1 and S2]
Action Extends and externally rotates the thigh

Piriformis
Origin Pelvic [anterior] surface of sacrum
Insertion Medial aspect of the superior border of the greater trochanter of the femur
Innervation S1 and S2 from the sacral plexus
Action Externally rotates the thigh

Tensor fasciae latae

Origin Outer aspect of iliac crest between the iliac tubercle and anterior superior iliac spine
Insertion Iliotibial tract
Innervation Superior Gluteal nerve [L4-S1]
Action Maintains knee extension and abducts the thigh

Quadriceps femoris
Origin AIIS [straight head of rectus femoris], superior rim of acetabulum [reflected head of
rectus femoris] femur [vastus medialis, intermedius and lateralis]
Insertion Tibial tuberosity via the patellar tendon which encloses the patella
Innervation Femoral nerve [posterior divisions of L2, 3 and 4]
Action Extends the knee, stabilizes the patella and flexes the thigh [through the action of rectus
femoris]

Tibialis anterior
Origin Upper half of the lateral aspect of the tibial shaft and interosseous membrane
st
Insertion Inferomedial aspect of the medial cuneiform and base of 1 metatarsal bone
Innervation Deep Peroneal nerve [L4 and L5]
Action Dorsiflexes and inverts the foot

Extensor hallucis longus

Origin Middle half of anterior aspect of fibula, interosseous membrane
st
Insertion Base of the dorsal aspect of the distal phalanx of the 1 toe
Innervation Deep peroneal nerve [L5 and S1]
Action Extends the big toe and dorsiflexes of the ankle

Peroneus longus
Origin Lateral tibial condyle, head and upper lateral aspect of fibula
st
Insertion Inferolateral aspect of the medial cuneiform and base of 1 metatarsal bone
Innervation Superficial Peroneal nerve [L5 and S1]
Action Plantar flexes and everts the foot

Gastrocnemius
Origin Posterior aspects of the medial and lateral femoral condyles
Insertion Posterior aspect of the calcaneus via the calcaneal tendon [Achilles]
Innervation Tibial nerve [S1 and S2]
Action Plantar flexes the ankle

Soleus
Origin Soleal line, middle third of the tibia and upper third of the fibula
Insertion Calcaneal tendon to the posterior surface of the calcaneus
Innervation Tibial nerve [S1 and 2]
Action Plantar flexes the ankle and aids in the venous return from the leg

Tibialis posterior
Origin Interosseous membrane and the upper parts of the tibia and fibula
nd th
Insertion Navicular, the three cuneiform bones and the bases of the 2 to 4 metatarsal
bones
Innervation Tibial nerve [L5 and S1]
Action Plantar flexes and inverts the foot; supports the medial longitudinal arch of the foot

47
REPRODUCTIVE ANATOMY

Embryology
 The reproductive system is derived from the mesoderm
 the Seminal vesicle, Epididymis, Ejaculatory duct and the Ductus deferens arise from the
mesonephric [Wolffian] duct
 the primitive testis develops from mesoderm lying on top of the kidney
 the uterus and upper third of the vagina are developed from the paramesonephric [Mullerian]
duct which runs parallel to the mesonephric duct
 the primitive ovary or testis develops from mesoderm on top of the kidney

Primitive gonad

Paramesonephric duct

Mesonephric duct

Fig 42: Reproductive Development

Male Genitalia-testis
 spermatozoa are produced in the seminiferous tubules of the testis
 under the influence of testosterone
 testosterone is secreted by the interstitial cells of Leydig which are under the influence of
Luteinizing hormone
 testosterone is attached to Sertoli cells found in the tubules of the testis
0
 the testis lies in the scrotum so that it is at a temperature 1 C less than the rest of the body
 the testis is a 1½ by 1 by ½ inch oval-shaped gonad weighing approximately ½ ounce
 it is suspended by the spermatic cord in the lower part of the scrotum
 the testis is enclosed in a thick fibrous capsule called the tunica albuginea
 it is divided by septa into 300 lobules each containing 1-4 seminiferous tubules
 the seminiferous tubules empty into 25 straight tubules which join to form the rete testis which
empty into the epididymis via 15-20 efferent ductules
 the testis is covered by the following seven layers from outside in:
o skin
o dartos muscle within Colles fascia [dartos muscle is under sympathetic control]
o external spermatic fascia from the external oblique aponeurosis
o cremasteric muscle and fascia from the internal oblique muscle
o internal spermatic fascia from transversalis fascia
o parietal and visceral layers of tunica vaginalis from the peritoneum
 sperm travel through the rete testes into the epididymis where they mature
 the epididymis continues as the ductus deferens where the sperm are stored
 on ejaculation, the sperm travel up the 18” long ductus deferens
 the ductus deferens is joined at its terminal end by the seminal duct forming the ejaculatory duct
 the ejaculatory duct opens into the posterior part of the prostatic urethra from where sperm
travel through the rest of the urethra to be deposited into the posterior vaginal fornix on ejaculation

48
Spermatic cord
 lies in the inguinal canal and is made up of 3 coverings, 3 arteries, 3 nerves and 3 other structures
 3 coverings: external spermatic fascia, cremasteric muscle and fascia and internal spermatic
fascia
 3 arteries: testicular, artery to the ductus deferens and cremasteric artery
 3 nerves: testicular nerves, genital branch of the genitofemoral nerve and ilioinguinal nerve [which
actually lies outside of the spermatic cord]
 3 other structures: ductus deferens, pampiniform plexus of veins and testicular lymphatics [drains
to the para-aortic lymph nodes]
Genital branch Testicular artery, pampiniform veins and
of the lymphatics
genitofemoral
nerve
Ductus deferens,
artery to the
ductus deferens
and testicular Internal spermatic fascia
nerves
External spermatic fascia

Cremasteric fascia
Cremasteric
artery and
vein . Ilioinguinal nerve

Fig 43: Spermatic Cord

Penis
 4-6 inch-long distensible organ which has two dorsally-located blood-filled corpora cavernosa and
a single inferiorly-located corpus spongiosum
 the corpora are enclosed within a fibrous sheath known as Buck’s fascia
 the penile urethra is contained within the corpus spongiosum
 the glans penis is the expanded distal end of the corpus spongiosum
 the penis is covered by hairless skin with very little fat
 it supplied by the deep penile and dorsal penile branches of the internal pudendal artery
 it is innervated by penile branches of the pudendal nerve and branches of the pelvic splanchnic
nerves both from S2, 3 and 4 [S2,3,4 keeps the penis off the floor]
 parasympathetic stimulation is responsible for erection [point]
 sympathetic stimulation is responsible for ejaculation [shoot]

Female Genitalia
 mons pubis is the hair bearing fat pad covering the symphysis pubis
 labia majora are two longitudinal folds of skin extending posteriorly from the mons pubis
 outer aspect of this fold is pigmented and hairy
 inner aspect of the labia majora is pink and hairless
 labia minora are two smaller folds between the labia majora and are divided into lateral and
medial parts
 lateral parts of the labia minora are fused above the clitoris forming the prepuce
 medial parts of the labia minora are fused below the clitoris forming the frenulum
 clitoris consists of erectile tissue:
o it is made up of two crura and a glans
o the clitoris is the female homologue of the penis in the male
 the vestibule is the space found between the labia minora with the urethral and vaginal orifices

Vagina
 develops mainly from the urogenital sinus
 highly distensible fibromuscular canal which extends from the vestibule to the cervix
 lower part of the cervix protrudes into the upper part of the vagina forming the anterior,
posterior and lateral fornices
 the urethra lies anterior and the rectum lies posterior to the vagina

49
Uterus
 pear-shaped fibromuscular organ weighing 30 to 40 grams with a fundus, body and cervix
 the cervix lies partly in the upper vagina
 the uterus measures 3” x 2” x1” and has a triangular cavity whose base is superior
 the normal uterus is anteverted [angled forwards to the vagina] and anteflexed [body is bent
forwards to cervix]
 the uterus is attached to the ovary by the ligament of the ovary and to the labia majora by the
round ligament of the uterus and to the broad ligament
 uterus and upper vagina are supplied by named branches of the anterior division of the internal iliac
artery
 fallopian [uterine] tubes are 4-inch long muscular tubes lined by ciliated columnar epithelium
with four parts:
o the fimbriated end is funnel-shaped [infundibulum]
o the large ampulla where fertilization occurs
o a long narrow isthmus
o a short intramural part which pass through the cornu [lateral horn] of the uterine cavity

Uterine tube
Ovary
Uterus

Bladder

Vagina

Fig 44: Internal Female Genitalia

Ovary
 1½ x ¾ x ½ inch oval female homologue of the testis
 lies in the ovarian fossa between the external and internal iliac arteries
 it is attached to:
o posterior aspect of the broad ligament by the mesovarium
o suspensory ligament of the ovary to the pelvic wall; contains ovarian blood vessels
o ligament of the ovary to the uterus
 supplied by the ovarian artery, a branch of the abdominal aorta at L2 level
 the right ovarian vein drains into the inferior vena cava
 the left ovarian vein drains into the left renal vein

Broad Ligament
 this is a double layer of peritoneum
 it covers the uterus [mesometrium] and the uterine tubes like a sheet
 it also contains two additional structures:
o ligament of the ovary
o round ligament of the uterus
 the round ligament of the uterus is the female equivalent of the gubernaculums testes in the male
 the ovary is attached to the mesovarium which is the posterior part of the broad ligament but it is
not enclosed in the broad ligament
 the part of the broad ligament between the mesovarium and the uterine tube is the mesosalpinx

50
 Ligament of the ovary Uterine tube
Fundus of the uterus

Ovary

Suspensory ligament
Round of the ovary
ligament of
the uterus

Vagina Broad ligament

F ig 45: B road L igament

Bones of the pelvis

 the pelvis is comprised of the following bones:
o os coxae which is made up of the following bones:
o ilium
o ischium
o pubis
o these three bones fuse with each other in the acetabulum
o sacrum
o coccyx

Ilium

Acetabulum
Greater sciatic notch

Greater sciatic notch Ischium

Ischial spine
Ischial spine
Lesser sciatic notch
Lesser sciatic notch
Pubic bone
Ischial tuberosity Obturator foramen

Fig 46: Bones of the Pelvis

 the male pelvis is different from the female pelvis in the following ways:
o heavier with more prominent muscular markings
o smaller heart-shaped pelvic inlet
0 0
o subpubic angle is narrow [45 in the male compared to 85 in the female]
o inverted ischial spines
o sacrum is more curved

51
RESPIRATORY ANATOMY

Embryology
 developed as a respiratory diverticulum from the upper end of the foregut
 from this two lung buds develop
 lung buds become the primary bronchi of each lung
 the primary bronchi subdivide into secondary [lobar] bronchi
 secondary bronchi divide into tertiary [segmental] bronchi
 the tertiary bronchi continue to divide and divide until the terminal bronchioles are formed
 terminal bronchioles give rise to respiratory bronchiole
 the alveoli develop later from the respiratory bronchioles in the third trimester
 an uncommon congenital defect is esophageal atresia with tracheo-esophageal fistula
o the upper end of the esophagus is blind-ending [atresia]
o the lower end is connected to the lower end of the trachea by a fistula

Tracheobronchial Tree
 the trachea begins at the lower border of the cricoid cartilage [C6]
 it is a rigid fibrocartilage tube lined by pseudo-stratified ciliated columnar epithelium
 the trachea is held open by 15-20 U-shaped rings
 it is 5 inches long and 1 inch in diameter
 each ring is incomplete posteriorly [linked by the trachealis muscle]
 it ends at the sternal angle [of Louis] T4/5 by bifurcating into the right and left bronchi
 there is a V-shaped cartilage that marks the bifurcation of the trachea called the carina
 the esophagus lies behind the trachea
nd th
 2 to 4 tracheal rings are crossed anteriorly by the isthmus of the thyroid gland
 the right bronchus is shorter, wider and is more vertical than the left
 the left bronchus is longer, narrower and lies more horizontal
 aspirated foreign bodies are more likely to go into the middle lobe of the right primary bronchus
 the right main bronchus divides into three secondary bronchi while the left divides into two
 each lobar bronchus divides within each lobe into segmental bronchi
 each segmental bronchus feeds a bronchopulmonary segment
 the segmental bronchus continues to subdivide until it reaches the terminal bronchiole
 from here the terminal bronchioles lead to the respiratory bronchioles which bear a number of
alveolar sacs

Trachea

Right primary bronchus

Left primary bronchus

Carina

Fig 47: Trachea, Bronchi and Lungs

52
Lungs
2
 provides a surface area for gaseous exchange over 40m per lung
 each lung has an apex [cervical], a base [diaphragmatic], a lateral [costovertebral] and a medial
[mediastinal] surface
 right lung is bigger, wider and longer than the left
 the left lung is smaller, narrower and shorter than the right
 each lung is made up of several bronchopulmonary [functional units] segments
 each bronchopulmonary segment is pyramidal in shape with its apex directed towards the hilum
 there are 10 segments in the right lung:
o upper lobe-apical, posterior and anterior
o middle lobe-lateral and medial
o lower lobe-superior, lateral, anterior, medial and posterior basal
 the left lung may have 8 or 9 segments:
o upper lobe-apicoposterior, anterior, superior and inferior lingual
o lower lobe-superior, anterior, lateral and posterior basal
 inter-segmental veins drain each segment and empty into either the azygos venous system or into
the pulmonary veins
 segmental arteries are derived from the bronchial branches of the aorta
 In the root of the lungs, the bronchus lies behind, the veins lie below
 the pulmonary artery lies in the Right lung root Anterior to the bronchus
 on the Left pulmonary artery lies Superior to the bronchus [RALeS]

Left Bronchus

Groove for the Groove for the

Pulmonary
arch of the azygos vein
artery
aorta

Horizontal
Oblique fissure fissure

Bronchus

LEFT RIGHT

Lingula

Pulmonary veins Pulmonary veins

Fig 48: Roots of the Lungs

Pleura
 2 layers of pleura: outer and inner layers which are continuous at the root of the lung
 the outer [parietal] layer lies against the inner aspect of the thoracic cage
 the inner [visceral] layer lies against the lungs
 the outer layer is sensitive to pain and is supplied by intercostal and phrenic nerves
 the inner layer is insensitive [has autonomic innervation mainly from the vagus]
 the pulmonary ligament is a sleeve of pleura at the root of the lung and functions as an
anatomical dead space allowing for expansion of the pulmonary veins
 the pleura have the following parts: costal, mediastinal, diaphragmatic and cervical
st
 the cervical pleura [cupola] extends above the 1 rib

53
  the extension of the lung into the neck is limited by the suprapleural membrane [Sibson’s fascia]
th
o this is a fibrous structure that extends from the tip of the transverse process of the 7
st
cervical vertebra to the inner border of the 1 rib
 the pleura are supplied by branches of the anterior and posterior intercostal arteries
 the upper 6 anterior intercostal arteries are derived from the internal thoracic artery, a branch
st
of the 1 part of the subclavian artery
 the lower 5 are derived from the musculophrenic branch of the internal thoracic artery
st nd
 1 and 2 posterior intercostal arteries are from the costal branch of the costocervical trunk of
the subclavian artery
rd th
 3 to the 11 posterior intercostal arteries are derived from the descending part of the thoracic
aorta
 venous drainage is via the azygos venous system
 lymphatics of the lung drain from the periphery of the lungs to:
o pulmonary nodes found in the lung parenchyma
o then to bronchopulmonary nodes located in the hilum of the lung
o then to tracheobronchial nodes located at the bifurcation of the trachea
o into para-tracheal nodes found on either side of the trachea
o finally into the mediastinal lymphatic trunks

Azygos Venous system

 the azygos vein lies on the right side of the lower eight thoracic vertebrae
nd th
 it receives 2 through to 11 posterior intercostal and right subcostal veins
 it passes through the diaphragm at T12 along with the aorta and the thoracic duct
 the hemiazygos vein lies on the left
 it receives the left subcostal and the 3 or 4 lower left intercostal veins
th th
 the accessory hemiazygos vein is formed by the 5 to the 8 left intercostal veins
 the hemiazygos and accessory azygos veins may communicate with each other and with the
azygos vein
st nd
 1 and 2 posterior intercostal veins may drain separately or together into the brachiocephalic
veins which are found in the superior division of the mediastinum
 there are many variations of this pattern

Left brachiocephalic vein

Superior Vena Cava

Accessory hemiazygos vein

Azygos vein
Thoracic duct
Hemi-azygos vein

Fig 49: Azygos Venous System

54
Diaphragm
 it is a fibromuscular septum that separates the thoracic cavity from the abdominal cavity
 embryology of the diaphragm:
o developed from four origins:
rd
 central tendon comes from the septum transversum which arises from the 3 ,
th th
4 and 5 cervical somites
 peripheral rim of the body wall
 pleuroperitoneal membranes
 dorsal mesentery of the esophagus
 its muscle fibers originates from four areas:
o the right crus from the bodies of L1-3
o the left crus from the bodies of L1 and L2
o the lower 6 ribs
o the sternum [posterior aspect of the xiphoid process]
 the muscular fibers are inserted into the central tendon
 there are three major openings in the diaphragm at T8, T10 and T12 respectively
o T8-IVC, the right phrenic nerve and pericardiacophrenic vessels
o T10-esophagus and the vagus nerves
o T12-aorta, thoracic duct and azygos vein
o the inferior vena cava passes through the central tendon
o the esophagus passes through the right crus
o the aorta passes between and behind the right and left crura
 the diaphragm is innervated by the phrenic nerve which is derived from C3, 4 and 5 [keeps the
diaphragm alive]
 it is covered by pleura on the superior aspect and peritoneum on the inferior aspect
 the peritoneum and pleura in the center of the diaphragm is innervated by the phrenic nerve
 the peritoneum and pleura in the periphery of the diaphragm are supplied by the lower six
intercostal nerves
 condensation of fascia over the psoas muscle is called the medial arcuate ligament
 the lateral arcuate ligament is the condensation of fascia over quadratus lumborum
 the median arcuate ligament connects the right and left crura and arches over the aorta

IVC

Central tendon
Esophagus

Medial
Lateral arcuate
arcuate ligament
ligament

Aorta
Median
Arcuate
Ligament
Left crus

Right crus

Fig 50: Diaphragm

55
RETICULO-ENDOTHELIAL ANATOMY

Lymph node
 small bean-shaped encapsulated lymphatic draining structure with a cortex and a medulla
enclosed within a thin fibrous capsule
 directly under the thin fibrous capsule is a space called the subcapsular sinus
 the cortex is further subdivided into outer and inner layers:
o outer cortex consists of mature B cells organized into the follicles
o these follicles have germinal centers containing activated B [plasma] cells
o inner cortex has mature T cells mainly
 the medulla contains lymphocytes, plasma cells and macrophages
 lymph flows from nearby afferent vessels towards the cortex to pass through the subcapsular
sinuses and into cortical sinuses
 eventually lymph drains through the medullary sinuses then to the efferent lymphatic vessels
that exit at the hilum
 the sinuses contain macrophages and reticular fibers arranged in a crisscross fashion which act
like a filter
 activated lymphocytes leave the lymph node via the hilum
Afferent lymphatic vessel

Cortex
Fibrous capsule

Medulla
Efferent lymphatic vessel

Artery Vein

Fig 51: Lymph Node

Spleen
 largest aggregation of lymphoid tissue
 develops from mesoderm within the dorsal mesentery of the stomach
 lies under the left dome of the diaphragm close to the lower ribs
 measures 1” thick x 3” wide x 5” long; weighs 7 ounces
th th
 lies between the 9 and 11 ribs in the left midaxillary line
 made up of red and white pulp enclosed in a thin fibrous capsule
 old red blood cells are destroyed in the red pulp
 the white pulp is involved in the immune system
 the spleen is attached by two ligaments:
o gastrosplenic ligament which contains the short gastric and left gastroepiploic
arteries and veins
o splenorenal ligament which contains the terminal part of the splenic artery
 visceral aspect of the spleen is related to the following structures:
o tail of the pancreas [hilum]
o stomach [anterior to the hilum]
o left kidney [posterior to the hilum]
o splenic flexure of the colon [below the hilum]

56
Liver
 considered as part of the reticulo-endothelial system as it has many Kupffer cells which filter
out bacteria
 largest internal organ in the body weighing 3 lbs [the skin is really the largest organ of the body
as an organ is defined as a body structure made up of several tissues contributing to many
functions]
 developed from a ventral outgrowth of the distal end of the foregut along with the biliary tree
 surrounded by a fibrous capsule and is suspended by the coronary ligament to the undersurface
of the diaphragm
 the coronary ligament is a continuation of the falciform ligament which extends
from the umbilicus to the liver and contains the round ligament of the liver [remnant
of the left umbilical vein in the fetus]
 covered almost completely by visceral peritoneum except in the region bounded by the
coronary ligament-the bare area and the part through which the inferior vena cava passes
 divided into four anatomical and two functional lobes
 4 anatomical lobes and 2 functional lobes:
 right right
 left left
 quadrate left
 caudate right half belongs to the right and the other half to the left
 right functional lobe is supplied by the right hepatic artery, a branch of the proper hepatic artery
 left functional lobe is supplied by the left hepatic artery

Coronary ligament
Diaphragm
Left
triangular
ligament
Right
triangular
ligament

Left lobe
Right lobe

Fundus of Falciform ligament

gallbladder Round ligament of the liver

Fig 52: Liver

 the liver is made up of functional units of sinusoids lined by hepatocytes and Kupffer cells
 sinusoids are fed by branches of the hepatic artery and tributaries of the portal vein
 the proper hepatic artery is a branch of the common hepatic artery from the celiac trunk
 the portal vein provides the liver with 70% of its blood supply and contains nutrients from the gut
 the portal vein is formed by the joining of splenic and the superior mesenteric veins behind the
head of the pancreas
 the inferior mesenteric vein drains into the splenic vein
 venous blood from the sinusoids drains into the central veins and from here to three hepatic
veins which open into the Inferior Vena Cava, ultimately draining in the right atrium
 the right and left hepatic ducts drain bile from the liver and are located in the porta hepatis
which lies between the caudate and quadrate lobes of the liver
 the porta hepatis also contains the right and left hepatic arteries, right and left tributaries of
the portal vein, autonomic nerves and lymphatic vessels
 the right and left hepatic ducts join to form the common hepatic duct
 the common hepatic duct joins up with the cystic duct from the gallbladder to form the common
bile duct

57
  the common bile duct joins the main pancreatic duct [of Wirsung] within the head of the
pancreas to open via the ampulla of Vater into the duodenum
 the ampulla of Vater is guarded by a smooth muscle sphincter [of Oddi] under the influence of
cholecystokinin [CCK] which is secreted by the small intestine in response to the presence of fat
in the duodenum
Quadrate lobe
Round ligament of the liver
Gallbladder in the falciform ligament

Right lobe

Left lobe
Porta hepatis

Caudate lobe
Inferior Vena Cava
Fig 53: Visceral Aspect of Liver

Thymus
rd
 the thymus is derived from the 3 pharyngeal pouch along with the inferior parathyroid glands
 it is a bi-lobed gland which is located in the anterior portion of the superior mediastinum
 it may extend into the upper part of the anterior mediastinum
 it is supplied by branches from the anterior intercostal and internal thoracic arteries
 its venous drainage is to nearby veins
 it is involved in T cell production
 it is almost completely atrophic in the adult
 macroscopically, it has a highly cellular cortex and a less cellular central medulla enclosed in a
loose connective tissue capsule
 cortex is comprised of immature and maturing T cells
 medulla has lymphocytes and a particular feature found only in the thymus-Hassall’s corpuscles
 Hassal’s corpuscles are oval bodies made up of a central area of degenerated cells surrounded
by concentrically arranged flattened keratinized epithelial cells

Thoracic duct
 it is an 18 inch-long multi-valve tube that begins at the cisterna chyli [L1]
 it passes through the diaphragm at T12 to the right of the aorta
 it lies in the posterior mediastinum and crosses over from right to left at T4/5
 it ascends into the left neck to empty into the junction of the left internal jugular and subclavian
veins
 it drains lymph from the following areas:
o lower half of the body
o left half of head and neck
o left half of the chest
 lymph from the right side of the head and neck, the right upper limb and right side of the
chest drain into the right lymphatic trunk
 other lymphoid collections include:
o tonsils in the pharynx:
 palatine tonsils
 tubal tonsils
 lingual tonsils
o Peyer’s patches in the small intestine
o the appendix

58
SKIN ANATOMY

The skin is the largest organ in the body and has the following functions:
 mechanical protection
 body temperature regulation
 Vitamin D synthesis
 salt excretion
 non-specific immune defense
 tactile sensation

Skin histology
 the skin is made up of the following three layers:
o epidermis
o dermis
o hypodermis
 the epidermis is made up of stratified keratinized squamous epithelium
 it is further subdivided into the following distinct layers from outside in [Californians Like Girls
in String Bikinis]:
o stratum Corneum
o stratum Lucidum [only found in thick skin e.g. palms and soles]
o stratum Granulosum
o stratum Spinosum produces keratin
o stratus Basale [aka stratum germinativum]
 the epidermis also contains melanocytes [pigment producing cells], Langerhan’s cells [cells
involved in immune identification], Merkel cells [mechanoreceptors] and naked nerve
endings [nociceptors and heat receptors]
 the epidermis is thickest in the soles and palms
 the dermis lies immediately underneath the epidermis which is anchored on to it
 it is made up of two indistinct layers:
o papillary layer which is made up of loose connective tissue containing fibroblasts
and collagen fibers
 this layer also contains Meissner’s corpuscles which are specialized
pressure sensitive structures along with Krause corpuscles which are
thought to be sensitive to cold
o reticular layer lies deeper and is made up mainly of collagen and elastic fibers
 the hypodermis is the deepest layer of the skin
 it is also known as the subcutaneous layer
 the hypodermis contains the Pacinian corpuscles which are sensitive to vibration
 along with Ruffini sensory corpuscles are sensitive to joint position sense
 the skin has the following appendages from which tumors may arise:
o hair follicles
o sweat glands [two types]:
 eccrine which are found all over the body
 these are innervated by cholinergic nerves
 eccrine glands produce water and salts which are excreted
through tiny tubules
 involved in thermoregulation
 apocrine glands are specialized glands found in the axilla, mons pubis
and around the anus
 these are innervated by adrenergic nerves
 apocrine glands are outgrowths of the upper portions of hair
follicles and secrete an oily mixture
 involved in body scent
o sebaceous glands which produce an oily secretion called sebum
 these occur everywhere EXCEPT where there is thick skin in the palms
and soles
 they are abundant in the scalp and face
 they are holocrine glands because their secretions are produced within the
cell followed by the rupture of the plasma membrane which releases the
cellular contents into the lumen

59
THORACIC ANATOMY

The Thoracic Cage

The thoracic cage is made of:
 the sternum anteriorly
 twelve thoracic vertebrae posteriorly
 connected by twelve pairs of ribs laterally Vertebra

Manubrium

Body of Sternum

Xiphoid process
Ribs

Fig 54: Thoracic Cage

Sternum
 7-inch long irregularly-shaped flat bone in the anterior chest
 3 parts: manubrium, body and xiphoid process
st nd
 manubrium articulates with the clavicles, 1 ribs, part of the 2 ribs and the body of the sternum
nd th
 body articulates with the manubrium, 2 to 6 ribs and xiphoid process
 xiphoid process articulates with the body

Classification of Ribs
 Ribs may be classified as:
o true [vertebrosternal]
o false [vertebrochondral]
o floating [vertebral]
 ribs 1-7 are classified as true ribs because they are articulate with the sternum
 ribs 8, 9 and usually 10 are called false ribs because their cartilaginous ends are articulate with
the cartilage of the rib above them
 ribs 11 and 12 are known as floating ribs as their anterior ends are not connected

Typical Ribs
rd th
 3 through to 9 ribs are described as typical ribs because of the following common features:
o a head with two articular demi-facets:
 the upper demi-facet articulates with the vertebra above
 the lower demi-facet articulates with the corresponding vertebra
o there is a neck between head and tubercle
o the upper border of neck has a crest for attachment of the superior costotransverse
ligament
o there is a tubercle with 2 areas:
 smooth oval facet for articulation with the transverse process of corresponding
vertebra
 rough part for attachment of the lateral costotransverse ligament
o the angle lies between tubercle and the shaft
o the shaft has external/internal surfaces and superior/inferior borders

60
 o the upper border is smooth and rounded
o the lower border is sharp and shelters the costal groove
o the costal groove passes along the inferior border of the internal surface
o the costal cartilage is the unossified anterior end of the rib
o the costal ends articulate with the sternum via synovial joints [2-7]
st
o all of the costosternal joints are synovial joints except the 1 which is primary
cartilaginous
Shaft
Head
Neck
Articular facet on tubercle

Costal groove
Costal end

Fig 55: Typical Rib

Atypical Ribs
st nd th th th
 the 1 , 2 , 10 , 11 and 12 ribs are atypical ribs
st
 the 1 is an atypical rib because:
o it is the shortest and most curvaceous
o its head has only one articular facet
o the rib has an additional tubercle [for the attachment of scalenus anterior]
o the rib has inner and outer borders and superior and inferior surfaces
o there is no costal groove but there is an extra groove for subclavian artery
nd
 the 2 rib is atypical because there is a large rough tuberosity near its middle for the
attachment of the serratus anterior
th st
 the 10-12 ribs like the 1 rib only possess one facet on the head

Intercostal Space
 the intercostal space lies between two adjacent ribs which are connected by three intercostal
muscles:
o external with its fibers running downwards and medially [hands-in-the-pocket fashion]
o internal with its fibers running upwards and medially [downwards and backwards]
o innermost with its fibers running upwards and medially [downwards and backwards]
 the neurovascular bundle runs between the internal and innermost intercostal muscles in the
following order from top to bottom in the costal groove:
o intercostal Vein which drains into the azygos venous system
o intercostal Artery from the internal thoracic artery and the thoracic aorta
o intercostal Nerve which is the ventral ramus of the thoracic spinal nerve
 it is covered by skin externally and by parietal pleura internally

External Intercostal muscle Vein

Artery
Nerve
Internal Intercostal muscle Innermost Intercostal muscle

Fig 56: Intercostal Space

61
Breast
 the female breast is variable in size and location
 it is a modified apocrine sweat gland located in the superficial fascia except for its tail [of
Spence] which is located under the deep fascia in the axilla
nd th
 usually lying over the anterior chest between 2 and 6 ribs
 there are 15-20 radially arranged lobules of acinar glandular tissue embedded in fat and fibrous
tissue
 glandular tissue is attached to the skin above and the pectoral fascia below by the suspensory
ligaments [of Cooper] of the breast
 glandular tissue opens on to the lactiferous ducts which are dilated towards the end as the
lactiferous sinuses before opening on to the nipple
 the nipple lies in the center of the areola which is the darkened area of skin on the breast
 supplied by the following arteries:
o lateral thoracic artery
o internal thoracic artery
nd th
o 2 to 4 anterior intercostal arteries
 lymphatic drainage:
o 75% of the breast drains to the anterior [pectoral] group of axillary nodes
o then to central group of axillary nodes and the apical group of axillary nodes
o most of the rest drains to nodes along the internal thoracic artery
o a small amount drains to the opposite side and downwards to the anterior abdominal wall

Central group Apical group

Lateral group Internal thoracic nodes

Posterior group

Anterior group Lactiferous duct and sinus

Areola

Fig 57: Axillary Lymph Nodes and Breast

Mediastinum
 this is the space between the lungs
 a horizontal line passing through the manubriosternal joint [angle of Louis] and the
intervertebral disc of T4 and T5 separates the superior from the inferior mediastinum
 in addition this horizontal line marks the following events:
o the manubriosternal joint between the manubrium and body of the sternum
o the articulation of the second rib with the sternum
o the bifurcation of the trachea
o the bifurcation of the pulmonary trunk
o the arch of the aorta begins
o the arch of the aorta ends
o the thoracic duct crosses from right to left
o the left recurrent laryngeal nerve passes under the aortic arch

62
  the superior division contains the following structures [TVPASTER]:
o Trachea
o Vagus nerves
o Phrenic nerves
o Arch of the aorta and its branches
o Superior Vena Cava
o Thoracic duct
o Esophagus
o Remnant of the thymus gland
 the inferior mediastinum is further subdivided into three compartments:
o middle compartment
o anterior compartment lies between the sternum and the heart
o posterior compartment lies between the heart and the thoracic vertebra
 the anterior compartment contains:
o connective tissue
o lymph nodes
o remnants of the thymus
 the middle compartment contains:
o heart
o pericardium
o roots of the great vessels
o phrenic nerves
 the posterior compartment contains the following structures [VS DATES]:
o Vagus nerves
o Splanchnic nerves
o Descending thoracic aorta and its branches:
 posterior intercostal arteries
 esophageal branches
 bronchial arteries
o Azygos venous system
o Thoracic duct
o Esophagus
o Sympathetic trunks

Esophagus
 10” long muscular tube lined by stratified squanous epithelium
 it begins at the inferior border of the cricoid cartilage at C6
 it passes behind the trachea in the lover part of the neck and in the superior mediastinum
 it lies behind the left atrium of the heart in the posterior mediastinum
 it passes through the diagphragm at the level of T10
 it ends at T11 by joining the stomach
 it has three layers:
o inner layer-stratified non-keratinized squamous epithelium
o middle layer-submucosa with esophageal glands
o outer layer-two layers of muscle, outer longitudinal and inner circular
 the esophagus may be divided into three thirds
 the upper third is surrounded by skeletal muscle
 the lower third is surrounded by smooth muscle
 the middle third is surrounded by a mixture of both
 the upper third is supplied by branches of the inferior thyroid artery
 the middle third is supplied by branches of the thoracic aorta
 the lower third is supplied by branches of the left gastric artery
 the venous drainage is via the inferior thyroid, esophageal and left gastric veins
 the upper third drains into lower deep cervical lymph nodes
 the middle third drains into mediastinal lymph nodes
 the lower third drains into left gastric lymph nodes
 there are three areas of narrowing in the esophagus:
o at C6 where it begins
o at T5 where it is crossed by the left bronchus
o at T10 where it passes through the diaphragm

63
URINARY ANATOMY

Embryology
 the kidney and ureter have a different embryological origin from the bladder
 the kidney develops in the mesoderm from three successive systems:
o pronephros-this disappears early
o mesonephros-this also disappears early leaving the mesonephric [Wolffian] duct
o finally from the metanephros which remains to develop into the secretory part of the
kidney
 the ureteric bud of the mesonephric duct develops into the collecting system and the ureter
 the bladder arises from the urogenital sinus [endoderm]

Pronephros

Mesonephros

Mesonephric duct
Ureteric bud

Metanephros

Fig 58: Urinary Development

Kidney
 bean-shaped retroperitoneal organ measuring 4” long by 2” wide by 1” thick
 right kidney lies ½” lower than the left because of the larger right lobe of the liver
 hilum is located in the medial indentation of the kidney and has the following structures situated
from anterior to posterior:
o renal vein
o renal artery
o ureter
 covered by three coverings:
o thin fibrous capsule
o peri-renal fat enclosed in a layer called the renal fascia
o surrounded by another layer of fat called extraperitoneal or para-renal fat
 posterior relations of the kidney include 4 muscles, 3 nerves, 2 vessels and 1 bone:
o 4 muscles-diaphragm, quadratus lumborum, psoas major and transversus abdominis
o 3 nerves-subcostal, iliohypogastric and ilioinguinal nerves
o 2 vessels-subcostal vein and artery
th th
o 1 bone-12 rib [add the 11 rib on the left side]
 supplied by the renal artery
o the renal artery is a branch of the abdominal aorta at L1 level
o each renal artery has five segmental branches from which the interlobar, then arcuate,
then interlobular arteries, afferent arterioles, glomerulus and efferent arterioles arise
 renal veins drain into the inferior vena cava
o right renal vein is shorter and has no tributaries
o left renal vein is longer and receives the following tributaries:
 left adrenal vein
 left gonadal vein

64
 Aorta

IVC

Renal vein

Renal artery

Ureter

Fig 59: Kidneys

Ureter
 10” long muscular tube lined by transitional epithelium
 leaves the hilum of the kidney behind the renal artery
 travels downwards lying on psoas major, passes over the bifurcation of the common iliac
artery and continues downwards to the lateral wall of the pelvis
 at the level of the ischial spine, the ureter turns medially and forwards to enter the lateral aspect
of the triangular-shaped posterior aspect [base] of the bladder
 in the male, it passes under the ductus deferens and in the female, under the uterine artery
 it then passes through the bladder wall obliquely
 supplied by branches from the renal, gonadal and internal iliac arteries

Hilum of kidney

Ureter

Fig 60: Ureters

Bladder
 highly distensible receptacle for urine with a capacity of 300 cc
its triangular base lies posteriorly
 the bladder lies superior to the prostate in the male
 the bladder lies inferior to the uterus in the female
 the bladder is made up of smooth [detrusor] muscle lined by transitional epithelium

65
  there are two bladder sphincters: internal and external
o internal sphincter is comprised of smooth muscle which is relaxed by the pelvic
splanchnic nerves [S2, 3 and 4] and is contracted by the sympathetic fibers
o external sphincter is skeletal and is controlled by the pudendal nerve [S2, 3, 4]

Prostate
 an unpaired fibromuscular gland found only in males
 it is pyramidal in shape with its apex pointing inferiorly and lies on the urogenital diaphragm
st
 it surrounds the 1 part of the urethra
 made up of 5 lobes: anterior, posterior, right and left lateral with the median lobe lying between and
above the ejaculatory ducts
 it is made up of 3 distinct zones-peripheral [70%], central [25%] and transitional [5%]
 it is covered by 2 capsules: true thin fibrous capsule and a false capsule which is a
condensation of endopelvic fascia
 the prostatic venous plexus lies in between the two capsules
 prostatic venous plexus communicates with the external and then internal vertebral venous
plexuses which have no valves [Batson] allowing for easy spread of prostatic cancer to lumbar
vertebrae via the basivertebral veins
 the prostate lies below the bladder, above the urogenital diaphragm, in front of the rectum
and behind the pubic bone

Ureter
Ductus deferens
Seminal vesicle

Prostate

Urethra
Fig 61: Prostate
Urethra
 approximately 8 inches long in the male and 1¾ inches in the female
 male urethra is divided into prostatic, membranous and penile parts
 membranous part is the shortest part measuring ½ to ¾ inch
 penile part passes through the corpus spongiosum and opens at the urethral orifice which is
located in the undersurface of the glans of the penis
 bulbourethral glands [of Cowper] in the male lie within the urogenital diaphragm and drain into
the penile part of the urethra
 shorter female urethra lies anterior to the vagina and its opening lies between the clitoris
anteriorly and the vaginal orifice posteriorly

Ductus deferens

Prostate
Spongy urethra
Epididymis

Testis

Fig 62: Relations of the Prostate

Genitalia

66
SPINAL ANATOMY

67
68
VERTEBRAL COLUMN

Vertebral Embryology
 develops in the mesoderm
 the notochord guides the development of the vertebral column and spinal cord
 the notochord gives rise to the nucleus pulposus of the intervertebral disc
 the notochord persists as the nucleus pulposus
 condensations of mesoderm around the notochord called somites are formed
 from the somites develop the following:
o sclerotomes from which the vertebrae develop:
 3 primary ossification centers:
 centrum [for the body]
 right and left halves of the neural arch
 5 secondary ossification centers:
 spinous process
 right and left transverse process
 upper and lower vertebral endplates
o myotomes from which muscle develops:
 somatic skeletal muscles
 splanchnic smooth muscles
 epimere extensor muscles
 hypomere flexor muscles
o dermatomes from which the peripheral nerves develop
 chondrification-mesoderm is replaced by cartilage
 ossification-cartilage is replaced by bone:
o intramembranous-bone is formed within a membrane
o intracartilaginous-bone is formed within cartilage

Typical Vertebra
 large weight bearing body anteriorly
 2 pedicles posterolaterally
 2 transverse processes laterally
 2 laminae forming the neural arch
 1 spinous process posteriorly
 superior articular process with its facet facing backwards
 inferior articular process with its facet facing forwards
 pars interarticularis between the superior and inferior articular processes
 vertebral canal behind the body

Spinous process Superior articular process

Pars interarticularis
Transverse process

Pedicle
Vertebral foramen

Body
Inferior articular process

Spinous process

Fig 63: Thoracic Vertebra

69
Regional Vertebral Characteristics
 cervical-rectangular body, bifid spinous process, transverse foramina in the transverse
process which possess anterior and posterior tubercles
 thoracic-heart-shaped body, sloping spinous process, costal facets on body and transverse
process
 lumbar-kidney-shape body, quadrangular spinous process, mammillary and accessory
processes
 atypical cervical vertebra:
 C1 [atlas]
 no body
 large lateral masses
 anterior arch and an posterior arch with a groove for vertebral artery
 C2 [axis or epistropheus]
 dens or odontoid process is present
 C7 [vertebra prominens]
 long non-bifid spinous process
 regional orientation of the superior articular facets differ also:
 cervical facets face backwards, upwards and medially [BUM] in the horizontal
plane
 thoracic facets face backwards, upwards and laterally [BUL] in the coronal plane
 lumbar facets face backwards and medially [BM] in the sagittal plane
 the inferior articular facets face in the opposite direction

Vertebral Ligaments
 anterior longitudinal ligament:
 extends from the sacrum to the basal part of the occiput
 thicker and stronger than the posterior longitudinal ligament
 prevents hyperextension of the spine
 posterior longitudinal ligament
 extends from C2 to the sacrum
 thin and weak, prevents hyperflexion of the spine
 this ligament continues as the tectorial membrane upwards and beyond C2
 supraspinous ligament:
 connects the tips of the spinous processes
 prevents hyperflexion
 this continues as the nuchal ligament upwards and beyond C7
 interspinous ligament:
 runs in between the spinous processes of adjacent vertebrae
 prevents posterior translation and limits flexion
 ligamentum flavum:
 extends between the laminae of adjacent vertebral
 contains lots of elastic tissue which limits flexion and prevents buckling in extension
 intertransverse ligament:
 runs between the transverse processes of adjacent vertebrae
 limits lateral bending
 alar ligament [aka check ligament]:
o originates from the posterior and lateral aspects of the dens
o inserts into the medial aspect of the condyle of the occiput
o limits axial rotation
 apical ligament:
 arises from the apex of the dens
 inserts into the anterior aspect of the foramen magnum
 limits flexion and extension of C2
 cruciate ligament:
 shaped like a cross
 transverse ligament extends from a small medial tubercle [colliculus atlantis] on the
lateral mass of the atlas to the same tubercle on the other side
 superior longitudinal ligament extends from the middle of the transverse ligament to the
anterior lip of the foramen magnum between tectorial membrane and the apical ligament
 inferior longitudinal ligament extends from middle of transverse ligament to body of C2
 limits lateral translation

70
Posterior longitudinal ligament Supraspinous ligament

Interspinous ligament
Anterior longitudinal ligament

Fig 64: Spinal Ligaments

Intervertebral Disc
 fibrocartilaginous sandwich with outer Type I and inner Type II collagen fibers
 the outer part is the anulus fibrosus which has 15-20 concentric laminae
0
 its fibers at 40-70 to the vertical
0
 the fibers of the next lamina run in the opposite direction at 120-130 to the vertical
 the inner aspect is called the nucleus pulposus
 it has a gelatinous consistency and is located posterocentrally in the lumbar region
 lies between two adjacent vertebral endplates which are considered as part of the disc
 thickest in the lumbar region and thinnest in the thoracic region
 only the outer third of the anulus fibrosus is innervated:
 the sinuvertebral [recurrent meningeal] nerve posteriorly
 sensory nerves which run in the gray sympathetic rami communicantes laterally
 the disc is not well-vascularized as it is nourished by diffusion from the vertebral endplates
 the diffusion [imbibition] is facilitated by movement of the spine
 there are 23 intervertebral discs as there is none between C1 and C2

Nucleus pulposus

Anulus fibrosus

Fig 65: Intervertebral Disc

Intervertebral Foramen
 it is bounded:
o superiorly by the pedicle and the inferior vertebral notch of the vertebra above
o anteriorly by the posterolateral aspects of adjacent vertebrae and intervening disc
o inferiorly by the pedicle and the superior vertebral notch of the vertebra below
o posteriorly by the anterior aspect of the zygapophyseal joint and capsule
 contains spinal nerve, spinal nerve roots, dorsal root ganglion, spinal artery, veins, two to
four sinuvertebral nerves, fat and transforaminal ligaments
 may be narrowed by large protruding osteophytes from the bodies of the adjacent vertebrae or
zygapophyseal joints or prolapsed discs that bulge postero-laterally
 spinal nerve roots may be irritated by inflammatory chemicals released from internal disc
disruptions
 associated with displacement of the nucleus pulposus through damaged rings of the anulus
fibrosus or more rarely be compressed by a posterolateral disc bulge

71
 Inferior vertebral notch

Transforaminal ligaments
Spinal nerve

Intervertebral disc

Facet joint capsule

Superior vertebral notch

Fig 66: Lumbar Intervertebral Foramen

Spinal Canal
 extends from the foramen magnum to the bottom of the sacrum
 lies posterior to the vertebral bodies
 bounded anteriorly by the bodies of the vertebrae
 laterally by the pedicles
 posteriorly by the neural arch made of the laminae
 contains the spinal cord, spinal nerve roots, three coverings [dura, arachnoid and pia mater],
cerebrospinal fluid [CSF], blood vessels and connective tissue
 the extra-dural [epidural] space lies outside of the spinal dura and contains semi-fluid fat and
blood vessels
 the spinal canal is smallest relatively in the thoracic region and largest in the cervical region
 cervical region of the spinal canal is the most common site for cord compression
[myelopathy] because the spinal cord is widest in this region [C6]
 the shape of the spinal canal in the cervical region is triangular, compared to oval in the thoracic
region and triangular or trifoliate in the lumbar region

Spinous process
Extra-dural space
Neural arch

Dura
Arachnoid

Spinal nerve

Pia

Fig 67: Contents of the Spinal Canal

72
SPINAL JOINTS

Atlanto-Occipital Joint
 Type Synovial
 Classification Condylar
 Bones involved Condyle of occipital bone and superior articular facet of C1
 Range of motion Flexion, extension and a little lateral bending and rotation
 Muscles acting Flexion-longus capitis and rectus anterior
Extension-SCM, semispinalis, splenius
Lateral bending-rectus lateralis, SCM and trapezius
 Innervation C1

Median Atlanto-Axial [Atlanto-Dental] Joint

 Type Synovial
 Classification Pivot
 Bones involved Anterior arch of C1 and the Dens of C2
 Range of motion Rotation
 Muscles acting Rotation-SCM and semispinalis capitis which are countered by the action of
rectus capitis posterior major, obliquus capitis superior and inferior
 Innervation C2

Lateral Atlanto-Axial Joint

 Type Synovial
 Classification Planar
 Bones involved Lateral masses of C1 and the superior articular facets of C2
 Range of motion Rotation and flexion/extension
 Muscles acting Rotation-SCM and semispinalis capitis against rectus capitis posterior
major, obliquus capitis superior and inferior
 Innervation C2

Zygapophyseal [facet] Joint

 Type Synovial
 Classification Planar
 Bones involved Inferior articular facet of superior vertebra and superior articular
facet of the adjacent vertebra
 Orientation Depends on the vertebrae involved:
Cervical superior facets face backwards, upwards and medial
Thoracic superior facets face backwards, upwards and lateral
Lumbar 1 to 4-superior facets face backwards and medial
Lumbar 5-the inferior facet faces backwards

Coronal Sagittal Horizontal

0 0 0
Cervical 0 90 45
0 0 0
Thoracic 15 75 60
0 0 0
Lumbar 90 0 90

 Range of motion: depends on the area

cervical facet joint capsules are long and loose:
 allows for greater movement
 especially rotation, flexion and extension
 50% of flexion and extension in the cervical region occurs at the C0-C1
joint
 50% of rotation in the cervical region occurs at C1-C2 joints
Thoracic facets allow primarily for rotation and secondarily flexion
lumbar facet joint capsules are short and tight:
 restricts movements limiting rotation and lateral bending
 Muscles acting paraspinal muscles
 Innervation medial branches of the dorsal rami of the corresponding spinal nerve and the
nerve below [and perhaps from the one above also]

73
Sacroiliac Joint
 Type Compound made up of an anterior synovial joint and posterior syndesmosis
 Classification Reciprocal interlocking planar which allows minimal gliding
 Bones involved Articular surface of the ilium and the auricular aspect of the sacrum
 Range of motion Nutation and counternutation around an axis passing through S2
 Nutation-forward movement of the base of the sacrum [like nodding]
 Counternutation-backward movement of the base of sacrum
 Muscles acting All muscles acting on the lower spine and hip:
mainly erector spinae and psoas major
 Innervation Superior gluteal nerve and branches from S1 and S2

Costovertebral Joint
 Type Synovial
 Classification Planar
 Bones involved Body of the vertebra and the head of the corresponding rib
 Range of motion Upper 6 joints-pump handle action; lower 6 joints-bucket handle action
 Muscles acting Intercostals and diaphragm
 Innervation Segmental spinal nerve

Costotransverse Joint
 Type Synovial
 Classification Planar
 Bones involved Tubercle of the rib and the transverse process of the corresponding
vertebra
 Range of motion Upper six costotransverse joints allow rotation and the lower six joints allow for
gliding
 Muscles acting Intercostal and diaphragm
 Innervation Segmental spinal nerve

Costochondral joint
 Type Primary cartilaginous
 Classification Synchondrosis
 Structures Distal end of the rib and cartilage
 Range of motion None
 Muscles acting Intercostal and diaphragm
 Innervation Segmental spinal nerve

Sternochondral joint
st nd th
 Type 1 is a primary cartilaginous and 2 to 7 are synovial
st
 Classification Synchondrosis for the 1 and planar for the others
 Structures Cartilage and sternum
 Range of motion Pump handle during respiration
 Muscles acting Intercostal
 Innervation Segmental spinal nerve

Manubriosternal joint
 Type Secondary cartilaginous
 Classification Symphysis
 Bones involved Manubrium and body of sternum
 Range of motion Slight increase and decrease angulation during respiration
 Muscles acting Intercostal
 Innervation Segmental spinal nerve

Xiphisternal joint
 Type Secondary cartilaginous
th
 Classification Symphysis, becomes an synostosis after the 40 year
 Bones involved Body of sternum and xiphoid process
 Range of motion very little
 Muscles acting Intercostals, diaphragm and rectus abdominis
 Innervation Segmental spinal nerve

74
BACK MUSCLES

The muscles of the back are arranged in layers:

 superficial
 intermediate
 deep
The superficial layer is made up Trapezius and Latissimus dorsi.
The intermediate layer is comprised of Levator scapulae, Rhomboid major and minor and Serratus
posterior superior and inferior.
The deep layer contains the following:
 Splenius capitis
 Splenius cervicis
 Erector spinae
 Semispinalis capitis and cervicis
 Rotatores costarum
 Interspinales
 Intertransversales
 Multifidus

Erector spinae
 arranged in three parallel groups from lateral to medial: iliocostalis, longissimus and spinalis
 each of these groups is further subdivided into subgroups: iliocostalis lumborum, thoracic and
cervicis, longissimus thoracic, cervicis and capitis and spinalis thoracis, cervicis and capitis
 there are architectural and functional differences in the thoracic and lumbar portions of these
muscles
 Bogduk et al recommended further partitioning of the lumbar and thoracic portions of longissimus
thoracis and iliocostalis lumborum into the following:
o longissimus thoracis pars lumborum
o longissimus thoracic pars thoracis
o iliocostalis lumborum pars lumborum
o iliocostalis lumborum pars thoracis
 the lumbar component of these muscles function differently that their thoracic counterparts
o their line of action is not parallel to the compressive axis of the spine but rather in a
posterior caudal obliquity causing a posterior shear force together with an extensor
movement of the superior vertebrae
 the thoracic portion of these two muscles is parallel to the compressive axis of the spine and results
a greater extension with minimal compression
 the erector spinae muscles are supplied by branches of the dorsal rami of the segmental spinal
nerves

Multifidus
 the multifidus [many splits] muscles are the most medial of the lumbar back muscles
 work differently from the more lateral extensors especially in the lumbar region where they slop
upwards from the laminae and mammillary processes to the spinous process of vertebrae 2 or 3
over their level of origin commencing at the upper part of the sacrum and ending at C2
 affect local areas of the spine and producing extension, lateral bending and contralateral rotation
 these muscles are loaded with mechanoreceptors
 acting more in providing information in initiation and correction of movement at the specific spinal
motor unit level and less in actual overall movement of the spine as a whole

Intertransversarii and interspinales

 the intertransversarii muscles are divided into medial and lateral components
 only the medial compartment is considered as part of the true back muscles as they are innervated
by the dorsal rami unlike the lateral group which is innervated by the ventral rami
 the interspinales are small short paired muscles that lie on either side of the interspinous ligaments
 the small intrinsic muscles are too small to cause any significant extension or rotation of the
vertebral column
 the main function of the small muscles such as multifidus, rotatores, interspinalis and
intertransversales are to serve as mechanoreceptors as they are packed with muscle spindles
 also serve to stabilize the vertebrae during local movement of the vertebral column

75
SPINAL CORD REVIEW

Embryology of the spinal cord

 the spinal cord is derived from the neural tube
st
 neural tube formation [neurulation] is affected by folic acid in the 1 trimester
 the neural tube is derived from ectoderm
th rd
 it starts distal to the 4 pair of somites in the 3 week of gestation:
o the lateral walls of the tube thicken
o the walls differentiate into a dorsal [alar] and ventral [basal] plates
o the dorsal plates differentiate into the sensory neurons
o the ventral plates differentiate into the motor neurons
o the neural canal becomes the central canal of the spinal cord
th
o the neural tube closes at the end of the 4 week of gestation
 tissue at the sides of the neural tube become the neural crest cells which give rise to:
o Dorsal Root Ganglia
o Adrenal medulla
o Melanocytes, Microglia and Meninges [arachnoid and pia]
o Enteric neurons
o Schwann cells
o Sympathetic ganglia

Spinal Cord
 18-inch-long structure begins at the foramen magnum and ends at L1/2 in an adult
 2 regional enlargements-cervical [largest at C6] and lumbosacral regions for the brachial
and lumbosacral plexuses respectively
 the dilated end of the spinal cord is called the conus medullaris [medullary cone]
 the nerves that leave the end of the spinal cord are known as the cauda equina
 the spinal cord is covered by three coverings or meninges:
o outermost is the tough dura mater [single layer compared to cranial dura]
o thin web-like arachnoid mater with subarachnoid space beneath with CSF
o thinner pia mater with filum terminale and two dentate ligaments [each with 21 teeth]
which anchor the spinal cord to the spinal dura
 the dural sac ends at S2
 the filum terminale is 20 cm long and is divided into two parts:
o filum terminale interna [15 cm long] extends from the conus medulla to the end of the
dural sac at S2
o filum terminale externa [5 cm long] fuses with the dura and extends to the coccyx
 the spinal cord lies within the spinal canal
 the spinal cord is subdivided longitudinally into 31 segments
 each segment of the spinal cord has a pair of ventral and dorsal roots that come together to
form the spinal nerves
 the dura and arachnoid extend along the spinal nerves as they pass through the IVF

Organization of the Spinal Cord

 the spinal cord has both white [myelinated] and gray matter [non-myelinated]
 the white matter is organized into three bundles or funiculi:
o posterior [dorsal]
o anterior [ventral]
o lateral [intermediate]
 fast-conducting myelinated axons form fasciculi [tracts] which ascend and descend for varying
distances
 glial cells [oligodendrocytes and astrocytes] lie in between these myelinated axons
 axon fibers with a common function are called tracts
 the posterior or dorsal columns tract carry vibration, fine touch [two-point discrimination]
and joint position sense and are separated into well-defined medially-located gracilis [from the
lower limb] and laterally-located cuneatus [from the upper limb] tracts
o fibers from the lower limb synapse in the nucleus gracilis in the medulla
o fibers from the upper limb synapse in the nucleus cuneatus in the medulla
 other ascending tracts carry unconscious proprioception [spinocerebellar], pain,
temperature, crude touch and pressure [spinothalamic]

76
  the descending tracts carry axons that control skeletal motor function, smooth muscles and
secretory glands
 all descending tracts are motor EXCEPT the raphespinal tract which modulates nociception
Fasciculus gracilis
Posteromedian sulcus Fasciculus cuneatus

Dorsal Spinocerebellar Lateral

Tract Corticospinal
Tract

Rubrospinal
Tract

Ventral
Ventral
Spinocerebellar Tract
Corticospinal
Anterolateral System Tract
Fig 68: Spinal Cord Cross Section

Ascending 1st Order Neuron 2nd Order Neuron Decussation 3rd Order Neuron
Dorsal column Mechano­receptors Nuclei gracilis and Medulla VPL nucleus of the
Vibration cuneatus thalamus
Fine touch
Spinothalamic Nociceptors, Lamina I and II in Spinal cord VPL nucleus of the
[Anterolateral thermoreceptors the dorsal horn of thalamus
System] and light touch the grey matter
receptors
Dorsal Unconscious Clarke’s nucleus Does not cross Cerebellum via
Spinocerebellar proprioception [dorsal nucleus] Remains inferior cerebellar
from the lower found in the ipsilateral peduncle
limb thoracic region
Ventral Unconscious Lamina VII Twice­first at the Cerebellum via
Spinocerebellar proprioception spinal cord and superior cerebellar
from both lower again in the pons peduncle
and upper limb It remains
ipsilateral
Table 1: Ascending Tracts
st
Descending 1 Order Neuron Decussation 2nd Order Neuron
Rubrospinal Red nucleus Midbrain Laminae V­VIII
Tectospinal Tectum of midbrain Midbrain Laminae VI and VIII
Lateral Corticospinal* Pre­central gyrus Medulla Laminae IV­IX
Ventral Corticospinal Pre­central gyrus Spinal cord at level of exit Laminae VI­IX
Reticulospinal Reticular Formation Various levels Laminae VIII
Vestibulospinal Vestibular nuclei Uncrossed Laminae VI and VIII
Raphespinal Raphe nucleus Uncrossed Laminae I, II and V

*aka known as the PYRAMIDAL TRACT as its primary neurons are the pyramindal cells in the cerebral cortex
Table 2: Descending Tracts

Descending Function
Lateral Corticospinal Voluntary control of the muscles in the limbs
Ventral Corticospinal Voluntary control of the muscles in the head, neck and trunk
Rubrospinal Excites proximal flexors and inhibits extensors mainly in the upper limb
Reticulospinal Restricts voluntary movements through the gamma motor neurons
Tectospinal Head and eye turning in response to light and sound
Vestibulospinal Involved in postural reflexes­neck muscles, extensors of back and limbs
Raphespinal Inhibits nociception by releasing serotonin and acts on the C fibers

Table 3: Function of Descending Tracts

77
 Post-central gyrus
Brodmann’s areas 3,1,2 Pre-central gyrus
Brodmann’s area 4

CEREBRAL CORTEX

THALAMUS
Posterior limb of
the Internal capsule

MIDBRAIN

Medial lemniscal tract

Nucleus cuneatus
Nucleus gracilis

MEDULLA

Dorsal Column Lateral Spinothalamic Tract

Lateral corticospinal tract

Fig 69: Pain, Temperature, Vibration and Proprioception Fig 70: Voluntary Motor Control

Organization of the grey matter

 the grey matter is arranged in horns: dorsal [sensory], ventral [motor] and lateral [sympathetic]
 the lateral [intermediolateral] horn is only found in the thoracic part of the spinal cord from T6 to
L1 and represents the region that carries sympathetic fibers
 these are further subdivided into 10 layers or laminae [Rexed]:
o Lamina I is the thin layer which lies beneath the dorsolateral fasciculus [of Lissauer]
 fibers from the first order sensory neurons may ascend and descend to adjacent
spinal cord segments in the dorsolateral tract
 this lamina contains neurons which synapse with the first order neurons and
send axons to the contralateral spinothalamic tracts
o Lamina II [substantia gelatinosa of Rolando] is made up of small neurons, some of
which respond to noxious stimuli including the C fibers:
 Substance P, a neuropeptide involved in pain sensibility, is found in high
concentrations in laminae I and II

78
 o Laminae III and IV as jointly referred to the nucleus proprius
 their main input is from fibers that carry mechanoreception and light touch
o Lamina V contains neurons that respond to both noxious and visceral afferent stimuli
o Lamina VI is the deepest layer of the dorsal horn and receives mechanical signals from
the skin and joints
o Lamina VII contains the dorsal nucleus [Clarke’s column] and the intermediolateral
horn or nucleus
 the intermediolateral horn is seen in the T1-L2 spinal cord segments and
contains the cell bodies of the preganglionic sympathetic neurons
 axons from Clarke’s nucleus ascend the spinal cord and carry unconscious
proprioception
o Laminae VIII and IX represents motor neuron groups in the ventral horn
o Lamina X is the small area of gray matter surrounding the central canal of the spinal cord
and is known as the grey commissure
Posterior spinal artery

Dura mater
Subarachnoid space
I
II
III
IV
V Intermediolateral
VI
VII
horn
X
IX
VIII

Arachnoid Pia mater

Anterior Spinal Artery

Fig 71: Spinal Cord Coverings and Laminae

Blood Supply of the Spinal Cord

 supplied by segmental spinal arteries derived from the spinal branches of the following arteries:
o ascending cervical
o deep cervical
o posterior intercostal
o lumbar
 segmental spinal arteries give rise to radicular and segmental medullary arteries
 segmental medullary arteries supplement the single anterior spinal and two posterior spinal
arteries from the vertebral arteries
 there is a relatively large radicular artery called the Great Radicular artery [of Adamkiewicz]
which usually supplies between lower half or two thirds of the spinal cord
 this artery usually arises on the left side as a branch of either the lower posterior intercostal or
the upper lumbar arteries
 the single anterior spinal artery supplies approximately the anterior two-thirds of the spinal cord
 the two posterior spinal arteries supply the posterior one-third of the spinal cord

Upper motor neuron versus lower motor neuron lesion

Upper motor neuron lesion Lower motor neuron lesion
Reflexes Increased with clonus Decreased or absent
Tone Spastic Flaccid
Atrophy Absent Present
Fasciculations Absent Present
Babinski sign Present [upgoing toe] Absent [downgoing toe]

79
CNS ANATOMY REVIEW

CNS embryology
 derived from the rostral [cranial] end of the neural tube
 development is guided by the underlying notochord
 it begins with 3 primary dilatations called vesicles
st
 1 vesicle is known as the prosencephalon [forebrain]:
o this further develops into secondary vesicles from which develop:
 the telencephalon from which the cerebral hemispheres and the lateral
ventricles ultimately develop
 the diencephalon which gives rise to the thalamus, epithalamus and
subthalamic nuclei
nd
 2 vesicle is the mesencephalon [midbrain]:
o this becomes the mid brain
rd
 3 vesicle is the rhombencephalon [hindbrain]:
o this vesicle further develops into:
 the metencephalon
 this develops into the pons and the cerebellum
 the myelencephalon
th
 this becomes the medulla and the 4 ventricle

Cerebral
Hemispheres
Telencephalon

Prosencephalon
Diencephalon Thalamus

Mesencephalon Mesencephalon Midbrain

Metencephalon Pons

Rhombencephalon

Myelencephalon Medulla

Fig 72: Brain Development

Types of cells in the CNS

 Neurons and neuroglia [1:10 ratio]
 Neuroglia cells are the connective tissue in the brain and include:
o Astrocytes
 helps with the blood brain barrier [no fenestrations in the capillaries except in the
hypothalamus and the area postrema]
o Ependymal cells
 line the ventricles and makes Cerebrospinal Fluid
o Oligodendrocytes and Schwann cells
 produce myelin in the CNS and PNS respectively [CoPs]
 Microglia cells
o these are the macrophages of the nervous system
o Microglia cells are derived from mesoderm and not neuroectoderm as the other cells

80
Lobes in the brain
 Frontal [thinking and motor function] lies in front of the central sulcus
 Parietal [sensory] lies between the central sulcus and the parieto-occipital fissure
 Occipital [visual] lies behind a line connecting the parieto-occipital fissure and preoccipital notch
 Temporal [hearing, smell and memory] lies onferior to he lateral fissure
Precentral gyrus [motor] Postcentral gyrus [sensory]
Parietal lobe

Central sulcus Parieto-occipital fissure

Frontal lobe
Occipital lobe

Lateral fissure
Preoccipital notch
Superior Ttemporal gyrius
Temporal lobe
Fig 73: Lobes of the Brain
Types of white fibers
 commissural [right to left cerebral hemisphere or right and left halves of the spinal cord]:
o anterior and posterior commissures, and corpus callosum in the brain
o white commissural fibers in the spinal cord for tracts that decussate
 association [from one part to another part on the same hemisphere]:
o visual and auditory association fibers
 projection [from brain to spinal cord and vice versa]: corticospinal tract

Blood supply of the brain

 the brain is supplied by two sets of arterial sources connected by the circle of Willis:
o anterior circulation [internal carotid artery]
o posterior circulation [vertebrobasilar system]
 the circle is completed by the Anterior Communicating Artery which connects the two Anterior
Cerebral arteries of the internal carotid arteries
 the Posterior Communicating Artery connect the terminal end of the Internal Carotid artery to
the Posterior Cerebral Artery which is a terminal branch of the basilar artery
 the Middle Cerebral Artery is not part of the circle of Willis

Anterior
Communicating
Artery Anterior Cerebral Artery
Internal Carotid Artery
Posterior
Communicating
artery Posterior
Cerebral
Artery Superior Cerebellar artery
Basilar artery
Labyrinthine artery
Posterior Inferior Cerebellar artery
Vertebral artery Anterior spinal artery

Fig 74: Circle of Willis

81
Distribution of blood supply
 Anterior Cerebral Artery
o medial aspect of the cerebral hemisphere up to the parieto-occipital fissure
 Middle Cerebral Artery
o rest of the cerebral hemisphere up to the parietal-occipital fissure
o upper part of the temporal lobe
 Posterior Cerebral Artery
o occipital lobe, inferior portion of the temporal lobe
o midbrain and thalamus
 Superior Cerebellar Artery
o superior part of cerebellum
 Anterior Inferior Cerebellar Artery
o anterior Inferior part of cerebellum
 Posterior Inferior Cerebellar Artery
o posterior Inferior part of cerebellum
 Basilar Artery
o pons which contains the nuclei for CN V, VI, VII and VIII
 Vertebral Artery
o medulla which contains the nuclei of the last 4 cranial nerves: CN IX, X, XI and XII
 The blood supply of the brain is regulated by the levels of CO2
o High levels of carbon dioxide causes vasodilation

Anterior Cerebral Artery

4 312
Middle Cerebral
Artery

45 44 22 17
17

Posterior Cerebral Artery

Fig 75: Distribution of Cerebral Arteries

Cranial Nerves-location of nucleus, development vesicle and general function

CN I On Olfactory Telencephalon [cerebrum] Sensory
CN II Old Optic Diencephalon [thalamus] Sensory
CN III Olympus Oculomotor Mesencephalon [midbrain] Motor
CN IV Towering Trochlear Mesencephalon [midbrain] Motor
CN V Tops Trigeminal Metencephalon [pons] Both
CN VI A Abducens Metencephalon [pons] Motor
CN VII Friendly Facial Metencephalon [pons] Both
CN VIII Viking Vestibulocochlear Metencephalon [pons] Sensory
CN IX Grows Glossopharyngeal Myelencephalon [medulla] Both
CN X Vines Vagus Myelencephalon [medulla] Both
CN XI And Accessory Myelencephalon [medulla] Motor
CN XII Hops Hypoglossal Myelencephalon [medulla] Motor

Mnemonic: Some Say Marry Money But My Brother Says Bigger Brains Matter Most

82
 Olfactory bulb of CN I

Olfactory tract of CN I

CN II

CN III

CN IV
CN V

CN VII CN VI
CN VIII
CN IX

CN X

CN XII

Fig 76: Cranial Nerves

CN I
 Olfactory nerves
 The specialized sensory bipolar neurons are located in the olfactory mucosa which is found in
the roof of the nasal cavity
 Axons from these bipolar neurons pass through the cribriform plate of the ethmoid bone
 Unlike other neurons, these neurons have the unique ability to regenerate after they are
destroyed like following the common cold
 The axons of these receptor cells synapse with the mitral cells in the olfactory bulb
 Most of the fibers from the mitral cells pass backwards in the olfactory tract
 These fibers end in the primary olfactory cortex which is located in the temporal lobe
 The olfactory cortex has connections with other parts of the brain including the hippocampus
linking smell with memory
 It is also linked with:
o hypothalamus-linking smell with the autonomic nervous system
o limbic system-linking smell with emotions
 It is the only cranial nerve that is not linked initially to the thalamus before its fibers terminate in
the primary olfactory cortex in the temporal cortex

83
CN II
 Optic nerve
 Specialized sensory neurons [rods and cones] are in the retina at the back of the eyeball
 Visual impulses are sent to the optic nerve via axons of the ganglion cells of the retina
 The optic nerves meet at the optic chiasm which lies above the pituitary fossa
 Impulses from the nasal retina [temporal field of vision] cross over at the chiasm
 Damage at the optic chiasm will present with bitemporal hemianopia
 Fibers from the optic nerve synapse in the lateral geniculate body of the thalamus
 Fibers from the thalamus continue as the optic radiation [geniculocalcarine tract] to the primary
visual cortex
 Damage to the optic radiation will present with homonymous hemianopia
 Primary visual cortex is located in the occipital lobe on either side of the calcarine fissure
[Brodmann’s Area 17]
 Damage to this area will result in homonymous hemianopia with macular sparing
Temporal visual field

Optic chiasm Nasal visual field

Optic nerve

Bitemporal hemianopia
Pituitary stalk

Optic tract

Lateral
Geniculate
Body

Homonymous hemianopia

Optic radiation

Homonymous hemianopia
with macular sparing
Primary Visual Cortex Area 17
Fig 77: Visual Pathways and effects of damage

CN III, IV and VI [SO4 LR6 Rest3]

 Motor nerves
 These cranial nerves are grouped together because they innervate the extra-ocular muscles
 CN III [oculomotor nerve] supplies all of the extra-ocular muscles of the eye, namely the superior
rectus [up], inferior rectus [down], medial rectus [in] and inferior oblique [up and out] except
superior oblique and lateral rectus
 The oculomotor nerve also carries parasympathetic fibers to the iris muscle via the ciliary
ganglion from the Edinger-Westphal nucleus which is located in the midbrain
 These fibers are responsible for constriction of the pupil in the iris and lens accommodation
 CN IV [trochlear nerve] supplies the superior Oblique muscle which turns the eye down and out
 Superior oblique muscle is tested clinically by asking the patient to look in and then down
 CN IV is the only cranial nerve that exits the brainstem dorsally
 CN VI [abducens nerve] innervates the lateral rectus muscle which abducts the eye

84
CN V
 Largest mixed cranial nerve
 The trigeminal nerve has two roots:
o large sensory
o small motor
 The motor nucleus of CN V is located in the pons and supplies the muscles of mastication:
Temporalis, Internal [medial] pterygoid, Masseter, External [lateral] pterygoid muscles plus the
mylohyoid, tensor tympani, tensor veli palatini and the anterior belly of the digastric muscle
 There are three parts of the sensory trigeminal nucleus:
o mesencephalic [carrying proprioception] is located in the midbrain
o main sensory [carrying touch] is located in the pons
o spinal [carrying pain and temperature] is located in the medulla and extends into the
upper cervical segments of the spinal cord
 CN V has three divisions which come off of the Gasserian ganglion:
o ophthalmic
o maxillary
o mandibular
 The ophthalmic division:
o gives the following branches [LEFT] which pass through the superior orbital foramen:
 Lacrimal
 Ethmoidal
 Frontal
 Trochlear
 The maxillary division:
o divides into the following branches [PINZ] after exiting through the foramen rotundum:
 Pharyngeal
 Infraorbital
 Nasopalatine
 Zygomatic
 The mandibular division:
o divides into anterior and posterior divisions after exiting the skull via the foramen
ovale
o before it divides, the trunk gives off one branch: the nerve to medial pterygoid
o the anterior division has the following terminal branches [3 motor and 1 sensory nerves]:
 deep temporal nerves [motor]
 nerve to the lateral pterygoid [motor]
 nerve to masseter [motor]
 buccal nerve [sensory]
o the posterior division has the following branches [3 sensory and 1 motor branches]:
 auriculotemporal [sensory]
 inferior alveolar [sensory]
 lingual [sensory]
 nerve to mylohyoid [motor]
 the ciliary ganglion is attached to the ophthalmic division of CN V [nasociliary nerve]
o this receives parasympathetic fibers from the Edinger-Westphal nucleus via CN III
 the pterygopalatine ganglion is attached to the maxillary division of CN V
o this receives parasympathetic fibers from the Superior Salivary nucleus via CN VII
 the otic ganglion is attached to the auriculotemporal branch of the mandibular division of CN V
o this receives parasympathetic fibers from the Inferior Salivary nucleus via CN IX
 the submandibular ganglion is attached to the lingual branch of the anterior division of the
mandibular division
o this receives parasympathetic fibers from the Superior Salivary nucleus via CN VII

CN VII
 very mixed nerve with four different nuclei:
o motor [motor nucleus in the pons]
o ordinary sensation [sensory nucleus of the trigeminal nerve]
o parasympathetic [superior salivary nucleus]
o taste [solitary tract nucleus]
 its motor nucleus is located in the pons
 it leaves the brain stem at the pontomedullary angle

85
  it enters the skull via the internal acoustic meatus located in the temporal bone
 it leaves the skull via the stylomastoid foramen located in the temporal bone
 it carries motor fibers to the muscles of facial expression via the following branches:
o Temporal
o Zygomatic
o Buccal
o Marginal mandibular
o Cervical
o Ten Zebras Broke My Car is the mnemonic for the 5 branches
 it also innervates the stapedius muscle in the middle ear plus the muscles of the ear and the
posterior belly of digastric
 it conveys taste from the anterior two thirds of the tongue to the nucleus solitarius
 it also carries parasympathetic innervation from the Superior Salivary nucleus to the
submandibular and sublingual salivary glands via the submandibular ganglion of CN V3
 the taste and parasympathetic fibers are carried by the chorda tympani which connects the
facial nerve to the lingual branch of CN V3
 taste sensation from the tongue:
o sweet and sour [sides of the tongue-CN VII]
o salt [tip of the tongue-CN VII]
o bitter [root of the tongue which is supplied by CN IX]
 the facial nerve also carries a few general sensory afferent fibers from the skin of the external
ear canal via the auricular branch of CN X
 these sensory fibers end in the trigeminal sensory nucleus before crossing over to the opposite
to synapse in the Ventral Posterior Medial nucleus of the thalamus

CN VIII
 sensory nerve [with a very very small motor component]
 it has two distinct parts:
o cochlear [hearing]
o vestibular [balance]
 the cochlear fibers arise from the central portions of the bipolar spiral ganglion cells of the
cochlea from the organs of Corti found in the inner ear
o these fibers traverse the internal auditory meatus to reach the lateral aspect of the
medulla
o these fibers terminate in the dorsal and ventral cochlear nuclei in the medulla
o the majority of the efferent fibers from these nuclei cross to the opposite side ending in
the nuclei in the trapezoid body
o from here fibers ascend through the inferior colliculus
o from here fibers go into the medial geniculate body in the thalamus
o from here fibers finally sweep laterally to the primary auditory cortex which is located in
the middle portion of the superior temporal gyrus [Brodmann’s area 22]
 the vestibular fibers on the other hand, arise from the semicircular canals [head turning-angular
acceleration], utricle and saccule [gravity-linear acceleration] in the inner ear
o these fibers enter the medulla just medial to the cochlear division of CN VIII
th
o the fibers end in the vestibular nuclei located in the floor of the 4 ventricle
o many of the efferent fibers from the vestibular nuclei pass to the cerebellum through the
inferior cerebellar peduncle
 there are a small number of efferent [motor] fibers which end up on the outer hair cells in the
organ of Corti in the inner ear
o they modulate the stiffness of the outer hair cells and attenuate loud sounds

CN IX
 mixed nerve
 it contains motor fibers from the nucleus ambiguus to one muscle-Stylopharyngeus
 sensation from the posterior third of tongue and pharynx to the sensory nucleus of CN V
 it carries taste from the posterior third of the tongue to the nucleus solitarius in the medulla
 it also carries parasympathetic innervation to the parotid gland via the otic ganglion of CN V3
from the inferior salivary nucleus in the medulla
 it leaves the skull via the jugular foramen
 its carotid branch runs down on the internal carotid artery to supply the carotid body
[chemoreceptors] and the carotid sinus [baroreceptors]

86
CN X
 mixed nerve: motor, sensory and parasympathetic
 the General Somatic Efferent component is derived from the nucleus ambiguus [skeletal motor]
 the General Visceral Efferent component from the dorsal motor nucleus of CN X [visceromotor]
 the General Somatic Afferent component is related to the spinal nucleus of CN V [sensory]
 the General Visceral Afferent fibers arise from the solitary nucleus [sensory]
 the Special Visceral Afferent fibers from the base of the tongue go to the solitary nucleus [taste]
 CN X leaves the brain stem in the groove between the olive and the cerebellum
 It passes through the jugular foramen after which it gives off its tympanic branch
 the tympanic branch enters the middle ear cavity to form the tympanic plexus
 below the jugular foramen, CN X passes between the superior and middle constrictors
 breaks up into its terminal branches to supply the root of the tongue, tonsils and muscles and
mucosa of the pharynx
 the vagus nerve passes through the neck and thorax and ends in the abdomen
 it carries parasympathetic innervation to the thorax and abdomen as far as the transverse
colon
 it also carries sensory fibers from the thorax and abdomen
 in fact the ratio of afferent [sensory] to efferent [motor] fibers in the vagus is 10:1

CN XI
 motor nerve
 there are two parts of the nerve:
o cranial [from the nucleus ambiguus] accessory
o spinal [from spinal nuclei in the C1-C5 spinal cord segments] accessory
 the cranial part:
o contains fibers of the cranial root emerge from the medulla as rootlets posterior to the
olive
o these rootlets unite to form a single nerve which is joined by the spinal part before
passing through the jugular foramen
o on leaving the skull, the cranial part leaves the nerve and joins the vagus nerve to
supply the muscles of the palate, pharynx and larynx
 the spinal part:
o arises from rootlets from the upper five cervical segments of the spinal cord
o they join together and pass upwards through the foramen magnum to join with the cranial
part of the cranial nerve
o on exiting the skull, it pierces and supplies the sternocleidomastoid muscle
o it passes through the posterior cervical triangle
o and ends up piercing and supplying the trapezius muscle

CN XII
 motor nerve
 all of the intrinsic and extrinsic muscles of the tongue are supplied by the hypoglossal nerve
EXCEPT:
o palatoglossus which is innervated by the pharyngeal plexus of the vagus
 the nerve begins as rootlets found in the groove between the pyramid and the olive in the medulla
 it exits the skull via the hypoglossal foramen located in the occipital bone
 it descends passing between the internal carotid artery and the internal jugular vein
 it then loops upwards and forwards crossing the hyoglossus muscle to enter the tongue from
below

Functional classification of cranial nerve fibers

 afferent and efferent [sensory and motor]
 somatic and visceral [body and organs]
 special
 GSE
o General Somatic Efferents-motor to skeletal muscle
 GVE
o General Visceral Efferents
o Sympathetic and parasympathetic motor to:
 heart, smooth muscle in the eye and gland

87
  SVE
o Special Visceral Efferents
o Motor to:
 Muscles from the branchial [pharyngeal] arches
 Arch 1 CN V muscles of mastication
 Arch 2 CN VII muscles of facial expression
 Arch 3 CN IX stylopharyngeus
 Arch 4 CN X muscles of the pharynx and larynx
 GSA
o General Somatic Afferents
o Ordinary sensation-pain, temperature, touch, vibration and proprioception
 GVA
o General Visceral Afferents
o Sensory from gut: distension and stretch
 SSA
o Special Somatic Afferents
o Special senses: vision, hearing and balance
 SVA
o Special Visceral Afferents
o Special Senses to do with the gut:
 taste
 smell

Cranial Nerve GSE GVE SVE GSA GVA SSA SVA

I +
II +
VIII +
IV +
VI +
XII +
III + +
XI + +
V + + +
VII + + + + +
IX + + + + +
X + + + + +
Table 4: Functional Components of the Cranial Nerves
Internal Capsule
 it is a small but very important structure in the brain
 it is important because of the fibers that it contains
 the anterior limb lies between the caudate nucleus and the lentiform nucleus
 the posterior limb lies between lentiform nucleus and the thalamus
 the thalamus acts as a relay station for all sensory input to the cortex except olfaction
 the globus pallidus, putamen and caudate nucleus are collectively called the basal ganglia
o the basal ganglia controls complex patterns of voluntary motor behavior
 the internal capsule is divided into three parts:
o anterior limb which carries thalamocortical fibers [sensory from below the head]
o genu [bend] which carries corticobulbar fibers [motor fibers to the head]
o posterior limb which carries corticospinal tract [motor to below the head], auditory and
visual association fibers and thalamocortical fibers
 blood supply:
o anterior limb: anterior and middle cerebral arteries
o genu: middle cerebral artery
o posterior limb: middle cerebral and anterior choroidal artery from the internal carotid
artery

88
 Caudate nucleus

Lentiform Putamen Anterior limb

Genu Internal
nucleus Capsule
Globus pallidus Posterior limb

Thalamus

Fig 78: Internal Capsule

Thalamus
Major transit area for all sensory input on the way to the cortex EXCEPT from the olfactory nerves
4 major thalamic nuclei to remember:
 VentroPosteroLateral: input from the neck and below
 VentroPosteroMedial: input from the head
 Lateral geniculate body: visual input [Light] connects with the Superior Colliculus
 Medial geniculate body: auditory input [Music] connects with the Inferior Colliculus

Basal Ganglia
These collections of interconnected neurons exert influence on the motor activity of the brain through
inhibition or facilitation. The ganglia or nuclei that make up the basal ganglia are:
 caudate nucleus
 lentiform nucleus which is made up of the putamen, globus pallidus externa and interna
o the corpus striatum is made up of the caudate nucleus and the putamen
o the anterior limb of the internal capsule separates the caudate from the putamen
 substantia nigra which has two parts:
o pars compacta
o pars reticulata

Cerebellum
 3 lobes:
o anterior [spinocerebellum]-balance of the arms and legs
o posterior [cerebrocerebellum]-receives information from the cortex
o flocculonodular [vestibulocerebellum]-balance of the trunk
 3 peduncles:
o superior [mainly output to the cerebral cortex]
o middle [mainly input from the cortex carrying the cortico-ponto-cerebellar fibers]
o inferior [minor input from the body via the dorsal spinocerebellar tract ]
 3 main nuclei [Flowers Grow Every Day-from medial to lateral]:
o Fastigial nucleus which is related to the spine
o Interpositus which is made up of:
 Globose nucleus which is related to proximal joints e.g. Glenohumeral
 Emboliform nucleus which is related to middle joints e.g. Elbow joint
o Dentate nucleus which is related to distal joints e.g. Digital joints
 3 cerebellar arteries:
o superior cerebellar artery from the basilar artery
o anterior inferior artery from the basilar artery
o posterior inferior artery from the vertebral artery

89
Blood Brain Barrier
 this barrier is formed by three structures:
o tight junctions between non-fenestrated capillary endothelial cells
o basement membrane
o the processes of astrocytes
 glucose and amino acids cross the Blood Brain Barrier by carrier-mediated transport
 lipid-soluble substances cross more readily than water soluble ones
 few specialized regions in the brain where there are fenestrated capillaries and no blood brain
barrier, namely the area postrema which facilitates vomiting in response to poisons and the
neurohypophysis [posterior pituitary lobe] for secretion of hormones

Vertebral Artery
o derived from the subclavian artery and has four parts
st
o Part 1 lies between its origin from 1 part of the subclavian artery to transverse foramen of C6
o passes between longus coli and scalenus anterior
o passes behind the carotid tubercle [anterior tubercle of C6 transverse process]
o Part 2 lies within the transverse foramina of C6 through to C1
o it is relatively fixed at C2 and C1
o it is accompanied by the vertebral veins and sympathetic nerves
o Part 3 extends from C1 to the foramen magnum
o this part of the vertebral artery is most prone to dissection
o passes posteriorly behind the lateral mass of CI to lie on the posterior arch of C1
o then it passes beneath the posterior atlanto-occipital membrane
o turns upwards to pass through the foramen magnum
o Part 4 is the section of the artery lying above the foramen magnum
o passes forwards to lie anterior to the medulla
o it ends at the lower pons by joining with its counterpart to form the basilar artery

th
4 part

rd
3 part

nd
2 part

st
1 part
Subclavian artery

Fig 79: Vertebral Artery

Branches of the vertebral artery

 cervical
 anterior spinal
 posterior spinal
 posterior inferior cerebellar artery
 few branches to the medulla

Vascular insufficiency syndromes

 Middle Cerebral Artery
o main blood supply to the cortex
o contralateral paralysis [Brodmann’s area 4-precentral gyrus]
o aphasia [damage to Broca’s speech area aka Brodmann’s areas 45 and 44]
o sensory loss only [anterior limb of internal capsule]
o motor loss only [posterior limb of internal capsule]

90
  PICA [aka Wallenberg or lateral medullary] syndrome
o occlusion of the vertebral or posterior inferior cerebellar artery
o dysphagia, ataxia, ipsilateral Horner’s syndrome, loss of sensation in the face, loss of
light touch and position sense in the limb on the same side and contralateral loss of
pain and temperature
 Medial medullary syndrome
o occlusion of the vertebral artery
o contralateral spastic hemiplegia, loss of touch, vibration and pressure
 Clause’s syndrome
o occlusion of the blood supply to the dorsal midbrain
o ipsilateral CN III palsy and contralateral ataxia and tremor
 Weber [aka medial midbrain] syndrome
o occlusion of the perforating branches of the posterior cerebral artery
o contralateral spastic paralysis with ipsilateral CN III weakness

CSF circulation
 CSF is produced mainly by the choroid plexus in the lateral ventricles
 CSF flows into the third ventricle through the interventricular foramina of Monro
 From the third ventricle to the fourth ventricle via the cerebral aqueduct of Sylvius
 CSF leaves the fourth ventricle via the lateral foramina of Luschka and the median foramen of
Magendie
 It circulates in the subarachnoid space and collects in large spaces called cisterna:
 cisterna magna [between the medulla and cerebellum-largest collection]
 pontine cistern [below the pons]
 interpeduncular cistern [between the cerebral peduncles]
 chiasmatic cistern [below the optic chiasm]
 CSF drains via arachnoid granulation which open into the superior sagittal sinus

Venous Dural sinuses

 Venous blood from the brain drains into numerous venous sinuses found in the cranial dura:
o superior sagittal sinus is found in the attached edge of the falx cerebri
 it drains into the right transverse sinus lying in the tentorium cerebelli
o inferior sagittal sinus is found in the free edge of the falx cerebri
 this drains into the straight sinus which empties into the left transverse sinus
o sometimes the superior sagittal and straight sinuses join to form the confluence of sinuses
o the confluence is as the torculus herophilus
o the transverse sinuses become the sigmoid sinuses
o superior petrosal sinus drains into the sigmoid sinus
o the sigmoid sinus passes through the jugular foramen to become the internal jugular
vein
o inferior sagittal sinus passes through the jugular foramen and drains into the superior
bulb of the internal jugular vein
o Intercavernous sinuses link the cavernous sinuses on either side of the sella turcica

Superior sagittal sinus

Superior petrosal sinus

Inferior sagittal sinus

Straight sinus

Transverse sinus

Sigmoid sinus
Internal Jugular Vein

Inferior petrosal sinus

Fig 80: Dural Venous Sinuses

91
SKULL, SCALP AND FACE

Bones of the cranium of the skull [The PEST OF 8 bones]

 Parietal [2]
 Ethmoid [1]
 Sphenoid [1]
 Temporal [2]
 Occipital [1]
 Frontal [1]
Vertex

PARIETAL

Pterion
Asterion
Bregma FRONTAL
PARIETAL
FRONTAL BONE Asterion
Sphenoid
Nasion Lambda
TEMPORAL
OCCIPITAL

Asterion

Fig 81 Skull
Important points on the skull
 Asterion: this is the point where the temporal, occipital and parietal bones meet
 Bregma: this is the meeting point of the frontal and parietal bones [anterior fontanelle]
o the anterior fontanelle should be closed by the first 18 months of life
 Glabella: this is the transverse ridge connecting the supraorbital ridges
 Inion: this is the highest point on the External Occipital Protuberance
 Lambda: this is the meeting point of the occipital and parietal bones [posterior fontanelle]
o the posterior fontanelle is closed by the first 2-3 months of life
 Nasion: this is the center of the frontonasal suture between the frontal and nasal bones
 Pterion: where frontal, sphenoid, parietal and temporal bones meet
 Vertex: highest point on the skull in the sagittal plane
 Basion: middle of the posterior aspect of the foramen magnum

Layers of the scalp

 Skin
 Closed Connective tissue:
o made up of fat packed into tight fascial compartments
o contains the blood vessels, nerves and lymphatics
 Aponeurosis
o this is the flattened tendon of the occipitofrontalis muscle
 Loose connective tissue
o this layer separates the scalp proper from the underlying pericranium
 Pericranum
o this is the periosteum of the calvarium [skull cap]
o the periosteum is attached to the underlying bone by Sharpey’s fibers
 Innervation
o the scalp is innervated by branches of CN V, C2 and C3 nerves
 Blood supply
o branches of the External Carotid Artery

92
 Cranial foramina, related bone and contents
 Foramen cecum [frontal/ethmoid] Nasal emissary vein
 Anterior/posterior ethmoidal [ethmoid] Anterior and posterior ethmoidal n/a/vs
 Cribriform foramina [ethmoid] Olfactory nerves [CN I]
 Optic canal [sphenoid] Optic nerve [CN II] and ophthalmic artery
 Superior Orbital Fissure [sphenoid] CN III, CN IV, CN V1, CN VI, ophthalmic veins
 Foramen rotundum [sphenoid] CN V2
 Foramen ovale [sphenoid] CN V3, accessory meningeal artery and vein
 Foramen spinosum [sphenoid] Recurrent meningeal branch of CN V3, middle
meningeal artery and vein
 Foramen lacerum [sphenoid/ Internal Carotid Artery, venous plexus, sympathetic
temporal] nerves passing horizontally rather than vertically
 Internal acoustic meatus [temporal] CN VII, CN VIII, nervus intermedius and the
labyrinthine artery
 Jugular foramen [temporal/ CN IX, X and XI, inferior petrosal sinus, sigmoid sinus
occipital] and the posterior meningeal artery
 Hypoglossal foramen [occipital] CN XII
 Foramen magnum [occipital] Medulla, vertebral, spinal arteries, spinal part of CN XI

FORAMINA BONE
Foramen cecum
Ethmoid bone
Anterior ethmoidal foramen

Cribriform foramina

Posterior ethmoidal foramen Frontal bone

Superior Orbital fissure

Foramen rotundum
Optic canal
Foramen ovale Sphenoid bone

Foramen spinosum

Temporal bone
Foramen lacerum Clivus

Internal Parietal Bone

Acoustic
Meatus

Jugular foramen

Hypoglossal foramen
Occipital Bone

Foramen magnum

Fig 82: Cranial Foramina

93
Muscles of facial expression
 around the eye:
o orbicularis oculi [closes the eye] and corrugator supercilii [furrows the brow]
 around the nose:
o dilator nares, compressor nares and procerus
 around the mouth:
o orbicularis oris, zygomaticus major and minor, depressor angularis oris, levator labii
superioris, depressor labii inferioris, rizorius, buccinator and platysma
nd
 all muscles of facial expression are derived from the mesoderm of the 2 branchial or pharyngeal
arch
 they are innervated by the following branches of CN VII [Ten Zebras Broke My Car]:
o Temporal
o Zygomatic
o Buccal
o Marginal mandibular
o Cervical
 Levator palpebrae superioris is not a muscle of expression and is supplied by CN III
 the frontalis muscle has a dual innervation meaning that each muscle is separately innervated by
branches of the facial nerves that arise from both sides of the brain
 this allows the differentiation of an upper motor neuron lesion from a lower motor neuron lesion
th
of the 7 cranial nerve to be made
th
 in an upper motor neuron lesion of the 7 cranial nerve [caused by a stroke] the patient is able
to raise the eyebrow on the affected side
o this is because the frontalis muscle is bilaterally innervated
th
 in a lower motor neuron lesion of the 7 cranial nerve [as seen in Bell’s palsy] the patient will
not be able to raise the eyebrow on the affected side
o the muscles of the face on the affected side will be paralyzed resulting in the inability of
the patient to:
o close the eyelids [orbicularis oculi]
o smile [rizorius]
o whistle [buccinator and orbicularis oris]
o blink the eye reflexively

Frontalis

Procerus Corrugator supercilii

Orbicularis oculi
Compressor naris

Levator labii superioris Dilator naris

Zygomaticus minor
Zygomaticus major

Rizorius
Depressor angularis Orbicularis oris

Depressor labii Mentalis

Fig 83: Muscles of Facial Expression

94
Derivatives of the branchial [pharyngeal] arches

ARCH Nerve Muscle Bone Cartilage

1 CN V Muscles of Mastication, Mandible, Malleus and Meckel’s cartilage
tensor veli palatini, tensor Incus
tympani and anterior belly
of digastric
2 CN VII Smiling muscles, Stapes, styloid process, Reichert’s cartilage
Stylohyoid, Stapedius and smaller [lesser] horn and
the posterior belly of the the superior part of the
digastrics muscle hyoid bone
3 CN IX Stylopharyngeus Greater horn and inferior None
part of the body of the
hyoid bone
4 CN XI via CN X Muscles of the pharynx None Thyroid and cricoid
except Stylopharyngeus cartilages
5 None None None None
6 CN XI via CN X Muscles of the larynx None Arytenoid,
corniculate and
cuneiform
cartilages

T able 5: Pharyngeal A rch Derivatives

Muscles in the head and neck region

 All of the muscles of the tongue are supplied by the Hypoglossal nerve
o EXCEPT the palatoglossus which is supplied by the pharyngeal plexus of the Vagus
 All of the muscles of the palate are supplied by the pharyngeal plexus of the Vagus
o EXCEPT the tensor veli palatini which is supplied by the mandibular division of the
Trigeminal nerve
 All muscles of the pharynx are supplied by the pharyngeal plexus of the Vagus
o EXCEPT the stylopharyngeus which is supplied by the Glossopharyngeal nerve
 All the muscles of the larynx are supplied by the recurrent laryngeal nerve of the Vagus
o EXCEPT the cricothyroid which is supplied by the superior laryngeal branch of CN X
The following are the muscles of the larynx [CTV PLOT]:
 Cricothyroid
 Thyro-arytenoid
 Vocalis
 Posterior cricoarytenoid
 Lateral cricoarytenoid
 Oblique arytenoid
 Transverse arytenoid
All of the above laryngeal muscles ADDUCT the vocal cords EXCEPT the following:
 posterior cricoarytenoid which abducts the cords
 cricothyroid which tenses the vocal cords
 thyroarytenoid which relaxes the vocal cords
 vocalis which relaxes the posterior part while tightening the anterior part

Paranasal sinuses
 frontal sinus
 lies in the frontal bone above and between the orbits
 drains into the hiatus semilunaris in the middle meatus of the nasal cavity
 ethmoid sinuses
 lies between the orbits: posterior, middle and anterior
 drains into the superior [posterior] and middle [middle and anterior] meatus
 maxillary sinus
 lies in the maxilla below each orbit
 drains into the hiatus semilunaris of the middle meatus
 sphenoid sinus
 lies in the sphenoid bone below the pituitary fossa
 drains into the sphenoethmoidal recess which lies above the superior concha

95
 PERIPHERAL NERVOUS SYSTEM ANATOMY REVIEW

Cervical Plexus
 derived from the ventral rami of C1, 2, 3, 4 and 5 forming the following:
o C1 supplies geniohyoid and thyrohyoid
o Ansa cervicalis [C1, 2 and 3] supplies all the other infrahyoid muscles:
 sternothyroid, sternohyoid and the superior and inferior bellies of omohyoid
o Lesser occipital [C2, perhaps C3] supplies the back of the head up to the vertex
o Great auricular [C2 and 3] supplies most of the ear
o Transverse cervical [C2 and 3] supplies skin over the anterior cervical triangle
o Supraclavicular [C3 and 4] supply skin over the clavicle
o Phrenic [C3, 4 and 5 keeps the diaphragm alive] innervates the diaphragm
o Note that the greater occipital nerve is derived from the dorsal ramus of C2
o Most of the above branches lie in the anterior cervical triangle

CN XII

Great auricular nerve C1

Transverse cervical nerve
C2
Lesser occipital nerve
C3 Ansa cervicalis

C4

C5
Phrenic nerve Supraclavicular nerve

Fig 84: Cervical Plexus

Brachial Plexus
 derived from the ventral rami of C5, 6, 7, 8 and T1
 its roots pass out between the scalenus anterior and medius muscles in the neck
 roots of the brachial plexus form three trunks located in the posterior cervical triangle:
o upper trunk from C5 and C6, middle trunk-C7, lower trunk-C8 and T1
 trunks divide into posterior and anterior divisions located behind the clavicle
 anterior and posterior divisions join to form three cords around the axillary artery:
o posterior cord from all the posterior divisions [C5,6,7,8 and T1]
o lateral cord from the anterior divisions of the upper and middle trunks [C5,6,7]
o medial cord from lower trunk anterior division [C8, T1]
 from the cords, come the five main nerves of the brachial plexus:
o radial nerve [C5, 6, 7, 8 and T1] supplies all of the muscles of the posterior [extensor]
compartment of the arm [Triceps] and forearm-Brachioradialis, all Extensors of the wrist,
Abductors of the thumb and Supinator muscles] [BEAST nerve]
o median nerve [C5, 6, 7, 8 and T1] supplies all of the muscles of the forearm [except
flexor carpi ulnaris and the ulnar half of flexor digitorum profundus] plus the LOAF
muscles of the thumb
o the anterior interosseous branch of the median nerve innervates flexor pollicis
longus, pronator quadratus and the radial half of flexor digitorum profundus
o ulnar nerve [C8 and T1] supplies all of the intrinsic muscles of the hand except the
st
LOAF muscles of the thumb [1 two Lumbricals, Opponens pollicis, Abductor pollicis
brevis and Flexor pollicis brevis which are supplied by the median nerve]
o musculocutaneous nerve [C5, 6 and 7] supplies Biceps, Brachialis and Coracobrachialis
and the skin of the lateral forearm [BBC nerve]
o axillary nerve [C5 and 6] passes through the quadrangular space and supplies the
deltoid and teres minor muscles and skin over the insertion of the deltoid muscle

96
 Roots C5

C6
Trunks
Divisions C7
Cords
C8
T1

Axillary nerve

Median nerve
Ulnar nerve
Musculocutaneous
nerve Axillary artery
Radial nerve
Fig 85: Brachial Plexus
 other branches include:
o branches from the roots:
 dorsal scapular [C5] supplies levator scapulae, rhomboid major and minor
 long thoracic [C5, 6 and 7] which supplies serratus anterior [damage of this
nerve results in a winged scapula]
o branches from the trunks:
 suprascapular nerve [C5 and 6] supplies supraspinatus and infraspinatus
 nerve to subclavius nerve [C5 and 6] supplies subclavius
o branches from the cords:
 posterior cord:
 upper and lower subscapular nerves supply the subscapularis
 thoracodorsal nerve [C6, 7 and 8] nerve supplies latissimus dorsi
 medial cord:
 medial pectoral nerve supplies pectoralis minor and major
 medial brachial cutaneous nerve supplies the medial arm
 medial antebrachial cutaneous nerve supplies the medial forearm
 lateral cord:
 lateral pectoral nerve supplies pectoralis major
 damage to C5 and 6 roots results in Erb-Duchenne palsy with the waiter accepting a tip
appearance [elbow extended, forearm pronated and fingers flexed]
 damage to C8 and T1 roots results in Klumpke’s palsy and presents with a claw hand

Lumbar plexus
 derived from the ventral rami of L1-4
 the plexus is formed within the psoas major
 all of its nerves leave the lateral aspect of the psoas major muscle except the following:
o genito-femoral nerve which exits the psoas major anteriorly
o obturator nerve which exits the psoas muscle medially
 branches include:
o iliohypogastric nerve [L1] innervates lower abdomen above the inguinal region
o ilioinguinal nerve [L1] supplies the inguinal region
o genitofemoral nerve [L1,2] -medial upper thigh and anterior part of genitalia
o lateral femoral cutaneous [L2,3] supplies the anterolateral aspect of the thigh
o femoral nerve [L2,3,4 posterior divisions] supplies the extensor thigh compartment
o obturator nerve [L2,3,4 anterior divisions] supplies the adductor thigh compartment
o contributes to the formation of the lumbosacral trunk [L4,5]

97
 T12
L1

L2
Iliohypogastric nerve
Ilioinguinal nerve L3
Genitofemoral nerve
Lateral femoral cutaneous nerve L4

Femoral nerve Obturator nerve

Fig 86: Lumbar Plexus

Lumbosacral plexus
 derived from the ventral rami of L4, 5, S1-4
 note that L4 ramus is shared by both the lumbar and sacral plexuses
 sacral nerves exit from the anterior sacral foramina and unite in front of the piriformis muscle
where they are joined by the lumbosacral trunk [L4 and 5]
 has the following main branches:
o superior gluteal nerve [L4, 5, S1]: supplies the gluteus medius, minimus and tensor
fasciae latae and passes through the greater sciatic foramen
o inferior gluteal nerve [L5, S1, 2]: passes through the lesser sciatic foramen and only
supplies gluteus maximus
o pudendal nerve [S2, 3 and 4]: supplies the external anal sphincter, deep and superficial
peroneal muscles, penis [or clitoris] and posterior scrotum [or labia]
o sciatic nerve [L4, 5, S1, 2, 3]:
 the largest nerve in the body and it passes beneath the piriformis through the
lesser sciatic foramen along with the inferior gluteal and pudendal nerves
 the sciatic nerve supplies the muscles in the posterior thigh and all the
muscles below the knee
 it supplies all of the skin below the knee EXCEPT for a thin strip along the
medial aspect of the leg and foot which is supplied by the saphenous branch
of the femoral nerve
 the sciatic nerve has two parts-tibial and common peroneal nerves

L4

L5

Superior Gluteal Nerve S1

Inferior Gluteal Nerve

S2

S3
Sciatic nerve
S4

Pudendal nerve

Fig 87: Lumbosacral Plexus

98
 o tibial nerve [L4, 5, S1, 2 and 3] supplies all of the following:
 all of the muscles in the posterior compartment of the leg
 all of the muscles in the plantar aspect of the foot
 divides into the medial and lateral plantar branches after it passed behind the
medial malleolus at the ankle
 also supplies all of the skin over the posterior aspect of the leg and the
plantar aspect of the foot
 the medial plantar nerve corresponds to the median nerve in the hand and
supplies the flexor digitorum brevis, flexor hallucis brevis, adductor hallucis and
the first lumbrical in the sole of the foot
 the lateral plantar nerve corresponds to the ulnar nerve in the hand and
supplies the rest of the muscles in the sole of the foot
o common peroneal nerve [L4, 5, S1 and 2] supplies the anterior and lateral
compartments of the leg:
 winds around the neck of the fibula and then divides into superficial and deep
peroneal nerves:
 superficial peroneal nerve supplies the muscles in the lateral compartment of
the leg:
 peroneus longus
 peroneus brevis
 also supplies the skin of most of the dorsum of the foot except the
web space between the first and second toes
 deep peroneal nerve passes through the peroneus longus [however it does not
supply it] and then enters the anterior compartment of the leg to supply the
following muscles:
 tibialis anterior
 extensor hallucis longus
 extensor digitorum longus
 peroneus tertius
 also supplies the skin of the web space between the first and second
toes

Structures passing through the greater sciatic foramen

o superior gluteal nerve, artery and vein
Structures passing through the lesser sciatic foramen [piano pi pan]
o piriformis, inferior gluteal artery, nerve, obturator internus, pudendal nerve and internal pudendal
artery and nerve

Spinal nerve, dermatomal distribution, specific muscle and reflex testing

Nerve Dermatome Muscle Reflex
C5 Shoulder Deltoid Biceps brachii
C6 Lateral forearm to thumb Biceps brachii Brachioradialis
C7 Middle finger Triceps Triceps
C8 Little finger to medial forearm Flexor digitorum profundus None
T1 Medial elbow None None
T2 Axilla None None
T7 Xiphoid region None None
T10 Umbilical region None None
T12 Suprapubic region None None
L1 Inguinal region None None
L2 Anterior thigh Iliopsoas None
L3 Lateral thigh Quadriceps femoris Patellar
L4 Medial leg and medial big toe Tibialis anterior Patellar
L5 Dorsum of foot Extensor hallucis longus Hamstring
S1 Lateral foot Peroneus longus Ankle

Table 6: MRS of Specific Spinal Nerves

The above areas are rough guides as the spinal dermatomes tend to overlap by as much as 50%. This is
because when the nerve fibers enters the dorsal horn of the spinal cord, some of its fibers may pass up or
down by as much as two spinal cord segments through the dorsolateral tract of Lissauer.

99
AUTONOMIC NERVOUS SYSTEM REVIEW

Divisions
 there are two major divisions:
o sympathetic aka the thoracolumbar outflow [Fight or Flight]
o parasympathetic aka the craniosacral outflow [Rest and Digest]

Sympathetic division
 originates in the posterior nuclei in the hypothalamus
 preganglionic fibers are derived from the intermediolateral horn of the spinal cord fromT1-12 and
L1-L4
 associated ganglia are located near the vertebral column [paravertebral]
 connected to the thoracic spinal nerves by white and grey rami communicantes
 preganglionic fibers are short and myelinated input [hence white] fibers
 postganglionic fibers are long and unmyelinated output [hence grey] fibers
 some of the fibers leave the sympathetic ganglia without synapsing in the ganglia
 these long preganglionic fibers pass on to other ganglia in the periphery where they synapse-the
splanchnic nerves synapse in the celiac, superior mesenteric and aortico-renal ganglia in the
abdomen before going to the gut, aorta and kidneys:
 cardiac plexuses from T1-T4 ganglia
 greater splanchnic nerves are derived from T5-T9 ganglia [ to the celiac ganglion]
 lesser splanchnic nerves are from T10 and T11 [to the superior mesenteric ganglion]
 least splanchnic nerves are from T12 [to the aortico-renal ganglion]
 Inferior hypogastric nerves are from L1 and L2
 some of the preganglionic fibers in T1 and T2 ganglia ascending in the trunk to synapse in the
inferior, middle and superior cervical sympathetic ganglia which are not connected to the
cervical spinal nerves
 sympathetic fibers are distributed to smooth muscle in blood vessels, bronchi, gut and the
arector pili and to sweat glands in the skin
 the main end organ neurotransmitter in the sympathetic system is norepinephrine
 EXCEPT for the sweat glands in which acetylcholine is the transmitter
 the neurotransmitter in the sympathetic ganglia is acetylcholine [nicotinic receptor]

Intermediolateral horn

Grey ramus communicans

with postganglionic fibers
[output fibers]

Thoracic spinal nerve

Preganglionic sympathetic fibers

White ramus communicans [input fibers]
with preganglionic fibers Sympathetic Ganglion
[input fibers]

Fig 88: Sympathetic Trunk

100
Parasympathetic division
 originates in the anterior nuclei in the hypothalamus
 carried by CN III, VII, IX and X and S2, 3 and 4 nerves
 its ganglia are closer to the end organs
 it has long preganglionic fibers and short postganglionic fibers
 Acetylcholine is the neurotransmitter in both the ganglia and end organs

Parasympathetic ganglia in the head

There are 4 cranial parasympathetic ganglia:
 Ciliary ganglion
o CN III located in the orbit on the nasociliary branch of CN V1
o distributed to the sphincter pupillae muscle and the ciliary muscles
 Pterygopalatine ganglion
o CN VII located in the pterygopalatine fossa on the trunk of CN V2
o distributed to the lacrimal, nasal and palatine glands
 Otic ganglion
o CN IX located just distal to the foramen ovale on the auriculotemporal branch of CN V3
o distributed to the parotid gland
 Submandibular
o CN VII located on the hypoglossal muscle hanging off of the lingual branch of CN V3
o distributed to the submandibular and sublingual salivary glands

Neurotransmitters
There are two types of neurotransmitters in the autonomic nervous system:
 cholinergic [acetylcholine]
 adrenergic [norepinephrine]
 all acetylcholine receptors are nicotinic
 including the ACH receptor in the neuromuscular junction which is also nicotinic in nature
 EXCEPT the postganglionic receptors which are muscarinic including the sweat gland receptors
 Not all tissues have both sympathetic and parasympathetic innervation, namely:
o Blood vessels [only sympathetic innervation]
o Arector pili muscle [only sympathetic innervation]
o Bronchial glands [only parasympathetic innervation]
o Adrenal medulla [only preganglionic sympathetic innervation]
o Sweat glands [only sympathetic innervation]

Difference Sympathetic Receptor Parasympathetic

Location of ganglia Paravertebral Nicotinic Ach receptor Intramural
Preganglionic fiber Short Nicotinic Ach receptor Long
Postganglionic fiber Long Muscarinic Ach receptor Short
Bronchial glands None Muscarinic Ach receptor Stimulates secretions
Sweat glands Increases sweat production Muscarinic Ach receptor None
Salivary glands Reduce secretions Muscarinic Ach receptor Stimulates secretion
Pupil size Dilates pupil [radial constriction] α Constricts pupil
Ciliary muscle Relaxes for far vision α Contracts for near vision
Blood vessels Causes vasoconstriction α None
Gut muscle Inhibits α Stimulates
Glands Inhibits secretion α Stimulates secretions
Sphincter Contracts α Relaxes
Bladder sphincter Contracts α Relaxes
Sex organs Causes ejaculation α Causes erection/engorgement
Cardiac muscle Increases rate and force β1 Slows the heart rate
Coronary vessels Causes vasodilatation β2 Causes vasoconstriction
Bronchial muscle Relaxes [bronchodilation] β2 Bronchoconstriction
Bladder wall Relaxes Β2 Contracts
Hair muscles Contracts arector pili β2 None
Skeletal blood vessels Vasodilation β2 None
Adrenal medulla Stimulates secretions Nicotinic Ach receptor None
Neurotransmitter Norepinephrine EXCEPT sweat glands Acetylcholine
Nuclei location Posterior Hypothalamus Anterior Hypothalamus

Table 7: Sympathetic versus Parasympathetic Distribution

101
Adrenergic receptors
 there are two types of adrenergic receptors: α and β
 All α adrenergic receptor type cause contraction of smooth muscle including the dilator
[radially-arranged fibers] pupillae muscle in the eye
 All β adrenergic receptors are β2 type EXCEPT those that are found in the heart which are β1
 The β1 receptors in the heart cause an increase in the heart rate and force of contraction
 All β2 receptors cause relaxation of smooth muscle EXCEPT the receptors to the arector pili
which causes contraction

Enteric Brain
 found within the wall of the intestine and it contains as many neurons as the spinal cord
 two major interconnected intramural plexuses:
o myenteric plexus of Auerbach:
 found between the inner circular and outer longitudinal smooth muscle
layers of the muscularis externa and regulates contraction of these muscles
o submucosal plexus of Meissner:
o lies under the mucosa and regulates the secretion of intestinal glands
 Auerbach plexus lies on the Autside and Meissner plexus lies on the inside
 these two plexuses contain both sympathetic and parasympathetic fibers
 the enteric brain contains many more neurotransmitters besides norepinephrine and acetylcholine
 it controls the gastrointestinal tract
 nociception from the esophagus to the splenic flexure is carried by fibers passing along the
sympathetic fibers
 afferent parasympathetic fibers carry nociception from the splenic flexure to the rectum and
from the bladder and prostate
 the enteric brain is also involved in autonomic mediated reflexes

Auerbach plexus
Meissner’s plexus

Mucosa

Submucosa Serosa
Circular muscle layer
Longitudinal muscle layer

Fig 89: Enteric Nervous System

Autonomic mediated reflexes

There are three types of reflexes that are mediated by the autonomic nervous system:
Viscerovisceral reflex
 this type of reflex begins with viscera and ends with viscera
 a good example is pressure on the carotid sinus in the neck results in a reflex which slows the
heart rate and causes a drop in blood pressure
 this reflex is mediated by CN IX [afferent] and the sympathetic nerves to the heart [efferent]
Viscerosomatic reflex
 this type of reflex originates in an internal organ and causes a peripheral muscle to contract or
relax
 for example, the Hering-Breuer reflex in which inflation of the lung triggers the diaphragm to
relax is mediated by the vagus [afferent] and phrenic nerves [efferent]
 another example is Inflammation of the gallbladder causing spasm of paravertebral muscles in
the region of T9 myotome [infrascapular muscles]
Somatovisceral reflex
 this type of reflex starts in segmental paraspinal muscles and ends in viscera
 an example is paraspinal muscle spasm triggered by internal disc disruption causing spinal
nerve root irritation which results in visceral dysfunction
 this is mediated through the sympathetic trunk which innervates both the outer layer of the
intervertebral disc and the internal viscera

102
PHYSIOLOGY

103
104
CARDIOVASCULAR REVIEW

Functions
1. muscular pump for blood circulation-5 to 6 liters per minute in a 70 kg man
2. endocrine:
 ANP [Atrial Natriuretic Peptide] in response to increased atrial pressure
 BNP [B-type Natriuretic Peptide] in response to overstretched ventricles

Cardiac muscle
o involuntary muscle with cross striations
o the individual cells are connected by intercalated discs with gap junctions
o the gaps junctions allow for the passage of ions between the myocytes
o these allow the action potentials to spread between the cardiac myocytes
o the intercalated discs allow the heart to contraction in synchrony as one unit [syncytium]

Cardiac muscle contraction

+ ++ +
 In the resting state, there is more Na and Ca outside the cell and more K inside the cell
+
 Phase 0: Na influx into cardiac myocytes causes rapid depolarization-the rapid upstroke
+ +
 Phase 1: inactivation of fast Na with K efflux with a notch of initial repolarization
++ ++
 Phase 2: Ca influx through L-type Ca channels-the plateau phase
++ +
 Phase 3: inactivation of Ca channels with K efflux-rest of repolarization
+ ++
 Phase 4: removal of excess Na and Ca with restoration of membrane potential
Phase 1

+20 Phase 2
0 mV
-20
-40 Phase 3
-60
Phase O
-80 Phase 4
-100

Fig 90: Electrical Changes in Ventricular Fibers

 Refractory periods:
i. absolute-no action potential can be initiated regardless of the stimulus strength
because the Na channels are closed as in Phase 1 and 2
ii. relative-an action potential can be elicited, however a greater stimulus is
needed-extends between the middle of Phase 3 to the start of Phase 4
iii. cardiac musce is incapable of sustained contration [tetany] as in skeletal muscle
because of the refractory period
 Digoxin acts by increasing the influx of calcium thus increasing the force of the contraction
 Frank-Starling law: cardiac output is directly proportional to the venous return
i. force of contraction of a myocardial fiber is proportional to the length of the
myocardial fiber
ii. the greater the amount of blood entering the heart during diastole [venous
return], the greater is the stretching of the cardiac myocytes
iii. greater stretch results in a greater force of contraction resulting in an increase
in the cardiac output
iv. Cardiac output is the volume of ejected blood from the heart per minute

Cardiac cycle
st
 1 heart sound due to the closure of the tricuspid and mitral valves [LUB]
nd
 2 heart sound due to the closure of the pulmonary and aortic valves [DUB]
rd nd
 3 heart sound occurs after the 2 heart sound-congestive heart failure [DUBup]
th st
 4 heart sound is heard just before 1 heart sound-hypertrophic ventricles [beLUB]
 systole [contraction] occurs between heart sounds 1 and 2
 diastole [relaxation] occurs between heart sounds 2 and 1

105
 Pressure in the aorta [80/120 mm Hg]

Pressure in left ventricle [0-120 mm Hg]

Pressure in right ventricle [0-25 mm Hg]

Heart Sounds 1, 2, 3 and 4
Jugular Venous Pressure [0-5 mm Hg]
a-right atrial contraction
c-right ventricular contraction
v-passive filling of the right atrium
Electrocardiogram

Fig 91: Cardiac Cycle

Electrocardiogram
 This is a reflection of the electrical activity in the heart as the impulse generated in the SA node
is propagated to the rest of the heart
 The initial impulse is generated by the SA node which has its own intrinsic rhythmicity of around
80-100 beats per minute
 The impulse is spread throughout the atria via intra-atrial bundles to cause both atria to contract
simultaneously
 The atria are separated from the ventricles by the 8-shaped annulus fibrosus
 The impulse is spread to the ventricles from the SA node to the AV node which has its own
intrinsic rhythmicity of around 40-60 beats per minute
 When the SA nodal rhythm is superimposed upon the AV nodal rhythm, the heart beats at 70 beats
per minute
 The impulse from the AV node is passed down through the Bundle of His into the right and left
bundle branches which are located in the muscular part of the interventricular septum
 The conduction velocity is slowest in the AV node and fastest in the Purkinje fibers
 These are the following parts in the ECG:
o P wave represents atrial depolarization
o PR interval-extends from the P wave to the start of the Q wave [,200 milliseconds]
o QRS complex-represents ventricular depolarization [<120 milliseconds]
o QT interval-extends from the beginning of the Q wave to the end of the T wave
o ST segment-extends from the end of the S wave to the start of the T wave
o T wave-ventricular repolarization
o Atrial repolarization is not seen on the ECG because it is buried by the QRS complex
o In some people there may be a U wave after the T wave
o The U wave may represent repolarization of the Purkinje fibers or the papillary muscles

P T

Q
PR ST

S
QT interval

Fig 92: EKG waves

106
Heart Rate Control-via the cardiac plexus
 sympathetic: [T1-T5, the middle and inferior cervical ganglia]
o increases heart rate [+chronotropism] by increasing rate of Phase 4
o increases conduction velocity [+dromotropism] by decreasing the PR interval
++
o increases force of contraction [+inotropism] by increasing Ca influx in Phase 2
 parasympathetic: [Vagus nerve via its cardiac branches]
o decreases heart rate [negative chronotropism] by decreasing rate of Phase 4
repolarization
o decreases conduction velocity [negative dromotropism] by increasing the PR interval
++
o decreases force of contraction [negative inotropism] by decreasing Ca influx in Phase 2

Blood Pressure
 systemic arterial blood pressure is 120/80 mm Hg
 120 mm Hg is the systolic pressure and 80 mm Hg is the diastolic pressure
 Blood pressure is the product of the Cardiac Output multiplied by the Peripheral Resistance
 Cardiac output is the product of the Stroke Volume multiplied by the Heart Rate
 70 ml x 70 beats per minute = approximately 5 liters per minute

Blood Pressure Control

 BP may be affected by either the heart rate, peripheral resistance or stroke volume
 two main mechanisms are involved, one fast and one slow:
 baroreceptors [fast due to neurotransmitter]
 renin-angiotensin-aldosterone mechanism [slow because it is hormonal dependent]
 baroreceptor mechanism:
o baroreceptors located in the carotid sinus and in the aortic arch [afferents are carried
by CN IX and CN X respectively] relay pressure information to the brain stem
o there is a reflexive response to a rise or drop BP via sympathetic or parasympathetic
system
o a drop in the blood pressure will cause the heart rate to increase

Peripheral Resistance
 Poiseuille’s law: Peripheral resistance [PR] is directly proportional to the viscosity of blood and
th
to the length of the vessel and inversely proportional to the radius of the vessel to the 4 power
 If the blood vessel radius decreases by a factor of 2, then the resistance increases by a factor of 16

Blood Flow
 blood flow through a tubular structure is governed by La Place’s law which states that pressure
within a blood vessel is related to the tension, size and shape of the vessel
 blood flow is inversely proportional to the diameter of the blood vessel
 blood flow in a normal blood vessel is smooth and laminar
 as the diameter of the vessel becomes smaller, the resistance to flow is increased
 60% of the total blood volume is contained in the venous system at any one time while 20% is in
the arteries and arterioles, 15% lies within the pulmonary system and 5% in the capillaries
 blood flow is greatest in the arteries and veins and least the capillaries

Capillary pressures
 intracapillary hydrostatic pressure which tends to force fluids out into the interstitial space [+]
 intracapillary oncotic [protein-related] pressure which tends to pull fluids into the capillary [-]
 interstitial hydrostatic pressure which forces fluids into the capillary [-]
 interstitial oncotic pressure which pulls fluid out of the capillary [+]
 imbalance in these forces may cause edema which is due to excess fluid in the interstitial space

Vascular Response to Exercise

 stimulation of the sympathetic nervous system results in:
o increase heart rate, conduction velocity and cardiac contractility [β1 effect]
o vasoconstriction in the skin, gut and inactive muscles [α effect]
o vasodilation of the blood vessels to active skeletal muscle [β2 effect]
o dilation of the coronary arteries [β2 effect]
 this leads to increased cardiac output and increased blood supply to the active skeletal muscles
 Prolonged exercise leads to cardiac muscle hypertrophy

107
ENDOCRINE REVIEW

The Pituitary Gland

 although the pituitary gland is called the master control gland in the endocrine system, it is under
the control of the hypothalamus
 the pituitary gland is divided into two structurally, embryologically and functionally different
lobes, namely the anterior and posterior lobes

Prolactin

LH

Oxytocin

FSH

ADH

TSH ACTH
Somatotropin

Fig 92: Endocrine Control

 anterior pituitary lobe
o aka adenohypophysis
o secretes the following hormones under the influence of releasing factors [with one
exception] from the hypothalamus:
o ACTH [stimulated by Corticotrophin Releasing Hormone-CRH]
 Adrenocorticotropin Hormone or corticotropin
 governs synthesis of cortisol in the adrenal cortex
 increased ACTH is seen in Cushing’s syndrome
o FSH [stimulated by Gonadotrophin Releasing Hormone-GnRH]
 Follicle Stimulating Hormone
 stimulates the follicles in the ovaries to produce estrogen
 stimulates the Sertoli cells for spermatogenesis
o LH [stimulated by Gonadotrophin Releasing Hormone-GnRH]
 Luteinizing Hormone
 stimulates ovulation and the production of progesterone in the ovary
 stimulates the interstitial cells of Leydig in the testis to produce testosterone
o GH [stimulated by Growth Hormone Releasing Hormone-GHRH]
 Growth Hormone or somatotropin
 stimulates bone and tissue growth through somatomedins A-C
 increased GH results in gigantism or acromegaly
 decreased GH is seen in pituitary dwarfism
o TSH [stimulated by Thyrotrophin Releasing Hormone-TRH]
 Thyroid Stimulating Hormone
 stimulates the thyroid to produce Thyroxin
 increased thyroxin results in hyperthyroidism [thyrotoxicosis]
 decreased thyroxin results in hypothyroidism [myxedema]

108
 o Prolactin [affected by Prolactin Inhibiting Factor and TRH]
 promotes breast development and milk production
 however it does not cause milk ejection from the breast
 posterior pituitary lobe
o aka neurohypophysis
o two hormones stored [but not secreted] in the posterior lobe
o Oxytocin is secreted by the paraventricular nucleus in the hypothalamus:
 it stimulates contraction of uterine muscle [labor] and the myoepithelial cells
in the breast [milk ejection]
 its released is stimulated by nipple stimulation
 it also plays a role in maternal bonding
o ADH is secreted mainly by the supraoptic nucleus of the hypothalamus:
 it acts on the collecting ducts in the kidney
 released in response to water deprivation
 prevents water from being excreted in the urine [diuresis]
 decreased ADH leads to diabetes insipidus-polyuria and polydypsia
 pars intermedia
o this lies between the anterior and posterior pituitary lobes
o it secretes Melanin Stimulating Hormone
 stimulates the production of melanin by the melanocytes in the skin

The thyroid gland

 under the stimulation of TSH, iodine combines [iodination] with tyrosine in the thyroglobulin
molecule [organification] located within the follicles to form mono-iodo-tyrosine [MIT]
o 2 molecules of MIT are coupled to form di-iodo-tyrosine [DIT]
o 2 DITs are coupled to form T4
o 1 DIT coupled with 2 DITs to form T3 which is the active hormone
 T4 [Tetra-iodothyronine or Thyroxin] increases metabolism and is less active than T3
 T3 [Tri-iodothyronine] increases metabolism and is more active than T4
 Hyperthyroidism [Graves disease] results in exophthalmos, weight loss and tremors
 Hypothyroidism results in cretinism in children and myxedema in adults with weight gain,
coarse hair and decreased metabolism
 in addition, the parafollicular cells of the thyroid gland secrete calcitonin
 Calcitonin takes calcium from the blood and puts it back into bone [tones the bones]
o this has the opposite effect of parathyroid hormone [PTH]
o calcitonin plays a minor role in calcium metabolism

The parathyroid glands

 PTH is secreted by the chief cells in the parathyroid glands
 PTH takes calcium from the bone and puts it into the blood
 PTH also increases calcium reabsorption in the kidney by acting on the cells in the distal
convoluted tubules
 in addition, PTH increases calcium absorption from the gut
 hypocalcemia due to hypoparathyroidism excites the nervous system and results in tetany and
muscle spasm
 hypercalcemia due to hyperparathyroidism results in muscle fatigue

The adrenal gland

 the adrenal gland is divided into two parts: cortex and medulla
 the adrenal cortex
o three layers from superficial to deep and secrete the following:
 zona glomerulosa-aldosterone [salty]
 zona fasciculata-cortisol [sweet]
 zona reticularis-androstenedione [sexy]
 aldosterone is a mineralocorticoid [salty]
o it acts on the kidney to regulate Na reabsorption from the distal convoluted tubule
o It causes water retention and an increase in blood pressure
o aldosterone is under the influence of renin which is secreted by the juxtaglomerular cells
of the kidney
o excess aldosterone is seen in primary hyperaldosteronism [Conn’s syndrome]-results
+ +
in high Na , hypertension and low K

109
  cortisol is a glucocorticoid [sweet] which regulates the metabolism of the following:
o fat [increases lipogenesis]
o carbohydrates [increases glycogenesis]
o proteins [increases gluconeogenesis at the expense of protein]
o maintains blood pressure by upregulating alpha-1 receptors in arterioles
o decreased bone formation
o suppresses inflammation [anti-inflammatory effect]
 estrogen, progesterone and testosterone are derived from androsteinone [sex] secreted by the
zona reticularis
 destruction of the adrenal cortex results in Addison’s disease
o it affects all three layers of the cortex
o it causes weight loss, low blood pressure and bronzing of the skin
 all of the adrenal cortex hormones are produced from cholesterol
 the adrenal medulla:
o secretes epinephrine [80%] and nor-epinephrine [20%]
o it behaves more like a sympathetic ganglion as it is supplied by preganglionic fibers
o nor-epinephrine is produced from tyrosine which is derived from phenylalanine
o epinephrine is produced from nor-epinephrine
 these two hormones are neurotransmitters in the sympathetic nervous system and are responsible
for the flight or fight response to stress:
o increase heart rate
o dilate coronary vessels
o dilate arteries to skeletal muscle
o dilate the bronchi and the pupil
o decrease gut motility
o constrict the bladder and bowel sphincters
o contract the erector pili muscles in the skin
o decrease salivary secretion
o increase sweat production
 increased secretion of nor-epinephrine is seen in pheochromocytoma
o results in 4 Ps: perspiration, heart palpitations, paroxysms of hypertension and
pressure headaches

Pancreas
 the endocrine cells in the pancreas are found in the islets of Langerhans
 Insulin is secreted by the beta type of islet cells
o moves glucose from in the blood to inside the cells
 there are several tissue specific transporters that carry glucose:
 GLUT 1 erythrocytes and brain
 GLUT 2 liver and beta islet cells
 GLUT 3 neurons
 GLUT 4 skeletal muscle and adipose tissue
o promotes synthesis of fat, glycogen and protein and cellular uptake of potassium
o inhibits gluconeogenesis, lipolysis and protein degradation
o anabolic hormone released when blood glucose levels are high
o insulin secretion is also stimulated by the amino acids alanine and leucine
o excess insulin is seen in insulin secreting tumors [insulinoma]
 produces low blood sugar levels
o decrease insulin secretion or function results in diabetes mellitus
 produces polyuria, polydypsia, polyphagia and pruritus
 Glucagon is secreted by the alpha cells
o causes the liver to convert glycogen to glucose [promotes glycogenolysis]
o released when blood glucose levels are low
 Somatostatin is secreted by delta cells of the pancreas
o it is also secreted by the D cells in the stomach and by the hypothalamus
o also known as Growth Hormone Inhibitory Hormone as it inhibits the following:
 Renin
 Insulin
 Growth hormone
 Gastrin
 Glucagon

110
GASTROINTESTINAL REVIEW

Functions
 GI tract has several functions:
o digestion
o absorption
o excretion
o endocrine
 function of the GI tract is best understood by looking at what happens in the various parts of the
gastrointestinal tract and in addition to what happens with the various food types as they pass
through the alimentary tract

Mouth
 mastication [chewing] breaks down food
 in addition salivary amylase [ptyalin] assists in the chemical breakdown of carbohydrates and
starches into maltose
 there is also lingual lipase which is secreted by lingual glands in the mouth

Stomach
 food on entering the stomach is mixed with secretions from the gastric glands
 gastric glands contain 3 types of cells:
o mucosal [neck] cells:
 secrete mucus and gastrin
 G cells produce gastrin which stimulates gastric secretions
o chief cells:
 produce pepsinogen
 in the presence of hydrochloric acid, pepsinogen is activated to form pepsin
 pepsin is necessary for protein digestion
o parietal cells:
 secrete hydrochloric acid and intrinsic factor
 HCl is needed for the activation of pepsinogen
 HCl will destroy many bacteria
 Intrinsic factor is necessary for the absorption of Vitamin B12 in the terminal
ileum
 the mixture of food and gastric secretions is called chyme

Small Intestine
 chyme is propelled through the small intestine by peristaltic waves
 the presence of chyme in the small intestine stimulates the release of secretin from the S-cells
found in the duodenum:
o secretin stimulates pancreatic acinar cells to release bicarbonate and water
o bicarbonate is also secreted by Brunner’s glands in the duodenum, neutralizes the
gastric acid and makes the pH alkaline
 it also protects the duodenal wall from digestion by the highly acidic gastric juice
being emptied into the duodenum
o in addition secretin decreases gastric motility
 the presence of fat in the duodenum stimulates the release of cholecystokinin [CCK]
o cholecystokinin is released by the I-cells in the duodenum
o it causes the gallbladder to contract
o CCK causes the sphincter of Oddi to relax
o this causes bile to be excreted into the duodenum
o it also stimulates the pancreas to secrete enzymes which aid in the digestion of fat,
starches and protein
o pancreatic amylase completes the breakdown of starch into maltose
 further digestion is assisted by secretion of others enzymes from enterocytes in the small intestine:
o maltase which breaks down maltose into two molecules of glucose
o lactase which breaks down lactose into glucose and galactose
o sucrase which breaks down sucrose into glucose and fructose
o lactase, sucrase and maltase are found in the brush border of the enterocytes
o there is also a small amount of intestinal lipase that is secreted which digests fat

111
 o some digested fat is absorbed into the central lacteals which drain into the thoracic duct
o intestinal peptidases digest the polypeptides released by the action of the proteolytic
pancreatic enzymes [trypsin, chymotrypsin, carboxypolypeptidase and proelastase] to
produce amino acids
 the final breakdown products of fat, starch and protein digestion are produced in the small intestine:
o fat to fatty acids and glycerol
o starch, sucrose and lactose to glucose, fructose and galactose
o proteins to amino acids
 these breakdown products are absorbed by the small intestine and transported to the liver
except some fat which is absorbed by the central lacteals which drain into the thoracic duct

Pancreas
 there are both exocrine and endocrine cells in the pancreas:
o exocrine cells make up the bulk of the pancreas and are arranged in acini to secrete:
 trypsinogen
 trypsinogen is activated to trypsin by enterokinase
 enterokinase is released by enterocytes in the small intestine
 chymotrypsin, carboxypolypeptidase and proelastase
 pancreatic amylase
 aids in the digestion of starch to produce maltose
 lipase
 breaks down fat into fatty acids and glycerol
o endocrine cells are located in the islets of Langerhans which secrete:
 Glucagon [alpha cells]
 Insulin [beta cells]
 Somatostatin [delta cells]

Large Intestine
 most of the water in food is absorbed in the large intestine
 undigested food is propelled down the large intestine and out through the anal canal as feces
 bacteria found in the large intestine produce Vitamin K
 the colon has numerous goblet cells which secrete mucus to aid in the passage of feces

Absorption of vitamins and minerals

 fat soluble vitamins [DAKE] are processed in the same manner as the other lipids in the diet
 some Vitamin K is made by bacteria in the colon
 water soluble vitamins [B, C and folic acid with the exception of Vitamin B12] enter the
+
enterocytes by secondary active transport mechanisms using Na -amino acid co-transporters
 all water-soluble vitamins exit the enterocytes by diffusion into the portal circulation
 Folic acid and iron are absorbed in the jejunum
o iron combines with apotransferrin in the blood to form transferrin
o Transferrin transfers the iron in the blood to the cells in the liver, spleen and bone marrow
o In the cell, the iron is bound to apoferritin to form ferritin
o The iron is release by the cells to form hemoglobin and myoglobin
 Vitamin B12 [cobalamin] in the diet is attached to Intrinsic Factor secreted by the parietal cells o
o Vitamin B12 – Intrinsic Factor complex is delivered to the terminal ileum where it is
bound to cubilin receptors on the enterocytes and transported into the enterocytes
o Vitamin B12 diffuses out into the portal blood

Role of the liver

 carbohydrate metabolism: glycogenesis, glycogenolysis and gluconeogenesis
 protein metabolism: builds proteins
 lipid metabolism: makes fat and cholesterol
 stores glycogen and vitamins A, D and B12
 detoxifies toxic substances such as hormones, drugs, poisoning including alcohol
 conjugates bilirubin
 produces antibodies
 makes steroid hormones
 manufactures clotting factors
 makes red blood cells in the fetus
 involved in the immune system through the Kupffer cells

112
Bilirubin metabolism
 bilirubin is a byproduct of red blood cell breakdown in the spleen
 old red blood cells [> 120 days] are broken down to release heme and globin
 the heme is further broken down into bilirverdin and iron
 bilirverdin is converted into bilirubin which is carried in the blood attached to albumin
 in this form, it is soluble in lipids but insoluble in water
 it is transported to the liver where it is conjugated with a glucuronide by glucuronyl transferase
 conjugation renders the previous water-insoluble [indirect] bilirubin into a water-soluble state
 conjugated [direct] bilirubin is secreted into the biliary tract and into the gallbladder
 when it is excreted by the gallbladder, the bile [bilirubin plus bile salts] saponifies [making it like
soap] fat rendering it more easily digested by pancreatic lipase
 the bilirubin in the gut is converted by bacteria to urobilinogen
 some of the urobilinogen is absorbed into the blood stream
 this is excreted in the urine where it is converted to urobilin which gives the urine its color
 the rest of the urobilinogen in the gut is converted to stercobilinogen
 stercobilinogen is oxidized to stercobilin which gives the characteristic color of the stool
 95% of the bile salts are reabsorbed and sent back to the liver [enterohepatic circulation]

Role of the gallbladder

 stores bile [approximately 50 cc] and concentrates bile
 excretes bile in response to the presence of fat in the duodenum
 controlled by cholecystokinin by the small intestine when fat enters the duodenum
 cholecystokinin causes the contraction of the gallbladder

Endocrine secretion from the gut

 gastrin
o from the G cells in the pyloric antrum of the stomach
o stimulates hydrochloric acid secretion from the parietal cells
o stimulates gastric motility
 somatostatin
o from the D cells in the stomach and delta islet cells in the pancreas
o inhibits gastric acid secretion
o inhibits gallbladder contraction
o decreases pancreatic secretion
 gastric inhibitory peptide
o secreted by the K cells in the small intestines
o inhibits the effect of gastrin on the parietal cells in the stomach
o decreases gastric acid secretion
 cholecystokinin
o from the I cells in the small intestine by the presence of fat in the duodenum
o stimulates the release of bile from the gallbladder
o stimulates pancreatic enzyme secretion
o stimulates contraction of the gallbladder
o relaxes the sphincter of Oddi and the lower esophageal [cardiac] sphincter
o inhibits gastric emptying
 secretin
o from the S cells in the intestinal crypts of Lieberkuhn
o stimulates the release of bicarbonate from the pancreas
o decreases gastric acid secretion
 glucagon-like peptide 1
o resembles glucagon
o secreted by the K cells in the duodenum and jejunum
o inhibits gastric emptying
 ghrelin
o P cells in the stomach
o increased before meals and decreased after eating
 motilin
o secreted by cells in the duodenum
o controls the cyclical movement of the gut
o increased in the fasting state

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HEMATOLOGY REVIEW

Function of Blood
 gas transport
 immunity
 clotting
 transport of nutrients
 transport of waste

Composition of Blood
 total blood volume is 5 liters in the average 70 kg man
 cells [45%] [equivalent to the hematocrit] made up of the following:
o red blood cells [4.5 to 6 million per milliliter of peripheral blood]
o white blood cells [5,000 to 10,000 WBCs per milliliter of peripheral blood]
o platelets [150,000 to 300,00 platelets per milliliter of peripheral blood]
 plasma [55%] which contains electrolytes, glucose, urea and protein

Production of Blood cells

 all blood cells come from pluripotential hemopoietic stems cells
 totipotent cells give rise to any and all cell types
 pluripotent cells may give rise to several cell types
 unipotent cells can only develop into one cell type
 these cells are located in the marrow in the adults and in the liver, spleen, lymph nodes and
bone marrow in the fetus
 two cell lines: myeloid and lymphoid
 lymphoid cell line gives rise to two cell lines:
o B cells [activated in the Bone marrow]:
 plasma cells
o T cells [activated in the Thymus]
 lymphocytes
 myeloid cell line gives rise to several cell lines:
o erythroblasts which develop into reticulocytes and finally adult red blood cells
 stimulated by erythropoietin released by the kidney
o granulocytes which develop into basophils, eosinophils and neutrophils
o monocytes which become macrophages once they migrate into the tissues
o megakaryocytes which develops into platelets

Red Blood Cells

 doughnut shaped cells carry hemoglobin which transports oxygen and carbon dioxide

White Blood Cells

 types
o Neutrophils Never Bacterial infections Biting [60%]
o Lymphocytes Let Viral or chronic infections Vines [30%]
o Monocytes My Macrophage activity in tissues Make [8%]
o Eosinophils Engine Parasitic infection Pain [2%]
o Basophils Blow Hypersensitivity or allergies Happen [0%]
 WBCs may be classified according to the presence or absence of granules stainable with the
standard Hematoxylin and Eosin dyes:
o Granulocytes: Basophils, Eosinophils and Neutrophils
o Agranulocytes: Lymphocytes and Monocytes

Phagocytosis
 this is the process by which white blood cells ingest offending agents in the tissue
 mainly done by neutrophils and macrophages
 macrophages are monocytes that have migrated from the blood into the surrounding tissue

114
  phagocytes [neutrophils and migrated monocytes] must be selective of the material they ingest
 most natural structures in the tissues have smooth surfaces which resist phagocytosis
 most natural substances have protective protein coats which repel phagocytes
 dead tissue and foreign particles have no protective coats which makes them more susceptible
to phagocytosis
 both neutrophils and macrophages have lysosomes filled with proteolytic enzymes
 after phagocytosis, the lysosomes come in contact with the ingested material and dump their
enzymes into the phagocytic vesicle and digestion begins
 in addition, both neutrophils and macrophages produce bactericidal agents which kill most
bacteria
 macrophages are found in the skin, subcutaneous tissue, lungs, lymph nodes, liver [Kupffer
cells], spleen and bone marrow

Blood clotting
 when tissue is damaged, some blood vessels may be torn and bleeding occurs
 in order to limit blood loss, the body initiates a clotting process
 two pathways-Intrinsic and Extrinsic connected to a common pathway
 Vascular damage activates the intrinsic pathway [XII,XI, IX, VIII and X]
o Factor XII is activated by chemical derived by damaged tissue
o Activated Factor XII activates Factor XI
o Activated Factor XI activates Factor IX
o Activated Factors IX and VIII activates Factor X
 Tissue damage activates the extrinsic pathway [VII and X]
o Factor VII is activated by chemical released by vascular damage
o Activated Factor VII activates Factor X
 Activated Factor X converts prothrombin [Factor II] to thrombin [activated Factor II]
 Thrombin [activated Factor II] converts fibrinogen [Factor I] to fibrin
 Fibrin forms the clot

Intrinsic Pathway Extrinsic Pathway

Vessel damage Tissue damage

Factor XII Activated Factor XII Activated Factor VII Factor VII

Factor XI Activated Factor XI

Factor IX Activated Factor IX

Factor VIIIa

Factor X Activated Factor X Factor X

Prothrombin Thrombin [activated Factor II]

[Factor II]

[Factor I] Fibrinogen Fibrin Clot

[activated Factor 1]
Fig 94: Clotting Cascade

Blood Groups
The common blood groups are ABO and Rh types based on the presence of A, B or Rh antigens on the
surface of the red blood cells.
Group O [no A or B antigens] blood can be safely given to patients with all blood types and is known as the
universal donor.
People with blood group AB can receive all blood types and is known as the universal recipient.
When incompatible blood is given to a patient [e.g. A, B or AB blood to a Group O patient], then the
antibodies to the A or B antigens will cause the transfused red blood cells to agglutinate and clump together.

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IMMUNITY REVIEW

Divisions
 2 major subdivisions:
o nonspecific [innate]
o specific [acquired-after initial exposure]

Nonspecific or Innate Immunity

 depends on physical barriers such as:
 mechanical-skin, GI, respiratory, GU epithelium
 chemical- acid pH in the stomach and vagina
 there are also vascular and phagocytic responses which are a result of injured or infected cells
 in addition, the complement system is involved as it is designed to defend against infection by
promoting phagocytosis and killing cells directly
 certain bacteria carry surface molecules which activate the complement system of plasma proteins
 complement activation produces a series of activities [OILCAN to grease the process]:
 Opsonization which makes target cells more susceptible to phagocytosis
o complement fragments known as opsonins bind to the surface of bacteria
o phagocytic cells with receptors for these fragments become attached to the
opsonized bacteria
o thus increasing the binding of bacteria for phagocytosis [C3b]
 Inflammation by activation of mast cells in anaphylaxis [C3a, C4a and C5a]
 Lysis due to the increased efficiency of bacterial phagocytosis [C5b6789]
 Chemotaxis to attract specific white blood cells [C5a]
 Agglutination: changes the surface of the invading bacteria making them sticky
 Neutralization of toxic sites on the surface of the antigen

Specific or Acquired Immunity

 involves the production of antibodies against specific foreign antigens by lymphocytes
 antigens [antibody generating substances] are usually large complex molecules
 smaller molecules called haptens may also stimulate antibody production
o only if attached to a protein for initial presentation to the immune system
 specific immune responses rely on lymphocytes
 may be mediated either by:
o humoral [antibody] responses
o cell-mediated
 products of immune cells include:
o Tumor Necrosis Factor
o Immunoglobulins
o Cytokines-interleukins 1-18
o Interferons
o Transforming Growth factor
 antibody mediated immunity depends on:
o B lymphocytes
 involved in the generation of humoral immunity
 mature in the bone marrow [Bursa of Fabricius in birds]
 make antibodies in the form of immunoglobulins
o T lymphocytes [95% of circulating lymphocytes]
 mature in the thymus
 involved in cell-mediated immunity
 through the production of activated T lymphocytes

Differentiation of T cells
 T cell precursors in the bone marrow go to the thymus where they differentiate into CD8 or CD4 T
cells
 The CD8 T cells become Cytotoxic T cells which kill virus-infected, neoplastic and donor graft cells
 The CD4 T cells further differentiate into Helper T cells which develop into Th1 and Th2 cells
o Th1 cells activate macrophages
o Th2 cells help B cells to make antibodies.

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Humoral Immunity
 antibodies belong to a class of proteins called immunoglobulins [Ig] in the shape of a Y
 the Fc [tail of the Y] region determine the type of immunoglobulin [IgM, IgD etc]
o IgG-most abundant, promotes phagocytosis and cell lysis, confers passive immunity
o IgA-present in saliva, tears and breast milk
o IgM- secreted early on, promotes agglutination, phagocytosis and cell lysis
o IgD-surface antibody on B lymphocytes, role unclear
o IgE-important in parasitic infections and some allergic responses
 the Fab [arms of the Y] is responsible for the antigen binding specificity
 antibodies bind to antigens, thus promoting their destruction:
o directly by Precipitating soluble antigens, Lysis of membranes, Agglutination [clumping
together], and Neutralization of toxins or inactivation of some viruses
o indirectly activating the complement system

Type Structure Size Comments Compliment Crosses

Fixation Placenta
IgG Monomer smallest Secondary response, most abundant Yes Yes
IgA Dimer larger Found in secretions-saliva, tears, breast milk No No
IgM Pentamer largest Primary response, first in the fetus No No
IgD Monomer smaller Activates basophils and mast cells No No
IgE Monomer smaller Type 1 hypersensitivity, parasitic disease No No

Table 8: Immunoglobulins

Cell-mediated Immunity
 relies on activated T lymphocytes
 important in combating viral and fungal infections as well as against potential cancer cells
 T cells are activated by exposure to foreign antigens which are bound by specific surface receptors
 three types of T lymphocytes with different functions:
o cytotoxic [killer] T lymphocytes:
 lyse cells carrying the antigens to which they are sensitive
o helper T lymphocytes [most numerous]
 activated by macrophage-processed antigens
 once stimulated, lymphokines are released: Interleukin 2-6 and Interferon
o suppressor T lymphocytes:
 inhibit lymphocytic function
 cell-mediated responses persist longer than antibody responses

Natural versus Artificial/Active versus Passive Immunity

 natural active: immunity involves the production of antibodies after an infection
 natural passive immunity occurs when the antibodies are produced in the mother and are
transferred at birth to the infant
 artificial active immunity: the antibody production is induced by immunizations
 artificial passive immunity: antibodies are produced elsewhere [like in horses] and injected into or
transferred to the patient
 natural active and artificial active immunity is longer-lasting compared to natural passive and
artificial passive immunity which is short-lived

Hypersensitivity Reactions [ACID]

o Type I-Anaphylactic
o the antigen reacts with IgE causing mast cells to release histamine, heparin, as seen in
allergies and asthma
o Type II-Cytotoxic
o IgG, IgM, destroys RBCs-erythoblastosis fetalis, acute transfusion reaction, ITP
o Type III-Immune complex
o IgG mediated-immune complex triggers inflammation, as seen in serum sickness, drug
reactions, SLE, RA, post-streptococcal glomerulonephritis and farmer’s lung
o Type IV-Delayed hypersensitivity
o T cell mediated as seen in Mantoux testing for TB, leprosy, Touching poison ivy contact
dermatitis, chronic Transplant rejection and Type 1 Diabetes mellitus
o No immunoglobulins are involved in this type of reaction

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MUSCULOSKELETAL REVIEW

Function of Joints
 main function of joints is to allow movement
o for joints to function, one needs an intact spinal cord, nerves and muscles

Skeletal Muscle
 muscle fibers are made up myofibrils which are organized in sarcomeres surrounded by a cell
membrane called the sarcolemma
 these units are connected by T tubules which allow calcium to be released and carry the Action
Potential into the sarcomeres
 the sarcomere is the functional unit of a muscle:
o it lies between two Z lines which bisects the I band
o the dark band is the A [anisotropic] band which has both actin and myosin
o H band bisects the A band and has only myosin [thick filaments]
o the light band is the I [isotropic] band and has only actin [thin filaments]
o the A band always remain the same length during contraction
o the HIZ bands shorten during contraction
 two types of myofibrils-thick and thin:
o the thick filaments contain myosin
o the thin filaments contain actin, troponin and tropomyosin
o there are three types of Troponin: C, T and I
 Troponin C binds to calcium ions
 Troponin T binds to tropomyosin
 Troponin I binds to actin and inhibits the interaction between actin and myosin
 Troponin is the calcium-binding protein in skeletal and cardiac muscle
o Actin and Myosin at a 2:1 ratio

Sarcomere

H band
Z line Z line

A band I band
Fig 95: Sarcomere
Neuromuscular junction
 the neuromuscular junction is a specialized region where the ends of the axons of the α-motor
neurons are connected to motor end plates of a specific group of muscle fibrils
 each NMJ has a nerve bouton that is filled with vesicles that release Acetylcholine when the
nerve is stimulated and calcium flows into the bouton
 released Acetylcholine passes through the presynaptic membrane and into the synaptic cleft
 the post-synaptic membrane [motor end plate] on the muscle contains nicotinic ACh receptors
 when acetylcholine binds with these receptors, an end plate potential is generated and this spreads
to cause the skeletal muscle to contract
 the enzyme acetylcholinesterase is found in the synaptic cleft

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  it hydrolyzes [breaks down] Acetylcholine into acetate and choline
 choline is reabsorbed and combined with Acetyl CoA in the presynaptic vesicles

Motor neuron axon

Bouton

ACh containing vesicle

Synaptic cleft Ach receptor

Fig 96: Neuromuscular Junction

Skeletal muscle contraction [sliding filament model]

 The action potential arrives at the end of the motor neuron
 Acetylcoholine is released
 Acetylcholine binds to receptors in the motor end plate
 This changes the permeability of the sarcolemma so that sodium rushes in generating an
action potential
 The action potential in the muscle passes into the T tubules
 This releases calcium from the cisterna of the sarcoplasmic reticulum
 Calcium binds to Troponin C causing the troponin to change its shape
 This change causes a shift in Tropomyosin exposing the binding sites on actin for myosin
 Myosin binds with Actin forming a cross bridge
 The myosin head pivots and pulls the actin closer [the sliding filament theory] using 1 ATP
++ ++
 During relaxation, Ca is pumped back into the sarcoplasmic reticulum by Ca ATPase
++
 This requires energy and the speed at which the sarcoplasmic reticulum pumps the Ca back in
will determine whether the muscle is a fast [Type I] or slow twitch [Type II] fiber
 Repetitive stimulation results in tetany [sustained contraction without relaxation]

Fast versus Slow twitch fibers

++
Skeletal muscles may be classified as to the speed at which the sarcoplasmic reticulum can pump Ca
back into the terminal cisternae:

Slow Twitch [ 1 Small Slow Red Ox] Fast Twitch [2 Fast Skinny White Chickens]
Type I Type II
Red fibers White fibers
Found more in long-distance runners More common in sprinters
Smaller fiber size Large fiber size for greater contraction
Uses less glycogen Large amounts of glycogen for quick energy release
Many mitochondria-increase oxidative metabolism Few mitochondria for increased anaerobic glycolysis
More myoglobin Less myoglobin

T able 9: F ast versus Slow T witch F ibers

Types of contraction
o isometric muscle fibers do not change length, e.g. pushing against a wall
o isotonic load remains same, e.g. keeping the elbow flexed with a weight in hand
o isokinetic speed of contraction remains the same throughout the contraction
o concentric muscle shortens during contraction, e.g. flexing elbow with a weight in hand
o eccentric muscle lengthens during contraction, e.g. extending the elbow slowly with a
weight in the hand

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Smooth muscle types
 multi-unit-behaves as separate motor units, found in the iris, ciliary body and ductus deferens
 single unit-permits coordinated contraction, present in the uterus, bladder, ureter and gut
 mixed-found in the walls of blood vessels

Smooth muscle contraction

++
 a generated action potential causes influx of Ca into the sarcoplasm
++
 Ca binds to Calmodulin [not Troponin as in skeletal and cardiac muscle]
++
 Ca -calmodulin binds to and activates Myosin Light Chain Kinase
 Myosin is phosphorylated by the Myosin Light Chain Kinase
 Myosin-P binds to actin and this causes the muscle to contract
 Myosin-P is dephosphorylated and relaxation occurs
 Dephosphorylation requires energy
 Actin: Myosin ratio in smooth muscle may be as high as 20:1

Motor reflexes
There are three main types of motor reflexes: flexor withdrawal, crossed extensor and deep tendon or
stretch reflexes.

The flexor withdrawal reflex

 consists of a painful stimulus in the skin passing along afferent [sensory] axons of A-delta and
class C dorsal root fibers located in the dorsal root ganglion
 its dendrites synapse in the dorsal horn of the spinal cord with an interneuron which in turn
synapses with an alpha motor neuron located in the ventral horn
 from here, the axon of the motor neuron [efferent] innervates a flexor muscle which allows the
limb to be withdrawn from the painful stimulus
 this is an example of a somatosomatic reflex

The crossed extensor reflex

 is activated by a noxious stimulus of the skin
 this excites A-delta and class C dorsal root fibers
 these fibers enter the spinal cord at the dorsal root and activate multiple interneurons within the
gray matter
 through polysynaptic pathways, the interneurons are connected to the extensor muscles on
both sides of the spinal cord
 so while the flexor withdrawal response is being facilitated by contraction of the flexor muscles on
the side of the stimulus, the interneurons facilitate the contraction of the extensors on the
opposite limb
 this provides support of the body during withdrawal of the affected limb as a righting reflex

The stretch or deep tendon [myotactic] reflex

 striking a muscle tendon with a reflex hammer causes the muscle spindle in the muscle to be
suddenly stretched
 this sudden stretch generates an impulse which travels along an afferent neuron
 this neuron synapses with the alpha motor neuron that innervates the stimulated muscle
 the stimulated muscle contracts
 at the same time a small branche from the afferent axon synapses with another small neurone
called a Renshaw cell which in turn synapses with the same alpha motor neuron
 Glycine is the neurotransmitter for the Renshaw cells which are located in Lamina IX
 the Renshaw cell generates an inhibitory impulse which causes the antagonist muscle to relax
 this stretch reflex is further modified by inhibitory influences from the brain
 these influences prevent the reflex from being too brisk
 removal of these inhibitory impulses will result in the deep tendon reflex being hyperactive
 this is known as an upper motor neuron lesion commonly seen in CVA and spinal cord damage
 an upper motor neuron lesion is characterized by the following:
o spastic paralysis
o hyperreflexia
o Babinski sign [up-going big toe when the sole of the foot is stroked]
o no atrophy
o no fasciculations

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NEUROPHYSIOLOGY REVIEW

Nerve conduction
 depends on the diameter of the nerve axon and the degree of myelination
 myelin is produced by Schwann cells in the PNS and by oligodendrocytes in the CNS
 electrical events are caused by the movement of ions across cell membranes
 potential difference exists across the membranes of all cells-membrane potential
+
 In the resting state, there are more K ions inside the cell than outside
+
 in these cells, there are more K channels that are open
 when an action potential is generated, the Resting Membrane Potential [RMP] becomes positive
[depolarization] for 1 millisecond
 after this the membrane potential is restored [repolarization] to its original negativity in a further 1-
2 milliseconds

Propagation of an Action Potential

 once triggered, the Action Potential will travel over the entire surface of an excitable cell
+ +
 this stimulus triggers Na channels to open allowing Na to enter and the RMP becomes positive
 this causes depolarization of the membrane
+ +
 when the peak is reached, the Na channels are closed and K channels are opened
 during the period of depolarization, the membrane will not respond to any further stimulus
[absolute refractory period] no matter how large the stimulus is
+
 as the membrane repolarizes, the high permeability of the cell to K makes it more difficult to
depolarize
 during this period, however a very strong stimulus may elicit a response [relative refectory period]
 after a brief period of hyperpolarization, the ion channels return to their resting state
 a generated AP follows an all-or-nothing law and leads to a change in the membrane polarity from
negative on the inside [-70mV] to positive [+40mV] in neurons compared to -70 to +40 mV in
muscle
 the current is propagated from one end of the neuron to the end of the axon
 when an axon is myelinated, the axonal membrane underneath cannot be depolarized
+ +
because myelin is an insulator and this prevents movement of NA and K across the membrane
 the only areas that can depolarize are at the nodes of Ranvier which are devoid of myelin
 thus the depolarization jumps from node to node [saltatory conduction] which allows for 50
times faster conduction compared to unmyelinated nerves
 saltatory conduction not only increases the speed but it also conserves energy

Synaptic conduction
 two basic types of synapses-electrical and chemical [more common]
 the electrical or gap-junction type has cytoplasmic connections between the pre- and post
synaptic elements which allow direct conduction of electrical current between cells and is bi-
directional
 the chemical type has a small space of cleft between the pre- and post-synaptic elements which
allow for the neurotransmitter to diffuse between the cells and is unidirectional
 when an action potential is generated [following depolarization of the presynaptic terminal], it opens
++
voltage-gated Ca channels in the synaptic end of the neuron
 the calcium influx activates calmodulin which causes the synaptic vesicles to fuse with the
presynaptic membrane
 this allows constant amounts or quanta of the neurotransmitter to be released
 the specific neurotransmitter diffuses into the synaptic cleft where it will activate receptors on the
post-synaptic membrane which leads to excitation or inhibition depending on the tissue

Types of nerve endings

 Merkel cells are found in the epidermis-crude touch and pressure
 Pacinian corpuscles are found deep subcutaneous tissue-vibration
 Meissner’s corpuscles in the dermal papillae-two-point discrimination [fine touch]
 Ruffini endings are found in deep subcutaneous tissue-joint position sense
 Naked nerve endings are found in the epidermis and dermis-pain and temperature
 Golgi tendon organs found in tendons and detect load or tension
 Muscle spindles found in muscle, detect changes in the length of the muscle

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Neurotransmitter classification
 CNS
o All are Excitatory [Glutamine, Serotonin, Acetylcholine, Norepinephrine and Dopamine]
EXCEPT Glycine and GABA [Gamma Amino Butyric Acid which are Inhibitory
o Glycine is found mainly in the spinal cord
 PNS
o Neuromuscular junction
 Acetylcholine
o Autonomic Nervous System
 Acetylcholine
 Norepinephrine

Autonomic Nervous System Neurotransmitters

 types of receptors:
o cholinergic [acetylcholine]
o adrenergic [norepinephrine]
 types of cholinergic receptors:
o all cholinergic receptors are nicotinic EXCEPT:
 parasympathetic postganglionic fibers which are muscarinic
o even the cholinergic receptors in the neuromuscular junction is nicotinic
 types of adrenergic receptors:
o alpha 1-smooth muscle in blood vessels, gut, sphincters and skin-constriction
o alpha 2-found in islets of Langerhan’s-decrease insulin secretion
o beta 1-found in cardiac muscle-increase rate and force
o beta 2-smooth muscle in bronchi, coronary vessels and skeletal muscle-dilation
o beta 3-found in brown fat-increase lipolysis

Nociceptor classification
1. specific: mechanical, cold thermal, heat thermal
a. fast conduction [A fibers] producing well-localized, sharp, pricking pain
2. silent: present in healthy tissue, not activated by noxious stimuli
a. only begin to fire when tissue becomes increasingly inflamed
3. polymodal: mostly group IV [C type] fibers, found in somatic and visceral tissue
a. may be activated by chemical, thermal or mechanical stimuli that may or may not be
noxious
b. have receptors for bradykinin, prostaglandin E2, serotonin, histamine, interleukin and TNF
c. slow conduction, poorly localized burning, dull aching pain

Nerve fiber classification

Nerves may be classified according to the following:
o speed of conduction
o size of the nerve fiber
o function of the fiber
o whether the nerve is myelinated or not

Type Diameter Speed Function Myelination

A 12­20 m 70­120 m/sec Motor to skeletal muscle Yes
A 5­12 m 40­70 m/sec Fine touch, vibration, proprioception Yes
A 3­6 m 10­50 m/sec Muscle spindles Yes
A 2­5 m 6­30 m/sec Fast pain, temperature and touch Yes
B 1­3 m 3­5 m/sec Preganglionic autonomic fibers Yes
C 0.5­1 m 3 m/sec Postganglionic autonomic, olfactory, slow pain No

T able 10: Nerve F iber T ypes

122
RENAL REVIEW

Function
 an excretory organ with endocrine function with two parts-cortex and medulla
 the main functions are:
o waste excretion
o electrolyte balance
o blood pressure control
o acid base balance
 functional unit of the kidney is the nephron:
o nearly 1 million nephrons [incapable of regeneration] in each kidney
o two types of nephrons-cortical [80%] and juxta-medullary [20%]
o each nephron has the following parts:
 a glomerulus enveloped in a double-layered Bowman’s capsule
 two convoluted tubules-proximal and distal
 two parts of the loop of Henle-thin descending and ascending thin and thick
 two hormones that are secreted by the kidney-erythropoietin and renin
 additional hormones that act on the kidney- ADH, aldosterone, ANP, 1,25
dihydroxycholecalciferol and parathormone

Renal blood flow

 its function is dependent on its blood flow
 kidney is only <1% of the total body weight
 uses 20% of the cardiac output [5 liters/minute] = 1 liter/minute
 renal plasma flow is 60% of the renal blood flow = 600 ml/minute

Glomerular Filtration
 glomerulus and Bowman’s capsule allow an ultrafiltrate to pass into the proximal convoluted
tubule
 influenced by opposing forces:
o hydrostatic [+60 mm Hg] pushes water out of the capillary
o oncotic pressure [-32 mm Hg] pulls water back into the capillary
o Bowman’s capsule pressure [-18 mm Hg] pushes water back into the capillary
o resulting in a positive net pressure of 10 mm Hg
 this causes filtration through the glomerulus at a rate of 120 ml/minute
 pores [fenestrations] in the capillary membrane, slits between the pedicles of the podocytes in
Bowman’s capsule and the specialized negatively-charged basement membrane sandwiched in
between allow free passage of small molecules and the repulsion of negatively charged proteins
 the size of the openings does NOT allow red blood cells to be filtered
+ + + ++
 Na , K , H , Ca and urea are filtered passively through the glomerulus and reabsorbed
actively according to the needs of the body
 glucose is filtered passively by the glomerulus
o glucose is reabsorbed actively by the Proximal Convoluted Tubule once the threshold is
exceeded [renal threshold for glucose is 180 mg/dL]

Proximal Convoluted tubule

 main function of the PCT is related to reabsorption
 most of the bicarbonate and phosphate are reabsorbed by the PCT
+ + + ++
 60-70% of Na [exchanged for H ], K , Ca and HCO3 occurs in the proximal convoluted tubule
 H2O and urea [50%] is absorbed by the PCT which is lined by cuboid cells with microvilli on the
luminal side
 100% of the filtered amino acids and glucose are reabsorbed here

Loop of Henle
 two structurally and functionally different parts of the loop of Henle-thin and thick
 the thin descending part is permeable to H2O and impermeable to urea
o purpose is to concentrate the urine as it moves from descending into ascending parts by
+ -
trapping Na and Cl
o water moves out of the descending limb and the urine becomes concentrated
 the thick ascending part is impermeable to H2O and is the diluting segment of the loop

123
Distal Convoluted Tubule
+ - ++
 it is involved in Na , Cl , H2O and Ca reabsorption
+
 Aldosterone acts mainly on the distal convoluted tubules to facilitate Na resorption [in
+ +
exchange for H ] and K secretion
 in addition, Parathormone converts 25 hydroxycholecalciferol to 1, 25 dihydroxycholecalciferol
which is the active form of Vitamin D
o Vitamin D produced by the skin is converted to 25 hydroxycholecalciferol in the liver
++
 1, 25 dihydroxycholecalciferol acts on the DCT to facilitate Ca resorption and PO4 secretion

Collecting duct
 Anti-Diuretic Hormone acts mainly on receptors in the cells of the collecting ducts and increase
water permeability which allows more water to be reabsorbed

Efferent arteriole
Collecting duct Distal Convoluted Tubule

Afferent arteriole
Bowman’s capsule
Glomerulus

Proximal Convoluted Tubule

Ascending loop of Henle-thick part

Descending loop of Henle

Ascending loop of Henle-thin part

Fig 97: Parts of the Nephron

Endocrine function
 the kidney produces the following hormones:
o Erythropoietin [produced by interstitial cells in the cortex] in response to hypoxia
 acts on myeloid tissue in the bone marrow
 increases the production of red blood cells
o Renin is produced by cells in the juxtaglomerular apparatus in response to a drop in BP
o Renin-Angiotensin-Aldosterone mechanism:
 drop in renal blood flow results in a decrease NaCl delivery to the macula
densa
 the macula densa is located in the distal convoluted tubule near the afferent
and efferent arterioles of the glomerulus
 it is sensitive to salt [NaCl] concentration
 this triggers the secretion of renin from cells of the juxtaglomerular apparatus
 the juxtaglomerular apparatus is made up of a segment of the distal
convoluted tubule in close relation with the afferent and efferent arterioles of
the glomerulus
 renin is released from the juxtaglomerular cells located in the walls of the
afferent arteriole immediately proximal to the glomerulus
 renin is a proteolytic enzyme which causes angiotensinogen secreted by the
liver to be converted into angiotensin I
 angiotensin 1 is converted to angiotensin II by Angiotensin Converting
Enzyme which is found in the lung

124
  angiotensin II is a powerful vasoconstrictor which will cause an elevation of
the blood pressure
 in addition, angiotensin II stimulates the release of aldosterone
 aldosterone causes NaCl reabsorption and thus water
 the increased water causes an increase in the blood volume
 this in turn causes an increase in venous return
 increased venous return increases the cardiac output which in turn raises the
blood pressure

Macula densa
DCT
Afferent arteriole
Efferent arteriole

Juxtaglomerular cells

Bowman’s capsule

Glomerulus

Proximal Convoluted Tubule

Fig 98: Juxtaglomerular Apparatus

 additional hormones act on the kidney on the cells in the DCT or collecting ducts:
o Anti-Diuretic Hormone [aka vasopressin]
 secreted by the supra-optic nucleus in the hypothalamus
 due to stimulation of osmoreceptors in the hypothalamus
 acts mainly on the principal cells in the collecting ducts of the kidney
 increases water permeability
 causes reabsorption of water
o Atrial Natriuretic Peptide
 peptide hormone produced by stretched atrial myocardial fibers
 causes decreased Na reabsorption resulting in increased urine production
 also causes relaxation of vascular smooth muscle causing decrease peripheral
resistance
o 1,25 dihydroxycholecalciferol acts on the distal convoluted tubule increasing Ca++
absorption
o Aldosterone acts mainly on the distal convoluted tubule increasing NaCl reabsorption

Acid Base Balance

 the other role of the kidney together with the lungs is acid-base balance
 the pH of the blood is in a very small range 7.35 to 7.45
 the pH is inversely proportional to the actual hydrogen ion concentration
o as the hydrogen ion concentration increases, the pH decreases and the acidity increases
 two types of acids are produced in the body: volatile and non-volatile acids
 the volatile acid is produced when CO2 reacts with H2O to form carbonic acid [H2CO3]
 carbonic anhydrase catalyzes the reversible reaction between CO2 and H2O
 the non-volatile acids include sulfuric acid [a product of protein metabolism], phosphoric acid
[a product of phospholipid breakdown], lactic acid [a product of glucose breakdown] and
ketoacids-acetone, acetoacetate and hydroxybutyrate [from fatty acid breakdown]
 excess acid is buffered by bases produced in the body in the form of HCO3, PO4 and
hemoglobin
 bicarbonate is the major buffer in the blood
 the kidney is involved in filtering out excess hydrogen and bicarbonate ions depending on the
needs of the body

125
 +
 the excess hydrogen ions are excreted as ammonium [NH4 ] in the kidneys
 the lungs are also involved in maintaining the balance between acids and bases
 If the body produces too much non-volatile acids [metabolic acidosis]:
o the lungs will compensate by blowing off H2O and CO2 through hyperventilation
 If the lungs are under-functioning, volatile acid CO2 will be retained causing respiratory
acidosis
+ -
o the kidneys will compensate by excreting excess H or increasing HCO3 reabsorption
 If excess hydrogen ions are lost [through vomiting or with diuretics] metabolic alkalosis results
o the lungs will compensate by decreasing the excretion of CO2 through hypoventilation
 If too much CO2 is blown off by the lungs by hyperventilation, this results in respiratory
alkalosis
-
o the kidneys will compensate by decreasing H+ excretion and HCO3 reabsorption
 it is easy to tell whether a patient has a respiratory or metabolic alkalosis or acidosis by first
-
checking the blood pH and then looking at the PCO2 and HCO3 levels
 Respiratory opposite:
o acidosis [decreased pH and raised CO2]
o alkalosis [increased pH and decreased CO2]
 Metabolic equals:
_
o acidosis [decreased pH and decreased HCO3 ]
_
o alkalosis [increased pH and increased HCO3 ]

Check arterial pH

pH < 7.35 ph > 7.45

Acidosis Alkalosis

Check PCO2

PCO2 > 40 mm Hg PCO2 < 40 mm Hg PCO2 < 40 mm Hg PCO2 > 40 mm Hg

Respiratory Acidosis Metabolic Acidosis Respiratory Alkalosis Metabolic Alkalosis

with compensation with compensation

Hypoventilation Diabetic ketoacidosis Hyperventilation Vomiting

-Airway obstruction Renal tubular acidosis Aspirin ingestion Diuretic use
-COPD Renal failure Hyperaldosteronism
-Narcotics Lactic acidosis
Aspirin poisoning [late]

Fig 99: Acid Base Balance

126
REPRODUCTIVE REVIEW

Sperm development
 spermatozoa are produced in the seminiferous tubules of the testis under the influence of
testosterone secreted by the interstitial cells of Leydig
 the Interstitial cells of Leydig are under the influence of Luteinizing Hormone
 testosterone is attached to receptors on the Sertoli cells
 Sertoli cells are found in the seminiferous tubules of the testis
 the sustentacular cells of Sertoli are under the influence of Follicle Stimulating Hormone
0
 the testis is housed in the scrotum so that it lies at a temperature 1 Centigrade lower than body
temperature
 higher temperatures decrease spermatogenesis
 sperm produced in the tubules mature in the epididymis
 200-600 million sperms are released during each ejaculation
 Each sperm has a head with an acrosome, a middle piece with mitochondria and a tail
 The sperm feeds on fructose produced by the seminal vesicles
 the sperm released from the testis during ejaculation are not capable of fertilizing the egg

Capacitation
 this is the process of transforming sperm so that they have the capacity to penetrate the corona
radiata which surrounds the ovum
 with the aid of a sperm membrane protein with hyaluronidase activity found in the acrosome of
the sperm
 capacitation occurs in the female genital tract
 it is aided by the low pH which is maintained by the production of acid by the numerous
lactobacilli that inhabit the vagina

Ovum development
 there are > 2 million primary oocytes present at birth
 only 400-500 become secondary oocytes waiting to be expelled at ovulation during the
reproductive period under the stimulation of FSH
o via a negative feedback loop involving estrogen: high estrogen leads to low FSH
 several follicles develop during each menstrual cycle
o only one matures and releases the ovum
 the empty follicle changes into the corpus luteum after ovulation
 the development of the corpus luteum is under the influence of LH via a negative feedback loop
involving progesterone and LH
 the ovum lives for 24 hours while the sperm lives 48 hours in the female

The Menstrual Cycle

 Proliferative Phase
o after menstruation, the residual basal layer of uterine endometrium regenerates under
the influence of estrogen
o estrogen is secreted by the ovarian follicles under the stimulation of FSH
 Ovulation
st
o on Day 14 [counting from the 1 day of menstruation], one Graafian follicle matures and
migrates to the periphery of the ovary to release its ovum covered by a layer of follicular
cells under the stimulation of a pre-ovulatory surge of LH
0
o this is associated with a 0.5 C rise in body temperature at the time of ovulation
 Secretory or Luteal Phase
o the empty ovarian follicle becomes the corpus luteum [yellow] which continues to
secrete estrogen and begins to secrete progesterone under the stimulation of LH
o progesterone will cause the regenerated uterine endometrium to become secretory in
anticipation of implantation of a fertilized ovum
 Menstrual Phase
o if fertilization does not occur, then at about Day 26, the corpus luteum dies [and
becomes the corpus albicans] and the level of progesterone drops precipitously
o this will cause the spiral arteries feeding the endometrium to go into spasm
o this leads to ischemia and death of most of the endometrium
o the dead endometrium is shed as menstrual blood and the cycle is repeated

127
 Fertilization
 if the woman has ovulated and sperm are in the neighborhood, then fertilization could occur in the
ampulla [largest part which has ample room] of the uterine tube
 hyaluronic acid in the acrosome on the head of the sperm assists in penetrating the corona
radiata and zona pellucida which surrounds the ovum
 the zona pellucida changes its configuration after fertilization preventing other sperm from entering
 the fertilized egg [zygote] travels down the uterine tube and develops into the morula at Day 3 and
into the blastocyst at Day 5

Implantation
 implantation occurs around Day 7 after fertilization, when the blastocyst makes contact with the
endometrial lining of the uterine cavity
 after implantation the blastocyst develops into the embryoblast
 the embryoblast develops into an inner cell mass and an outer cell mass
 the inner cell mass becomes the embryo and further differentiates into two layers:
o the outer layer is known as the epiblast
 the epiblast becomes the ectoderm
o the inner layer is known as the hypoblast
 the hypoblast becomes the endoderm
o later a third layer develops between these two layers and this becomes the mesoderm
 the outer cell mass becomes the trophoblast which later becomes part of the placenta

Placentation
 the trophoblast on implantation develops into outer and inner layers
o the outer layer of the outer cell mass becomes the syncytiotrophoblast and secretes
βHCG
 βHCG maintains the hormonal activity of the corpus luteum during the early
stages of pregnancy
 the syncytiotrophoblast erodes endometrial cells allowing maternal blood to seep
in and out of vascular lacunae forming the uteroplacental circulation
o the inner layer of the outer cell mass becomes the cytotrophoblast
 the cells in the cytotrophoblast proliferate and grow into the syncytiotrophoblast
 these cellular projections form the chorionic villi which later develop into the
placenta
 the placenta produces a number of hormones:
o Estrogen which contributes to uterine growth, increased uterine vascularity,
proliferation of the ducts in the mammary gland
o Progesterone which prepares the endometrium for implantation, inhibits uterine
contraction, inhibits T lymphocyte-mediated activity [preventing immunological
rejection of the fetus by the mother] and prepares the breast acini for lactation
o Relaxin which relaxes the pelvic ligaments and softens the cervix at the time of delivery
o Human Chorionic Somatomammotropin which causes partial development of the
breast in early pregnancy, decreases insulin sensitivity and promotes the growth of protein
tissue in the same way that growth hormone does

Lactation
 estrogen causes proliferation of the mammary ducts
 progesterone prepares the acini for milk synthesis
 milk synthesis is dependent on high levels of prolactin in association with cortisol and insulin
 prolactin secretion is high during pregnancy
 but it has no effect during pregnancy as its action is inhibited by the high levels of estrogen
 the sudden drop in estrogen levels after delivery removes this inhibition
 milk is produced by the breast acini and accumulates in the glandular tissue
 oxytocin is released from the posterior pituitary lobe by stimulation of the nipple by suckling
 oxytocin causes the myoepithelial cells around the glandular tissue in the breast to contract
causing the milk let-down reflex
 continued lactation is dependent on the removal of milk at regular intervals
 failure to empty the breast regularly will cause lactation to cease within a week

128
RESPIRATORY REVIEW

Functions
 two main functions:
o gaseous exchange
o acid base balance

Gaseous Exchange
Gaseous exchange is dependant on:
1. Ventilation
2. Perfusion
3. Diffusion
 Ventilation deals with the amount of gas delivered by the lungs
 Boyle’s law: when the temperature is constant, the volume of a fixed amount of gas is
inversely proportional to its pressure
 Charles’ law: when the pressure is constant, the volume of a fixed amount of gas is
directly proportional to the absolute temperature
 Perfusion deals with the amount of blood delivered by the heart to the lungs
 Diffusion deals with the amount of gas that passes through the air-blood barrier
 The air-blood barrier is made up of the capillary endothelium, basement membrane
and Type I pneumocytes [90% of the cell types in the alveolus]
 Type II pneumocytes produce surfactant [dipalmitoyl phosphatidylcholine], which
reduces the surface tension in the alveoli
 Rate of diffusion is governed by Fick’s law
 diffusion through a tissue membrane is inversely proportional to the tissue thickness
 Ventilation/perfusion ratio:
 VA/Q where VA is 4 L/min and pulmonary blood flow is 5L/minute [4L/5l = 0.8]
 VA/Q is highest in the apex [3], lowest in the base [0.6] and closer to the ideal in the midzone
 Ventilation is highest in the apex
 Perfusion is greatest in the base

Oxygen carrying capacity of the blood

 this depends on the amount of O2 in plasma and the amount carried as oxyhemoglobin
 4 factors cause a shift to the right [decrease Hb affinity for O2, therefore more O2 is released]
with 97% of the oxygen in blood being carried by hemoglobin:
o acidosis [decreased pH]
o carbon dioxide increase
o temperature increase
o 2,3-DPG [2,3-diphosphoglycerate]
 Increased CO2 and decreased pH cause the oxyhemoglobin to give up O2–Bohr effect

Shift to the right

PaO2

Oxygen saturation

Fig 100: Bohr Effect

Carbon Dioxide carrying capacity of the blood
 blood carries much more CO2 than O2 [4 ml compared to 1.35 ml of O2 per 100 ml of blood]
 CO2 is transported in three forms:
+ -
o bicarbonate [70%] [H2O+CO2  H2CO3 H + HCO3 ] mainly

129
 o carbaminohemoglobin [23%]
o dissolved in plasma [7%] least
o Haldane effect-binding of O2 to Hemoglobin tends to displace CO2
o High O2 levels in the lungs displaces CO2 and low O2 levels in the tissues binds more CO2

Control of Respiration
 rate and depth of breathing are regulated so that arterial PCO2 = 40 mm Hg
 under normal circumstances the concentration of CO2 in blood is the major determinant of
breathing
 breathing is controlled by centers in the brain stem:
o pneumotaxic center in the upper pons turns off or inhibits the inspiratory center [-]
causing a decrease in the depth of inspiration which results in an increase in the
respiratory rate
o apneustic center in the lower pons prevents turning off of the inspiratory center [+]
o dorsal [inspiratory] and ventral [expiratory] centers in the medulla [DIVE]
o higher centers in the cerebral cortex act on the medullary centers

Pneumotaxic center
Apneustic center

Inspiratory center
Pons Expiratory center

Medulla

Fig 101: Central Respiratory Control Centers

 CO2 freely crosses the blood brain barrier and enters the CSF
+ -
 in the CSF, CO2 combines with H2O to form H2CO3, which dissociates to form H and HCO3
+
 the medulla senses levels of H in the CSF directly and CO2 in the blood indirectly
 the medullary receptors are not sensitive to O2
 chemoreceptors in the carotid body and adjacent to the aorta are peripheral chemoreceptors
that are stimulated by first by raised PaCO2, then by decreased arterial pH [acidosis] and
finally by decreased PaO2 [<60 mm Hg]
 Cheyne-Stokes breathing is characterized by periods of rapid breathing with increasing then
decreasing tidal volume followed by a period of apnea as seen in Congestive Heart Failure
 Kussmaul breathing is characterized by deep rapid regular breathing [aka air hunger]
o this is seen in diabetic ketoacidosis
 Biot’s respiration is characterized bouts of irregularly irregular breathing and apnea
o this is seen in brain stem compression
 Hering-Breuer reflex-limits over-inflation of the lungs
o this reflex is mediated by stretch receptors found in the smooth muscle in the airways
with afferents via the vagus nerve and efferents via the phrenic nerve

Lung Compliance
 This is a measure of the distensibility of the lungs and chest wall
 It is the change in lung volume caused by a given change in the respiratory pressure [C= V/P]
 It is related to the elastic fibers, water content, surfactant in the lungs
 It is inversely related to the amount of elastic tissue and proportional to force needed to
expand chest
 The elasticity of the lungs tends to collapse the lung
 Surfactant helps to counter this tendency to collapse
 Emphysema increases the compliance allowing the lungs to over-expand
 Pulmonary fibrosis and pulmonary edema decrease lung compliance
 Ankylosing spondylitis decreases the ability to the chest wall to expand
 Kyphoscoliosis will cause a decrease in the chest wall’s ability to expand

130
Lung Volumes
 Total Lung Capacity [total volume held in the lungs] 5800 ml
 Vital Capacity [volume expired after maximal inspiration] 4600 ml
 Inspiratory Reserve Volume [volume inspired above tidal volume] 3000 ml
 Tidal Volume [volume of a normal breath] 500 ml
 Expiratory Reserve Volume [volume expired after normal breath] 1100 ml
 Residual Volume [lung volume left after maximal expiration] 1200 ml
 Functional Residual Capacity [air left in lungs after normal expiration] 3300 ml
 Forced Expiratory Volume1 [volume expired after 1 second/FVC] 80%

6000 ml

5000 ml

Inspiratory Reserve Volume

Volume
Vital Capacity 4000 ml

Total
Lung 3000 ml
Capacity
Tidal Volume

2000 ml
Expiratory Reserve Volume

1000 ml

Residual Volume

Fig 102: Lung Volumes and Capacities

IRV TLC Total Lung Capacity 5800 ml

IC VC Vital Capacity 4600 ml
TV VC IRV Inspiratory Reserve Volume 3000 ml
TLC IC Inspiratory Capacity 3500 ml
TV Tidal Volume 500 ml
ERV
ERV Expiratory Reserve Volume 1100 ml
FRC RV Residual Volume 1200 ml
RV RV
FRC Functional Residual Capacity 3300 ml

131
132
PATHOLOGY

133
134
GENERAL PRINCIPLES

The body is in a dynamic state of balance [homeostasis] and responds to changes in its environment.
When excessive stress is placed on tissues, the cells respond by either adapting, developing reversible
injury or may suffer from irreversible damage and die. Inflammation is the body’s innate response to
injury.

The 5 Cardinal Signs of inflammation are rubor, dolor, calor, tumor and functio laesa:
 rubor or redness due to vasodilation caused by histamine
 dolor or pain due to kallikrein and bradykinin
 calor or heat due to the increased vascularity due to histamine and serotonin
 tumor or swelling due to increased vascular permeability-histamine and serotonin
 functio laesa or loss of function due to decreased cell functioning

When tissues are injured or inflamed, there is a sequence of events involving cellular response and
hemodynamic [vascular] changes:
 cellular response:
o margination is the process of the WBCs move to the periphery of the blood vessel by
chemotaxis
o chemotaxis is due to inflammatory chemical compounds which attract WBCs
o pavementation refers to WBCs sticking to the endothelium
o emigration is the passage of WBCs through blood vessels [diapedesis or
transmigration] by chemotaxis
o phagocytosis is the process of ingestion of bacteria by macrophages which are
derived from monocytes from the blood
 hemodynamic changes:
o initial transient vasoconstriction lasting less than a few seconds
o followed by massive vasodilation mediated by:
 histamine [released by basophils]
 bradykinin and kallikrenin [responsible for nociception]
 prostaglandins [responsible for further inflammation]
o increased vascular permeability due to endothelial cell contraction which increases
the size of the pores [fenestrations] between the endothelial cells
o blood stasis due to increased viscosity which allows the white blood cells to
marginate and the blood to clot

Acute inflammation is an immediate response to injury. It is a short lived process which may end in
complete healing, abscess, ulcer, fistula, scarring or it could progress to become chronic:
 abscess is a pus-filled cavity
 ulcer results when there is loss of surface epithelium
 fistula is an abnormal communication between two epithelial surfaces
 sinus is a blind-ending track connected to one epithelial surface
 scar occurs when tissue healing characterized by fibrous tissue
 keloid is a tumorous overgrowth of fibrous tissue in a scar

Chronic inflammation is a response to persistent injurious agent-viral, bacterial or fungal in which

epithelioid cells, Langhan’s giant cells and granulomas are found:
 epithelioid cells are activated macrophages found in granulomatous conditions like Tuberculosis
 Langhan’s cells are giant cells found in granulomatous diseases [Tuberculosis] due to fused
epithelioid cells
 granulomatous change is characterized by specialized macrophages surrounded by rim of
activated lymphocytes
With chronic inflammation, the epithelial tissue may undergo certain changes:
 metaplasia refers to the reversible change in which one cell type is replaced by another cell
type; e.g. Barrett’s esophagus which occurs in chronic GERD
 dysplasia refers to the disorderly but non-neoplastic growth:
o it may be mild [and reversible if the stimulus is removed]
o it may be severe [and irreversible]
o severe dysplasia is precancerous and may lead to carcinoma in situ

135
  anaplasia is the term used to describe the disorganized, uncontrolled growth with lack of
differentiation
 neoplasia is the term used to describe new growth of cells and is synonymous with a tumor

Tissue injury may be caused by ischemia, hypoxia or anoxia:

 ischemia is caused by lack of blood supply
 hypoxia is due to oxygen deprivation
 anoxia refers to the absence of oxygen

When tissues are deprived of a blood supply, the following might occur:
 agenesis refers to the complete absence of an organ
 aplasia is due to the failure of an organ or tissue to develop normally; a small remnant is left
 hypoplasia refers to the underdevelopment of an organ or tissue resulting in decrease in the
number of cells

Tissue may also respond to injury or stress by the following:

 hyperplasia which is the increase in the number of cells in an organ
 hypertrophy is the increase in the size of cell or organ not related to increase in the number of
cells
 atresia is the congenital absence or closure of a normal body opening
 atrophy is the term used to describe the decrease in the size of an organ or tissue

When the damage is too much for the cell to handle, cell death or necrosis will occur. There are several
types of necrosis:
 coagulative necrosis in infarctions in the heart and is due to protein denaturation
 liquefactive necrosis as seen in infarctions in the brain
 caseous necrosis as seen in tuberculosis
 enzymatic necrosis as seen in acute pancreatitis
 fatty necrosis as seen in liver damage and injury to fatty tissue

In addition there are two types of degeneration:

 Zenker’s degeneration is the waxy hyaline seen in skeletal muscle damage
 Wallerian degeneration is the dying back [antegrade] of the nerve axons after injury to the nerves

There is a special type of cell death which is programmed. This is known as Apoptosis and is regulated by
nitric oxide and requires ATP. Apoptosis is characterized by the following:
 no inflammatory response in the surrounding tissue
 unlike necrosis which is accompanied by an inflammatory response in the surrounding tissue

When a cell is injured, the nucleus undergoes specific changes in order of progression:
 pyknosis-reversible nuclear chromatin condensation or clumping [pH changes]
 karyorrhexis-irreversible chromatin fragmentation [Ca++ influx]
 karyolysis-enzymatic breakdown of DNA after cell death
o complete disappearance of stainable nuclear material

Immune deficiencies
The body’s ability to defend itself and respond by inflammation may be compromised by specific genetic
diseases which affect the immune system like:
 Bruton’s agammaglobulinemia
o X-linked tyrosine kinase defect blocks B cell maturation; seen in Boys
 DiGeorge syndrome
rd th
o Thymic and parathyroid aplasia due to failure of 3 and 4 pharyngeal arch development
 Severe Combined Immune Deficiency
o Often X-linked with defective B and T cell activation
 Wiskott-Aldrich syndrome
o X-linked defect with progressive depletion of B and T cells
 Chediak-Higaski syndrome
o Autosomal recessive defect in phagocytosis

Patients with the above deficiencies present with recurrent infections.

136
GENETIC DISORDERS

Genetic disorders are caused by mutations which are permanent alternation in DNA. The mutations may
affect an entire chromosome or may affect specific base pairs in the DNA sequencing of specific genes. The
mode of inheritance of genetic disorders could be autosomal or sex-linked and are either dominant or
recessive:
 autosome
o any chromosome other than the X or Y chromosomes
 sex-linked
o linked to one sex; e.g. Duchenne’s muscular dystrophy and hemophilia in males
 autosomal dominant
o having a 50% chance of inheritance if the gene is present in one parent
o e.g. Sickle Cell trait
 autosomal recessive
o having a 25% chance of inheritance if the gene is present in both parents
o e.g. Sickle Cell Disease

Of the autosomal chromosomal diseases, the following are important:

 Down’s syndrome
st
o Trisomy 21: extra 21 chromosome, mental retardation, mongoloid facies, transverse
palmar crease [simian line] and an increase risk of acute leukemia
 Klinefelter’s syndrome
o XXY: extra X in tall, thin sterile males with small testes, gynecomastia and low IQ
 Turner’s syndrome
o XO: missing X in short females, web neck, widely spaced nipples, small breasts

The following are important autosomal dominant diseases:

 Marfan’s syndrome
o genetic defect in fibrilin-1 which is a glycoprotein found commonly in large blood vessels
and in the suspensory ligaments of the lens
o relatively common [1:3000-5000]
o tall thin body habitus
o long spider-like fingers [arachnodactyly]
o lens dislocation
o mitral valve prolapse or regurgitation
o aortic incompetence
o aortic aneurysm
 Ehlers-Danlos syndrome:
o excessive elastic tissue in skin and joint capsule
o hypermobile joints leading to severe joint degeneration
 Osteogenesis imperfecta:
o defective collagen synthesis
o frequent broken bones
o blue sclera
 Adult Polycystic Disease of the kidney:
o multiple cysts in both kidneys
o hypertension
o berry aneurysms

Autosomal recessive disorders include many of the genetic metabolic disorders:

 Glycogen storage disorders:
o Von Gierke-Glucose-6 Phosphatase deficiency-accumulates in the liver
o McArdle-muscle phosphorylase deficiency-accumulates in the muscle
o Pompe-maltase deficiency affects the heart pump
 Lysosomal storage disorders:
o Tay-Sachs-gangliosides accumulation in the brain; rapidly fatal
 cherry red macula
 severe mental retardation
o Gaucher-glucocerebrosides accumulate in the liver and spleen-most common
o Niemann Pick-sphingomyelin accumulation in the liver and brain

137
  Amino acid disorders:
o Phenylketonuria
 accumulation of phenylalanine due to lack of PA hydroxylase; mental
retardation
 restrict dietary phenylalanine if the Guthrie test for PKA is positive
o Alkaptonuria
 deficiency in homogentisic acid
 urine turns black on standing
 dark damaged cartilage-ochronosis
 Metabolic
o Cystic fibrosis
 Autosomal recessive condition causing defective chloride transport
 impaired mucociliary action and thick vicid secretions
 recurrent infections in lung and sinuses
 salty sweat
 Hemopoietic:
o Sickle Cell Disease
 recessive gene
 valine replaces glutamine at position 6 of the beta chain in hemoglobin
 common in African-Americans [2% has the disease]
 causes microvascular occlusion triggered by hypoxia, acidosis, fever
 painful bones with anemia, jaundice and fatigue
 hepatosplenomegaly in children
 priapism [prolonged erections]
 increased risk of salmonella osteomyelitis and pneumococcal pneumonia
 protects from Plasmodium falciparum type of malaria
o Sickle Cell Trait
 autosomal dominant present in 8% of African-Americans
 asymptomatic unless severely stressed
o Thalassemia
 More common in Americans of Mediterranean descent [β Thalassemia]
 defect in either the α or β globin chains of hemoglobin A
 α Thalassemia is more common in South East Asia and West Africa
 β Thalassemia is more common in Americans of Greek or Italian descent
 results in sub-optimal hemoglobin synthesis
 presents with varying degrees of anemia and fatigue
 Thalassemia persons are also resistant to the malaria parasite

The following are important recessive sex-linked disorders [mainly males];

 Duchenne muscular dystrophy:
o Total absence of dystrophin
o progressive muscle weakness
o pseudohypertrophic calf muscles
 muscles are infiltrated with fat and connective tissue
 muscles are weak
o Gower’s sign-climbing up the legs in order to strand upright
o Death from cardiorespiratory problems before the age of 20
 Becker’s muscular dystrophy
o Milder form of Duchenne’s with decrease levels of dystrophin
 Hemophilia A or B is due to the lack of Factor VIII [A] or Factor IX [B]
o prolonged bleeding
o hemarthrosis [bleeding into joints]
 Lesch-Nyhan syndrome is due to the lack of HGPRT [Hypoxanthine Guanine Phosphoribosyl
Transferase is an enzyme in purine metabolism]
o gout in children
o congenital pain insensitivity which leads to self-mutilation

The only dominant sex-linked disorder is:

 Vitamin D resistant rickets [renal rickets or renal osteodystrophy]
o Rickets that does not respond to Vitamin D therapy

138
NEOPLASIA

Neoplasia is the term used to describe new cell growth and is synonymous with a tumor. It could be
benign or malignant. The term tumor is synonymous with neoplasia. Tumors may be classified according to
the following:
 behavior
 tissue of origin
 degree of differentiation

Behavior
 Benign tumors are slow growing, encapsulated masses of orderly cells
 Malignant tumors are caused by genetic mutations that allow for uncontrolled growth
 Oncogenes are mutated genes whose products are associated with neoplastic transformation
 Malignant tumors are not well encapsulated, fast growing and invasive with the ability to
metastasize
 Only malignant tumors metastasize [seed] elsewhere

Tissue origin

Tissue Benign Malignant

Fibrous Fibroma Fibrosarcoma
Fat Lipoma Liposarcoma
Vascular Angioma Angiosarcoma
Smooth muscle Leiomyoma Leiomyosarcoma
Skeletal muscle Rhabdomyoma Rhabdomyosarcoma
Bone Osteoma Osteosarcoma
Cartilage Chondroma Chondrosarcoma
Nerve Neuroma Neurosarcoma
Lymph node Lymphoma
White blood cell Leukemia
Gland Adenoma Adenocarcinoma
Table 11: Tumor Examples
Degree of differentiation [histological grade]
 This refers to how well the tumor follows the pattern of cells and the architecture of the normal
tissue
 Benign tumors are usually well-differentiated tumors
 A poorly-differentiated tumor does not resemble the normal tissue of origin
 Malignant tumors can be well, moderately or poorly differentiated
 The prognosis is worse when the tumor is not well-differentiated

Specific neoplasia
 Burkitt’s lymphoma is characterized by a starry-sky appearance
o it is caused by the Epstein Barr virus and is more common in children
 Hodgkin’s lymphoma is common in adults
o it is characterized by Reed-Sternberg cells
 Pheochromocytoma is an adrenal medulla tumor which secretes excess nor-epinephrine
o it is characterized by paroxysms of palpitations, perspiration and pressure headaches
 Wilms’ tumor is a mixed [mesenchymal, stromal and epithelial cells] tumor of the kidney
o it is the most common renal tumor in children
 Multiple myeloma is the most common primary bone cancer in adults:
o characterized by malignant plasma cells in the bone marrow
o M spike [due to elevated IgG]
o Bence Jones protein in urine
o nocturnal bone pain
o recurrent infections due to improperly formed immunoglobulins
 Osteosarcoma is the most common primary bone cancer in children
o it commonly affects the bones around the knee joint-lower femur and upper tibia
 Ewing’s sarcoma is a malignant bone tumor which mimics osteomyelitis

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  Uterine leiomyoma [fibroid] is the most common benign smooth muscle tumor in the uterus in
females
 Leukemia is a blood malignancy characterized by numerous immature WBCs
 There are 4 main types of leukemia:
o Acute Lymphoblastic Leukemia [ALL]-commonest leukemia in children under 5 years
o Acute Myelogenous Leukemia [AML]-80% of acute leukemias in adults, Auer rods+
o Chronic Myelogenous Leukemia [CML]-30 to 60 years; Philadelphia chromosome,
anemia, bleeding and infection
o Chronic Lymphocytic Leukemia [CLL]- >60 year-old men; lymphadenopathy is
common

Cancer etiology
 Oncogenes
o Genetic mutations which are associated with many cancers
• BCR-abl on the Philadelphia chromosome in Chronic Myelogenous Leukemia
• N-MYC in neuroblastoma
• L-MYC in lung cancer
• BRCA 1 in breast cancer
• p16 in melanoma
 Carcinogens
o Chemical
• Nitrosamine esophageal cancer
• Asbestos mesothelioma
• Benzene leukemia
• Aflatoxin hepatocellular carcinoma
o Radiation
• UV light melanoma
• X-ray thyroid cancer
• Uranium lung cancer
o Microbiological
• HPV infection 16, 18 cervical cancer
• HHV 8 Kaposi sarcoma
• Epstein-Barr virus Burkitt’s lymphoma
• Hepatitis B/C hepatocellular carcinoma

Tumors and Tumor Marker

 Choriocarcinoma β-HCG [Human Chorionic Gonadotropin]
 Colon cancer CEA [CarcinoEmbryonic Antigen]
 Hepatocellular carcinoma AFP [Alpha FetoProtein]
 Prostate cancer PSA [Prostate Specific Antigen]
 Ovarian cancer CA-125
 Melanoma S-100
 Adenocarcinoma Acanthosis nigricans

Acanthosis nigricans
 symmetric velvety hyperpigmented plaques in the axilla, groin, neck
 may be associated with:
o lung, breast and stomach cancer
o it is also seen in insulin-resistant states such as obesity and diabetes

Common anatomical sites for metastases in order of frequency

 lung, liver, bone, brain and adrenal gland

Primary versus Metastases

 primary tumors tend to be large and local
 metastatic tumors are small and multifocal

Cancer Epidemiology
 Males: prostate [32%], lung [16%] then colon and rectum [12%
 Females: breast [32%], lung [13%] then colon and rectum [12%]

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CARDIOVASCULAR PATHOLOGY

Diseases of the cardiovascular system may be classified according to the structure affected such as heart,
artery or vein or by the type of underlying pathology such as trauma, infectious, degenerative or neoplastic.

Congenital
 It may be either cyanotic or acyanotic:
o Cyanotic Heart Disease is due to a right to left shunt in the heart
o Acyanotic Heart Disease is seen in left to right shunt as in VSD, ASD and PDA
 Fallot’s tetralogy is the most common cyanotic congenital heart disease and consists of:
o pulmonary stenosis
o ventricular septal defect
o right ventricular hypertrophy
o overriding [dextro-position] aorta
 Patent Ductus Arteriosus is caused by failure of the ductus arteriosus to close shortly after birth
 ASD is due to a defect in the atrial septum: failure of the ostium secundum to close
 VSD is due to a defect of ventricular septum: most common congenital heart disease [30%]
 Transposition of the Great Vessels is an uncommon cause of congenital cyanotic heart disease
in which the aorta is connected to the right ventricle and the pulmonary trunk to the left ventricle
 Coarctation of the aorta is due to narrowing of the arch near the ligamentum arteriosum

Infections
 Rheumatic fever is due to a post-strep infection
o it is characterized by Aschoff bodies [granulomas with giant cells], Anitschkow cells and
MacCallum’s patches
 MacCallum’s patches are found in the left atrium
o Jones major criteria in diagnosing rheumatic fever include:
 Sydenham’s chorea
 Polyarthritis
 Erythema marginatum
 Carditis
 Subcutaneous nodules
 Endocarditis is the inflammation of endocardium [affecting the valves] and may be caused by
Streptococcus pyogenes, Streptococcus viridans or Staphylococcus aureus
o Subacute Bacterial Endocarditis-infection of previously damaged valves
 seen more commonly as a sequel of rheumatic fever [S. viridans]
 fever, new murmur, splinter hemorrhages, Olser’s nodes and Janeway nodules
o Acute Bacterial Endocarditis-infection of previously health valves
 seen more commonly in intravenous drugs users [Staph. aureus]
o Libman Sacks Endocarditis is the sterile [non-infective] endocarditis of pulmonary and
tricuspid valves seen in SLE
 Syphilitic aortitis often affect the arch of the aorta
o Treponema pallidum infection leading to aortic aneurysm, aortic stenosis and angina
pectoris

Vascular
 Thrombus is a clot formed within an atherosclerotic vessel with lines of Zahn
 Embolism is a dislodged mass of undissolved material in blood vessel travelling in the blood
o arterial embolism: painful, pale, pulseless, perishingly cold limb
 Arteriosclerosis refers to the thickening of the arteries with loss of elasticity and contractility
due to infiltration of the tunica intima by collagen and smooth muscle fibers
 Atherosclerosis is commonly caused by lipid/calcium deposits in tunica intima:
o risk factors include cigarette smoking, fatty diet, obesity, hypertension, diabetes and
homocysteinemia and bad cholesterol [Lethal LDL cholesterol]
o pathology includes subendothelial fatty streaks, fibrosis, atheroma and rupture with
eventual occlusion or embolus formation
 Ischemic Heart Disease is caused by coronary atherosclerosis and leads to angina,
myocardial infraction or Congestive Heart Failure
 Angina pectoris is caused by reversible inadequately perfused myocardium and the pain
relieved by rest

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  Prinzmetal [variant] angina is angina that occurs at rest and is caused by coronary artery
spasm
 Myocardial Infarction is related to ischemic necrosis of myocardium due to blocked coronary
artery, mainly the Left Anterior Descending artery; the pain is NOT relived by rest
o results in the release of cardiac enzymes such as Troponin and Creatine Kinase-MB
[myocardial band] and Lactic Dehydrogenase

Degenerative
 Aneurysm is the localized dilation of an artery; congenital or acquired
 Atherosclerotic aneurysms are most often affect the abdominal aorta-AAA
o Abdominal aortic aneurysm is due to atherosclerosis and presents with pulsatile
abdominal mass with a bruit and low back pain
 Dissecting aneurysm results from a longitudinal intraluminal tearing of the ascending thoracic
aorta and is seen in Marfan’s and Ehlers-Danlos syndromesand longstanding hypertension
 Syphilitis aneurysm results from tertiary syphilis and mainly affects the arch of the aorta
rd
 Berry aneurysms are congenital weaknesses that only present in the 3 decade and onwards
o may be associated with adult polycystic disease of the kidney
o commonly in the anterior part of the circle of Willis in the brain
o may cause subarachnoid hemorrhage in young adults
o may present with severe sudden headache, neck stiffness and loss of consciousness

Miscellaneous
 Hypertension is defined as the elevation of BP >140/90 on 3 or more occasions
o Hypertension is classified as essential or secondary:
o Essential hypertension is unknown [95%]:
 risk factors include:
 family history
 high salt intake
 stress
 obesity
o Secondary hypertension [5%]:
 unilateral renal artery stenosis
 hyperthyroidism
 Cushing’s
 pheochromocytoma
o Malignant hypertension is rapidly progressing with severe vascular damage
 may lead to an early death from a stroke or heart failure
 Congestive Heart Failure is caused by coronary artery disease, hypertension, valvular heart
disease, congenital heart disease or cardiomyopathy
 Cardiomyopathy is diseased myocardium
o caused by:
 alcohol
 pregnancy
 viral infections
o there are three types:
 dilated [most common]
 hypertrophic
 restrictive [rare]
 Cor pulmonale is right heart failure due to:
o COPD
o pulmonary embolism
 Cardiac tamponade occurs when the heart is compressed due to excess fluid in pericardial
sac
o it is characterized by Beck’s triad:
 Hypotension
 Heart sounds are distant
 High venous pressure
 Peripheral Vascular Disease is caused by:
o atherosclerotic narrowing of large arteries
o presents with intermittent claudication
 pain in the calves on walking and relieved by rest

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  Deep Vein Thrombosis is related to Virchow’s triad:
o Viscosity-increased clotting which may be related to the contraceptive pill
o Stasis in the veins from prolonged immobilization
o Damage to vessel wall due to trauma
o may present with a painful swollen leg
 Pulmonary Embolism
o related to deep vein thrombosis-leg or pelvis
o a piece of the clot breaks off [embolus]
o the embolus travels up into the inferior vena cava and into the heart
o from the heart the clot travels up the pulmonary trunk
o occludes one of the pulmonary arteries or a smaller branch
o causes a ventilation/perfusion mismatch
o presents with a triad of shortness of breath, pleuritic chest pain and hemoptysis
 Varicose veins
o tortuous dilated superficial veins
o may lead to thrombophlebitis
 Thrombophlebitis
o inflammation of the vein wall and may lead to thrombosis
o presents with a swollen tender superficial cord under the skin
 Raynaud’s disease
o Decreased blood flow triggered by cold and emotion and is characterized by:
 vasospasm [white]
 cyanosis [blue]
 vasodilation [red]
 often in young females with no known cause
 Raynaud’s phenomenon
o secondary to:
 SLE
 Atherosclerosis
 Scleroderma
o may be part of the CREST syndrome:
 Calcinosis cutis
 Raynaud’s phenomenon
 Esophageal dysfunction
 Scleroderma
 Telangiectasia
 Polyarteritis nodosa
o Inflammation due to a Type III hypersensitivity reaction
o affects medium size arteries, 30% are seropositive for Hepatitis B
o may present with fever, joint, abdominal pains and palpable purpura
 Thromboangitis obliterans [aka Buerger’s disease]
o due to idiopathic segmental inflammation of medium size arteries and veins
o seen in male smokers between 20 and 40 years
o intermittent claudication and weakened distal pulses
 Temporal arteritis is the localized giant cell inflammation in small arteries
o associated with a raised ESR
o in the elderly mainly
o may affect other small arteries like branches of the ICA and vertebral arteries
o may cause blindness if not treated promptly
 Takayasu’s arteritis [pulseless disease]
o due to inflammation of the aorta; possible autoimmune
o more common in Asian females < 40 years
o presents with absent pulses, mainly in the upper limbs

Neoplastic
 Hemangioma is a benign blood vessel tumor
 Kaposi sarcoma may be caused by HHV type 8 in HIV/AIDS
 Atrial myxoma is a benign myxomatous tumor in the region of the fossa ovalis

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ENDOCRINE PATHOLOGY

Diseases of the endocrine may be classified according to the structure affected such as pituitary, thyroid,
parathyroid, adrenal or gastrointestinal or by the type of underlying pathology such as trauma, infection or
neoplasm.

Pituitary disorders
 Gigantism
o due to excess Growth Hormone before 18 years
o may be associated with a functioning pituitary adenoma and presents with:
 overgrowth of tissues in the entire body-large hands and protruding jaw
 headache
 visual disturbance
 Acromegaly
o due to excess GH after growth plate has closed
o functioning pituitary adenoma presenting with:
 protruding jaw, large spatulate hands and large feet
 headache
 visual disturbance
 Cushing’s disease
o caused by excess ACTH from a functioning pituitary adenoma
o this causes excess cortisol production by the adrenal cortex resulting in:
 moon-face, buffalo hump, truncal obesity and hypertension
 purple striae on the abdomen and hyperpigmented skin creases
 muscle wasting in the extremities, recurrent infections
 Pituitary dwarfism
o GH deficiency in children
o may be related to a non-functioning pituitary tumor presenting with:
 growth retardation
 Sheehan’s syndrome
o ischemic necrosis of anterior pituitary lobe
o following a severe postpartum hemorrhage
o afterwards there is no secretions from the anterior lobe resulting in:
 amenorrhea
 cessation of lactation
 loss of axillary and pubic hair
 Hyperprolactinemia
o secreting prolactin pituitary adenoma presenting with:
 galactorrhea
 milky discharge from a non-lactating breast
 amenorrhea
 absent menstruation
 prolactin inhibits GnRH release from the hypothalamus
 infertility
 inability to conceive in spite of unprotected sex for a year
 Diabetes insipidus
o ADH deficiency
o caused by head injury, pituitary tumors, kidney disease and sarcoidosis presenting
with:
 polyuria-frequent passage of copious diluted and colorless urine
 polydypsia-excessive water consumption
 constant specific gravity of urine < 1.006 in spite of dehydration

Thyroid disorders
 Hypothyroidism [myxedema in adults and cretinism in infants]
o thyroxin deficiency may be:
 primary or secondary
o Primary hypothyroidism
 low T3, T4 and high TSH
 fatigue, constipation, brittle hair, slow to relax reflexes, weight gain

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 o Secondary hypothyroidism
 low T3, T4 and low TSH: pituitary hypofunctioning
o Hashimoto’s thyroiditis
 anti-thyroglobulin antibodies, goiter and hypothyroidism
o Riedel’s thyroiditis
 lymphocytic fibrotic thyroid disease leading to hypothyroidism
 Hyperthyroidism
o Primary hyperthyroidism
 elevated T3, T4 with low TSH
 Graves disease [most common form of hyperthyroidism]:
 autoimmune disorder-IgG antibodies bind to TSH receptors
 exophthalmos, goiter, fine tremors of the hands, nervousness, diarrhea,
weight loss despite increased appetite, HLA B8 predisposition
 exophthalmos-bilateral bulging eyes
 goiter-diffuse enlarged thyroid gland
 Plummer’s disease: toxic multinodular goiter and no exophthalmos
o Secondary hyperthyroidism
 elevated T3, T4 with high TSH: TSH-secreting pituitary tumor

Parathyroid disorders
 Hyperparathyroidism
o functioning parathyroid adenoma
o hypercalcemia
o fatigue
o brown bone cysts due to decomposed blood and hemosiderin pigment
 Hypoparathyroidism
o incidental removal of the parathyroids in total thyroidectomy
o causes hypocalcemia
o presents with tetany and muscle twitching
o Chvostek test may be positive:
 tapping the facial nerve in front of the ear causing facial twitching

Adrenal disorders
 Addison’s disease
o chronic underfunctioning of the adrenal cortex
o may be an autoimmune disorder or associated with tuberculosis infection
o low glucocorticoids and aldosterone
o hyperpigmented skin creases and bronze skin
o low Na, low BP, high K and high ACTH
 Waterhouse-Friderichsen syndrome
o acute adrenal bleeding secondary to Neisseria meningitidis septicemia
o results in shock and hemorrhagic rash
 Conn’s disease
o overfunctioning of the zona glomerulosa layer of the adrenal cortex
o due to an adrenal adenoma which produces excess mineralocorticoids
o low potassium, low renin, metabolic alkalosis and high BP
 Cushing’s syndrome
o may be due to exogenous steroids or a tumor of the adrenal cortex
o truncal obesity, moon face and buffalo hump, hypertension, hyperglycemia
o poor wound healing purple abdominal striae but no hyperpigmentation
 Neuroblastoma
o Most common adrenal medulla tumor in children, associated with the N-myc oncogene
 Pheochromocytoma
o adrenal medulla tumor which presents with:
 palpitations, perspiration, pressure headaches and periodic hypertension
 vanilyl mandelic acid is found in excess in the urine
 known as the 10% tumor:
 10% are bilateral
 10% are malignant
 10% occur outside of the adrenal gland
 10% are familial

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Gastrointestinal disorders
 Diabetes mellitus Type 1
o Insulin Dependent DM
o due to insulin deficiency
o caused by beta cell destruction
o associated antibodies to beta cells of the pancreas
 weight loss
 more prone to Diabetic KetoAcidosis
 common in children and teens
o HLA DR3 or 4 genetic predisposition
 Diabetes mellitus type 2
o insulin insensitivity
o Non-Insulin Dependent DM
o insulin levels may be even elevated
o common in obese adults
o many have a family history of diabetes
o presents with:
 polyuria
 polydypsia
 polyphagia
 prone to HyperOsmolar Non-Ketotic coma
o some complications may be due to accumulation of Advanced Glycated End products
o causing narrowing of small and medium-size vessels
o premature cataracts and retinopathy may be related to accumulation of sorbitol
 MODY type
o Mature Onset Diabetes in the Young
o not dependent on Insulin, no antibodies and not obese
o under 25 years of age
 Gestational diabetes
o occurs in 4% of all pregnancies
o usually resolves with the end of the pregnancy
o some may progress to type 2 DM
 Carcinoid syndrome
o tumors of neuroendocrine cells in the gut
o results in recurrent diarrhea, cutaneous flushing and bronchial wheezing
o 1/3 metastasize
o 1/3 are multiple
 Insulinoma
o pancreatic beta-islet cell tumor
 hypoglycemia relieved by food
 Gastrinoma
o excess gastrin from GI tumor
 recurrent peptic ulcer disease
 aka Zollinger-Ellison syndrome
 may be part of MEN type 1

Multiple Endocrine Neoplasia subtypes

 MEN type 1 [Wermer’s syndrome] - 3 P’s
o Pituitary adenoma
o Parathyroid adenoma
o Pancreas adenoma
 MEN type 2a [Sipple’s syndrome] - 2 P’s + 1 M
o Medullary thyroid cancer
o Pheochromocytoma
o Parathyroid hyperplasia
 MEN type 2b - 1 P and 3 Ms
o Marfanoid features
o Medullary thyroid cancer
o Mucosal neuromas
o Pheochromocytoma

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GASTROINTESTINAL PATHOLOGY

Diseases of the gastrointestinal tract may be classified according to the structure affected such as
esophagus, stomach, intestinal, liver or gallbladder or by the type of underlying pathology such as trauma,
infection or neoplasm.

Esophageal disorders
 Achalasia
o failure of Lower Esophageal Sphincter to relax; dysphagia for fluids not solids
 Hiatal hernia
o protrusion of stomach into the chest through the diaphragm
 Esophageal varices
o dilated veins in the lower esophagus seen in portal hypertension
 GERD
o chronic inflammation of lower esophagus due to acid regurgitation
 Barrett’s esophagus
o premalignant metaplastic change of lower esophagus due to GERD
 Esophageal cancer
o squamous cell carcinoma
o excess nitrosamines in the diet and smoking
o adenocarcinoma; Barrett’s esophagus
 Mallory-Weiss syndrome
o linear tear in lower esophagus due to protracted vomiting and retching

Gastric disorders
 Peptic Ulcer Disease
o H. pylori infection, ulcer along lesser curvature of stomach [70%] or duodenum [95%]
o Epigastric pain is greater with meals in gastric ulcers and decreases with duodenal ones
 Congenital Pyloric Stenosis
o young male infants > 6 weeks, projectile vomiting, hypertrophic pylorus
 Atrophic Gastritis
o H. pylori infection; predisposition to pernicious anemia and cancer
 Gastric Carcinoma
o H. pylori infection, high nitrosamines in diet; smoked meats
o Unexplained weight loss and Troisier’s node
 Troisier’s sign: Virchow’s node in left supraclavicular fossa
 metastatic spread from intra-abdominal cancer

Small Intestinal disorders

 Crohn’s disease [regional ileitis]
o non-caseous granulomas, cobblestone terminal ileum, skip lesions and fistula
 Meckel’s diverticulum
o remnant of the vitelline duct; 2” long. 2’ from Ileocecal valve, 2% of people
 Celiac disease [celiac sprue]
o gluten sensitivity causing malabsorption in small intestine, vomiting, diarrhea
 Whipple’s [tropical sprue] disease
o Trophermya whipplei [Gram + rod] infection causes steatorrhea and arthritis

Large Intestinal disorders

 Appendicitis
o inflammation of appendix following blockage of its lumen by a fecalith
o periumbilical pain radiating to the RLQ pain with tenderness at McBurney’s point
 Diverticulosis
o Condition of numerous outpouchings of the large bowel-older people
 Diverticulitis
o inflammation of a diverticulum in the bowel
o causes left lower quadrant pain and blood in the stool in an older patient
 Intussusception
o telescoping of a proximal part of bowel into a distal segment
o presents with abdominal pain and intestinal obstruction in a child

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  Hirschsprung’s disease
o arrested neural crest cell migration, congenital aganglionosis of the colon
o presents with chronic constipation in a child
 Ulcerative colitis
o chronic ulcerative inflammation mainly confined to the rectum
o presents with bloody diarrhea, toxic megacolon and an increased risk of colon cancer
 Carcinoma of the colon
o third most common cancer in both sexes
o unexplained weight loss and change of bowel habits in the older population
 Volvulus
o twisting of part of the bowel on itself; more common in sigmoid colon and in blacks
o presents with intestinal obstruction and abdominal pain
 Peutz-Jegher syndrome
o oral pigmentation and multiple intestinal polyps
 Irritable Bowel Syndrome [IBS]
o spastic colon of unknown cause
o presents with pain relieved by defecation, bloating, diarrhea and/or constipation

Liver disorders
 Hepatitis: inflammation of liver caused by viral infections, alcohol or drugs
o Hepatitis A: fecal/oral transmission; water borne infection
o Hepatitis B: intravenous drug use and sexually transmitted; chronic carrier state
o Hepatitis C: used to be the most common cause of post-transfusion hepatitis
 Nutmeg liver: chronic passive venous congestion
o seen in congestive heart failure
 Cirrhosis [Laennec’s]
o chronic liver condition with damage, fibrosis and regeneration nodules:
 presents with portal hypertension
o portal hypertension:
 obstruction to portal blood flow to the liver due to liver fibrosis
 causes ascites which is the accumulation of excess fluid in the abdomen
 may also be due to decrease protein and increased aldosterone levels
o caput medusae:
 dilated varicose veins radiating from umbilicus due to portal hypertension
 Reye’s syndrome
o rare cause of childhood hepatoencephalopathy caused by the use of aspirin in children
with some febrile illnesses-chickenpox and influenza
 Hepatocellular carcinoma [aka malignant hepatoma]
o liver cancer associated with Hepatitis B and C cirrhois, raised α-fetoprotein
o may be associated with fungal [aspergillus] aflatoxins
o may present with painful hepatomegaly, anorexia, fatigue andweight loss

Gallbladder disorders
 Cholecystitis: inflammation of gallbladder
o fair, fat, fertile, flatulent females over forty with right upper quadrant pain
o 95% is caused by gallstones [cholelithiasis]:
 cholesterol, pigment or mixed stones
 70 to 80% of people with gallstones are asymptomatic
Pancreatic disorders
 Pancreatitis: inflammation of the pancreas
o caused by alcohol, gallstones, trauma, steroids, mumps and hypercalcemia
o swollen pancreas with leakage of pancreatic enzymes into the abdominal cavity
o severe abdominal pain, bluish discoloration [Cullen’s sign] around umbilicus or in the
flanks [Grey Turner’s sign]
 severe epigastric pain radiating through to the back
 nausea and vomiting
 Pancreatic cancer: malignancy arise from the pancreatic ducts [adenocarcinoma]
o painless jaundice
o clay-colored stool if the cancer is in the head of the pancreas
o weight loss due to malabsorption and anorexia; very poor prognosis

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MUSCULOSKELETAL PATHOLOGY

Musculoskeletal diseases may be classified according to the tissue of origin such as bone, joint, muscle or
neuromuscular junction or according to the type of pathology such as traumatic, infectious, metabolic or
neoplastic.

Benign bone disorders

 Osteoporosis
o loss of bone quantity while bone quality is normal
o more common in postmenopausal women due to lack of estrogen
o senile type is due to lack of growth hormone and more common in older men
 Osteomalacia
o loss of bone quality with softening of the bone
o decreased Vitamin D in adults
o Looser’s zones on x-rays of long bones
 Rickets
o loss of bone quality
o decreased Vitamin D in children
o bowlegs and rachitic rosary [swollen costochondral joints]
 Osteitis fibrosa cystica
o due to hyperparathyroidism
o brown [hemosiderin] bone cysts
 Paget’s disease
o aka osteitis deformans
o possible paramyxovirus infection
o older people with thickening of bones and deformities
 Achondroplasia
o autosomal dominant
o short limbs with normal head and trunk
 Charcot’s joint
o neuropathic joint disease: joint destruction because of loss of pain
o caused by:
 tabes dorsalis
 diabetes mellitus
 syringomyelia
 leprosy
 Osteogenesis imperfecta
o autosomal dominant
o brittle bone disease
o blue sclera
o defective collagen synthesis
 Osteomyelitis
o blood borne bone infection
o Staphylococcus aureus is the most common
o Salmonella organisms in Sickle Cell Disease
o Pseudomonas organisms in intravenous drug users
 Osteochondroma
o bone outgrowth [exostosis]
o capped by cartilage
 Enchondroma
o most common benign tumor in hand
o expansile benign cartilage tumor in bone
 Ollier’s disease
o multiple enchondromas
 Osteoma
o dense, mature bone island in the skull or spine
 Giant cell tumor
o benign metaphyseal bone tumor extending into the epiphysis
 Aneurysmal Bone Cyst
o eccentric soap bubble x-ray appearance extending from diaphysis into metaphysis

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Malignant bone disorders
 Multiple myeloma
0
o most common 1 bone cancer in adults
o more common after 50 years
 nocturnal bone or back pain
 recurrent infections
 hypercalcemia: stones, bones, moans and abdominal groans
o punched-out lesions on x-ray
o raised IgG causing an M [myeloma] spike on serum electrophoresis
o Bence Jones proteins [light chain Ig] in urine
 Osteosarcoma [aka osteogenic sarcoma]
0
o second most common malignant bone tumor; most common 1 bone cancer in teenagers
o may be seen in patients with Paget’s disease
o Codman’s triangle of periosteal elevation on x-ray
 Chondrosarcoma
o third most common malignant bone tumor; men aged 30-60 years
 Ewing’s sarcoma
o malignant tumor mimicking osteomyelitis
o onion skin appearance on x-ray

Arthritides
 Seropositive arthritis
o Rheumatoid Factor is positive: RA and SLE
 Rheumatoid arthritis
o autoimmune bilateral small joint disease in HLA-DR4 positive patients
o Rheumatoid factor [IgG antibody] in 70-80% of patients
o Joint inflammation characterized by pannus formation:
 inflamed granulation tissue in the joint space destroying articular surface
o joint deformities
 swan neck
 ulnar deviation
 boutonnière
 Haygarth’s nodes-metacarpophalangeal joint swelling
 Bouchard’s nodes-proximal interphalangeal joints [also seen in OA]
 Still’s disease
o Juvenile Rheumatoid Arthritis
 affects small and medium-size joint pains mainly wrist and knee
 lymphadenopathy and splenomegaly in children and teenagers
 Felty’s syndrome
o splenomegaly
o neutropenia
o seen in patients with RA
 Systemic Lupus Erythematosus
o unknown cause
o autoimmune disorder: AntiNuclear Antibodies, anti ds-DNA antibodies
o more common in younger females
o more severe in young black females
o affects multiple organ systems
 joints: polyarthritis-small and large joint
 skin: butterfly [malar] rash and photosensitivity
 kidney: nephrotic syndrome
 heart: Libman-Sack’s endocarditis
 Sjðgren’s syndrome
o dry eyes [xerophthalmia], dry mouth [xerostomia] and arthritis
o may be seen in both RA and scleroderma
o more common in women between 40 and 60 years
o antibodies to ribonucleoproteins [SS-A and SS-B]
 Seronegative arthritis
o Rheumatoid Factor is negative
o HLA-B27 is positive
o Reiter’s syndrome, Psoriatic arthritis, Ankylosing Spondylitis

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  HLA-B27+ arthritis [PAIR]
o Psoriatic arthritis, Ankylosing Spondylitis, Reiter’s syndrome
 Psoriatic Arthritis:
 polyarthritis with silvery-scales over extensor aspects
 autoimmune disorder causing rapid turnover of skin
 pitted nails and dactylitis [sausage fingers]
 Ankylosing Spondylitis [aka Marie Strumpell’s disease]:
 Sacroiliitis and low back pain
 bamboo spine and a positive HLA B27 genetic marker
 Inflammatory Bowel Disease like Ulcerative Colitis
 some patients with ulcerative colitis present with joint pains
 Reiter’s syndrome: [can’t pee, can’t see and can’t dance with me]
 Urethritis
 Arthritis-joint or heel pain
 Conjunctivitis
 may be caused by Chlamydia or Shigella infection
 Osteoarthritis
o degenerative disease affecting weight-bearing joints:
 hips
 knees
 spine
o causes subchondral sclerosis, osteophytes, Heberden’s and Bouchard’s nodes
o Heberden’s nodes
 primary osteoarthritis in distal interphalangeal joints of the fingers
 in females mainly
o Bouchard’s nodes
 swelling of the proximal interphalangeal joints seen in OA and RA
 Gout
o aka podagra [when it affects the foot] or gonagra [when it affects the knee]
o due to hyperuricemia [raised uric acid]
o more common in males
o may be associated alcohol and purine-rich foods
o alcohol metabolites compete for the same excretion site in the kidney as uric acid
st
o acute gout: sudden onset of severe 1 metatarsophalangeal joint pain
o chronic gout is characterized by tophi:
 accumulation of uric acid crystals in the ear and skin over joints
o uric acid crystals are needle-shaped and negatively birefringent with polarized light
[yellow with parallel light]

Periarticular disorders
 Lyme disease
o named after the town of Lyme, Connecticut where a number of case were seen in 1975
o caused by Borrelia burgdorferi
o transmitted by deer tick: Ixodes scapularis
o polyarthritis with bulls-eye lesion [erythema chronicum migrans]
Neuromuscular disorders
 Myasthenia gravis
o acetylcholine receptor antibodies
o major peak incidence in 30+ year-old females; second peak in 60+ year-old males
o diplopia, ptosis, problems chewing, fatigue with repetitive muscle use
o Tensilon [injection of edrophonium chloride] test is positive
o 80% of female myasthenic patients have thymic pathology:
 65% have thymic hyperplasia
 15% have a thymic tumor [thymoma]
 Lambert-Eaton syndrome
o auto-antibodies to the pre-synaptic voltage-gated calcium channels in the
neuromuscular junction
o prevents acetylcholine from being released by the vesicles
o seen in small [oat] cell lung cancers
o older male population-60+ years
o weakness improves with repetitive use
o Tensilon test is usually negative

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Myopathies
 Dermatomyositis
o Unknown cause
o Autoimmune disorder
o More common in females
o Causes a heliotrope rash [reddish purple eyelids and papules on the knuckles of the
hands [Gottron’s papules]
o Produces antinuclear antibodies and anti-Jo-1 antibodies
o 10% associated with underlying malignancies of the lung, breast, gut or ovary
 Duchenne’s muscular dystrophy
o sex-linked recessive
o absence of Dystrophin
o males predominantly
o pseudohypertrophic calves
 muscle infiltrated by fat and connective tissue
 although the muscle appears to be big and strong, it is actually weak
o death from cardiorespiratory failure before age 20 years
 Becker’s muscular dystrophy
o sex-linked recessive
o inadequate dystrophin levels
o not as severe as Duchenne’s muscular dystrophy; tend to live beyond 40 years

Neuropathies
 Charcot-Marie-Tooth disease
o progressive hereditary nerve damage
o peroneal muscular wasting
o inability to evert the foot

Miscellaneous conditions
 Legg-Calvé-Perthes Disease
o ischemia and subsequent avascular necrosis of the head of the femur
o unknown cause
o more common in young boys
 Slipped Capital Femoral Epiphysis
o displacement of the epiphysis of the head of the femur
o more common in overweight children and teens
o possible traumatic Salter-Harris type 1 epiphyseal fracture
 Polymyalgia rheumatica
o unknown cause
o older females > 50 years
o pain and stiffness in the shoulder and hips
o malaise and fever
o associated with temporal arteritis
o may lead to blindness
o highly elevated ESR with normal creatine kinase

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NERVOUS SYSTEM DISORDERS

Diseases of the nervous system may be divided into the following categories:
 Central Nervous System
 Peripheral Nervous System
 Autonomic Nervous System

CNS disorders may be classified as follows:

 Vascular
 Infectious
 Neoplastic
 Degenerative
 Idiopathic
 Congenital
 Autoimmune
 Traumatic
 Endocrine

Congenital disorders may result from failure of the neural tube to form properly:
 Spina bifida is a neural tube defect due to folic acid deficiency in the first trimester
o Spina bifida occulta present with failure of the neural arch to close and with a tuft of hair
over a dimple in the region of the lumbar spine
o Spina bifida vera is a more severe form with failure of neural arch to close with meninges
herniation under skin
o associated with elevated levels of alpha-fetoprotein
 Meningocele refers to the protrusion of meninges through defect in the spinal column
 Myelomeningocele is when there is protrusion of meninges & spinal cord through spinal column
defect
 Anencephaly is the failure of the brain and cranial vault to develop

Sometimes the defect may affect the ventricles and the flow of CSF:
 Hydrocephalus is the accumulation of excessive CSF in the ventricles
 Obstructive hydrocephalus is caused by obstruction to the flow of CSF: non-communicating type
 Normal pressure hydrocephalus: dilated ventricles in the elderly
o reversible cause of dementia
o presents with incontinence, ataxia and dementia [wet, wobbly and wacky]
 Arnold-Chiari deformity is characterized by a small posterior fossa with cerebellar herniation
into foramen magnum
o Arnold-Chiari type 1 herniation of cerebellar tonsils into foramen magnum
o Arnold-Chiari type 2 herniation of cerebellar vermis and medulla into the
foramen magnum
 Dandy-Walker syndrome is characterized by:
o a large posterior fossa
th
o with cystic dilation of the 4 ventricle

Some brain damage may be due to brain anoxia at the time of birth:
 Cerebral palsy is the non-progressive motor disorder due to prenatal brain anoxia
o scissors gait is the upper motor neuron gait seen in cerebral palsy

Trauma to the skull may result in the following:

 Subdural hematoma is the accumulation of blood under dura: trauma in the elderly; tear of dural
veins
 Extradural hematoma refers to the accumulation of blood outside of dura; trauma in the adults;
meningeal artery tear
 Subarachnoid hemorrhage is the accumulation of blood under arachnoid, this may be due to a
ruptured berry aneurysm
o berry aneurysm is a saccular congenital swelling in a cerebral artery
o there is an increase incidence of berry aneurysms in adult polycystic disease of the
kidney
 Contrecoup injury refers to damage to the part of brain opposite to the site of injury

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Vascular supply interruption will cause brain damage:
 Cerebrovascular Accident [stroke] is the sudden contralateral motor/sensory loss due to
interrupted blood supply to brain
 Transient Ischemic Attacks [mini stroke] are similar but brief episodes of neurological dysfunction
caused by small emboli lasting less than 24 hours
 Thrombosis refers to a clot formed within an atherosclerotic blood vessel
 Embolism is a mass of undissolved material in blood vessel brought by the blood
 Intracerebral hemorrhage refers to the accumulation blood inside the brain:
 The most commonly affected are the lenticulostriate branches of the middle cerebral artery

Infections may cause neurological disease:

 Encephalitis is a viral infection of brain
 Arthropod Borne [mosquito] viruses: WEE, EEE, SLE
 Meningitis is an infection of meninges: N. meningitidis, E. coli, H. influenza
 Brain abscess is the collection of pus in brain lobe; from sinusitis and otitis media
 Creutzfeldt-Jakob disease is the human form of Bovine Spongiform Encephalitis-Mad Cow
Disease
 Kuru is a prion disease associated with eating of brains of the dead in Papua New Guinea
o Prions are infectious protein particles
 Poliomyelitis is caused by an enterovirus which causes flaccid paralysis due to destruction of
anterior horn cells in the spinal cord
 Congenital syphilis is due to intrauterine infection of the fetus and results in interstitial keratitis,
deafness, saddle nose, rhagades, Hutchinson’s teeth and saber shin:
o Interstitial keratitis is the inflammation of the cornea leading to blindness
o Rhagades are the linear fissures in the skin particularly at the corners of the mouth
o Hutchinson’s teeth are notched central incisors

Degenerative disorders include:

 Alzheimer’s disease is characterized by diffuse cerebral atrophy, pronounced memory loss,
Hirano bodies, amyloid plaques and neurofibrillary tangles
 Parkinson [paralysis agitans] is characterized by pale substantia nigra, decrease dopamine with
Lewy bodies [eosinophilic intracytoplasmic inclusion bodies], resting [pill-rolling] tremors, mask
face and a festinating gait
o festinating gait is the gait with ever-increasing speed
 Huntington’s chorea is due to basal ganglion damage [caudate mainly] and is characterized by
decreased GABA, chorea and mental deterioration in middle-aged adults
 Amyotrophic Lateral Sclerosis [aka Lou Gehrig’s disease] is characterized by progressive upper
and lower motor neuron lesions in the lower and upper limbs
 Multiple sclerosis is a patchy autoimmune demyelination with some regeneration in brain and
spinal cord
o seen more commonly in younger females of Northern European descent
o more common in colder climates and is associated with Charcot’s triad:
 Scanning speech
 Intention tremor
 Nystagmus

Deficiencies of certain vitamins may cause brain disease:

 Wernicke’s syndrome is due to thiamine deficiency as seen in alcoholism and deficient diets
 Korsakoff’s psychosis is the syndrome characterized by memory loss accompanied by
confabulation [lying]; this is also seen in Thiamine deficiency
 Posterolateral sclerosis [aka subacute combined degeneration of the spinal cord] is due to
Vitamin B12 deficiency and results in dorsal columns and spinothalamic tract damage

Neoplastic diseases of the CNS include:

 most common brain tumors are metastases from breast, renal, gut, airway, skin and elsewhere
o
 most common 1 brain tumor is a glioblastoma multiforme; worst prognosis
 most common in children is a medulloblastoma; good prognosis with treatment
nd
 2 common brain tumor is a meningioma; benign lesion in falx cerebri, psammoma bodies
 acoustic neuroma is a benign tumor [schwannoma] in internal acoustic meatus: unilateral
deafness and facial paralysis

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  Von Recklinghausen’s disease is characterized by multiple neurofibromas in skin, spinal cord
and brain with café au lait skin lesions
 Von Recklinghausen’s disease is Type 1 [peripheral] neurofibromatosis and may be associated
with pheochromocytoma
 Type II neurofibromatosis is the central variety and is characterized by bilateral acoustic
neuromas

Poisoning may also cause CNS diseases:

 fetal alcohol syndrome results in retardation, microcephaly, indistinct philtrum and maxillary
hypoplasia
 carbon monoxide poisoning is due to inadequately ventilated heaters in winter and results in
cherry-red skin color
o carbon monoxide binds irreversible with hemoglobin

The causes of some CNS diseases are unknown [idiopathic] and include:
 epilepsy is characterized by seizures of unknown origin: grand mal or petite mal
 Friedreich’s ataxia is characterized by progressive spinocerebellar tract damage, ataxia,
scoliosis, speech and heart problems
 syringomyelia is the dilation of central spinal canal; results in a cape-like pattern of loss of
pain and temperature but intact proprioception and vibration

Peripheral Nervous System diseases

Damage to the peripheral nerves causes peripheral neuropathy. The following are examples of various
types of peripheral nerve damage:
 trauma or compression
 poisoning
 infection
 metabolic

Trauma
 Erb-Duchene’s palsy is due to C5, 6 roots damage during delivery or sports injury
o results in elbow extended, internal shoulder rotation and pronation of the forearm
 Klumpke’s palsy is due to C8 and T1 root damage during breech delivery or sports injury
o results in claw hand deformity

Compression neuropathies
 Carpal Tunnel Syndrome is caused by the median nerve compression at wrist: Phalen’s, Tinel’s
and wrist compression tests may be positive-pain or numbness in the lateral 3½ digits
 Elbow Tunnel Syndrome is caused by compression of the ulnar nerve at the elbow-pain or
numbness along the ulnar aspect of the forearm and medial 1½ digits
 Cheiralgia paresthetica is caused by compression of the superficial radial nerve near the wrist
and presents with pain over the lateral aspect of the distal forearm
 Piriformis syndrome refers to the compression of the sciatic nerve when it or a part of the nerve
passes through the piriformis muscle-pain radiates into the back of the thigh and leg
 Meralgia paresthetica is caused by compression of the lateral femoral cutaneous nerve-
numbness in the anterolateral aspect of the thigh
 Gonalgia paresthetica is caused by compression of the saphenous nerve at the knee in obese
patients-medial knee and medial leg pain
 Tarsal Tunnel Syndrome is due to compression of the posterior tibial nerve and results in pain
in the plantar surface of the foot

Types of nerve damage

 Neuropraxia: transient injury with rapid and complete recovery
 Axonotmesis: axon is damaged by sheath is intact, slow recovery as the axon regenerates
 Neurotmesis: axon and sheath are completely transected; permanent damage, no recovery

Poisoning
 Lead poisoning
 aka plumbism
 due to lead paint ingestion or lead paint inhalation

155
  presents with:
o Anorexia and anemia
o Belly pain and Burton’s blue gum line
o Clumsiness or Constipation
o Developmental delays or Dementia or Drop wrist
o Emesis [vomiting]
o Fatigue due to a microcytic hypochromic anemia
 Minamato disease is due to mercury poisoning
o excessive mercury in tuna fish in Japan
o characterized by peripheral neuropathy
o with numbness and hypotonia

Metabolic disorders
 Diabetes mellitus causes a peripheral neuropathy
o due to damage to vasa nervora and presents with glove and stocking paresthesia
o this is caused by the accumulation of Advanced Glycated End products
 Leprosy
o caused by Mycobacterium leprae
o bacterium loves cool areas: skin and peripheral nerves
o causes peripheral neuropathy
o claw hand
o loss of outer third of eyebrow
o anesthetic hypopigmented skin lesions
 Herpes zoster
o caused by HHV type 3 infection
o presents with a dermatomal rash on one side
o following a prodrome of pain and hypersensitivity over the same area
 Guillain-Barré syndrome
o infectious ascending demyelinating polyneuropathy
o due to possible viral infection or immunizations
o presenting with progressive motor loss starting in the legs
o may affect the diaphragm causing respiratory problems

Autonomic Nervous System diseases

The following are neurological diseases that affect the autonomic nervous system:
 Hirschsprung’s disease
o results from arrested neural crest cell migration
o with the result in congenital aganglionosis of colon
o affected segment of gut is unable to relax normally
o presents with chronic constipation
 Achalasia of the esophagus
o due to a decreased myenteric plexus
o causing dysphagia mainly for liquids
 Megaesophagus
o due to destruction of the ganglionic cells
o caused by Trypanosoma cruzi
o results in Chagas disease
o presents with dysphagia [difficulty swallowing]
 Horner’s syndrome is characterized by unilateral:
o Ptosis
o Anhydrosis
o Miosis
o “PAM is Horny”
o caused by destruction of the cervical sympathetic trunk
o as may be seen with Pancoast tumor [apical lung cancer]
 Reflex sympathetic dystrophy
o aka Sudeck’s atrophy
o aka Complex Regional Pain Syndrome
o caused by a severe local dysfunction of sympathetic nerves following minor injury
o characterized by pain and swelling in the affected limb
o more common in the foot and in females

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NUTRITIONAL PATHOLOGY

Nutritional diseases are usually classified in terms of deficiencies or accumulation.

Protein Calorie deficiency

 Protein Calorie Malnutrition
o deficient protein and calorie diet in infants and children
 Marasmus
o severe calorie deficiency causing wasting
 Kwashiorkor
o severe protein deficiency causing red hair, flaky-paint dermatitis and ascites

Vitamin deficiencies
 Vitamin B1 [thiamine] deficiency
o Beriberi
o seen in alcoholics, dietary deficiency, anorexia, bulimia and hyperemesis gravidarum
o Dry Beriberi
 B1 deficiency with peripheral neuropathy
 Causes numbness and foot drop
o Wet Beriberi
 B1 deficiency with heart failure
 Causes swollen ankles, tachycardia
o Wernicke-Korsakoff syndrome
 B1 deficiency affecting the brain
 Causes confusion, confabulation [telling lies], coma in chronic alcoholics
 Vitamin B2 deficiency
o hyporiboflavinosis
 cheilosis [cracked lips]
 glossitis [sore tongue]
 seborrheic dermatitis [itchy scaly scalp]
 B3 [niacin] deficiency
o Pellagra
 Diarrhea
 Casal’s necklace may be present:
o V-shaped dermatitis seen in sun-exposed part of chest
 Dermatitis
 Dementia
 Death
 B9 [folic acid] deficiency
o neural tube defect in the newborn: spina bifida
o megaloblastic anemia [large red blood cells] in adults: fatigue and beef-red tongue
 B12 deficiency
o pernicious anemia
 due to lack of Intrinsic Factor secreted by the parietal cells of the stomach
o other causes include:
 deficient in diet
 poor absorption due to disease in the terminal ileum
o causes a macrocytic [megaloblastic] anemia and spinal cord degeneration
o fatigue, ataxia, upper motor neuron signs, urinary and fecal incontinence
 Vitamin C deficiency
o inability to hydroxylate proline and lysine residues in collagen
o this weakens the capillaries
o results in scurvy
 tissue hemorrhage with bleeding swollen gums and loose teeth
 poor wound healing
 impaired bone formation [in children]
 Vitamin A deficiency
o nyctalopia, xerophthalmia and keratomalacia
 nyctalopia [night blindness] seen in Vitamin A deficiency
 xerophthalmia [dry eyes]
 keratomalacia [soft cornea]

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 Vitamin D deficiency
o rickets in children
 soft bones with bowed legs
 rachitic rosary
 swollen costochondral junctions in rickets
 pectus carinatum
 pigeon chest seen in rickets
o osteomalacia in adults
 Looser’s zones [pseudofracture]
 Vitamin E deficiency
o causes hemolytic anemia
 destruction of red blood cells leading to low red blood cell count and low Hb
 fatigue
 Vitamin K deficiency
o hemorrhagic disease of newborns
 abnormal bleeding from the umbilicus
o easily preventable by giving the newborn an injection of Vitamin K

Mineral disorders
 Iodine deficiency
o myxedema and goiter in adults
o cretinism in infants
o severe hypothyroidism in an infant
o usually caused by failure of the thyroid gland to develop
 mental retardation
 hoarse cry
 thick scrotal tongue [macroglossia]
 umbilical hernia
 Iron deficiency
o microcytic, hypochromic anemia
o anemia = low hemoglobin and decreased red blood cell count
o red blood cells are small [microcytic] and pale [hypochromic]
o diet deficient in iron rich foods such as meat and dark green leafy vegetables
o excess blood loss as seen in bleeding peptic ulcer or heavy menstruation
 severe anemia may be accompanied by pale mucosa and nails
 the tongue is also pale and smooth-glossitis
 koilonychia [spoon-shaped nails] may also be present
 when iron-deficiency anemia, glossitis with dysphagia occur in a post-
menopausal woman it is known as Plummer-Vinson syndrome
 Excessive Iron absorption
o Hemochromatosis
o affects the liver, heart and endocrine glands including the pancreas and gonads
o may be genetic [autosomal recessive] or acquired [excessive dietary iron]
o presents with the following:
 Arthritis
 Bronze skin
 Cirrhosis
 Diabetes mellitus
 Erection problems due to testicular failure
 Excessive copper absorption
o Wilson’s disease
o aka hepatolenticular disease
o autosomal recessive disease
o lack of ceruloplasmin-major copper-carrying protein in the blood
o results in excessive copper deposition in brain and liver
o may present with damage to the liver, brain and eyes:
 Asterixis [coarse flapping tremor of the wrist when it Is extended]
 Basal ganglia degeneration [Parkinson-like tremors]
 Cirrhosis, corneal deposits [Kayser-Fleisher rings] due to copper accumulation
 Dementia

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RENAL DISEASES

Diseases of the urinary tract may be classified according to the structure affected such as kidney, ureter or
bladder or by the type of underlying pathology such as trauma, infection or neoplasm.

 Nephritic syndrome
o Glomerulonephritis
o most commonly associated with post-streptococcal infections
o antigen-antibody complex damage to the glomeruli
o activation of the complement system causes inflammation
o causes leakage of RBCs [hematuria] and protein in the urine [proteinuria]
o red blood cells casts are present in the urine
o inflammation of the glomerulus results in renal ischemia
o the ensuing renal ischemia results in hypertension by the activation of the renin-
angiotensin system
o the resulting renal damage causes edema
 edema is the accumulation of fluid in the interstitial tissue
 due to raised hydrostatic pressure
 Nephrotic syndrome
o idiopathic in many cases
o may be caused by diabetes, SLE or drugs
o minimal change damage to the basement membrane
o large holes appear in the basement membrane allowing for loss of protein in the urine
o causes massive proteinuria more than 3.5 grams/24 hour period
o results in hypoproteinemia and hypoalbuminemia in the blood
o as a result of the low protein content in the blood, there is edema
 due to a decrease in the oncotic pressure
 there may be ascites or pleural effusions if severe
o there is also hyperlipidemia
 related to the hypoproteinemia and increased lipoprotein synthesis
 Pyelonephritis
o ascending E. coli infection from cystitis usually
o inflamed collecting tubules and renal pelvis
o causes white blood cell casts to be present in the urine
o presents with chills, fever, nausea, vomiting and costovertebral angle tenderness
o chronic pyelonephritis will result in a shrunken kidney and hypertension
 Diabetic nephropathy
o causes nephrotic syndrome:
 massive proteinuria > 3.5 grams of protein per 24 hours
 hyperlipidemia
 recurrent infections
o may also cause Kimmelstiel-Wilson disease
 kidney damage which is characterized by nodular sclerosis of the glomeruli
 Urinary Tract Infection
o ascending infection with enteric organisms
o most commonly due to E. coli
o causes dysuria, increased urinary frequency and nocturia
o WBCs, bacteria and nitrites are found in the urine
o many bacteria possess a reductase which reduces urinary nitrates to nitrites
 Interstitial cystitis
o uncommon bladder inflammation
o caused by leakage of urine beneath the bladder epithelium
o unknown etiology resulting in damage to the mucus lining the bladder mucosa
o causes superficial cracks and Hunner’s ulcers of the bladder mucosa
o seen more commonly in females
o presents increased frequency and nocturia
o urinalysis shows white blood cells but no bacteria or nitrites
 Wilms tumor
o aka nephroblastoma or mixed tumor
o most common malignant kidney tumor in children
o presents with a mass in the flank and hematuria

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 Renal Cell Carcinoma
o most common type of adult renal cancer
o aka Grawitz tumor
o presents with painless hematuria
o mass in the flank
 Adult Polycystic Disease of the Kidney
o autosomal dominant disorder
o presents with bilateral kidney enlargement and hypertension
o increased incidence of berry aneurysms of the circle of Willis in the brain
 Goodpasture’s syndrome
o affects the parenchyma of the kidney and lung
o antibodies against Type IV collagen fibers
o presents with hemoptysis and hematuria
 Renal Calculi
o stone formation in the ureter and pelvis of the kidney
o calcium oxalate is the most common urinary stone
o 85% of renal stones are radiopaque
o other types [which are radiolucent] include:
 cystine
 uric acid
 phosphate
o presents with:
 severe colicky loin [flank] to groin pain
 hematuria

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RESPIRATORY PATHOLOGY

Diseases of the respiratory tract may be classified according to the structure affected such as
tracheobronchial tree, lung or pleura or by the type of underlying pathology such as trauma, infection or
neoplasm.

Tracheobronchial tree
 Asthma
o reversible bronchospasm due to hypersensitivity of the bronchi
o extrinsic: allergens, eczema and hay fever; intrinsic: exercise
o bronchial mucosa inflammation and constriction of bronchial smooth muscle
o Curschmann spirals and Charcot-Leyden crystals may also be found in the sputum
o presents with paroxysms of shortness of breath and wheezing worse at nights
 Bronchiectasis
o chronic dilation of bronchi
o due to bronchial obstruction by mucous plugs
o may be associated with cystic fibrosis
o copious foul smelling mucopurulant sputum early in the morning
 Kartagener’s syndrome
o immotile cilia which present with a clinical triad consisting of:
 chronic sinusitis
 bronchiectasis
 situs inversus

Lung
 Atelectasis
o collapse of or incomplete expansion of alveoli
o compression atelectasis
 collapse due to external pressure like:
 pleural effusion
 pneumothorax
o resorption atelectasis
 collapse distal to an obstructed bronchus by:
 foreign body
 tumor
o contraction atelectasis
 collapse due to interstitial fibrosis and loss of elastic recoil
 commonly seen in pulmonary tuberculosis
 COPD [Chronic Obstructive Pulmonary Disease]
o Emphysema
 Pink puffers who tend to thin
 alveolar wall destroyed, loss of elastic recoil, good oxygenation
 centriacinar type of emphysema:
 smoking related, affects respiratory bronchioles, barrel-chest
 panacinar type of emphysema:
 α1-antitrypsin deficiency
 affects all pulmonary acini
 destruction of elastic tissue in alveolar wall, younger patients
o Chronic Bronchitis
 Blue Bloaters who tend to be overweight
 chronic cough >3 months for at least 2 consecutive years
 bronchial gland hyperplasia due to infection
 cyanosis [blue]
 right-sided heart failure [bloater]
 Pneumonia
o inflammation of lung tissue
o lobar pneumonia:
 inflammation of a lobe with red then grey hepatization
 Streptococcus pneumoniae
o bronchopneumonia
 patchy inflammation of both lungs usually in the bases

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 o interstitial pneumonia
 involved both lungs
 caused by Mycoplasma or Chlamydia pneumoniae
o pneumocystis jiroveci pneumonia [PJP]
 opportunistic infection by Pneumocystis jiroveci [carinii]-AIDS
 causes ground glass appearance on chest x-ray
 Lung abscess
o pus-filled cavity in the lung
o Staph aureus and Klebsiella pneumoniae are common causes
o seen more often in alcoholics and epileptics
 Pneumoconiosis
o occupational lung disease
o caused by inhalation of inorganic industrial particles
 anthracosis
 lung disease caused by coal dust in coal miners
 silicosis
 lung disease caused by silica dust in quarry workers: quartz and sand
 asbestosis
 lung disease caused by asbestos fibers in miners
 increased risk of mesothelioma
 siderosis
 lung disease caused by iron dust in iron miners
 Caplan’s lung
 pneumoconiosis with progressive pulmonary fibrosis in RA
 Hypersensitivity pneumonitis
o allergic lung reactions caused by organic dust
 byssinosis
 allergic lung reactions cause by cotton dust from mill workers
 bagassosis
 moldy fibrous waste [bagasse] in sugar cane workers
 farmer’s lung
 allergic lung reactions cause by moldy hay in farmers
 silo-filler’s lung
 caused by nitrogen dioxide found in corn-filled silos
 Sarcoidosis
o Type IV hypersensitivity reaction
o non-caseous granulomas with epithelioid macrophages
o bilateral hilar lymphadenopathy and pulmonary fibrosis-dyspnea and dry cough
o may affect the spleen, eye, nerves or skin also:
 splenomegaly
 uveitis
 Bell’s palsy
 erythema nodusum [red painful bumps over the shins]
o elevated serum calcium due to increased conversion of Vitamin D in the epithelioid
macrophages
o associated with raised levels of Angiotensin Converting Enzyme in 40-80% of patients
o ACE is also produced by the epithelioid cells in the granulomas
 Tuberculosis
o Ghon focus: caseous granulomas in the lung
 epithelioid cells and Langhan’s giant cells
 epithelioid cells are activated macrophages
 lower part of the upper lobe or the upper part of the lower lobe
o Ghon complex:
 peripheral Ghon focus with involvement of regional lymph node
 seen in primary tuberculosis
o Langhan’s giant cells:
 fused epithelioid cells with the nuclei arranged in a horse-shoe pattern
o Apical cavitations are common in secondary tuberculosis
 Bronchogenic carcinoma
o most common lung cancer
o associated with chronic cigarette smoking, mining, industrial cities

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 o squamous cell type is most common
o more common in males
o may present with chronic cough, hemoptysis and weight loss
o may also present with evidence of the following [SPHERE]:
 Superior vena cava syndrome [distended neck and upper limb veins]
 Pancoast’s tumor [mass in the lung apex]
 Horner’s syndrome [ptosis, miosis and anhydrosis]
 Endocrine [paraneoplastic ectopic hormone secretions]
 Recurrent laryngeal damage [hoarseness]
 Effusions [pleural or pericardial]
 Small cell lung carcinoma [25% of lung cancers]
o previously called an oat cell carcinoma
o uncommon cause of lung cancer
o associated with ectopic hormone production such as:
 Parathormone
 ACTH
 ADH
 SIADH
o Syndrome of Inappropriate ADH secretion
o secreted by some small cell lung cancers
 Pancoast tumor
o bronchogenic carcinoma in one of the lung apices
o may invade roots of the brachial plexus, first rib, sympathetic trunk, subclavian vein
or artery
o may cause Horner’s syndrome due to damage to the sympathetic trunk in the neck:
 Ptosis
 Anhydrosis
 Miosis
 Mnemonic: Horny PAM

Pleura
 Pneumothorax
o air within the pleural cavity
o spontaneous-no previous underlying lung disease
o secondary-traumatic, underlying asthma or emphysema
o tension
 trapped air in the pleural space cannot escape and builds up in the space
causing mediastinal shift away from the affected side
 Empyema
o pus-filled pleural cavity
o secondary to bacterial infection in the lungs
 Pleural effusion
o fluid-filled pleural cavity
o may be an exudates or a transudate
o exudates are as a result of localized inflammation
o transudates are related to systemic diseases
o protein content is useful to distinguish between the two:
 exudate has more protein [>2 g/dl]
o exudates are seen in:
 pneumonia
 tuberculosis
 lung cancer
 pulmonary embolism
o transudates are seen in:
 congestive heart failure
 nephrotic syndrome
 renal failure
 liver failure
 Mesothelioma
o malignant tumor of the pleura
o associated with prolonged exposure to asbestos

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SEXUALLY TRANSMITTED DISEASES

Diseases transmitted by sexual intercourse may be classified according to the structure affected such as
penile, urethra, vulvar, vaginal, cervical or uterine or by the type of underlying causative agent such as viral,
bacterial or fungal. Some of these infections can also be transmitted from an infected mother to her infant
via the placenta or during child birth.

Penile lesions
 Syphilis
o Treponema pallidum
o spirochete infection
o primary stage:
 painless hard genital ulcer-chancre
 disappears spontaneously
o secondary stage:
 generalized maculopapular rash
 generalized lymphadenopathy
 condylomata lata [flat-topped genital warts]
o latent stage:
 asymptomatic
o tertiary stage:
 thoracic aortic aneurysm
 Argyll-Robertson pupil [easily accommodates, slow to react to light]
 gummas [chronic granulomatous lesions in the bone and soft tissue]
 Charcot’s joint [grossly destroyed joint due to loss of pain]
 General Paralysis of the Insane
 tabes dorsalis [dorsal column disease]
 Chancroid
o Hemophilus ducreyi
o bacterial infection
o painful soft yellow genital ulcers [ducreyi makes you cry]
o painful swollen inguinal nodes
 Granuloma inguinale
o Klebsiella [formally Calymmatobacterium] granulomatis
o bacterial infection
o painless beef red genital ulcers
 Herpes genitalis
o HHV type 2 infection
 Lymphogranuloma venereum
o Chlamydia trachomatis Type L1-3
o bacterial infection
o transient genital ulcer
o buboes [swollen painful lymph nodes]
o sign of the groove in the inguinal region
o rectal stricture

Urethral discharge
 Urethritis
o inflammation of urethra
o caused by Chlamydia trachomatis or Neisseria gonorrhea infection
 Chlamydia urethritis
o Chlamydia trachomatis
o most common cause of a urethral discharge in the USA
o mucoid penile discharge
o dysuria
 Gonococcal urethritis
o Neisseria gonorrhea
o second most common cause of a urethral discharge in the USA
o purulent penile discharge, dysuria and infection of Bartholin’s gland in females
o may cause ophthalmia neonatorum
o may also cause septic arthritis

164
Vulvar disease
 Vulvovaginitis
o Candida albicans infection
o opportunistic fungal infection seen more commonly in females
o thick cheesy vaginal discharge with itching
o recent antibiotics and diabetes mellitus
 Condyloma accuminata
o Human Papilloma Viral infection
o Most common STD in the USA
o Affects more women than men
o types 16 and 18 are associated with cervical cancer
o cauliflower-type warts [compared to the flat-topped warts seen in secondary syphilis]

Vaginal disease
 Bacterial vaginosis
o Gardnerella species
o Fishy-smelling watery vaginal discharge
o Clue cells +++ [vaginal epithelial cells studded by numerous bacteria]
o Whiff test-amines are released when the slide is flooded with KOH
 Trichomoniasis
o Trichomonas vaginalis
o motile protozoal infection
o malodorous green frothy discharge
o motile flagellates seen on wet mount preparation

Cervical disease
 Cervical carcinoma
o Squamous cell cancer
o HPV type 16 and 18
o post-coital bleeding [bleeding after sex]
 Cervicitis
o Chlamydia [most common] or Gonococcal infection
o pus from external os
o may be part of Pelvic Inflammatory Disease

Uterine
 PID
o Pelvic Inflammatory Disease
o Chlamydia, Gonorrhea or E. coli
o infection of the cervix, uterus, uterine tube and pelvic connective tissue
o lower abdominal pain, dysmenorrheal, dyspareunia and pain on cervical movement
 Salpingitis
o inflamed tube seen in PID
o may result in an abscess formation
o may heal with fibrosis and partial obstruction of the tube
o leading to an ectopic pregnancy or infertility

TORCHeS Infections
 infections caused by microbes which pass from mother to the fetus:
o Toxoplasmosis
o Others including HIV and Hepatitis B
o Rubella
o Cytomegalovirus
o Herpes simplex Type II
o Syphilis
All of the above can be transmitted across the placenta EXCEPT:
 Herpes simplex Type II which is transmitted to the baby as it passes through the birth canal of a
mother infected with the virus during labor

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SKIN DISEASES

Skin diseases
 infections caused by viruses, bacteria, fungi or parasites
o viral
 cold sores is caused by herpes simplex virus
 chickenpox and shingles is caused by varicella-zoster virus
 measles is caused by a Paramyxo virus
 hand, foot and mouth disease is caused by Coxsackie virus
 Kaposi’s sarcoma is caused by Human Herpes Virus Type 8
o bacterial
 impetigo which may be caused by Strep and Staph infections
 acne vulgaris is caused by Propionibacterium acnes
 lupus vulgaris is caused by Mycobacterium tuberculosis
 leprosy is caused by Mycobacterium leprae
 syphilis is caused by Treponema pallidum
o fungal
 tinea [ringworm] is caused by a variety of dermatophytes including:
 Trichophyton
 Epidermophyton
 Microsporum
 pityriasis versicolor is caused by Malassezia furfur
 candidiasis is caused by Candida albicans
 sporothricosis is caused by Sporothrix schenckii
o parasitic
 scabies is caused by Sarcoptes scabiei
 cutaneous larva migrans is caused by Toxocara canis
 unknown such as:
o psoriasis:
 possible autoimmune
 increased turnover of the epidermal cells
 silvery scales over the extensor surfaces of the elbows and knees
 pitted finger nails
 inflammatory arthritis in some patients [10%]
 tumors such as benign nevi, malignant melanoma and skin cancer
o basal cell carcinoma
 this is the most common type of skin cancer [60%]
 it is the least dangerous because it rarely metastasize
 arises from the stratum basalis
 appears first as a small shiny bump
 later develops a central depression and a beaded pearly edge
o squamous cell carcinoma
 second most common skin cancer [20%]
 arises from the keratin-producing cells in the stratum spinosum
 it often spread locally and metastasizes to nearby lymph nodes
 presents as a raised reddened scaly lesion which later ulcerates
o malignant melanoma [1%] contains malignant melanocytes and may present with:
 Asymmetric shape
 Border irregular
 Color change
 Diameter greater than 6 mm in diameter
 Expanding or evolving lesion

Causes of a red rash in childhood [xanthemas]

 Rubella: rash begins in the head and moves down; postauricular lymphadenopathy
 Measles: red rash one head then trunk and limbs with Koplik’s spots
 Chickenpox: vesiculopustular rash on trunk spreads to face and limbs
 Slapped cheek syndrome: red rash on cheeks after a fever
 Hand-foot-mouth disease: vesicular rash on palms and soles with oral ulcers
 Scarlet fever: red rash on the body with a strawberry tongue
 Roseola: red rash after several days of high fever

166
MICROBIOLOGY

167
168
HISTORY OF MICROBIOLOGY

Historical background
 Lazzaro Spallanzani
o disproved the spontaneous generation of life theory
 Girolamo Fracastoro
o suggested transferable spores caused disease such as syphilis
 Robert Hooke
o first to see cells in thin slices of cork using a crude microscope
 Anton van Leeuwenhoek
o inventor of the microscope
 Ignazio Semmelweiss
th
o introduced hand washing in the 19 century
 Joseph Lister
o introduced surgical asepsis using carbolic acid
 Edward Jenner
o developed the smallpox vaccine from cow [vacca] pox in milkmaids
 Robert Koch
o Father of Microbiology who identified the bacillus that caused anthrax
o 4 microbiological postulates:
 agent must be found in all patients with the disease
 must be able to prepare a pure culture of the agent
 injected agent must cause the same disease in new patients
 must recover same organism from the newly infected patients
 Hans Christian Gram
o Developed a 7-step process staining process for bacteria:
 Add Crystal violet [blue stain] and leave for 1 minute
 Wash off with H2O
 Add Iodine [mordant-fixer] and leave of 1 minute
 Wash off with H2O
 Add Acetone alcohol [decolorizer-removes the blue stain] for 5 seconds
 Counter stain with Safranin stain [red] and leave for 20 seconds
 Wash off finally with H2O
o Gram Positive-blue stain and Gram Negative-red stain
 Louis Pasteur
o inventor of the pasteurization process
o germ theory
o developed vaccine against rabies and anthrax
 Paul Ehrlich
o developed chemicals that killed micro-organisms like syphilis
o sulfa drugs and salvarsan
 Alexander Fleming in 1928
o discovered Penicillin
 Dmitiri Ivanowski in 1898
o first to postulate the existence of viruses while working with infected tobacco plants
 Ernst Ruska in 1931
o made the first electron microscope which was used to prove the existence of viruses
 Fredrick Griffith
o discovered transformation of non-virulent bacteria to a more virulent form
 Walter Reed
o proved mosquitoes carried Yellow Fever
 Jonas Salk
o developed the vaccine from killed polio organisms
 Albert Sabin
o developed the vaccine from attenuated live polio virus [Sabin your life]
 Stanley Prusiner
o coined the term prion for diseases caused by protein particles
o prion diseases: mad cow disease [cows] and Cruetzfeld Jacobs disease [humans]
 Barry Marshall discovered a bacterial cause of peptic ulcers-Helicobacter pylori

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GENERAL PRINCIPLES

Classification of microorganisms
Microorganisms can be classified according to the following:
 Size
 Presence or absence of a nucleus
 Nature of genetic material;
 Number of chromosomes
 Nature of cell wall if present
 Type of cell membrane sterols

Comparison of microorganisms

Viruses Bacteria Fungi Parasites

Cell Acellular Prokaryotic Eukaryotic Eukaryotic
Nucleus None None Present Present
DNA/RNA DNA or RNA Both Both Both
Chromosome Nucleocapsid 1 chromosome More than 1 More than 1
Ribosome None 70S ribosome 80S ribosome 80S ribosome
Cell Wall None Peptidoglycan Chitin None
Membrane sterols No membrane None Ergosterol Sterol

Table 12: Comparisons of microorganisms

Not all microorganisms affect humans. The human gut is filled with all kinds of microorganisms which
contribute to the health and well-being of the body. When some of these escape this natural environment,
they may cause problems. Whether they cause problems in humans or not depends on the infectivity of the
microorganism.

Infectivity
Infectivity is defined as the ability of a pathogen to establish an infection. The infectivity of a microorganism
is dependent on its pathogenicity, adherence, invasiveness, antigenic switching and virulence:
 Pathogenicity
o ability to cause disease
 Adherence to host cells
o some bacteria for example Escherichia coli use pili [fine hair-like microscopic structures]
to adhere to the surface of host cells
o others like Group A streptococci have fimbriae which have the same effect
o other bacteria have surface particles that allow them to stick to the host cells
o In each of the above situations, adherence enhances the infectivity of the microorganism
by preventing it from being carried away by mucus or being wasked away by fluid flow in
the bowel or the bladder
 Invasion
o ability to penetrate host defense
o some microorganisms have enzymes that facilitate their invasiveness
o for example collagensase and hyaluronidase
 Antigenic switching
o some microorganisms have developed the ability to change the shape of their surface
antigens to escape detection by the body’s antibody surveillance
o for example the trypanosoma organism on entering the body stimulates the production of
antibodies for specific antigens found in the surface of the organism
o within a matter of hours, some of the trypanosome switch the variable surface
glycoprotein coat and cover themselves with a new antigenically different VSG coat and
slips through the body’s defense mechanism much like the cloaking mechanism
popularized by the Star Wars movies
 Virulence
o ability to cause serious illness
o some micro-organisms produce poisons or toxins which are extremely harmful to the
human
o for example, the toxin produced by Clostridium botulinum

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Other terms related to medically important microorganisms:
 Nosocomial
o hospital acquired infection
 Iatrogenic
o disease caused by health professionals
o these are often caused by health professionals washing their hands
o one common hospital-acquired infection is caused by he spread of Clostridium difficile
which has become very difficult to treat and can be fatal
 Commensal
o organism that is part of normal flora
o one benefits and the other is unaffected
 Symbiosis
o two dissimilar organisms living together
 Synergism
o both organisms benefit and are needed for function

Bacterial Growth Phases

Stationary

Death

Log

Lag

Fig 103: Bacterial Growth Phases

 Lag phase
o number of cells constant in preparing for growth; metabolic activity without division
 Log phase
o exponential growth phase; the doubling time varies among strains and conditions
 Stationary
o new growth matches rate at which they die off as the organisms run out of nutrients
 Death phase
o all the nutrients are used up and bacteria start to die due to buildup of waste products

Bacterial growth can be controlled by subjecting bacterial population to:

 Heat
 Irradiation
 Antimicrobial chemicals
 Antibiotics

Disease Triangle
 There is an interaction between the host, the agent and the environment that will affect whether
or not the host becomes infected
 Some texts call this the Disease Triangle while others call it the Communicable Disease or the
Epidemiological Triangle
 The host is the human being
 The agent is the microbe
 The environment deals with those external factors that cause or allow the disease to spread
 It is a delicate balance because not all hosts will be infected with a known pathogen if the
environment is not conducive

Adaptations of micro-organisms to promote survival

 Viruses undergo antigenic shift
 Bacteria form spores
 Fungi form spores
 Parasites form cysts

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 MEDICALLY IMPORTANT VIRUSES

RNA DNA

Double Stranded Single Stranded Single Stranded Double Stranded

Icosahedral
Non-enveloped
Parvo B19
REO [ Respiratory -5th disease aka
Enteric Orphan] Slapped Cheek
(+) sense (-) sense Syndrome
-Rota virus
Non-enveloped Enveloped
Diarrhea in infants

Paramyxo-Mumps and measles Adeno-Pharyngitis,

Rhabdo-Rabies Conjunctivitis
Orthomyxo-influenza Human Papilloma Virus
Filo-Ebola fever Types 16, 18 cause cervical
Arena-Lassa fever cancer
Bunya- California Equine Polyoma-JC and BC viruses
Encephalitis and Congo fever cause demyelination and UTI
respectively

Hepatitis D-incomplete
virus-coexists with
Hepatitis B

Non-enveloped Enveloped
HepaDNA-Hepatitis B
Icosahedral
Pox-Variola [Smallpox]
-Molluscum contagiosum
Calici-Norwalk virus and Human Herpes Virus
Hepatitis E Icosahedral
1-HSV 1: oral herpes
PicoRNA Flavi-Hepatitis C 2-HSV 2: genital herpes
-Hepatitis A -Yellow fever 3-Varicella zoster: chickenpox
-Polio -Dengue fever and herpes zoster
-Rhino: UR -West Nile fever 4-EBV: mononucleosis
-Coxsackie: diarrhea and -St Louis encephalitis 5-CMV: meningitis in AIDS
hand, foot and mouth Helical
Retro-HIV 8-Kaposi sarcoma in AIDS
disease Toga-Rubella, WEE, VEE
-ECHO-meningitis
Corona-Common cold and SARS

General Rules
All viruses are RNA except 6 which are very HHHAPPPy to be DNA
All RNA viruses are single stranded except the REO virus 1st disease: Measles
All single stranded RNA viruses are + sense except the PROFAB 6 2nd disease: Scarlet fever
All the hepatitis viruses are RNA except Hepatitis B 3rd disease: German measles
All of the hepatitis viruses are spread by orofecal route except B and C 4th disease: Dukes’ disease
which are spread by blood and sex 5th disease: Slapped Cheek syndrome
All the DNA viruses are double stranded except the Parvo viruses 6th disease: Roseola infantium

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VIRAL MICRO-ORGANISMS

General rules regarding viruses:

 All viruses are RNA except 6 which are DNA:
o 3 of these are enveloped:
 Hepa, Herpes and Pox
o 2 are naked [non-enveloped]-Adeno and Papova
o 1 is single-stranded-Parvo
 All DNA viruses are double-stranded except Parvo virus
 All DNA viruses are icosahedral except Pox virus which has a complex shape

DNA Viruses
 Herpes simplex 1 and 2
o Human Herpes virus types 1 and 2 spread by direct contact
o causes cold sores [fever blisters] and multiple painful shallow genital ulcers
 Chickenpox and herpes zoster
o Human Herpes Virus type 3 virus spread by aerosol droplets
o cause chickenpox in children and shingles in adults
 Mononucleosis
o Human Herpes Virus type 4 [Epstein Barr virus] spread by kissing
o causes sore throat, fatigue, cervical lymphadenopathy and hepatosplenomegaly
o Downey cells [atypical lymphocytes] are present and the Paul Bunnel test is positive
o the virus may also cause Burkitt’s lymphoma and nasopharyngeal carcinoma
 Cytomegalovirus infection
o HHV type 5 causing interstitial pneumonia in the immunocompromized patient and
congenital abnormalities, brain calcification and hepatosplenomegaly in the neonate
th
 Exanthema subitum [Roseola infantium or 6 disease]
o Human Herpes viruses type 6 and possibly 7
o causes a sudden rash in children after a fever
 Kaposi’s sarcoma
o Human Herpes Virus type 8
o causes purplish oral or skin lesions in AIDS patients
th
 Slapped Cheek Syndrome [Erythema infectiosum or 5 disease]
o Parvo type B 19
o causes a red rash on face after fever
 Hepatitis B
o HepaDNA virus which is spread by blood or sex
o causes jaundice and tender hepatomegaly
 Viral conjunctivitis
o Adeno virus group spread by aerosol droplets
o causes pink eye [epidemic viral conjunctivitis]
 Smallpox [variola]
o Pox virus spread by aerosol droplets
o Guarneri inclusion bodies in the affected epidermis
o irradicated in 1976
 Human Papilloma virus
o Papova virus spread by diect contact
o HPV types 16 and 18 causes genital warts and are associated with cervical cancer
o types 1 and 4 causes warts on the hands and the feet
 Molluscum contagiosum
o Pox [ds enveloped DNA] virus spread by direct contact
o causes papular lesions with central indentation [umbilication]

General Rules regarding RNA viruses:

 All RNA viruses are single-stranded except the REO group which is double-stranded:
o Rota virus belongs to this group
 All negative single stranded RNA viruses are helical and enveloped
 Only three RNA viruses are naked:
o Calici, PicoRNA and REO viruses
 All hepatitis viruses are RNA EXCEPT Hepatitis B which is an DNA virus

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 All hepatitis viruses are spread by the oro-fecal route EXCEPT:
o B and C which are spread by sex, blood transfusions or use of intravenous drugs
o causes jaundice, fever, anorexia, vomiting and tender hepatomegaly
 Hepatitis C
o Flavi RNA virus spread by blood and sex
o Blood transfusions [10%], intravenous drug use [40%] and sexual transmission [10%]
o associated with a Carrier state, Cirrhosis and hepatocellular Carcinoma
 Hepatitis A
o Pico RNA virus transmitted by the oral-anal [orofecal] route
 Hepatitis D [Delta agent or dane particle depends on Hepatitis B to casue an infection]
o Single-stranded RNA virus [Defective virus incapable of infecting on its own]
 Hepatitis E
o Calici RNA virus spread by the orofecal route
 Human Immune Deficiency Virus
o Single-stranded RNA retro virus spread by sex and blood transfusion
o destroys CD4 T cells causing AIDS and presents in 4 stages:
 Flu-like illness [acute]
 Feeling fine [latent]
 Failing CD4 count [with recurrent opportunistic infections]
 Cryptococcus meningitis
 CytoMegaloVirus retinitis
 Candidiasis
 Crypotosporidium diarrhea
 Final crisis with Pneumocystis jiroveci pneumonia
st
 Measles [aka Rubeola or the 1 disease]
o Paramyxo virus spread by aerosol droplets
o causes Koplik spots, coryza, conjunctivitis and a fine maculopapular erythematous rash
 Mumps
o Paramyxo virus spread by dirfect contact and aerosol droplets
o causes parotitis, pancreatitis and orchitis
rd
 Rubella [aka German Measles or the 3 disease]
o Toga RNA virus spread by aerosol droplets
o causes sore throat, cervical lymph nodes and a fine maculopapular erythematous rash
 Influenza
o Orthomyxo [- ss RNA] virus causes fever, sore throat and severe myalgia
 Common cold
o Corona [+ss, enveloped, helical] RNA virus spread by aerosol droplets
o causes fever, sore throat, runny eyes and nose
 Upper Respiratory Tract Infection
o Rhino virus of PicoRNA family causes runny eyes, nose, sore throat and fever
 Croup [viral]
o Parainfluenza virus causes a braking cough, stridor and hoarseness
 Childhood dysentery
o Coxsackie virus of the PicoRNA virus family causes diarrhea with blood in the stool
o may also cause hand, foot and mouth disease-vesicles in these regions
 Rabies
o Bullet-shaped Rhabdo RNA virus presenting as Negri bodies in brain
o more commonly spread from raccoons, bats and skunk bites in the USA than dog bites
o causes hydrophobia, dysphagia, agitation, paralysis and coma
 Poliomyelitis
o Pico RNA virus causes flaccid muscle paralysis due to anterior horn cell damage
 ARBO viruses [Arthropod Borne] [all are caused by Flavi viruses except California encephalitis]
o Encephalitis is spread by a variety of mosquitoes
 Western and Venezuelan Equine Encephalitis [Flavi virus]
 California encephalitis [Bunya virus]
o Yellow fever
 Flavi virus carried by Aedes aegypti mosquito-fever and jaundice
o West Nile fever
 Flavi virus carried by Culex pipiens mosquito
o Dengue fever [breakbone fever]
 Flavi virus carried by Aedes aegypti mosquito

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 MEDICALLY IMPORTANT BACTERIA

Lack cell Rigid cell wall Flexible cell

wall wall

Spirochetes
Mycoplasma Faintly Gram (-)
pneumoniae Borrelia burgdorferi
-Lyme disease
Leptospira interogans
Obligate intracellular Free living -Weil disease
parasites Treponema pallidum-
Syphilis

Rickettsiae Chlamydia
R. rickettsi-RM Spotted Fever C. trachomatis-PID, Reiter’s
R. prowazekii-epidemic typhus syndrome, LGV
R. typhi-endemic typhus C. pneumoniae-pneumonia Gram Stain Ziehl Neelsen Stain
R. tsutsugamishi-scrub typhus C. psittaci-bird fancier’s disease

Mycobacterium
M. tuberculosis-Tuberculosis
Bartonella henselae-cat scratch disease Thick waxy wall with mycolic acid
Acid Alcohol Fast Bacillus
Culture Lowenstein-Jensen medium
M. leprae-Leprosy
95% of the world is immune
Gram (+) Gram (-) Cultured only in armadillos

COCCI BACILUS COCCI

Staphylococcus B. anthracis Neisseria BACILLUS COMMA
S. aureus -Anthrax N. gonorrhea-ferments Vibrio
-Scalded Skin -wool sorter’s disease glucose: gonorrhea V. Cholera
syndrome, Toxic shock Clostridium Thayer Martin medium -severe
syndrome, C. difficile- N. meningitidis- diarrhea with
osteomyelitis, Impetigo pseudomembranous ferments maltose: rice water
Coagulase + enterocolitis meningitis stool
Catalase + C. tetany
S. saprophyticus -tetanus
-UTI in young female C. perfringens
Streptococcus -gas gangrene
-Coagulase negative C. botulinum NON-ENTERIC ENTERIC
S. pneumoniae -botulism Bordetella pertussis Helicobacter pylori
- α hemolytic Corynebacterium -whooping cough -PUD and stomach cancer
-pneumonia, otitis C. diphtheriae Brucella abortus Klebsiella pneumoniae
media, sinusitis -diphtheria -undulant [Bang] fever -pneumonia and UTI
S. pyogenes Francisella tularensis Proteus mirabilis-UTI
- β hemolytic - rabbit fever Salmonella typhi-typhoid fever
-Rheumatic fever, Legionella pneumophila S. typhimurium-food poisoning
glomerulonephritis, -pneumonia Shigella sonnie/flexneri
scarlet fever Pseudomonas -bacillary dysentery
S. viridans aeroginosa-infected burns Escherichia coli
- α hemolytic -lactose fermenting, catalase +
-dental caries and -MacConkey medium
subacute -UTI, meningitis, food poisoning
bacterial endocarditis -possess O, H and K antigens
-O157 H7 type causes Hemolytic
Uremic Syndrome

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BACTERIAL MICRO-ORGANISMS

Bacterial Characteristics
 prokaryotic [no nucleus]
 single circular DNA
 peptidoglycan wall
 organisms with 70S ribosomes

Bacterial types
 3 types: lacking cell wall, flexible cell wall and rigid cell wall
o LACKING CELL WALL
 Mycoplasma pneumoniae
 atypical “walking” pneumonia [x-ray looks worse than the patient]
o FLEXIBLE CELL WALL [spirochetes]
 Leptospira interogans [spirochete with a terminal hook]
 causes Weil disease which presents with jaundice and hemorrhage
 Borrelia burgdorferi [big spirochete]
 Lyme disease: bull’s eye rash [erythema migrans] and joint pains
 Borrelia recurrentis
 Causes relapsing fever
 Treponema pallidum [thin spirochete with periplasmic flagella]
 causes syphilis which presents with a painless genital ulcer
o RIGID CELL WALL
 Needs to live inside cell [obligate intracellular organism-can’t make ATP]
 Chlamydia psittaci
o Bird fancier’s disease [psittacosis]
o cough and fever [another cause of atypical pneumonia]
 Chlamydia trachomatis
o Type A, B and C: Trachoma
 Africa, Blindness, Chronic disease
o Types D-K: Reiter’s syndrome:
 Conjunctivitis, urethritis and arthritis
o Type L1, 2 and 3: Lymphogranuloma venereum
 Transient genital ulcer followed by draining buboes
 Rickettsia organisms
 Fever and rash [Rickettsia rash on the wRists, Typhus on the Trunk]
o Rickettsia rickettsii:
 Rocky Mountain Spotted Fever [ticks]
o Rickettsia prowazekii:
 Epidemic typhus [lice]
o Rickettsia typhi:
 Murine endemic typhus [rat fleas]
o Rickettsia quintana:
 Trench fever [lice]
o Rickettsia [orientia] tsutsugamishi:
 Scrub typhus [mites]
 Barteonella henselae
o Cat-scratch disease [scratched by infected cats]
 FREE LIVING BACTERIA
 Gram stainable wall: positive or negative
 Coccus, Bacillus or Vibrio groups
COCCUS
 Staphylococcus
 Gram + bacteria, Catalase positive coccus in bunches like grapes
 Staphylococcus aureus
o coagulase positive, golden colonies on blood agar culture
o Scalded Skin Syndrome, Toxic Shock Syndrome, impetigo,
osteomyelitis, carbuncles and acute bacterial endocarditis
 Staphylococcus saprophyticus
o common cause of UTI in teenagers, no nitrites in the urine

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 Streptococcus
 Gram + bacteria, catalase negative coccus in strips
 Streptococcus pyogenes
o Lancefield group A beta-hemolytic diplococci
o rheumatic fever
o impetigo
o erysipelas
o glomerulonephritis
nd
o scarlet fever [2 disease]
 Streptococcus viridans [green]
o alpha-hemolytic [green color-partial hemolysis] streptococcus
o dental cavities [S. mutans]
o affects damaged heart valves
o causes subacute bacterial endocarditis
 Streptococcus pneumoniae
o alpha-hemolytic streptococcus
o causes meningitis, otitis media, pneumonia associated with
rust-colored sputum and sinusitis
 Neisseria gonorrhoeae
 Gram negative intracellular diplococci
 Thayer-Martin chocolate agar medium and glucose fermenting
 causes gonorrhea, septic arthritis or ophthalmia neonatorum
 Neisseria meningitidis
 Gram negative cocci
 Thayer-Martin medium and maltose and glucose fermenting
 causes meningitis and meningococcemia
 Mycobacterium tuberculosis
 Lowenstein-Jensen medium culture needed
 faintly Gram stainable because of thick waxy wall of mycolic acid
 stained with Ziehl Neelsen stain
 causes tuberculosis
 Mycobacterium leprae
 only grown in armadillos and the foot pads of suckling mice
 prefers cool temperatures like in the skin and peripheral nerves
 causes leprosy

BACILLUS
 All bacilli are Gram negative EXCEPT the following which are Gram positive:
 Bacillus
 Clostridium
 Corynebacterium
 Listeria
 Bacillus anthracis [spore-forming rod]
 woolsorter’s disease: lung infection
 malignant pustule: skin infection leads to bacteremia and death
 Clostridium botulinum
 Botulism caused by preformed toxin: blocks acetylcholine release
 diplopia
 dysphagia
 flaccid paralysis
 due to improperly canned foods especially honey in infants
 Clostridium difficile
 pseudomembranous colitis after broad-spectrum antibiotics
 C. difficile is part of the normal gut flora
 broad spectrum antibiotics kills off the helpful gut flora which allows this
organism to proliferate
 Clostridium tetani
 tetanus caused by bacillus with terminal spores
 exotoxin produced-tetanospasmin affects the neuromuscular junctions
 causing muscle spasm and trismus [lockjaw]

177
 Clostridium perfringens
 gas gangrene following infection of deep puncture wounds
 produces lecithinase which cause muscle necrosis with bubbles
 Corynebacterium diphtheriae
 diphtheria caused by club-shaped bacilli, Chinese-letters appearance
 grey pseudo-membrane in throat causing suffocation
 bacteriophage-related exotoxin is produced-damages heart muscle and
nerves
 Schick test is positive
 Listeria monocytogenes
 unpasteurized milk and cheese
 only Gram + bacteria with an endotoxin
 causes meningitis in neonates due to vaginal transmission at birth
Gram Negative Enteric [lives in the gut] Bacilli
 Helicobacter pylori
 multiple polar flagella
 urease positive which produces ammonia to neutralize gastric acid
 peptic ulcer: gastric [85%] and duodenal [95%]
 stomach cancer
 Campylobacter jejuni
 fever, diarrhea, blood and pus in stool
 Yersinia pestis
 bubonic plague [black death]
 transmitted by infected rat fleas
 buboes and pneumonia
 Salmonella enterides
 food poisoning 1-2 days after ingestion
 Shigella dysenteria, sonnei or flexneri
 non-lactose fermenting enteric bacillus
 bloody diarrhea [dysentery]
 Salmonella typhi
 non-lactose fermenting motile enteric bacillus
 Typhoid fever-looks like typhus hence the name typhoid
 step-ladder fever, diarrhea, rose spots on the abdomen
 transmitted by Food, Fingers, Feces and Flies
 Escherichia coli
 lactose fermenting catalase positive enteric bacillus
 O, H and K antigens
 traveler’s diarrhea [Montezuma’s, Delhi belly]
 may also cause UTI, food poisoning, meningitis and HUS
 Hemolytic Uremic Syndrome-causes liver and kidney failure
o caused by a very virulent form of E. coli [subtype 0157:H7]
o this is found in contaminated hamburger meat
 Proteus mirabilis
 urea splitting, maltose fermenting enteric bacillus
 urinary tract infection
 Serratia marcescens
 infection producing red pus
 Klebsiella pneumoniae
 Gram negative lactose fermenting enteric bacillus
 causes pneumonia and lung abscess in alcoholics and UTI in diabetics
 red-currant jelly sputum with the pneumonia

Gram negative non-enteric bacilli

 Bordetella pertussis
 whooping cough
 paroxysms of cough followed by an inspiratory whoop
 Francisella tularensis
 tularemia or rabbit fever
 fever and cough after skinning infected rabbits

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  Brucella abortus
 brucellosis or undulant fever
 from infected cows, goats or swine
 fever with an undulating pattern
 Legionella pneumophila
 lung infection [atypical pneumonia]
 from contaminated air-conditioning
 Pseudomonas aeroginosa
 non-lactose fermenting, oxidase positive enteric bacillus
 blue-green pus in infected burns
 due to pyocyanin [blue] and pyoverdin [green] pigments
 causes Pneumonia, Sepsis, External otitis, UTI, Drug use Osteomyelitis
 Hemophilus aegypti
 also known as Koch-Weeks bacillus
 causes conjunctivitis [pink eye]
 Hemophilus ducreyi
 Chancroid caused by Gram negative bacillus
 causes yellow painful genital sore [it is so painful that you do cry]
 Hemophilus influenzae
 also known as Pfeiffer’s bacillus
 causes pneumonia, epiglottitis, croup and meningitis in children

VIBRIO
 Vibrio cholerae [Gram negative enteric organism]
 cholera caused by comma-shaped with single polar flagellum
 produces an exotoxin which stimulates cAMP which in turn greatly
increases fluid secretion from the gut
 this results in severe diarrhea with rice water stool and raid dehydration

TOXINS
 many bacteria produce toxins or poisons which enhance their virulence
 2 types:
o endotoxin
o exotoxin
 endotoxins
o produced and not secreted from dead Gram negative bacteria
o derived from the lipopolysaccharide found in the cell walls of Gram negative bacteria
o all are heat-stable
o causes system-wide effects such as fever and shock
 exotoxins
o produced by live Gram + or - bacteria
o they are polypeptides secreted by bacteria
o heat-labile toxin [except Staphylococcal enterotoxin and E. coli toxin]
o antigenic properties
 denatured [by formaldehyde] toxin is a toxoid
 toxoids are used to stimulate immunity
o toxins targets specific tissues like nerve, muscle and connective tissue
 tetanus tetanospasmin nerve
 botulism botulinin muscle
 diphtheria diphtheria toxin connective tissue

Bacterial Classification according to their oxygen needs

 obligate aerobes-cannot live without oxygen: Pseudomonas, Bacillus and Mycobacterium
 obligate anaerobes-can survive without oxygen: Clostridia
 facultative anaerobes-can live with no oxygen but prefers oxygen

Bacterial Classification according to their temperature references

0
 thermophiles are bacteria that like a warm temperature of 45-90
0
 psychrophile are bacteria that like a cold temperature of 0-20
0
 mesophile are bacteria that like a moderate temperature 20-45

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FEVERS
 Q fever
o Coxiella burnetti via unpasteurized milk from infected cattle or by aerosol spread
 Rocky Mountain Spotted fever
o Rickettsia rickettsii
 Trench fever
o Rickettsia quintana
 Recurrent [relapsing] fever
o Borrelia recurrentis
 Rabbit fever
o Francisella tularemia
 Undulant fever
o Brucella abortus
 Rheumatic fever and Scarlet fever
o Streptococcus pyogenes
 Lancefield Group A beta-hemolytic streptococcus

TYPHUS [Fever with a rash on the trunk]

 Murine [Endemic] Typhus
o Rickettsia typhi
 Epidemic Typhus
o Rickettsia prowazekii
 Scrub typhus
o Rickettsia tsutsugamishi
 Typhoid fever
o Salmonella typhi

FOOD POISONING
 Staphylococcus aureus
o 2-4 hours after ingestion; preformed enterotoxin: rapid onset of symptoms
o vomiting and diarrhea
 Clostridium botulinum
o 6-8 hours; preformed enterotoxin: rapid onset of symptoms
o vomiting followed by flaccid paralysis, diplopia and dysphagia
 Clostridium perfringens
o 10-12 hours; preformed enterotoxin: rapid onset of symptoms
o vomiting and diarrhea
 Salmonella enterides
o vomiting and diarrhea 12-24 hours after ingestion
o fever, heat resistant toxin produced after bacteria colonizes the gut
 Campylobacter jejuni
o 1-7 days after ingestion
o Fever, vomiting and diarrhea; most common cause of food poisoning
 Escherichia coli
o Vomiting and diarrhea 1-10 days after ingestion
o Toxin formed after the bacteria colonizes the gut

DYSENTERY [bloody diarrhea]

 Traveler’s diarrhea [Montezuma’s revenge, Delhi belly]
o Escherichia coli
 Hiker’s diarrhea
o Giardia lamblia
 Bacillary dysentery
o Shigella dysenteriae
 Amebic dysentery
o Entameba histolytica
 Childhood dysentery
o Coxsackie viruses
 Infantile gastroenteritis
o Rota virus of the Respiratory Enteric Orphan family of RNA viruses
 Common cause of gastroenteritis in children under 2 years

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MENINGITIS [Infection of the coverings of the brain]
 Neonates
o Escherichia coli
 Children
o Hemophilus influenzae
 Adolescents and adults
o Neisseria meningitidis
 Elderly
o Streptococcus pneumoniae
 HIV/AIDS
o Cryptococcus neoformans

ATYPICAL PNEUMONIAS [pneumonias not caused by the more common causes]

 Mycoplasma pneumoniae
 Chlamydia pneumoniae
 Chlamydia psittaci
 Legionella pneumophila
 Coxiella burnetti

OSTEOMYELITIS
 Most people: Staphylococcus aureus
 Sexually transmitted: Neisseria gonorrhoea
 Drug addicts: Pseudomonas aeruginosa
 Sickle cell disease: Salmonella species

URINARY TRACT INFECTIONS

 Escherichia coli [most common]
o Gram negative enteric lactose fermenting bacillus; part of the normal gut flora
o nitrite positive [contains a reductase which converts urinary nitrate into nitrite]
 Staphylococcus saprophyticus [second most common]
o Gram positive coagulase negative coccus; part of the normal vaginal flora
o nitrite negative [does not contain nitrate reductase]
o most common cause of UTI in young sexually active females
 Proteus✔ mirabilis
o Gram negative enteric maltose fermenting bacillus; part of the normal gut flora
o nitrite and urease positive
 Klebsiella pneumoniae
o Gram negative enteric lactose fermenting non-motile bacillus; part of the normal gut flora
o nitrite positive

ANTIBIOTIC TARGETS
Antibiotics are chemicals that have the capacity to kill bacteria in vivo and do so through a variety of ways
including:
 blocks cell wall synthesis by inhibiting of peptidoglycan cross-linking
o Isoniazide, ethambutol, β-lactams like penicillin, ampicillin and cephalosporin
 blocks cell wall synthesis by inhibiting peptidoglycan synthesis
o Vancomycin
 causes cell wall damage
o Bacitracin and Polymyxin
 blocks nucleotide synthesis acting as antimetabolites
o Sulfonamides and Trimethoprim
 preventing DNA replication
o Metronidazole
o Quinolones [ciprofloxacin]
 preventing RNA Synthesis
o Rifampicin
 blocking protein synthesis by acting on:
o 50S ribosomal subunit
 Choramphenicol and Clindamycin
o 30S ribosomal subunit
 Tetracycline and aminoglysides such as Streptomycin and Neomycin

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 MEDICALLY IMPORTANT FUNGI

SUPERFICIAL SUBCUTANEOUS
SYSTEMIC

Dry skin Sporothrix schenckii Lung Histoplasma capsulatum

Common among
gardeners and rose
growers
Tinea Brain Coccidioides immitis
Presents with bumps
along the lymph
channels in the leg or
forearm
Mouth/nose Paracoccidioides brasiliensis
Head-Tinea capitis
Body-Tinea corporis
Groin-Tinea cruris Madurella grisea
Feet-Tinea pedis Chronic infection of the Blastomyces dermatidis
Bone/skin
Hand-Tinea manum foot
Nails-Tinea ungium Presents with a
Caused by swollen foot with
Microsporum, draining sinuses
Trichophyton and
Epidermophyton fungi Opportunistic

Others
Pneumocystis jiroveci
infects the lungs causing
pneumonia

Pityriasis versicolor
caused by Malassezia Aspergillus fumigatus
furfur which gives a Infects the lungs causing a
characteristic meatballs chronic cough and
and spaghetti hemoptysis
appearance on KOH
prepared skin scrapings

Cryptococcus neoformans
infects the brains and its
Moist Skin coverings causing meningitis

Candida albicans
It is a dimorphic
organism which exists in
two forms depending on
the temperature: Candida albicans
-cold-mold May be systemic in
-warm-yeast immunocompromized
It causes oral or vaginal patients like those with
thrush presenting with a AODS
thick white cheesy
discharge

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FUNGAL MICRO-ORGANISMS

Fungal Characteristics
 Eukaryotic organism with Ergosterol in membranes
 Reproduction by sporulation
o Conidia [asexual] and zygospores [sexual]
 Special culture medium is needed for fungi
 Grows best on Sabouraud’s medium
 Fungal organisms may be classified according to the sites of infection:
o cutaneous or dermatophytes
o subcutaneous
o systemic
o opportunistic
 Some fungi can exist in two forms [dimorphic] either as a mold or as a yeast
o These tend to cause systemic infections
 Candida albicans
 Histoplasma capsulatum
 Coccidioides immitis
 Blastomyces dermatidis
 Paracoccidioides brasiliensis
o The above are thermal dimorphic:
 mold or yeast depending on the temperature
O
 room temperature [25 C]
 cold mold
o multicellular with branching septate or non-septate hyphae
O
 body temperature [37 C]
 heat yeast
o unicellular which reproduce by budding

Dermatophytes
Fungal organisms which require keratin for growth
 Trichophyton
o skin, hair and nails
 Microsporum
o hair and skin
o pets are reservoirs
 Epidermophyton
o nails and skin
 Tinea [ringworm]
o capitis-head [Trichophyton tonsurans is most common]
o corporis-body
o cruris-groin [jock itch]
o pedis-feet [athlete’s foot]
o manum-hand
o unguium-nail

Other superficial fungal infections

These are not dermatophytes as they do not require keratin for growth
 Pityriasis versicolor
o caused by Malassezia furfur [pathogenic form of Pityrosporum orbiculare]
o fine scaly patches of hyperpigmentation and hypopigmentation on the skin
o degradation of lipids in the skin produce acids which inhibits melanin production
o “spaghetti and meatball” appearance of KOH treated skin scrapings
 Candida albicans
o itching red rash in moist places like armpits, vagina or groin in infants [diaper rash]
o increased incidence in diabetics and patients on broad-spectrum antibiotics
 Piedra hortae
o black nodules on hair
 Trichosporum beigelli
o white or beige nodules on hair

183
Subcutaneous fungi
 Sporothrix schenckii
o Dimorphic fungus which lives on vegetation
o bumpy skin lesions in legs or arms of rose growers or gardeners
o causes rose gardener’s disease [sporothricosis]
 Madurella mycetomatis or grisea
o warty lesions on the feet of woodcutters-Madura foot

Systemic Fungi
 Histoplasma capsulatum
o Histoplasmosis aka Ohio Valley fever also found in the Mississippi river valley
o transmitted by inhalation of spores and not from person to person
o bat droppings in cave explorers [spelunkers], chicken poop in poultry farms
o asymptomatic in immunocompetent persons
o hides inside macrophages
o systemic infection in immunocompromized patients affecting:
o lung
o spleen
o liver
o adrenals
 Coccidioides immitis
o Coccidiomycosis aka San Joaquin Valley fever
o found in the desert areas of the southwestern United States
o transmitted by inhalation of spores
o Systemic infection:
 lung infection
 joint pains
 erythema nodosum [painful red bumps on the legs]
 Blastomyces dermatidis [North American Blastomycosis]
o East coast of the United States
o transmitted by inhalation of spores
o skin, bone and lung infections
 Paracoccidioides brasiliensis [South American Blastomycosis]
o Common in Latin America
o 90% of the affected population is male
o transmitted by inhalation of spores
o spores with multiple buds like the spokes of a wheel
o mouth and nose ulcerations

Opportunistic fungi
 affects HIV/AIDS and other immunocompromized patients
 Aspergillus fumigatus
o decaying vegetation
o Inhalation of spores
o fungal ball in lung
o hemoptysis
 Cryptococcus neoformans
o pigeon poop and other bird droppings
o transmitted by inhalation of spores
o Indian ink preparation shows owl eye appearance
o pneumonia
o meningitis and brain abscess
 Candida albicans
o severe systemic infection in HIV/AIDS patients
o causes thrush which presents with severe sore throat and dysphagia
o dimorphic fungus
o pseudohyphae and budding yeasts on tissue scrapings
 Pneumocystis jiroveci [carinii]
o causes pneumonia in HIV/AIDS patients
o ground glass appearance on chest x-ray
o previously classified as a protozoa [formerly P. carinii]

184
 MEDICALLY IMPORTANT PARASITES

PROTOZOA METAZOA

Entameba histolytica NEMATODES

Ameba

Intestinal

Flagellate Ascaris lumbricoides

-roundworm
Necator americanus
-hookworm
Trichomonas vaginalis Enterobius vermicularis
-pinworm
Strongyloides stercoralis
Gardia lamblia-hiker’s diarrhea -threadworm
Trichuris trichuria
-whipworm
Trypanosoma Trichinella spiralis
-pork roundworm

T. cruzi-Chagas disease
-Reduviid sand fly bite Tissue
T. gambiense-Sleeping sickness
-Tsetse fly bite
Onchocerca volvulus
-river blindness
Leishmania -Simulium blackfly bite
Wuchereria bancrofti
-elephantiasis
L. donovania-kala azar -Aedes aegypti mosquito
-phlebotomous sandfly bite Loa loa
L. brasilliensis-espundia -Eye worm
-phlebotomous sandfly bite -Chrysops fly bite
Sporozoa

TREMATODES
Cryptosporidium parvum

Schistosoma
Toxoplasma gondii S. hematobium
CESTODES -bladder
S. mansoni
-liver
Plasmodium S. japonicum
-gut
Taenia Clonorchis sinsensis
T. solium-pork tapeworm -Chinese liver fluke
T. saginatum-beef tapeworm Paragonimus westermani
P. falciparum Diphyllobothrium latum -lung fluke
-most deadly form of malaria -largest fish tapeworm
-causes convulsions and death Hymenolepis nana
-may cause Blackwater fever -smallest [dwarf] tapeworm
P. malariae Echinococcus granulosus
P. ovale -hydatid disease
P. vivax Sheep raising areas
Female Anopheles mosquito bite Accidental contact with contaminated
dog feces

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PARASITIC MICRO-ORGANISMS

General characteristics
 Parasite
o organism that requires another organism to survive
 Primary host
o required to complete sexual reproductive cycle, e.g. humans in intestinal worms
 Secondary host
o involved in asexual reproduction, for example snails in schistosomiasis
 Vector
o secondary organism needed to transmit disease, e.g. mosquitoes in malaria

Classification
 Number of cells
o Unicellular parasites
 protozoa
o Multicellular parasites
 metazoa
 Protozoa may be further classified by the mode of locomotion in the trophozoite form:
o Ameba [movement by pseudopodia]
 Entameba histolytica
 Naegleria fowleri
o Flagellata [movement by flagella]
 Giardia lamblia
 Trichomonas vaginalis
 Leishmania donovani
 Trypanosoma cruzi and brucei
o Ciliate [movement by cilia]
 Balantidium coli
o Sporozoa [no movement]
 Cryptosporidium parvum
 Toxoplasma gondii
 Plasmodium falciparum, vivax, ovale and malariae

Protozoal infections
 Ameba:
o Entameba histolytica
 amebic dysentery presenting with stool with flecks of blood and mucus
 may invade the liver causing an abscess
o Naegleria fowleri
 found in warm waters in the south states during summer
 invades the brain via the cribriform plate in the nasal cavity
 causes a rapidly fatal meningoencephalitis
 Flagellata:
o Trichomonas vaginalis
 sexually transmitted disease
 greenish frothy malodorous vaginal discharge
 asymptomatic in males
o Giardia lamblia
 hiker’s diarrhea aka beaver fever
 most common intestinal parasite in the USA
 drinking contaminated stream water
 foul smelling loose stools
o Trypanosoma brucei gambiense/rhodesiense
 causes sleeping sickness
 transmitted by the Tsetse fly
o Trypanosoma cruzi
 transmitted by the kissing [reduviid] bug which craps in its bite
 causes Chagas disease
 dysphagia due to mega-esophagus
 heart failure due to dilated cardiomegaly

186
 o Leishmania donovani
 kala-azar
 phlebotomous sand files bites
 hepatosplenomegaly
o Leishmania brasiliensis
 espundia
 phlebotomous sand fly bites
 mucocutaneous ulcerations
 Ciliate
o Balantidium coli
 diarrhea
 Sporozoa
o Toxoplasma gondii
 sporozoa infection from infected cat feces; crosses the placenta
 causes miscarriages, chorioretinitis, intracranial calcification
o Cryptosporidium parvum
 opportunistic infection in HIV/AIDS patients
 severe chronic recurrent diarrhea and dysentery
o Plasmodium
 Malaria spread by female Anopheles mosquitoes
 most deadly malaria parasite:
 Plasmodium falciparum-daily cycles of fever
 causes cerebral infection with convulsions and death
 blackwater fever is due to excessive hemoglobin in the urine
 less severe forms of malaria: Plasmodium ovale, vivax or malariae
 gametocytes are the form ingested by the mosquito
 gametocytes develop into sporozoites in the mosquito
 sporozoites are injected into uninfected human
 the sporozoites become merozoites in the liver
 merozoites change into trophozoites which later become gametocytes

Metazoan infection
 Nematode infections: intestinal and tissue or blood
 Intestinal roundworms which are spread by the orofecal route:
o Enterobius vermicularis
 Pinworms are the most common intestinal nematode in the USA
 Causes perianal itching and a positive scotch tape test
o Ascaris lumbricoides
 Roundworms are the second most common intestinal nematode in the USA
 uncommon cause of intestinal and common bile duct obstruction
o Strongyloides stercoralis
 threadworms
 causes perianal itching at night
o Trichuris trichuria
 whipworms
 causes weight loss, abdominal pain, bloody diarrhea and rectal prolapse
o Trichinella spiralis
 pork roundworm which causes Trichinosis
 causes fever, muscle pain and periorbital edema
o Necator americanus
 most common hookworm in the USA
 causes an iron deficiency anemia
 Tissue or blood worms which are spread by biting insects
o Onchocerca volvulus
 transmitted by the Simulium blackfly
 causes river blindness, hyperpigmented skin [black fly, black skin, black vision]
o Wuchereria bancrofti
 elephantiasis; filariasis; chronic lymph blockage, carried by Culex filariasis
 blood is best tested at 10 pm when the parasites are in the bloodstream
o Loa loa
 transmitted by the Chrysops biting fly
 causes eye worm [worm is seen under the conjunctiva]

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 Cestode infections
 Tape worms which are spread by eating contaminated food
o segmented hermaphrodite worms
o Diphyllobothrium latum
 largest fish tapeworm [10 meters long] in the world
 Vitamin B12 deficiency [not pernicious anemia]
o Hymenolepis nana
 smallest [dwarf] tapeworm; eggs found in contaminated cereal
 causing diarrhea, abdominal pain and weight loss
o Taenia solium
 from undercooked infected pork
o Taenia saginatum
 from undercooked infected beef
o Echinococcus granulosus
 common in sheep-raising areas
 accidental contact with contaminated dog feces
 hydatid cysts in the liver causing hepatomegaly or cysts in the lung

 Trematode infections
 Flukes
o non-segmented flattened worms
o Schistosoma species
 female worm lies in a split in the body of the male worm
 transmitted by snails which are the intermediate hosts
 immature stages include cercariae which are found in the intermediate host
 causes bilharziasis [named after the German helminthologist-Theodor Bilharz]
 Schistosoma hematobium
o egg with a terminal spine found in the urine
o common in Africa and Middle East
o affects the bladder
o causes hematuria and squamous cell bladder cancer
 Schistosoma japonicum
o egg with a rudimentary spine
o common in Asia
o affects the gut and the liver
o eggs found in the stool
 Schistosoma mansoni
o egg with a lateral spine
o affects the gut and liver
o liver cirrhosis and portal hypertension
o eggs found in the stool
o swimmer’s itch due to schistosoma species found in ducks in
the costal part of New Jersey in the US
o Clonorchis sinensis
 Chinese liver flukes
 affecting over 30 million people worldwide eating undercooked infected fish
 endemic in the Far-East
 feeds on the bile in the liver
 may present with fever, tender hepatomegaly and mild jaundice
 chronic cholangitis and cholangiocarcinoma are late complications
o Fasciola hepatica
 liver flukes
 from infected sheep
 the aquatic snail is the intermediate host
 humans are accidentally infected by eating contaminated water cress
 may cause diarrhea and abdominal pain
o Paragonimus westermani
 lung flukes
 undercooked crab meat from infected crabs and crayfish
 endemic in Asia, Africa and South America
 presents with chronic cough and hemoptysis

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TESTS FOR MICRO-ORGANISMS

Specific lab tests

 Ascoli test
o this is a test for detecting anthrax bacilli in animal hides and meat
 Catalase test
o separates Staphylococci (+) from Streptococci (-)
 Coagulase test
o separates Staphylococcus aureus from other staph which are coagulase negative
 Dick test or Schultz Carlton reaction
o these tests are positive in scarlet fever
 Schick test
o this is a test for diphtheria

Specific culture media

 Blood agar medium for most bacteria
o the pattern of hemolysis is helpful in distinguishing certain streptococci
 beta [complete]- Strep. pyogenes
 alpha [partial]- Strep. pneumoniae
 gamma [none]- Strep. fecalis [now knows as Enterococcus fecalis]
 Bordet-Gengou [potato] agar
o Bordetella pertussis
 Chocolate [lysed sheep blood agar-not real chocolate] agar
o Hemophilus and Neisseria organisms
 Eaton’s agar
o Mycoplasma pneumoniae
 Hektoen enteric agar
o Salmonella and Shigella species
 Loeffler’s medium contains horse serum, beef broth and dextrose
o Corynebacterium diphtheriae
 Lowenstein-Jensen [or Middlebrook] medium
o Mycobacterium
 MacConkey’s agar inhibits the growth of Gram + bacteria
o promotes the growth of Gram negative lactose-fermenting bacteria
 Purified Chick Embryo Culture [PCEC]
o used to culture viruses
 Regan-Lowe agar
o Bordetella pertussis
 Sabouraud medium has a low pH medium with gentamicin inhibits bacterial growth
o fungi organisms
 Tellurite agar
o Corynebacterium diphtheriae
 Thayer-Martin medium [chocolate agar plus vancomycin and nyastin]
o Neisseria gonorrhoeae
 Thiosulfate-Citrate-Bile salts-Sucrose [TCBS]
o Vibrio cholerae

Special stains or microscopic techniques

 Darkfield microscopy
o Treponema. Borrelia and the microfilariae of Wuchereria bancrofti
 Eosin-Methylene Blue
o Escherichia coli
 Indian ink
o Cryptococcus neoformans gives the typical owl-eye appearance
 Wood’s lamp
o Fungal infection; observe the fluorescence
 Wright-Giemsa stain
o Blood or bone marrow smears to detect syphilis and parasites including protozoa
 Ziehl-Neelsen stain
o Mycobacterium tuberculosis

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Specific blood tests
 Anti-Streptolysin O Titer >160 Todd units
o recent streptococcal infection
o Streptococcus pyogenes produces toxins called Streptolysin O and S which are
responsible for the β–hemolytic pattern of hemolysis on blood agar
o Streptolysin O stimulates the production of antibodies
o seen in rheumatic fever and post-streptococcal glomerulonephritis
 Coombs test
o Rhesus factor
o Hemolytic anemia
o Erythroblastosis fetalis in Rhesus negative mothers
 ELISA [Enzyme-Linked Immunosorbent Assay]
o HIV and Lyme disease
o it is a sensitive test but not specific as there are many false positives
 FTA-ABS [Fluorescent Treponemal Antibody Absorption] test
o confirmation test for Syphilis
o remains positive long after the syphilis is successfully treated
 Ligase chain reaction
o special lest for Chlamydia organisms
o it is a variation of the Nucleic Acid Amplification Test
 Mitsuda test
o uses an intradermal injection of lepromin to detect leprosy
o a reaction in the skin at the site of the injection is positive for Mycobacterium leprae
 Paul Bunnel test
o Mononucleosis
o uses sheep red blood cells
 RPR [Rapid Plasma Reagin] test
o Screening test for syphilis
 VDRL [Venereal Diagnostic Research Lab] test
o Screening test for syphilis
o becomes negative after syphilis is successfully treated
o if VDRL is positive but the FTA-ABS is negative, it is probably a false positive
o many causes of a false positive VDRL:
 Viral infections: mononucleosis, hepatitis
 Drugs
 Rheumatic fever
 Leprosy
 SLE
 Weil-Felix test
o Patient’s serum is mixed with Proteus antigens
o if the patient has antibodies to Rickettsiae, the antibodies react with the Proteus antigens
and cause agglutination of red blood cells
o positive for Rickettsiae
o negative test result in Coxiella infection
 Western Blot [there are also Southern and Northern Blot tests]
o used to confirm HIV infection after a positive ELISA
o tests for viral protein fragments [Southern blot uses DNA and Northern blot used RNA]
o this is a highly specific test which is used to rule in the disease
 Widal test
o Typhoid fever

Skin tests
 Kveim test
o Sarcoidosis
o injection of splenic extra from a patient with sarcoidosis causes a specific skin reaction
o skin reaction will show non-caseous granulomas in 4-6 weeks after the injection
 Mantoux or Heaf test or Tine test
o Tuberculosis using an intradermal injection of PPD
 Purified Protein Derivative from TB bacillus
 Positive skin test [>10 mm] indicates exposure to TB

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Others
 Urea-splitting bacteria
o Helicobacter pylori
 This bacterium secretes an enzyme called urease which breaks down urea to
form ammonia and carbon dioxide
 The ammonia neutralizes the hydrochloric acid in the stomach preventing the
gastric acid from destroying the bacteria
 This allows the bacteria to multiple and proliferate in the stomach mucosa
causing gastritis and peptic ulcers
o Proteus mirabilis
 this bacterium also secretes urease
 the resulting alkaline environment in the urine promotes the precipitation of
struvite stones
o Klebsiella pneumoniae
 This organism also produces urease
 This is helpful in distinguishing it in the lab
 Ames test
o this is a biological assay that assesses the mutagenic potential of chemical compounds
o it uses several strains of Salmonella typhimurium
o when positive, the chemical has the potential to cause mutation of genes and thus may
be carcinogenic
 Quellung reaction
o German word for “swelling”
o this test is a biochemical reaction in which anticapsular antibodies bind to the capsule of
a bacterium, causing the capsule to swell
o this makes the bacterium more visible
o Strep. pneumoniae has such a capsule and would show a positive Quellung reaction
o Others include Klebsiella pneumoniae, Hemophilus influenzae, Salmonella and
Neisseria meningitides

Sensitivity and Specificity of Test Results

 The interpretation of laboratory results is influenced by the reliability of the test results
 In the ideal situation, a diagnostic test should be positive in the presence of a pathogen or disease
[this is called the true positive] and negative when the pathogen or disease is not present [this is
called the true negative]
 This does not occur in practice and no one test is perfect
 Sometimes there are false positives [the test is positive but no pathogen or disease is present]
 Sometimes the test is negative yet the pathogen or disease is present [false negative]
 Therefore it is necessary to determine the reliability of any test and this is expressed in terms of its
sensitivity and specificity
 This is facilitated by the construction of a simple 2 x 2 table:

Pathogen present Pathogen absent

Test positive a b
Test negative c d

Sensitivity [a/a+c] is calculated by taking the number of patients with a True positive and dividing it by the
total number of patients with the disease
 A highly sensitive test if the result is negative is good at excluding the diagnosis
 Sensitive tests are useful in screening out diseases
 In a very sensitive test, if the result is negative, then one can rule out the disease [SnOut].

Specificity [d/d+b] is calculated by taking the number of patients with a True negative divided by the total
number of patients without the pathogen
 Highly specific tests if the results are positive are useful in confirming or ruling in diagnoses
 In a test with a high specificity, if the result is positive, then the person has the disease [SpIn]

These can also be applied to the presence of a particular symptom or sign.

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INFECTION CONTROL

3 ways to reduce pathogens

 Pasteurization: exposure of milk to progressively higher temperatures
 Sterilization: using heat or chemicals to destroy all life
 Disinfection: using chemicals to destroy most pathogens

7 steps in water purification

 Filtration: allowing water to pass through materials with pores of different sizes
 Flocculation: addition of aluminum which precipitates certain materials
 Sedimentation: allows the precipitate to settle out
 Sand filtration: allowing water to pass through sand which removes anaerobic bacteria
 Sludge digestion: addition of anaerobic bacteria
 Aeration: bubbling oxygen through water to kills anaerobic bacteria
 Chlorination: adding chlorine which kills all remaining bacteria

US Agencies related to health issues

 Department of Agriculture: meat and milk inspection
 Food and Drug Administration: quality of drugs, cosmetics, food, advertizing of health products
 Public Health Department: disease surveillance and restaurant inspections
 Environmental Protection Agency: water and air quality
 United States Dairy Association: quality of dairy products
 Occupational Safety Health Administration: workplace safety, handling of hazardous materials
 Centers for Disease Control: epidemiological research and health statistics
 Health Services Administration: oversees health care to the underserved
 National Institutes of Health: oversees disease research and provided funding

Epidemiological terms
Epidemiology: the study of the causes, distribution and control of diseases in populations
Incidence: number of new cases in the population in a given time
Prevalence: number of people with the disease at a given time
Mortality: number of people who die from a particular disease
Morbidity: number of people who have a certain disease
Life Expentancy: An estimate as to how long the general population will live
Epidemic: sudden increase in the number of disease locally
Endemic: normal occurrence of a disease in a particular locality
Pandemic: sudden rise in the number with the disease worldwide
Emerging disease: disease that has newly appeared
Re-emerging disease: disease which has existed previously but is rapidly increasing in incidence or in
the geographic extent

Emerging or Re-emerging Diseases

Examples of emerging diseases:
 Ebola
 Lassa fever
 Lyme disease
 HIV/AIDS
 Hantavirus infection
 SARS
 H1N1 [swine flu]

Examples of re-emerging diseases:

 Multi-Drug Resistant Tuberculosis
 Methicilin Resistant Staphylococcus Aureus.

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CHEMISTRY

193
194
GENERAL PRINCIPLES

There are three energy systems in the body:

 aerobic
 anaerobic
 phosphagen
Aerobic metabolism uses the Krebs cycle and the Electron Transport System which are located in the
mitochondrion. Anaerobic metabolism uses Glycolysis and is located in the cytosol. Anaerobic metabolism
is faster than aerobic metabolism and produces less ATP than aerobic metabolism-36-38 ATPs. The
phosphagen energy system uses high-energy phosphate compounds such as ATP in the ligase-mediated
reactions.

Chemical reactions
An enzyme is a protein which speeds up the rate of a chemical reaction by lowering the activation energy:
 enzymes are not consumed by the reaction that they catalyze, nor do they alter the equilibrium of
these reactions. Enzymes do not change the ΔG, [Gibbs free energy]
 enzymes are specific to the reactions they catalyze
 A pro-enzyme (aka zymogen) is an inactive enzyme precursor which requires a biochemical
change for it to become an active enzyme
 An apoenzyme is the protein component of an enzyme to which the coenzyme is attached
Oxidation is the process in which there is loss of hydrogen electrons or a gain of oxygen
 oxidase is an enzyme that causes the oxygen in a compound to be changed to water
 dehydrogenase is an enzyme which oxidizes a compound by removing hydrogen
Reduction is the process in which there is a gain of hydrogen electrons or a loss of oxygen
 a reductase is an enzyme which adds hydrogen to a compound
Carboxylation is the chemical process by which a carboxyl group [-COOH] is added or displaces a
hydrogen atom
 carboxylase is the enzyme which catalyzes the addition of a carboxyl group
Decarboxylation is the process in which the carboxyl group [-COOH] is removed from an organic
compound as CO2, and is commonly replaced by a hydrogen atom
 decarboxylase is the enzyme that catalyzes the release of CO2 from compounds
Hydrolysis refers to the cleavage of a compound by the addition of water, the hydroxyl group being
incorporated in one fragment and the Hydrogen atom in the other
 hydrolase is the enzyme that facilitates hydrolysis as in sucrase in the breakdown of sucrose
Phosphorylation is the process of introducing a phosphate group into an organic molecule:
 phosphorylase is the enzyme which adds inorganic phosphate to a substrate without using ATP
 phosphatase is the enzyme that removes a phosphate group from its substrate by hydrolyzing
phosphoric acid monoester into a phosphate ion and a molecule with a free hydroxyl group
Kinase is an enzyme that transfers a phosphate group from high-energy donor molecules, such as ATP,
to a specific substrate
Transferase is an enzyme that catalyzes the transfer of a functional group from one molecule to another
Ligase is an enzyme that catalyzes the joining of two molecules
Vmax refers to the maximum velocity of a reaction and is proportional to enzyme concentration
Kmax [Michaelis-Menten constant] is the amount of substrate required to reach ½ of the Vmax.
An inhibitor is any substance which slows down the rate of reaction of any enzyme
There are three ways of enzymatic regulation:
 non-competitive inhibition
 competitive inhibition
 allosteric regulation
In non-competitive inhibition, the inhibitor always binds to the enzyme at a site other than the enzyme's
active site and is irreversible. It reduces Vmax. Increasing the concentration of the substrate does not affect
the activity of the inhibitor.
In competitive inhibition, the inhibitor binds to the same active site as the normal enzyme substrate,
without undergoing a reaction and is reversible. Increasing the concentration of the substrate will overcome
the activity of the inhibitor, thus Vmax will not change.
In an allosteric regulation, an enzyme’s activity is regulated by binding an effector molecule at the
enzyme's allosteric site (a site other than its active site):
 effectors that enhance the protein's activity are referred to as allosteric activators
 whereas those that decrease the protein's activity are called allosteric inhibitors

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Energy compounds
Nicotinamide adenine dinucleotide phosphate (NADP) is the phosphorylated form of NAD [Nicotinamide
Adenine Dinucleotide]. It is used in anabolic reactions, such as lipid and nucleic acid synthesis and pentose
phosphate pathway, which require NADPH as a reducing agent. NADH is the reduced form of NAD and is
given off in the Krebs cycle to make ATP. Both NAD and FAD [Flavin Adenine Dinucleotide] facilitate the
transport of electrons from the Krebs cycle to the Electron Transport Chain. The following are the 4 basic
energy fuels of the body:
 carbohydrates [4 kcal/mol]
 proteins [4 kcal/mol]
 fats [9 kcal/mol]
 alcohol [7 kcal/mol] [empty calories as they have no nutrients]
Catabolism of energy fuels results in heat generation and ATP synthesis.
ATP [Adenosine Triphosphate] is the universal energy currency of the body.
Catabolism is a degradative process which breaks down large molecules into smaller units releasing useful
energy.
Anabolism is a biosynthetic process which constructs large molecules from smaller units. These reactions
require energy.

Types of chemical bonds

Peptide bond is a covalent bond formed between two molecules when the carboxyl group of one molecule
reacts with the amino group of the other molecule, thereby releasing a molecule of water (H2O).
 This is a dehydration synthesis reaction (also known as a condensation reaction), and usually
occurs between amino acids.
Hydrogen bond results from a dipole-dipole force with a hydrogen atom bonded to nitrogen, oxygen or
fluorine (highly electronegative atom).
 H-bonds are the chemical bonds found between the bases in DNA and RNA.
Ester bond is the chemical covalent bond between glycerol and fatty acids.
 Esters consist of an inorganic or organic acid in which at least one -OH (hydroxyl) group is
replaced by an -O-alkyl (alkoxy) group.
Glycosidic bond is the chemical bond between two sugars.
Phosphodiester is the chemical bond between two nucleotides. It is a group of strong covalent bonds
between the phosphorus atom in a phosphate group and two other molecules over two ester bonds

Generalizations about metabolic pathways

When metabolic pathways are discussed, the following should be described:
 Purpose
o general statement regarding either the substrate or the end product
 Tissue location
o particular sites in the body where the pathway is most important
 Cell site
o where in the cell the pathway occurs: cytosol or mitochondria or both
 mitochondria-fatty acid oxidation, TCA cycle and oxidative phosphorylation
 cytoplasm-glycolysis, fatty acid synthesis, HMP shunt and protein synthesis
 both-heme synthesis, urea cycle and gluconeogenesis [HUGs take two]
 Sequence of events
o the overall reaction sequence and the number of stages or reactions
 Key steps
o steps that form control [rate limiting] points or for main branch points
 Rate limiting step
o a crucial step that controls how fast or slow the pathway goes
 Glycolysis phosphofructokinase
 Gluconeogenesis fructose-1,6 bisphosphatase
 TCA cycle isocitrate dehydrogenase
 Glycogen synthesis glycogen synthase
 Glycogenolysis glycogen phosphorylase
 HMP shunt glucose-6-phosphate dehydrogenase
 Urea cycle Carbamoyl phosphate synthetase
 Fatty acid synthesis Acetyl-CoA carboxylase
 Fatty acid oxidation Carnitine acyltransferase
 Cholesterol synthesis HMG-CoA reductase

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CARBOHYDRATE METABOLISM

Digestion
Types of carbohydrates we eat:
 Starch
 Sucrose
 Lactose
 Cellulose
Starch is a polysaccharide carbohydrate consisting of a large number of glucose monosaccharide units
joined together by glycosidic bonds. This complex carbohydrate is similar in function to glycogen as its main
function is to provide an energy source. All plant seeds and tubers contain starch predominantly as amylose
and amylopectin
 Amylose is a long, unbranched chains of glucose linked at C1 and C4-α1,4 link, also known as
α1,4 bonds.
 Amylopectin is a highly branched polymer of glucose, with glucose units linked in a linear way with
α 1,4 bonds. Branching takes place with α1,6 bonds occurring every 24 to 30 glucose units.
Sucrose is a disaccharide made up of glucose and fructose found in table sugar and in fruit
Lactose is the sugar found in milk and is made up of galactose linked to glucose
Humans can only process sugars with the D conformation [right-handed] not the L [left-handed]
conformation; think D for delicious.
Cellulose is a polysaccharide consisting of a linear chain of several hundred to over ten thousand beta 1,4
linked D-glucose units. It is the primary structural component of the primary cell wall of green plants.
Humans cannot digest cellulose because they lack the enzyme cellulase to break it down
Salivary amylase breaks starch down into maltose
 present in the mouth where it begins the chemical process of digestion; deactivated by acid stomach pH
Pancreatic amylase, (aka alpha amylase) facilitates starch breakdown in small intestine cleaving 1,4 links
to release di- and trisaccharides
Trisaccharidase breaks down trisaccharides into di- and monosaccharides
Disaccharidase breaks down disaccharides into the monosaccharide-glucose, fructose, galactose
Sucrase breaks down sucrose into fructose and glucose.
Lactase is secreted by the intestinal villi
 This enzyme breaks down lactose into two subunits; galactose and glucose for absorption.
Some people with lactose intolerance might not digest lactose because of a lack of lactase.
 Undigested lactose remains in the gut and ferments causing bloating and diarrhea
Glucose is absorbed and stored in the body as glycogen in skeletal muscle and the liver.
When glucose is needed, glycogen in storage in the liver and muscle is broken down.
This breakdown process of glycogen is called glycogenolysis.
The breakdown process of glucose is called glycolysis.

Glucose transport
Glucose is found in the blood and needs to be transported actively from the blood to the cytoplasm of the
cells. Glucose is transported across various cell membranes using a variety of tissue specific transporters
namely GLUT 1-14 of which the more important ones are:
 GLUT 1: red blood cells, brain, placenta and testis
 GLUT 2: beta cells in the pancreas
 GLUT 3: neurons
 GLUT 4: adipose cells, skeletal and cardiac muscle

GLYCOLYSIS [sugar breakdown]

It is the process by which one 6-carbon glucose molecule is converted to two 3-carbon molecules
[pyruvate]. Two molecules of ATP and 2 NADHs molecules are the net yield for each glucose molecule that
is converted to two molecules of pyruvate. This is the simplest form of metabolism in the cells and it takes
place in the absence of oxygen [anaerobic]. This is a cytoplasmic pathway used by all cells to generate
energy from glucose. This pathway is also known at the Embden-Meyerhof pathway.
 Purpose
o principal breakdown route of glucose to produce energy
 Tissue location
o all cells in the body
o red blood cells and neurons do not have mitochondria to finish the rest of cellular
respiration

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  Cell site
o Takes place in the cytoplasm
 Sequence of events
o There are 10 steps leading to the production of 2 molecules of pyruvate from one glucose
molecule
 Key enzymes in glycolysis
o Hexokinase/Glucokinase
o Phosphofructokinase [this is the rate limiting step]
o Pyruvate kinase
There are two phases of the glycolytic pathway:
 preparatory phase consisting of the first 5 steps
 pay off phase of the last 5 steps.

Preparatory Phase
Step 1
 Glucose to Glucose 6-Phosphate
 This step is catalyzed by Glucokinase in liver and Hexokinase in all other cells
 This step traps the glucose within the cell as glucose 6-phosphate cannot diffuse out of the cell
 1 molecule of ATP is used up in this process
 This is an irreversible step

Step 2
 Glucose 6-Phosphate to Fructose 6-Phosphate
 This step is facilitated by phosphoglucose isomerase
o An isomerase is an enzyme which changes spatial arrangement of a molecule without
affecting its chemical composition

Step 3
 Fructose 6-Phosphate to Fructose 1,6 Bisphosphate
 This step uses another molecule of ATP
 This step is catalyzed by phosphofructokinase [PFK]
o This enzyme is irreversible also
o This is the most important rate limiting step in glycolysis
o It is an allosterically regulated enzyme that is the major point of regulation for the entire
glycolysis pathway

Step 4
 Fructose 1,6 Bisphosphate to Glyceraldehyde 3-Phosphate and Dihydroxyacetone
phosphate [DHAP]
 This step is catalyzed by aldolase

Step 5
Since DHAP is not a desired substrate for continuing the glycolysis pathway, it is converted to
Glyceraldehyde 3-Phosphate
 This step is facilitated by triose phosphate isomerase
 This reaction is an isomerization reaction, converting a ketone into an aldehyde.

Pay Off Phase

Step 6
 Glyceraldehyde 3-Phosphate to 1,3 bisphosphoglycerate
 This is catalyzed by G3P dehydrogenase
+ +
 NAD + Pi is required and NADH + H is produced

Step 7
 1,3 bisphosphoglycerate to 3-phosphoglycerate
 This is an energy yielding step which results in the production of 1 ATP molecule for each 3-
phosphoglycerate produced
o So there is a total of 2 ATP that are produced from one molecule of Glucose
 This step is catalyzed by phosphoglycerate kinase
o This is known as the BREAK EVEN point as the 2 ATP used in Steps 1-5 is balanced out
by the 2 ATP in this step

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Step 8
 3-phosphoglycerate to 2-phosphoglycerate
 This step is catalyzed by phosphoglycerate mutase
 This enzyme moves the phosphate group from one carbon to another carbon within the molecule.

Step 9
 2-phosphoglycerate to Phosphoenolpyruvate facilitated by enolase
 Enolase is an enzyme which removes a molecule of water

Step 10
 Phosphoenolpyruvate to Pyruvate
 This is the final step in glycolysis
 This is facilitated by Pyruvate kinase
 This is the final energy releasing step in glycolysis
 Each Phosphoenolpyruvate converted to pyruvate releases 1 ATP
 Therefore there are 2 ATP created in this step
 As a result, there is a net total of 2 ATP that are produced from one glucose molecule entering the
glycolytic pathway
o 4 ATP produced in Steps 6-10 minus 2 ATP used in Steps 1-5

Regulating Enzymes in Glycolysis

Hexokinase converts glucose into glucose-6-phosphate
 found in most tissue
2-
 uses MgATP
 it is an allosterically regulated enzyme, inhibited by its product, glucose-6-phosphate
 this prevents too much glucose 6-phosphate from accumulating within the cell
 too much G6P will cause the cell to be swollen
Glucokinase does the same as the above as it is an isoenzyme
 it is found in the liver
 it is activated by Insulin, and inhibits by fructose-6-phosphate
 It works only at relatively high levels of glucose
 It is regulated differently than Hexokinase

Phosphofructokinase is the most important control point-RATE LIMITING STEP in glycolysis

 PFK inhibited by ATP citrate (an intermediate of TCA cycle), NADH and Glucagon
 activated by AMP and ADP which indicate low energy levels in the cell, Insulin and F26BP
 The reason for regulation at the third step is because G6P, the product of the first reaction can
branch off to other metabolic pathways besides glycolysis.
o The third reaction, however, is the first reaction unique to glycolysis and commits the cell
to the glycolysis pathway.

Pyruvate kinase is the final regulating enzyme

 activated by fructose 1,6-biphosphate and AMP
 inhibited by ATP, fatty acids, alanine and acetyl CoA ( major intermediate for catabolism)

Fate of Pyruvate
+,
Pyruvate cannot actually be the end point of glycolysis. The cell has a limited supply of NAD and without
+ +
regeneration of NADH back to NAD , eventually all NAD will end up as NADH and glycolysis will stop due
+
to lack of NAD .

4 possible fates: Oxidation, Reduction, Carboxylation and Transamination

 Oxidation: in aerobic reactions, pyruvate is oxidized to acetyl CoA which enters the TCA cycle.
o this is facilitated by pyruvate dehydrogenase which is inhibited by ATP, Acetyl CoA and
NADH
+
 Reduction: in anaerobic reactions, a different approach to regenerating NAD
+
o one pathway converts pyruvate into lactate in a step which produces NAD
o this is facilitated by lactate dehydrogenase
 Carboxylation: pyruvate is converted into oxaloacetate by pyruvate carboxylase
 Transamination: pyruvate may be converted to alanine by alanine transaminase

199
Glycolysis is not a very energy efficient way to producing energy.
Pyruvate enters the mitochondrion and is converted to acetyl CoA to enter the Krebs cycle where a lot more
energy can be efficiently produced.

G lucose
A TP 1
Glucokinase/Hexokinase

G lucose 6-Phosphate
2
Phosphoglucose isomerase

F ructose 6-Phosphate
3
A TP Phosphofructokinase

F ructose 1,6 bisphosphate

4 5
Aldolase Triose Phosphate Isomerase

G lyceraldehyde 3-Phosphate Dihydroxyacetone Phosphate

6
G3P dehydrogenase
NADH
1,3 Bisphosphoglycerate
7
A TP Phosphoglycerate kinase

3 Phosphoglycerate
8
Phosphoglycerate mutase

2 Phosphoglycerate
9
Enolase

Phosphoenolpyruvate + H 2 O
10
A TP Pyruvate kinase

Pyruvate

Fig 104: Glycolysis

Sorbitol
An alternative method of dealing with glucose in the cell is to covert it to its alcohol counterpart, called
sorbitol, via aldose reductase. Some tissues which contain sorbitol dehydrogenase, converts the sorbitol
to fructose which can enter the glycolytic pathway by being converted to Fructose 1-phosphate and then
to Glyceraldehyde.
Tissues lacking this enzyme are at risk of sorbitol accumulating within the tissue. Examples of tissue that
lack sorbitol dehydrogenase are the lens, retina and Schwann cells. Sorbitol is osmotically active and
draws water into the cell and this damages the lens, retina and peripheral nerves resulting in premature
cataracts, retinopathy and peripheral neuropathy.

200
GLUCONEOGENESIS

This is a pathway for de novo synthesis of glucose from non-carbohydrate substrates such pyruvate,
lactate from RBCs and muscle during anaerobic exercise, glycerol from adipose tissue, and glucogenic
amino acids from muscle protein, using both mitochondrial and cytosolic enzymes found only in the liver,
kidney and intestinal epithelium. Gluconeogenesis mainly occurs in the liver. During prolonged starvation,
the kidneys become the major glucose-producing organs.

It serves to provide glucose especially for the brain and RBCs which require glucose for energy.
Gluconeogenesis occurs during fasting, starvation or intense exercise and is highly endergonic (energy
requiring). Remember that humans cannot make glucose from Acetyl Co-A.

Purpose:
To maintain blood glucose levels in the fasting state by reversing the process glycolysis.
All of the 10 steps in glycolysis are reversible EXCEPT 3:
The 3 irreversible glycolytic enzymes are the enzymes used in Steps 1, 3 and 10:
 Glucokinase/Hexokinase replaced by Glucose 6-Phosphatase
 Phosphofructokinase replaced by Fructose-1,6 bisphosphatase
 Pyruvate kinase replaced by Pyruvate carboxylase and PEP carboxykinase

Mnemonic: Pathway Produces Fresh Glucose

4 replacement enzymes are needed to replace the 3 irreversible glycolytic enzymes. The vast majority of
gluconeogenesis takes place in the cytosol of liver cells [and to a smaller extent the kidney and small
intestinal cells]. Gluconeogenesis uses lactate and amino acids as substrates.

Lactic acid, formed during anaerobic respiration in skeletal muscle, is a common substrate for
gluconeogenesis. Lactic acid may also come from red blood cells, which obtain energy solely from
glycolysis as they have no membrane-bound organelles for aerobic respiration. Lactate is transported back
to the liver where it is converted into pyruvate by the Cori cycle using the enzyme lactate
dehydrogenase:
 Alanine is an amino acid
o It is derived from the Glucose-Alanine cycle
 Both Lactate and Alanine will be converted first to Pyruvate before entering the gluconeogenesis
pathway
 The Cori cycle is an energy sapping cycle and comes at a cost of a net loss of 4 ATP/cycle.
 This cycle prevent lactic acid from building up in skeletal muscle.

The first part of gluconeogenesis is in the mitochondrion and the rest in the cytosol.

Step 10 reversal
The replacement for Pyruvate Kinase is a 2-step process:
 The first step converts Pyruvate to Oxaloacetate which occurs in the mitochondrion
o Pyruvate carboxylase is the replacement enzyme
o Biotin is an essential coenzyme for this step
 biotin is vitamin B7
 biotin deficiency will result causing pyruvate to build up
 this results in excess lactic acid production
o Oxaloacetate passes out into the cytoplasm
o ATP and Acetyl CoA are allosteric activators
 The second step takes Oxaloacetate to Phosphoenolpyruvate
o this occurs in the cytoplasm
o this is catalyzed by PEP carboxykinase
o lots of energy is required for this step
 energy is provided in 2 ways:
 1) decarboxylation is a favorable reaction
 2) GTP is hydrolyzed
o this enzyme is facilitated by:
 glucagon
 cortisol

201
Step 3 reversal
PhosphoFructoKinase converts Fructose 6-Phosphate to Fructose 1,6-bisphosphate
 the replacement enzyme for PhosphoFructoKinase is Fructose 1,6 Bisphosphatase
 this is the RATE LIMITING STEP for gluconeogenesis
 it is stimulated by ATP and citrate
 inhibited by AMP and Fructose 2,6 bisphosphate
Step 1 reversal
Glucokinase converts Glucose to Glucose 6-Phosphate
 Glucose-6 Phosphatase converts Glucose 6-Phosphate to Glucose
o It is present in the ER of liver and kidney cells making gluconeogenesis possible
o G6P is hydrolyzed as it passes into the ER
 Muscle and brain cells do not do gluconeogenesis
 ER vesicles filled with glucose diffuse to the plasma membrane, fuse with it and open releasing
glucose into the bloodstream
 Gluconeogenesis is inhibited by insulin and stimulated by glucagon

Energy usage
Gluconeogenesis is an energy consuming process.
 6 ATPs used in Gluconeogenesis in producing one new Glucose molecule.
 Purpose of this ATP consumption is to store energy in the form of Glycogen.
 Acetyl CoA is not used as it requires more energy to make glucose from Acetyl CoA than from
lactate or alanine.

Fate of new Glucose

If the new glucose is not used immediately, it is converted to and stored as Glycogen in the liver or in
skeletal muscle

Glucose

Glucose 6-Phosphatase

Glucose 6-Phosphate

Fructose 6-Phosphate

Fructose 1,6-Bisphosphatase

Fructose 1,6 bisphosphate

Glyceraldehyde 3-Phosphate

1,3 Bisphosphoglycerate

3 Phosphoglycerate

2 Phosphoglycerate

Phosphoenolpyruvate
PEP carboxykinase
Oxaloacetate

Pyruvate Carboxylase and Biotin

Pyruvate

Fig 105: Gluconeogenesis

202
KREBS CYCLE

The Tricarboxylic Acid Cycle, the Citric Acid Cycle and the metabolic hub are other names for the
Krebs cycle. The Krebs cycle is located in the mitochondrial matrix that occurs under aerobic conditions.
The substrates for Krebs cycle are the breakdown products of carbohydrates, fats and protein metabolism.
The fuel used to drive this cycle is Acetyl CoA. The end product of carbohydrate breakdown is pyruvate
which is turned into Acetyl CoA. Each acetyl-CoA generated from pyruvate is used to produce 3 NADH, 1
FADH2,1 GTP and 2 CO2. Both the NADH and FADH2 deliver electrons to the Electron Transport Chain to
generate energy by the process of oxidative phosphorylation.

Starting point of Krebs Cycle

 Prior to the TCA cycle itself, a very important preliminary reaction occurs in which the two pyruvate
molecules from glycolysis are converted to acetyl groups, losing CO2
 The two acetyl groups are activated by attaching them to a carrier molecule known as Coenzyme
A, forming the compound acetyl CoA
 The enzyme complex responsible for this step is named pyruvate dehydrogenase complex and is
located in the mitochondria
 Next, the 2-carbon acetyl group from acetyl CoA is joined to a 4-carbon compound to produce a 6-
carbon compound
 A 6-carbon compound is much easier to oxidize than is a 2-carbon compound.
 The 6-carbon compound goes through a series of reactions, several of which are oxidation-
reduction reactions
 Two molecules of CO2 are lost from the 6-carbon compound, regenerating the 4-carbon compound.
Thus all six carbons of the original glucose molecule are converted to carbon dioxide, a waste
product of catabolism
 The oxygen molecules of the glucose molecule ultimately end up as a part of the carbon dioxide.
 NADH [a high-energy compound] is produced at this step

There are 8 steps in the Krebs cycle.

Mnemonic: Can I Keep Selling Sex For Money, Officer?

Citrate-Isocitrate-Ketoglutarate-Succinyl CoA-Succinate-Fumarate-Malate-Oxaloacetate
st
1 Step
 [Can] Citrate [a 6 carbon molecule] is formed when Oxaloacetate [a 4 Carbon molecule] is
combine with Acetyl CoA [a 2 Carbon molecule]
o Citrate Synthase is used to catalyze this reaction
nd
2 Step
 [I] Isocitrate is produced from Citrate
o This reaction is catalyzed by Aconitase
rd
3 Step
 [Keep] α-ketoglutarate is produced from Isocitrate
o Isocitrate dehydrogenase is used in this reaction
o This is the RATE LIMITING enzyme in the Krebs cycle
o One NADH is produced
o One molecule of CO2 is released

4th Step
 [Selling] Succinyl CoA is produced from α-ketoglutarate [Selling]
o α-ketoglutarate dehydrogenase catalyzes this reaction
o One NADH is produced
o One molecule of CO2 is released
th
5 Step
 [Sex] Succinate is produced from Succinyl CoA
o Succinate thiokinase (aka succinyl CoA synthetase) catalyzes this reaction
o 1 high-energy GTP is produced
o GTP can react with ADP to get ATP and GDP by transferring a phosphate group

203
 th
6 Step
 [For] Furmarate is produced from Succinate
o Succinate dehydrogenase catalyzes this reaction
 Succinate dehydrogenase is the only TCA cycle enzyme that is bound to the
mitochondrial membrane instead of being soluble in the mitochondrial matrix
 It is also the only TCA cycle enzyme that directly uses FAD. The FAD is a
covalently-bound prosthetic group.
o 1 FADH2 is produced
th
7 Step
 [Money] Malate is produced from Fumarate
o Fumarase catalyzes this reaction
th
8 Step
 [Officer] Oxaloacetate is produced from Malate
o Malate dehydrogenase is the catalyst for this reaction
o Oxaloacetate is added to Acetyl CoA to re-enter the cycle
o 1 NADH is produced at this stage

STEP Product Enzyme Activated by Inhibited by Energy Product

1 Citrate Citrate synthase ADP Citrate, NADH,
succinyl CoA
3 α-ketoglutarate Isocitrate ADP ATP, NADH NADH
dehydrogenase CO2 [No]
4 Succinyl CoA α-ketoglutarate ATP, NADH, NADH
dehydrogenase succinyl CoA CO2 [No]
5 Succinate Succinate thiokinase GTP [Go]
6 Fumarate Succinate Oxaloacetate FADH 2 [Find]
dehydrogenase
8 Oxaloacetate Malate dehydrogenase NADH [Nymph]

Table 12: Key enzymes in Krebs cycle

What is produced in the Krebs cycle?

 3 NADH, 1 FADH2, 1 GTP and 2 CO2 are produced.
 These high energy compounds enter the Electron Transport Chain through the process of
Oxidative Phosphorylation
 Since NADH and FADH2 cannot physically cross the mitochondrial membrane, the electrons must
be shuttled into the mitochondria by organ-specific shuttles, namely via the glycerol-3-phosphate
and malate-aspartate shuttles.

After entering the Electron Transport Chain which is located in the Inner Mitochondrial Membrane:
 each NADH produces 3 ATPs
 each FADH2 produced 2 ATPs
Each GTP is equivalent 1 ATP and does not go through the ETC.
Therefore each pyruvate molecule eventually yields 12 ATPs [3 NADH+H + 1 GTP + 1 FADH2 = 9 + 1 + 2 =
12]
2 molecules of pyruvate from 1 glucose molecule will yield 24 ATPs from the Krebs cycle.

Total Energy Production

Glucose [C6H12O6] 6CO2 + 6H2O
2 ATP [4 ATPs – 2 ATPs] 2 ATPs
2 NADH+H 6 ATPs
Pyruvate to Acetyl CoA [2 NADH+H] 6 ATPs
Acetyl CoA to Oxaloacetate 24 ATPs

Total 38 ATPs

NB. No ATP is actually produced in the Krebs cycle as the ATP is only released when NADH and FADH2
enters the Electron Transport Chain in the mitochondrion.

204
In addition to using carbohydrates, proteins and fat can enter the Krebs cycle. Here are the four points at
which proteins can enter [SOFA]:
 Succinyl CoA
 Oxaloacetate
 Fumarate
 α-ketoglutarate

There are two points at which fats can enter the Krebs cycle [AS]:
 α-ketoglutarate
 Succinyl CoA

C O2 + N A D H
PYRUV A T E A C E T Y L CoA
Pyruvate Dehydrogenase

Citrate synthase

1 CITRATE

8 OXALOACETATE Aconitase
Malate dehydrogenase 2 ISO C I T R A T E
NADH

7 MALATE M IT O C H ONDRION Isocitrate Dehydrogenase

F A D H2 C O2 + N A D H
Fumarase 3 α-K E T O G L U T A R A T E

6 FUM ARA T E G TP α-ketoglutarate dehydrogenase

C O2 + N A D H
4 SU C C I N Y L CoA
Succinate dehydrogenase Succinate Thiokinase
5 SU C C I N A T E

Fig 106: Krebs Cycle

Below is a diagram showing how the metabolic intermediates are all related:

Glucose

Glucose 6-pshospahate

Glycogen Pyruvate Ribose-5-Phosphate

Lactate Acetyl-CoA Alanine Oxaloacetate

Fatty Acids
HMG-CoA

Cholesterol Ketone Bodies

Fig 107: Common Metabolic Intermediates

205
ELECTRON TRANSPORT CHAIN

The Electron Transport Chain is located in the inner mitochondrial membrane [IMM] and uses a series of
carrier enzymes that pass electrons in a stepwise fashion from NADH and FADH2 to oxygen. The NADH
and FADH2 produced in the Krebs cycle are reduced in this process. The purpose of this process is to
liberate energy that can be used to make ATP. This is done by oxidizing NADH and FADH2 in a process
whereby five protein complexes [I, II, III, IV and V] are used to catalyze the oxidation reactions freeing up the
electrons. NADH produced in the cytosol by the process of glycolysis, cannot directly cross the
mitochondrial membrane. Therefore, the electrons are passed from the cytosol into the mitochondrial
electron transport chain by two systems, namely the malate-aspartate and the glycerol-3-phosphate
shuttles.

Malate-aspartate shuttle
 Cytosolic oxaloacetate is reduced to malate by NAHD
 Malate enters the mitochondrion carrying an electron
 It is oxidized to oxaloacetate regenerating NADH in the mitochondrial matrix
 Thus bringing the electron into the matrix
 Oxaloacetate cannot cross the mitochondrial membrane
 It has to be converted to aspartate
 This can now cross the mitochondrial membrane back into the cytosol where it is reconverted to
oxaloacetate

Glycerol-3-phosphate shuttle
 Cytosolic DiHydroAcetone Phosphate [DHAP] is reduced to glycerol-3-phosphate by NADH
 Glycerol-3-phosphate enters the mitochondrion and reacts with a Flavin Adenine Dinucleotide
[FAD]-linked dehydrogenase to enter the inner mitochondrial membrane
 This allows the electron to enter the matrix
 DHAP is regenerated from this and re-enters the cytosol
 The FADH2 generated gives up its electrons to Complex II

There are five key players in the Electron Transport Chain:

o Cytochromes which are proteins that contain iron
 the iron is part of an iron-porphyrin group called heme:
 there are three main types of cytochromes with slightly different hemes,
designated a, b, and c
 hemoglobin differs from cytochromes is the latter carries electrons, and the
former carries oxygen
 when participating in redox reactions, cytochromes undergo the same transition
as iron-sulfur groups, with the iron picking up one electron
o Iron-sulfur proteins which participate in redox reaction:
 by using iron-sulfur groups, with the sulfur being either inorganic sulfur atoms
and/or sulfur atoms of Cysteine in the protein
 each iron participates in redox and carries one electron
o Flavin-linked dehydrogenases which use FAD or FMN
 These groups generally function as prosthetic groups that are tightly bound,
sometimes covalently, to the enzyme
 FAD and FMN actually have three oxidation states
 They may carry one or two hydrogens, although carrying two is more common
 This flexibility allows FAD and FMN to pick up one hydrogen at a time
o Pyridine-linked dehydrogenases which use NAD+ or NADP+
 These are pyridine derivatives
 NAD+ and NADP+ usually function as coenzymes that associate with the
enzyme temporarily
 They remove two hydrogens from the substrate:
 one in the form of hydride ion which attaches to the NADP +
 one in the form of a proton which is released into the medium.
o Quinones which are small organic molecules, not proteins:
 they also can participate in biochemical redox reaction
 Ubiquinone, also called Coenzyme Q, is a component of the ETC
 Coenzyme Q is lipid-soluble, with three oxidation states that can carry one or
two hydrogens, picking up one at a time

206
There are 5 complexes in the process of oxidative phosphorylation.
The first four complexes [I-IV] are involved in the transfer of electrons.
They are located in the inner mitochondrial membrane [IMM]
The last complex [ATP synthase] is where oxidative phosphorylation occurs and ATP is generated.
 Complex I: NADH dehydrogenase complex with Coenzyme Q
o The first component of the ETC through which most excess electrons are funneled
o The hydrogen ions pass from the incoming NADH to FMN and then to Iron sulfur centers
+ +
o In this step, a hydride ion H passes to FMN which then picks up an additional H from the
surrounding aqueous medium
o As a result, NADH is oxidized to NAD and FMN is reduced to FMNH2 which enters the
next stage
 Complex II: Succinate dehydrogenase complex with Coenzyme Q
o The FADH2 formed in the TCA cycle enters the ETC
o This FADH2 is oxidized by passing its hydrogens to the iron sulfur groups, which in turn
pass the excess electrons to Coenzyme Q
+
o Coenzyme Q then picks up an additional H ion from the surrounding aqueous medium
o The reduced form of Coenzyme Q, produced by reaction with Complex I and Complex II,
is very lipid soluble and easily diffuses within the inner mitochondrial membrane to the
next ETC component
 Complex III: Cytochrome reductase or Cytochrome c complex with Coenzyme Q
o This complex removes in a stepwise fashion two electrons from CoQH2 at the QO site and
sequentially transfers them to two molecules of cytochrome c, a water-soluble electron
carrier located within the intermembrane space. The two other electrons are sequentially
passed across the protein to the Qi site where quinone is reduced to quinol
 Complex IV: Cytochrome c oxidase
o Cytochromes, iron-sulfur clusters and copper atoms designated CuA and CuB located
between Coenzyme Q and Oxygen
o The electrons are passed successively from Cytochrome c to CuA, which undergoes a
Cu2+---> Cu+ transition
o The copper passes the electron to Cytochrome a, which in turn passes the electron to Cu B
o A second electron passing through Complex IV also is picked up first by CuA, then by
Cytochrome a, and then finally ends up on Cytochrome a3
 Complex V: ATP synthase
o This is the final step in the process of the electron transport chain
+
o The oxygen molecule picks up 2 H from the surrounding medium to make H2O
o This is the only point in which oxygen is consumed and ATP is actually generated
o Oxygen is the electron acceptor

In summary, there are 2 drop-off points in the Electron Transport Chain:

 NADH at Complex I
 FADH2 at Complex II
+ + + +
H H H 3H

CoQ Cyt
Complex Complex C Complex Complex IMM
I III IV V
Complex
II
NADH NAD ½ O2 H2 O ADP + Pi ATP + H2O
+
2H
FADH2 FAD Matrix
+ +
2H 3H
Figure 108: Electron Transport Chain

NADH gives up its electrons and produces 3 ATPs

FADH2 gives up its electrons and produces 2 ATPs

Cytochromes
 They are heme [iron]-containing compounds that receive electrons from CoQH2
 The reduced oxygen produced is used to form H2O and is catalyzed by ATP Synthase
 Copper is also important in the Electron Transport Chain
 Cyanide and Carbon Monoxide inhibit Cyctochrome C oxidase in the Electron Transport Chain

207
CORI CYCLE

This is a metabolic pathway that is used to prevent lactic acid produced by anaerobic glycolysis from
building up in the muscle. This cycle occurs in the liver and is also known as the Lactic Acid Cycle.
 During fasting or exercise, lactate from RBCs or skeletal muscle is sent to the liver to make
glucose that can be returned to the RBCs or muscle
 Pyruvic acid is reduced to lactic acid by lactate dehydrogenase, which removes the protons
from the NADH that were created during glycolysis and transfers them to pyruvic acid, creating
lactic acid
 This occurs in order to maintain a concentration of NAD+ that can be reduced during glycolysis
 Lactic acid goes to the liver where it is converted back to pyruvic acid and then to glucose
through gluconeogenesis
 Glucose then re-enters the blood and returns to the muscles to be used for energy
 It provides quick ATP production during anerobic glycolysis in the muscle and red blood cells
 If muscle activity has ceased, then the glucose is converted back into muscle glycogen to be stored
for future use
 The Cori cycle is an energy consuming pathway as it uses up 4 molecules of ATP making the
cycle unable to be sustained on a continuous basis

PENTOSE PHOSPHATE PATHWAY

The other names for this pathway are the Hexose Monophosphate Shunt and Phosphogluconate
Oxidative Pathway. This pathway occurs in the cytosol. There are two distinct phases in the pathway.
The first is the oxidative phase, in which NADPH is generated. The second phase is the non-oxidative
synthesis of 5-carbon sugars like ribose. Ribose is used in DNA and RNA synthesis.

The purpose is to produce NADPH which is required for the following:

 fatty acid synthesis
 detoxification
 protection from free radicals

The Pentose Phosphate Pathway takes place in the cytosol:

 The rate limiting enzyme in this pathway is Glucose 6-Phosphate dehydrogenase [G6P]
 2 NADPH per Glucose 6-Phosphate are produced in this pathway
 There is no net gain or loss of ATP in this pathway
G lucose 6-Phosphate
N A DP
Glucose 6-Phosphate Dehydrogenase (Oxidative Phase)
N A DP H Rate L imiting Step

6-Phosphogluconolactone
H2O
Gluconolactonase (Oxidative Phase)
H+
6-Phosphogluconate
N A DP

N A DP H 6-Phosphogluconate dehydrogenase (Oxidative Phase)

C O2

Ribulose 5-Phosphate

Phoshopentose isomerase
(Non-Oxidative Phase)

Ribose 5-phosphate Nucleotide synthesis

Fig 109: Pentose Phosphate Pathway

208
GLYCOGEN METABOLISM

Glycogen storage occurs primarily in skeletal muscle and in the liver. Both glycogen synthesis and
breakdown take place in the cytosol. Glycogen is a branched polymer of glucose which can be used
during hypoglycemia or muscle contraction. Synthesis of glycogen [glycogenesis] is mediated by
glycogen synthase while its breakdown [glycogenolysis] is facilitated by glycogen phosphorylase.
Branching of the glycogen polymer occurs via a branching enzyme which breaks an α-1-4 bond and
transfers a block of glucosyl residues to create a new α-1,6 bond.

GLYCOGENESIS:
Process of glycogen synthesis in which glucose molecules are added to chains of glycogen for
storage in the liver and skeletal muscle

The initial step in glycogen synthesis is initiated by the enzyme glycogen synthase:
 rate limiting step
 used to lengthen the glycogen chain
 catalyzes the attachment of UDP-glucose to Glycogenin
 Glycogenin is a protein which serves as the site at which the initial glucose unit is attached
The glucose units are linked by glycosidic bonds:
 these are chemical bonds between glucose molecules
 the main backbone is made up of 1-4 links
 the branches are 1-6 links
Glycogenesis Control and Regulation:
 is activated by insulin response to high glucose levels
 is inhibited by epinephrine (epinephrine release signals a need for glycogen breakdown not
synthesis) and glucagon

Advantages of many reducing ends:

 increases the rate of synthesis
 increases the rate of degradation
 increased solubility

G L U C OSE

Glucokinase/Hexokinase

G lucose 6-Phosphate

Phosphoglucomutase

G lucose 1-phosphate

UDP-Glucose Pyrophosphorylase

UPD-G lucose
G lycogenin
(a small protein that forms the primer) Glycogen synthase
Rate limiting E nzyme

G lycogenin-(α-1,4) – glucose G lycogen

G lucosyl (4:6) transferase facilitates the branching

Fig 110: Glycogen Synthesis

209
GLYCOGENOLYSIS

This is the process of breaking down glycogen into glucose unit.

The major degradation enzyme is:
 Glycogen phosphorylase A and B
o RATE LIMITING enzyme
o Releases glucose from glycogen stores
o Occurs in the heart, liver and muscle
 activated by phosphorylation
 inhibited by dephosphorylation
 Three steps involved:
o Step One:
 cleaves the bond at the 1 position by substitution of a phosphoryl group
 breaks down glucose polymer at alpha 1-4 linkages until 5 linked glucoses are
left on the branch by the action of a phosphorylase
o Step Two:
 involves the debranching enzyme that moves the remaining glucose units to
another non-reducing end
 the final action of the debranching enzyme leads to the original glucose 1-P
connected to 1, 4 to another branch being releases
o Step Three:
 converts G1P to G6P through the enzyme phosphoglucomutase

Hormonal regulation of glycogenolysis:

 involves cyclic AMP
 stimulated by glucagon and epinephrine
 inhibited by insulin

Role of cAMP
 Cyclic AMP (cAMP) act as a secondary messenger
 It is synthesized from ATP by the action of adenylyl cyclase
 cAMP activates phosphorylase kinase
 This in turn activates glycogen phosphorylase
 cAMP inhibits glycogen synthase
 It also regulates the passage of calcium through ionic channels
 It is also used for intracellular singal transduction such as transferring the effects of glucagon and
epinephrine which cannot pass through cell membranes

210
FAT METABOLISM

Lipids in the form of triacylglycerols [aka triglycerides] are a major component [90%] of our diet and
are an important calorie source as it stores a large amount of energy. While metabolism of carbohydrates
and proteins produce between 4 to 5 kcal/g, metabolism of triacylglycerols produces 9 kcal/g. The
remainder of dietary lipids consists of cholesterol, phospholipids and free fatty acids. Triglyceride digestion
begins in the small intestine by the action of lipase which hydrolyzes the ester bonds between fatty acids
and glycerol. Lipase is produced in the pancreas and works best in water. The products produced by lipase
are:
 monoacylglyerol
 2 fatty acids
o fatty acid:
 end product of fat digestion
 a carbon chain with a carboxyl group at one end
 carboxyl group:
 this is a group consisting of carbon with oxygen and an
attached hydroxyl [-COOH] group

These are absorbed by the enterocytes. Some are transported to the liver via the portal vein while others
are re-esterified [an ester bond links fatty acids and glycerol] and combined with protein to form
lipoproteins. Chylomicrons are absorbed by the central lacteals in the villi of the small intestine and are
transported via the thoracic duct. There are five main types of lipoproteins depending on their density:
 HDL[High Density Lipoproteins]-Happy Cholesterol; cis form; double bonds
 IDL[ Intermediate Density Lipoprotein]- Bad Cholesterol; similar to LDL
 LDL [Low Density Lipoproteins]-Lethal Cholesterol; trans form
 VLDL[Very Low Density Lipoproteins]-Transports triglycerides from liver to tissues
 Chylomicrons-are large lipoprotein particles; they transport dietary lipids from the intestine to other
locations in the body

Function of fatty acids

Fats are stored as triacylglycerols in adipose tissue and in the liver. In order for energy to be released,
the triacylglycerols must be broken down once again by a lipase enzyme which catalyzes the hydrolysis of
the molecule into glycerol and fatty acids. There are four main types of fatty acids:
 saturated versus unsaturated and essential versus non-essential

Saturated fatty acid

 a saturated fatty acid is one with no double bond between the carbon atoms
 thus they are fully “saturated” with hydrogen atoms
 examples include:
o Palmitic acid [contains 16 carbon atoms]
o Stearic acid [contains 18 carbon atoms]
o Arachidic acid [contains 20 carbon atoms]

Unsaturated fatty acid

 this is a fatty acid with one [mono] or more [poly] double bonds between the carbon atoms
 unsaturated fatty acids can be classified according to the location of the closest double bond to
the methyl end of the carbon chain furthest from the carboxyl group
 this is done by specifying an omega number for the fatty acid
 for example, Omega-3 or Omega-6

Essential fatty acids

 those that are not made by the body and must be consumed in the food we eat
 linoleic acid is an omega-6 fatty acid with 18 carbon atoms
 linolenic acid is an omega-3 fatty acid with 18 carbon atoms

Non-essential fatty acids

 those that can be manufactured in the body
 arachidonic acid is an unsaturated fatty acid with 20 carbon atoms
o It is made from linoleic acid
o arachidonic acid becomes an essential fatty acid when linolenic acid is absent
from the diet

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Fatty acids are use to make cholesterol from which are made:
 Bile acids
 Cell membranes
 Hormones
 Prostaglandins
 Vitamin D

LIPOLYSIS OF FATTY ACIDS

The breakdown of fatty acids occurs in the mitochondria of adipocytes and its purpose is to produce
acetyl CoA which enters the Krebs cycle where it can be used to produce energy.
This process occurs in three steps:
 activation:
o fatty acid is converted to a coenzyme derivative
o this occurs on the outer surface of the mitochondria
o it is catalyzed by Fatty Acyl-CoA synthetase
 transport:
o a transport protein carries the Acyl-CoA fatty acid derivative across the mitochondrial
membrane into the matrix where it can be oxidized
o this is done by a special carnitine carrier system
o carnitine drives the fatty acids into the mitochondrial matrix
o once activated, the Acyl CoA is transported in the mitochondria matrix via three steps:
 Acyl CoA is conjugated to carnitine by carnitine acyltransferase (palmitoyl
transferase)
 this enzyme is located on the outer mitochondrial membrane
 Acyl carnitine is shuttled inside by translocase
 Acyl carnitine is converted to Acyl CoA by carnitine acyltransferase
 this enzyme is located on the inner mitochondrial membrane
 the liberated carnitine returns to the cytosol
 beta oxidation:
o once on the inside of the mitochondria of hepatocytes, the molecule is oxidized
o the acyl-fatty acid derivative is shortened two carbons at a time
o e.g. if a 18 Carbon fatty acid were used, there will eventually be 9 two carbon fragments
o beta oxidation is a four step process: [reduced hydration reduces cleavage]
 reduction using FAD hydration
 hydration
 reduction using NAD
 cleavage
o Acetone, acetoacetate and β-hydroxybutyrate are ketone body byproducts
o Acetoacetate and β-hydroxybutyrate are converted to Acetyl CoA which enters the TCA
o NADH and FADH2 are made and sent directly to the Electron Transport Chain

Regulation enzyme
 Hormone-sensitive lipase
 Malonyl-CoA can prevent Acyl-CoA derivatives from entering the mitochondria by inhibiting
carnitine acyltransferase, therefore inhibiting beta oxidation
 High citrate levels inhibit beta oxidation

Ketone body synthesis

 30 minutes after sustained exercise, all the glycogen stores are used up and fat is then used
 Ketone body synthesis occurs in the mitochondria of hepatocytes when fatty acids are in high
concentration in the blood [during fasting, starvation or uncontrolled diabetes mellitus]
 β-oxidation produces NADH and results in the accumulation of acetyl CoA
 Two molecules of acetyl CoA condense to form acetoacetyl CoA which is catalyzed by thiolase.
 Acetoacetyl CoA and acetyl CoA combine to form Hydroxymethylglutaryl CoA [HMG CoA] which
is then split to form acetyl CoA and acetoacetate
 The acetoacetate is converted into acetone and -hydroxybutyrate
 The acetone is excreted in the breath and causes the fruity breath in diabetic ketoacidosis
 Acetoacetate and -hydroxybutyrate pass into the blood and are converted into acetyl CoA
 Acetyl CoA is taken up by the Krebs cycle in the muscle, kidney and brain and is used to produce
energy

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LIPOGENESIS

Lipogenesis is the process of building up fatty acids de novo.

 Excess glucose in the diet is first converted to glycogen which is stored in the liver and muscle
 After these stores are saturated, the excess glucose is converted to acetyl CoA which in turn
converted to Malonyl CoA which in turn is used to make fatty acids
 The fatty acids are combined with glycerol to make triglycerides which are stored in adipose
cells in the body
 This process is stimulated by insulin and ATP
 This explains the increased weight gain in patients with Type 2 diabetes in which there is insulin
receptor insensitivity resulting in increased levels of insulin
 Lipogenesis is inhibited by glucagon and epinephrine

This process is located in the cytoplasm of cells in the liver, adipose tissue and kidney. It uses the
following start up substrates [big MAC]:
 Malonyl CoA
 Acetyl CoA (the ultimate precursor-primary substrate)
 Citrate (required for the activation of the synthesis pathway)
Acetyl CoA carboxylase converts Acetyl CoA to Malonyl CoA and is the RATE LIMITING enzyme in
lipogenesis. This process also has 4 steps: [Condensation Reduces Dehydration even Further]
 Condensation
 Reduction of NADPH
 Dehydration
 Further reduction

STEROID HORMONE PRODUCTION

Steroid hormones are produced from cholesterol in gonads and adrenal glands. Only 20% of the
cholesterol in our body actually comes from the diet. The rest is made by the liver from excess
carbohydrates. Cholesterol is made from Acetyl CoA mainly in the liver, although some is synthesized in
the adrenal cortex and reproductive tissues:
 first two acetyl CoA molecules condense to form acetoacetyl CoA
 a third molecule of acetyl CoA is added and HMG CoA is produced
 HMG CoA is reduced to mevalonic acid by HMG CoA reductase
 through a series of steps mevalonic acid is converted into squalene
 squalene is converted into lanosterol
 lanosterol is converted into cholesterol

HMG CoA reductase

 Rate limiting step in cholesterol synthesis
 Anchored to the membrane of the endoplasmic reticulum
 it converts HMG CoA to mevalonate
 this enzyme is the target of widely available cholesterol-lowering drugs known as statins

Sequence of events in steroid hormones

 Cholesterol is converted to pregnenolone
o this step is controlled by desmolase which is the rate-limiting step
 Pregnenolone is converted to progesterone
 Progesterone is then converted to:
o Cortisol
o Aldosterone
o Dehydroepiandrosterone
o Androstenedione
 DHEA is converted to Androstenedione
 Androstenedione is converted to testosterone
 Testosterone is converted to estradiol by an aromatase enzyme
 Estradiol is the predominant active form of estrogen

213
PROTEIN METABOLISM

Proteins are large organic molecules made up of long twisted chains of amino acids. Proteins are the
building blocks of life. There are more than 100,000 different protein molecules in the body and all of
these diverse chemicals are built on only 20 amino acids. An amino acid is a compound characterized by
the presence of an amine [NH2] and a carboxyl group [COOH] on the first [alpha] carbon atom. There are
10 essential and 10 non-essential amino acids. An essential amino acid is one that cannot be
synthesized by the body. The non-essential amino acids are manufactured in the liver.
The essential amino acids are [PVT TIM HALL]:
 Phenylalanine Tyrosine L-Dopa Dopamine Norepinephrine Epinephrine
 Valine
 Threonine
 Tryptophan Serotonin Melatonin
 Isoleucine
 Methionine
 Histidine [essential only during periods of growth and pregnancy] Histamine
 Arginine [essential only during periods of growth and pregnancy] Creatinine and Nitric oxide
 Leucine
 Lysine

The rest are non-essential amino acids [PT GAGA GAS C]:
 Proline
 Tyrosine is also used to manufacture thyroxin [T4]
 Glycine Porphyrin Heme
 Alanine
 Glutamine
 Aspartate
 Glutamate GABA and Glutathione
 Asparagine
 Serine
 Cysteine
Some amino acids are derived from intermediates of glycolysis namely:
 Glycine is made from serine
 Alanine is made from the transamination of pyruvate
 Serine is made from 3-phosphoglycerate
 Cysteine is made from serine
Other amino acids are derived from the TCA cycle or its intermediates namely:
 Glutamate is derived from α-ketoglutarate
 Aspartate is derived from the transamination of oxaloacetate
 Glutamine is derived from glutamate
 Asparagine is produced from aspartate
 Proline is derived from glutamate
 Arginine is derived from glutamine

Protein structure
Proteins are made in the ribosomes where the genetic code is decoded via strands of mRNA. The shape
of a protein develops in stages or structures:
 primary structure
o linear sequencing of amino acids forming a polypeptide chain
 secondary structure
o the secondary structure is formed as the protein begins to twist in accordance with the
chemical forces within the primary linear structure
o this occurs in one of two forms:
 α-helix [left-handed coil]
 β-pleated sheets [folded back on itself in pleats]
o the end product is a 3-D structure stabilized by hydrogen bonds
 tertiary structure
o this controls the overall three-dimensional shape of a single protein molecule
o it is the spatial relationship of the secondary structures to one another
o the twisted or pleated secondary form is folded on itself
o tertiary structure controls the basic function of the protein

214
  quaternary structure
o refers to the spatial arrangement of subunits in a protein containing two or more
polypeptide chains; each polypeptide chain is known as a subunit
o for example hemoglobin which is made up of 2α and 2β subunits.

Degradation of amino acid

 there are two major groups of amino acids depending on their degradation products:
 glucogenic [4]
 ketogenic [2]
 both [3]
 four essential amino acids are glucogenic as they produce pyruvate and other intermediates in
the Krebs cycle which could be used to produce new glucose [gluconeogenesis]
 Histidine, Methionine, Threonine and Valine [His Majesty’s TV]
 two essential amino acids are ketogenic as they produce ketone bodies such as acetyl CoA and
acetoacetate which can be used an alternative source in starvation or in diabetes mellitus:
 Lysine and Leucine
 three essential amino acids are both ketogenic and glucogenic: [they belong in a separate PIT]
 Phenylalanine, Isoleucine, Tryptophan
 All of the non-essential amino acids are glucogenic except Tyrosine which is ketogenic

Ways of nitrogen removal

When proteins are broken down, nitrogen is released and is removed by the following manner:
 transamination
 transfer of NH2 from one molecule to another
 enzyme involved is transaminase or aminotransferase
 deamination
 deamination occur in the liver
 it is the process by which amino acids are broken down when too much protein has been
taken in:
 the amino group is removed from the amino acid and converted to ammonia
 removal of the amine [NH2] group:
 deamination of glutamate produces α-ketoglutarate
 deamination of aspartate produces oxaloacetate
 deamination of alanine and serine produces pyruvate
 ammonia formation
 hydrogen is added to the NH2 group to form ammonia [NH3]
 urea formation
 changes the toxic ammonia into the non-toxic urea [(NH2)2C=O] which is excreted in the
urine

Urea cycle
 Ammonia is toxic especially to the central nervous system and must be removed from the body
 the cycle produces urea (NH2)2C=O from ammonia (NH3), aspartate and CO2
 the main sources of nitrogen atoms are Glutamate and Alanine which are degraded to ammonia.
 ammonia enters the Urea cycle which consists of 5 steps
 the first two steps occur in the mitochondrion
 the other three in the cytosol
 Step 1: Ammonia is converted to Carbamoyl Phosphate
 Step 2: Carbamoyl Phosphate reacts with Ornithine to form Citrulline
 Step 3: Citrulline passes out into the cytosol where it is combined with Aspartate to form
Arginonosuccinate
 Step 4: Arginosuccinate is split to form Fumarate and Arginine
 Step 5: Arginine is cleaved to form Ornithine and Urea
 Ornithine is transported back into the mitochondrion where it could be used for another round
of the cycle and urea is excreted in the urine
st
 the key RATE LIMITING enzyme in the urea cycle is the 1 step:
 Carbamoyl Phosphate Synthase which converts NH3 to Carbamoyl Phosphate

Mnemonic: Ordinarily Careless Crappers Are Also Frivolous About Urination

Ornithine+Carbamoyl phosphate=Citrulline+Aspartate=Argininosuccinate Fumarate & Arginine Urea

215
NUCLEOTIDE AND NUCLEOSIDE METABOLISM

Nucleotides and nucleosides are two important classes of molecules in the body.
Nucleotides are composed of three subunits:
 Pentose sugar: either ribose [for use in making RNA] or deoxyribose [for making DNA]
 Nitrogen base: either purine or pyrimidine
 Phosphate group
Nucleosides are composed of only two subunits:
 pentose sugar
 nitrogenous base
The first major role of nucleotides is in the formation of energy-rich compounds like ATP [adenosine
triphosphate], GTP [guanosine triphosphate] and UTP [uridine triphosphate]. Nucleotides are built from
molecules called pyrimidine or purine bases.

Pyrimidine bases are used to CUt The Py:

 Cytosine
 Uracil
 Thymine
Purine [pure uric acid] bases are Pure As Gold:
 Adenine
 Guanine
The genetic code for specific amino acids is encoded in the sequencing of 3 base pairs called a codon.
The base pairs are:
 Cytosine and Guanine (contains 3 hydrogen bonds between them) for DNA and RNA
 Adenine and Thymine (contains 2 hydrogen bonds between them) for DNA
 Adenine and Uracil (contains 2 hydrogen bonds between them) for RNA
All Tall Cute Girls Dance for DNA.
All University Girls Come Running for RNA.

DNA synthesis
 DNA is made up of two polynucleotide chains joined by hydrogen bonds
 Deoxyribose is the sugar base on which the base pairs are attached.
 Adenine is paired with Thymine and Guanine is paired with Cytosine
 The two strands are twisted to form a double helix
 DNA is synthesized by replication
 Replication is both bidirectional [begins at a site of origin and simultaneously moves out in both
directions from this point] and semiconservative [after replication, each daughter molecule of DNA
contains an intact parental strand and one newly synthesized strand joined by base pairs]
 The parental double strands separates and the helix unwinds ahead of a replication site\
 DNA polymerases catalyze the synthesis of DNA and RNA serves as the primer for DNA
polymerase. ATP, CTP, GTP and TTP serve as precursors.

RNA synthesis
 RNA is different from DNA in that RNA contains the sugar ribose instead of the deoxyribose in
DNA, uracil replaces thymine and RNA is a single strand compared to the double strands in DNA
 RNA existed in three forms: mRNA [messenger], rRNA [ribosomal] and tRNA [transfer]
 RNA is synthesized through a process called transcription
 This is initiated by an RNA polymerase which does not require a primer like in DNA
 Transcription involves a DNA template. ATP, CTP, GTP and UTP which serve as precursors

Protein synthesis
 mRNA moves out of the nucleus into the cytoplasm where it will carry the code to the ribosome
 tRNA brings amino acids to the rRNA in the ribosomes on the rough endoplasmic reticulum in the
correct sequence in order to make the particular protein
 Transcription of RNA comes before translation into protein [C before L in the alphabet]

Breakdown of DNA and RNA

 Cell death results in the release of DNA and RNA producing xanthine
 Xanthine is converted by xanthine oxidase into uric acid
 Excess uric acid production results in gout

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VITAMINS AND MINERALS

Vitamins are vital nutrients that serve as coenzymes or cofactors. Vitamins may be classified as water
soluble or fat soluble. Vitamins D, A, K and E are fat-soluble and Vitamins B and C are water soluble.
The antioxidants are A, C and E plus the mineral Selenium [ACES].

Vitamin A includes the compounds retinal, retinol, and many carotenoids which are found in:
 liver
 dark green leafy vegetables
 yellow-orange fruits and vegetables
 meat, fish and poultry
Retinal is used to make rhodopsin and helps in the differentiation of epithelial tissue.
The active form of Vitamin A is retinoic acid.
A deficiency in Vitamin A results in:
 nyctalopia
o night blindness
 xerophthalmia
o dry eye
 Bitot’s spots
o build-up of keratin debris in small opaque plaques in the conjunctiva
 phrenoderma
o dry bumpy skin
o due to follicular plugging

Vitamin D is essential for calcium uptake from the gut and resorption from the kidney.
It is much more than a vitamin and should be considered as a prohormone as it affects many tissues.
Vitamin D is found in:
 eggs, fatty fish like salmon, tuna and sardines
 It is also produced in the skin by exposure to sunlight
The active form of Vitamin D is 1, 25, dihydroxycholecalciferol [Vit D3] and is located in the kidney.
Vitamin D deficiency results in:
 rickets in children
o soft bones that bend-bow legs
o rachitic rosary [swollen costochondral joints] in the chest
 osteomalacia in adults and the elderly
o soft demineralized bones in adults
o pseudofractures called Looser zones

Vitamin K catalyzes carboxylation of glutamatic acid residues in making clotting factors II, VII, IX and X.
Vitamin K is found in:
 green leafy vegetables
 liver
It is also produced by the bacterial flora in the large intestine.
Vitamin K deficiency results in:
 Hemorrhagic disease of the newborn
o prolonged bleeding from the umbilicus in the newborn and may lead to kernicterus
o kernicterus is brain damage by high levels of bilirubin from excess RBC destruction

Vitamin E [tocopherol] is an antioxidant which protects erythrocytes and membranes from free radical
damage.
Vitamin E is found in:
 vegetable oils like soy bean, corn, sunflower, almonds and hazel nuts
 wheat germ
A deficiency will cause:
 red blood cells are fragile which leads to hemolytic anemia:
o due to the premature destruction of the fragile red blood cells
o this will present with:
 fatigue, malaise and muscle weakness
 shortness of breath
 pale mucous membranes

217
Vitamin B1 [Thiamine] is a cofactor in pyruvate kinase and α-ketoglutarate dehydrogenase.
Thiamine is found in:
 brewer’s yeast
 milk
 liver
 beans and nuts
Thiamine deficiency can occur in alcoholics and in fad diets and may present as:
 dry beriberi:
o dermatitis and peripheral neuritis with numbness in the extremities
 wet beriberi:
o tachycardia, warm skin, edema and high-output heart failure
 Wernicke-Korsakoff syndrome:
o Confabulation [telling lies]
o Apathy
o Loss of memory
o Muscle weakness

Vitamin B2 [Riboflavin] is a cofactor for FMN and FAD in the mitochondrial ETC and redox reactions.
Riboflavin is found in:
 milk and dairy products
 collard greens
 liver
 meat, fish and poultry
Lack of riboflavin is called ariboflavinosis and may present with:
 dermatitis
 angular stomatitis [cheilosis]

Vitamin B3 [Niacin] is a precursor for NAD and NADP in the mitochondrial Electron Transport Chain.
It is essential in glycolysis and is paired with Magnesium.
Niacin is found in:
 eggs
 milk
 meat
 legumes
It is also formed in the body from dietary tryptophan.
Niacin deficiency may present with:
 pellagra
o dermatitis [with Casal’s necklace]
 Casal’s necklace:
 flaky scaly dermatitis
 in the sun exposed skin in the shape of a V below the neck
o diarrhea
o dementia
o death

Vitamin B5 [Pantothenic acid] is an acyl carrier and is an essential component of Coenzyme A.

Pantothenic acid is found in:
 yogurt
 lentils
 eggs
 avocados
Vitamin B5 deficiency is very uncommon and may be associated with:
 fatigue
 irritability
 burning feet syndrome

Vitamin B6 [Pyridoxine] is a cofactor for several transamination and decarboxylation reactions.

Pyridoxine is found in:
 meats
 cereal grains and nuts
 bananas

218
Pyridoxine deficiency will cause:
 glossitis [burning tongue]
 neuropathy [burning pain in the extremities]

Vitamin B7 [Biotin] is used in carboxylation reactions such as the one that converts oxaloacetate to
phosphoenolpyruvate. It also plays a part in the production of fatty acids and the metabolism of fats and
amino acids.
Biotin is found in:
 royal jelly
 brewer’s yeast
 legumes
 beans
 liver
 meat and poultry
 egg yolk
Avidin found in raw eggs avidly binds to biotin prevents its absorption and will cause a deficiency which
will present with:
 dermatitis
 fatigue
 depression
 alopecia [hair loss]
 lactic acidosis

Vitamin B9 [Folic acid] is used in the transfer of 1-Carbon units in DNA and RNA synthesis, to make
methionine and purines necessary for DNA synthesis and for the transfer of methyl groups.
Folic acid is found in:
 liver
 green leafy vegetables
 legumes
 cauliflower
 sweet potato
 citrus fruits
Folic Acid deficiency is seen in pregnant womrn and alcoholics and causes:
 megaloblastic anemia
o low hemoglobin with fatigue
 neural tube defects but no spinal cord damage [which distinguishes it from Vitamin B12 deficiency]
o spina bifida-failure of closure of the posterior neuropore

Vitamin B12 [Cobalamin] is a cofactor for methionine and succinyl CoA manufacture.
Source:
 meat
 dairy products
 eggs
Vitamin B12 deficiency:
 may be due to lack of intrinsic factor associated with atrophic gastritis
 lack of food containing vitamin B12:
 decreased vitamin B12 absorption in the terminal ileum:
o Crohn’s disease
o infestation with Diphyllobothrium latum
 may cause the following:
o megaloblastic [macrocytic] anemia
o if the deficiency is due to a lack of intrinsic factor, this is known as pernicious anemia
 sub-acute combined degeneration of the spinal cord

Vitamin C [Ascorbic acid] is a cofactor in hydroxylation of proline and lysine in the synthesis of
collagen. It also facilitates iron absorption from the gut by keeping it in the reduced state which is more
absorbable.
Vitamin C is found in:
 citrus and other fruit like strawberries and cherries
 peppers
 cauliflower and broccoli

219
Vitamin C also enhances the absorption of iron from the gastrointestinal tract.
Vitamin C deficiency results in scurvy which presents with:
 sore, bleeding swollen gums
 loose teeth
 poor wound healing

Minerals
Certain minerals are essential for health. These following are necessary for certain biochemical pathways in
the body:
 iron
 copper
 zinc
 selenium
 iodine
 calcium
 magnesium

Mineral Source Biochemical Function Deficiency

Iron Dark green leafy Essential component in the Defective hemoglobin
vegetables formation of hemoglobin and production resulting in a
Red meat-most myoglobin hypochromic, macrocytic
absorbable Used in the Electron Transport anemia
Beans Chain
Wheat germ
Egg yolks
Copper Prunes Component of many oxidases in Muscle weakness
Yeast the Electron Transport Chain Abnormal collagen cross
Black pepper [oxidative phosphorylation] linking
Cocoa Necessary in the manufacture of Microcytic anemia
neurotransmitters and of collagen
Zinc Meats Component of many oxidase Growth retardation
Eggs enzymes Impaired wound healing
Seafood Cofactor of carbonic anhydrase Hypogonadism
Whole grain Cell-mediated immunity Alopecia
Selenium Brazil nuts Component of glutathione Cardiomyopathy
Tuna peroxidase which is an antioxidant [Kenshan’s disease]
Meats that protects the cells from
Eggs oxidative [free radicals] damage
Cereal
Iodine Seafood Essential in the synthesis of Cretinism in children
Iodized salt thyroid hormones Myxedema in adults
Calcium Dairy products Essential in the formation of Paresthesia
Fish with bones-salmon bones and teeth Muscle cramps
and sardines Essential for normal nerve and Tetany
Collard greens muscle function Bone fracture
Essential in blood clotting Osteoporosis
Magnesium Dairy products Binds to the active sites of many Paresthesia
Grains enzymes Muscle cramps
Nuts Forms complexes with ATP Tetany
Seizures if prolonged
Chromium Oysters Glucose transport into cells Impaired binding of
Whole grain cereals Helps insulin to bind to the cells insulin to cells resulting
Liver in impaired glucose
Potatoes tolerance

Table 13: Minerals: Sources, Functions and Deficiencies

220
METABOLIC PATHWAY SUMMARY TABLE

PATHWAY FUNCTION LOCATION SUBSTRATES PRODUCTS VITAMINS

Glycolysis Breaks down Cytoplasm Glucose 2 Pyruvate,

sugar for the 2 ATP and
Krebs cycle 2 NADH
PPP [HMP shunt] Shunts Glucose- Cytoplasm Glucose-6- Ribulose-5- Thiamine
6-Phosphate to phosphate phosphate,
form Ribulose-5- NADPH2
Phosphate for and CO2
nucleotide
formation
AND the
regeneration of
NADPH
Cori cycle Prevents lactic Shuttles Lactate Glucose and
acid lactate from Uses 6 ATP 2 ATP
accumulation in muscle to liver
muscle
Glycogenesis Maintains Cytoplasm of Glucose Glycogen
glucose muscle and
homeostasis liver
Glycogenolysis Maintains Cytoplasm of Glycogenesis Glucose
glucose heart, muscle
homeostasis and liver
Fatty acid Produces acetyl Mitochondria Fatty acids NADH, Niacin
oxidation CoA FADH2, Riboflavin
acetyl CoA Biotin
and ketone
bodies
Electron Move high- Mitochondria NADH, FADH2 ATP and H2O Riboflavin
Transfer Chain energy electrons with O2 acting as Niacin
from NADH and the last electron
FADH2 to ATP acceptor
Krebs cycle Produce high- Mitochondria Pyruvate 3 NADH, Thiamine
energy Alternately fats I FADH2, Pantothenic
compounds and proteins 2 CO2, acid
such as NADH, after they are 1 GTP
FADH2 and GTP converted into
acetyl CoA
+
Urea cycle Excretion of Mitochondria C02, NH3 and Urea
toxic NH3 from and aspartate
amino acid cytoplasm
metabolism
Gluconeogenesis Makes glucose Mitochondria Fatty acids Glucose Biotin
from fatty acids and ending up as
and amino acids cytoplasm of pyruvate
kidney, liver
and gut
epithelium
Malate-aspartate Transfer NADH Mitochondria Oxaloacetate Oxaloacetate
shuttle electrons to and
mitochondrial cytoplasm
FADH2
Glycerol-3- Transfers NADH Mitochondria DHAP DHAP
phosphate electrons to and
shuttle mitochondrial cytoplasm
FADH2

Table 14: Metabolic Pathway Summary Table

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 GLYCOGENESIS GLYCOLYSIS HMP SHUNT
cytosol cytosol cytosol

GALACTOSE GLUCOSE DNA/RNA synthesis

ATP ATP 1
ADP 14 ADP
Galactose 1-Phosphate Glucose 6-Phosphate 6-Phosphogluconolactone
2 Ribulose 5-Phosphate

Glucose 1-Phosphate Fructose 6-Phosphate Xylulose 5-Phosphate

ATP 3
13 ADP
UDP-Glucose Fructose 1,6 Bisphosphate Fructose 1-Phosphate FRUCTOSE
4 5
Glycogen G
L Glyceraldehyde 3-Phosphate Dihydroxyacetone Phosphate
U NAD 6
GLYCOGENOLYSIS C NADH
O 1,3-Bisphosphoglycerate Glyerol 3-Phosphate
cytosol N ADP 7 ATP LIPOLYSIS
E ATP ADP
O 3-Phosphoglycerate Glycerol cytosol
G 8
E
N 2-phosphoglycerate TRIGLYCERIDES
E 9
S L
I Phosphoenolpyruvate I
S ADP 10 Cysteine P
ATP Alanine O
Lactate Pyruvate Serine G
In muscle Threonine E
1 Glucokinase/Hexokinase* Glycine N
2 Phosphoglucose isomerase Acetyl-CoA Malonyl CoA Fatty acids E
3 Phosphofructokinase* S
4 Aldolase Phenylalanine I
5 Triose Phosphate Isomerase Acetoacetate Leucine S
6 G3P dehydrogenase Lysine
7 Phosphoglycerate kinase 12 11 Tryptophan
8 Phopshoglycerate mutase Tyrosine cytosol
9 Enolase Citrate
10 Pyruvate kinase* a B-hydroxybutyrate
11 Pyruvate carboxylase b
12 PEP carboxykinase Oxaloacetate Isocitrate
13 Fructose 1,6 bisphosphorylase c CO2 + NADH Proline
14 Glucose 6 phosphatase h Histidine
Asparagine Malate KREBS CYCLE α-ketoglutarate Glutamate Arginine
Mitochondrion NADH mitochoncrion Glycine
NH3 + CO2 g d CO2 + NADH
Aspartate Fumarate Succinyl CoA Methymalonyl CoA
f
Carbomyl e Methionine
Phosphate Citrulline Succinate Isoleucine Propionyl CoA
FADH2 GTP Threonine
Argino-succinate Valine
UREA CYCLE Fatty acids
liver cytosol Tyrosine a. citrate synthase
Phenylalanine b. aconitase
Ornithine Arginine c. isocitrate dehydrogenase
d. α-ketoglutarate dehydrogenase*
Urea e. succinate thiokinase
*important regulatory enzyme f. succinate dehydrogensase
g. fumarase
H2O h. malate dehydrogenase
NADH NAD FADH2 FAD ½ O2 H2O ADP+ Pi ATP + H2O

Complex I Complex II Complex III Complex IV Complex V Inner Mitochondrial Membrane

H+ H+ H+ H+

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RAPID REVIEW

223
224
CLASSIC CLINICAL PRESENTATIONS

Clinical Presentation Disease

Abdominal pain, blue gum line and constipation Lead poisoning
Abdominal pain and tenderness in the right iliac fossa Appendicitis
Abdominal pain following an alcoholic binge Pancreatitis
Abdominal pain in right iliac fossa and diarrhea Crohn’s disease
Abdominal pain in left iliac fossa, blood in stool, young female Ulcerative colitis
Abdominal pain in left iliac fossa, blood in stool, older male Diverticulitis
Abdominal pain, splenomegaly in a black child Sickle Cell Disease
Adrenal hemorrhage and shock Waterhouse-Friderichsen syndrome
Amenorrhea, no lactation after postpartum hemorrhage Sheehan’s syndrome
Arachnodactyl, lens dislocation, hypermobile joints Marfan’s disease
Argyll-Robertson pupil, aortic aneurysm and angina pectoris Tertiary syphilis
Ataxia, heart problems and scoliosis Friedreich’s disease
Beef-red tongue and fatigue Vitamin B12 deficiency
Bilateral hilar lymphadenopathy, erythema nodosum Sarcoidosis
Bilateral ptosis, diplopia and difficulty in chewing in female Myasthenic gravis
Bitot’s spots in the eye Vitamin A deficiency
Bladder or bowel control problem Cauda Equina syndrome
Bleeding swollen gums Scurvy
Blue lips, swollen ankles and dyspnea Chronic bronchitis
Blue sclera and frequent fractures in an infant Osteogenesis imperfecta
Bone pain, head enlargement and deafness Paget’s disease of bone
Bronze skin, cirrhosis and diabetes mellitus Hemochromatosis
Buffalo hump, obesity and purplish abdominal striae Cushing’s syndrome
Buboes in the groin, sign of the groove Lymphogranuloma venereum
Bull’s eye rash Lyme disease
Butterfly rash and multiple painful joints in a young female Systemic Lupus Erythematosus
Café-au-lait spots and skin nodules Neurofibromatosis
Calf pseudohypertrophy and a positive Gower’s sign Duchenne’s muscular dystrophy
Cape-like distribution of loss of pain Syringomyelia
Caput medusa Cirrhosis with portal hypertension
Carditis, chorea, polyarthritis and subcutaneous nodules Rheumatic fever
Casal’s necklace Pellagra
Cat scratch, fever and local lymphadenitis Cat Scratch Disease
Cauliflower-like lesions on the hands or genitals Human Papilloma Viral infection
Cherry-red spot on the macula Tay-Sachs disease
Cherry-red skin and headaches Carbon Monoxide poisoning
Chest pain worse on lying down and better on sitting forward Pericarditis
Chest pain worse with exertion, better with rest Angina pectoris
Chest pain with sweating and feeling of apprehension Myocardial infarction
Chills, fever, vomiting and costovertebral angle tenderness Pyelonephritis
Chorea and dementia Huntington’s disease
Chronic non-healing ulcer on ear or nose Basal cell carcinoma
Cirrhosis and Kayser-Fleisher rings Wilson’s disease
Clubbing and cyanosis in an infant with heart murmur Fallot’s tetralogy
Cold intolerance and slow reflexes Hypothyroidism
Condylomata accuminata Human Papilloma virus infection
Condylomata lata Secondary syphilis
Coryza, conjunctivitis and “C”oplick spots Measles
Deep labored breathing with acetone smell on breath Diabetic ketoacidosis
Dermatitis, diarrhea and dementia Pellagra
Dry eyes, dry mouth and arthritis Sjögren’s syndrome
Dysphagia, glossitis and iron deficiency anemia Plummer-Vinson syndrome
Dyspepsia worse with eating food Gastric type of peptic ulcer disease
Elastic skin with hypermobile joints Ehlers-Danlos syndrome
Enlarged nerves and anesthetic hypopigmented rashes Leprosy
Fair, fat, fertile female over 40 with abdominal pain Cholecystitis

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Fever, cough, chest pain in a parrot breeder Bird fancier’s disease
Fever, headache and skin rash on wrists and feet Rocky Mountain Spotted Fever
Fever, conjunctivitis, coryza and fine rash on trunk Measles
Fever, neck stiffness and headache Meningitis
Fever, night sweats, weight loss, cough or hemoptysis Tuberculosis
Fever, maculopapulovesicular rash on trunk Chickenpox
Foul floating feces, fatigue and weight loss Celiac disease
Frequent urination with burning on micturition Urinary Tract Infection
Frothy urine, recurrent infections with normal blood pressure Nephrotic syndrome
Frothy malordorous vaginal discharge Trichomonas vaginitis
Galactorrhea and amenorrhea Prolactinoma
Gumma Tertiary syphilis
Gottron’s papules and heliotrope eyelids Dermatomyositis
Gout and self-mutilation in a child due to pain insensitivity Lesch-Nyhan syndrome
Haygarth’s nodes Rheumatoid arthritis
Heartburn worse on lying down after meals Gastro-Esophageal Reflux Disease
Heat intolerance, fine tremors, weight loss or exophthalmos Hyperthyroidism
Heberden’s and Bouchard’ s nodes Osteoarthritis
Hematemesis following protracted vomiting and retching Mallory-Weiss syndrome
Hemoptysis in a chronic cigarette smoking Lung cancer
Hemoptysis and hematuria Goodpasture syndrome
Honey-colored crusts on the face near the mouth and nose Impetigo
Hyperpigmented oral cavity and intestinal polyps Peutz-Jegher syndrome
Hyperpigmented skin creases, bronze skin and fatigue Addison disease
Hypertension, hypokalemia and metabolic acidosis Conn’s disease
Hypertension, exophthalmos and goiter Graves disease
Indurated painless penile lesion Primary syphilis
Infant with red hair and swollen abdomen Kwashiorkor
Infant with microcephaly and rocker-bottom feet Trisomy 18 [Edwards syndrome]
Infant with microcephaly and indistinct philtrum Fetal Alcohol Syndrome
Infant with mongoloid eyes and mental retardation Trisomy 21 [Down syndrome]
Irregularly irregular breathing Biot’s respiration
Jaundice , chills and fever Ascending cholangitis
Jaundice, ascites and firm non-tender hepatomegaly Cirrhosis
Jaundice with tender hepatomegaly Hepatitis
Large spatulate hands, protruding jaw Acromegaly
Loss of the outer third of eyebrows and slow reflexes Hypothyroidism
Low back pain, bamboo spine in young male adult Ankylosing Spondylitis
Lower abdominal pain and 6-8 weeks of amenorrhea Ectopic pregnancy
Koilonychia Iron deficiency anemia
Koplik spots and fever followed by maculopapular rash Measles
Male child with recurrent infection and no B cells Bruton’s disease
Mental retardation, large scrotal tongue, umbilical hernia Down syndrome
Middle-aged male smoker with intermittent claudication Buerger’s disease
Midsystolic click and atypical chest pain Mitral Valve Prolapse
Mole with irregular margins, change in color or size Malignant melanoma
Mucoid urethral discharge in a sexually active male Chlamydia urethritis
Muscle cramps with a positive Chvostek test Hypoparathyroidism
Newborn with paralyzed arm after difficult vertex delivery Erb-Duchenne palsy
Newborn with claw hand after difficult breech delivery Klumpke’s palsy
Night blindness, dry eyes and dry skin Vitamin A deficiency
Nocturnal back pain, recurrent infections and fatigue Multiple Myeloma
Obesity, hirsutism and irregular periods Polycystic Ovarian syndrome
Osler nodes , Janeway nodules or Roth spots Subacute Bacterial Endocarditis
Painful, pale, cold fingers and toes Raynaud’s syndrome
Painful fingers, wrists bilaterally with morning stiffness >1 hr Rheumatoid arthritis
Painful limp in a young child Legg-Calve-Perthes disease
Painful limp in overweight teenager Slipped Capital Femoral Epiphysis
Painful, pulseless, pale perishingly cold limb Arterial embolism

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Painful yellow genital ulcer Chancroid
Painless beef-red genital ulcer Granuloma inguinale
Painless jaundice and weight loss Cancer of the head of the pancreas
Pale mucous membranes and spoon-shaped nails Iron deficiency anemia
Palpitations, sweating and pressure headaches Pheochromocytoma
Pancreatic, pituitary and parathyroid tumors Wermer’s syndrome [MEN1]
Pectus excavatum Rickets
Pheochromocytoma, mucosal tumors and thyroid cancer MEN 2b
Pink color, purse-lipped breathing and barrel chest Emphysema
Polyuria, polydypsia but no polyphagia or glycosuria Diabetes insipidus
Polyuria, polydypsia, polyphagia and glycosuria Diabetes mellitus
Ptosis, anhydrosis and miosis on one side Horner’s syndrome
Puffy eyelids, smoky urine and hypertension in a child Glomerulonephritis
Purplish lesions on the arms, legs and oral cavity Kaposi’s sarcoma
Purulent urethral discharge in a sexually active male Gonorrhea
Rachitic rosary Rickets
Rash in palms and soles, oral ulcers and fever in a child Hand, Foot and Mouth disease
Radiofemoral delay Coarctation of the aorta
Recurrent crops of painful vesicles on face Herpes simplex Type 1
Recurrent crops of painful ulcers on the genitals Herpes simplex Type 2
Recurrent episodes of wheezing in a child Asthma
Recurrent peptic ulcers Zollinger-Ellison syndrome
Red-currant jelly sputum with fever an cough Klebsiella pneumonia
Regularly irregular breathing-increase with apneic spells Cheyne-Stokes breathing
Resting tremors, mask-like facies and shuffling gait Parkinson’s disease
Rose-colored spots on trunk, fever and diarrhea Typhoid fever
Rust-colored sputum, cough, fever and pleuritic chest pain Streptococcal pneumonia
Scanning speech, intention tremor and nystagmus Multiple myeloma
Shortness of breath, fatigue and erythema nodosum Sarcoidosis
Short stature, web neck and widely spaced nipples Turner’s syndrome
Single transverse palmar crease and mental retardation Down syndrome
Severe sore throat and swollen postauricular lymph nodes Mononucleosis
Situs inversus, chronic sinusitis and bronchiectasis Kartagener’s syndrome
Skin rash along a dermatome with prodrome of local pain Herpes zoster
Splinter hemorrhages Subacute Bacterial Endocarditis
Strawberry tongue, fever and rash Scarlet fever
Sudden onset of dyspnea, hemoptysis and chest pain Pulmonary embolism
Sudden onset of severe painful swollen big toe Gout
Sudden tearing chest pain, sweating and feeling of doom Dissecting Thoracic Aneurysm
Swollen ankles, shortness of breath and distended neck veins Congestive Heart Failure
Swollen bleeding gums and painful joints in a child Scurvy
Tall, thin male with gynecomastia and small testes Klinefelter’s syndrome
Thyroid, parathyroid and adrenal tumors Sipple’s syndrome [MEN 2a]
Unilateral facial palsy with hyperacusis Bell’s palsy
Unilateral facial palsy with vesicles in the ear Ramsey Hunt syndrome
Unilateral facial palsy with deafness in the same side Acoustic neuroma
Unilateral facial weakness with weakness in the arm and leg Cerebrovascular accident
Unilateral ptosis, anhydrosis and miosis Horner’s syndrome
Unilateral throbbing headache with aura Classic migraine
Unilateral throbbing headache without aura Common migraine
Unilateral swollen leg after long distance travel Deep Vein Thrombosis
Urethritis, conjunctivitis and arthritis Reiter’s syndrome
Vomiting blood in a jaundiced patient Ruptured esdophageal varices
Web neck, widely spaced nipples, underdeveloped breasts Turner’s syndrome
Weight loss and change in bowel habits Carcinoma of the colon
Weight loss, diarrhea, fever and arthritis Whipple’s disease
Weight loss, recurrent infections in young adult HIV/AIDS
Wet, wacky and wonky [incontinence, dementia, ataxia] Normal pressure hydrocephalus
Worst headache in my life Ruptured berry aneurysm

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KEY PATHOLOGY WORD ASSOCIATIONS

Feature Disease
Alpha-fetoprotein elevation in amniotic fluid Spina bifida
Alpha-fetoprotein elevation in adult Hepatocellular carcinoma
Amyloid deposits in the brain Alzheimer’s disease
Antibodies to acetylcholine receptors in NMJ Myasthenia gravis
Antibodies to Calcium influsx pumps in NMJ Lambert Eaton syndrome
Anti-Glomerular basement membrane antibodies Goodpasture disease
Anti-IgG antibodies Rheumatoid Arthritis
Anti-Nuclear Antibodies SLE
Apical cavitations Tuberculosis
Antischkow cells Rheumatic fever
Apical lung tumor Pancoast tumor
Aschoff bodies Rheumatic fever
Auer’s rods Acute Myelogenous Leukemia
Basophilic stippling Lead poisoning
BCR-abl oncogene Chronic Myelogenous Leukemia
Bence Jones proteins Multiple Myeloma
Berry aneurysms Adult polycystic disease of the kidney
Bilateral adrenal heamorrhage Waterhouse-Friderichsen syndrome
Bilateral hilar lymphadenopathy Sarcoidosis
BRCA-1/2 tumor marker Breast cancer
Brown cysts in bone Hyperparathyroidism
Buffalo hump and truncal obesity Cushing’s syndrome
CA-125 Ovarian cancer
Carcinoembryonic antigen Colon cancer
Caseous granulomas Tuberculosis
Cerebellar tonsillar herniation Arnold-Chiari malformation
Charcot-Leyden crystals Asthma
Chocolate cysts in the pelvis Endometriosis
Clue cells Bacterial vaginosis
Coagulative necrosis Myocardial infarction
Cobblestone appearance of intestinal mucosa Crohn’s disease
Codman’s triangle on x-ray Osteosarcoma
Congenital aganglionosis of the colon Hirschsprung’s disease
Curschmann’s spirals Asthma
Dark urine and dark cartilage Alkaptonuria
Downey cells Mononucleosis
Dry eyes and dry mouth Sjorgen syndrome
Dystrophin defect Duchenne’s muscular dystrophy
Eburnation Osteoarthritis
Fatty necrosis Liver damage
Fibrillin defect Marfan’s syndrome
Ghon’s focus and complex Primary Tuberculosis
Guarneri bodies Smallpox
Heterophil antibodies Mononucleosis
Hirano’s bodies Alzheimer’s disease
HLA-B8 Graves disease
HLA-B27 AS, Reiter’s syndrome, ulcerative colitis
HLA-DR3 or 4 DM type 1, RA and SLE
Hypercoagulabilty, venous stasis and vessel wall damage Virchow’s triad
Hyperelasticty of skin and joint capulse Ehlers-Danlos syndrome
Hyperpigmented skin with fatigue Addison’s disease
Immotile cilia with sinusitis, bronchietasts and situs inversus Kartagener’s syndrome
Kimmelstiel-Wilson nodules Diabetic nephropathy
Langhan’s giant cells Tuberculosis
Lewy bodies Parkinson’s disease
Lines of Zahn Thrombus

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Liquefactive necrosis Nerve damage
Liver and brain damage after aspirin ingestion Reye syndrome
L-MYC oncogene Colon cancer
Looser’s zone Osteomalacia
MacCallum’s patch in lefrt atrium Rheumatic fever
Macrocytic normochromic anemia Folic acid or Vitamin B12 deficiency
Malignant plasma cells Multiple Myeloma
Microcytic hypochromic anemia Iron deficiency anemia
Minimal change of the basement membrane Nephrotic syndrome
Most common cancer in men Prostate cancer
Most common cancer in women Breast cancer
Most common cause of osteomyelitis Staphylococcus aureus
Most common malignant bone tumor Metastases
Most common benign brain tumor Meningioma
Most common kidney tumor in children Wilms tumor
Most common malignant brain tumor in adults Glioblastoma multiforme
Most common malignant brain tumor in children Neuroblastoma
Most common primary bone cancer in adults Multiple Myeloma
Most common primary bone cancer in teens Osteosarcoma
M spike on serum electrophoresis Multiple Myeloma
Needle-shaped negatively birefringent crystals Gout [uric acid crystals]
Negri bodies Rabies
Neurofibrillary tangles Alzheimer’s disease
N-MYC oncogene Neuroblastoma
Non-caseous granulomas in the gut Crohn’s disease
Non-caseous granulomas in the lung Sarcoidosis
Nutmeg liver Congestive Heart Failure
Onion-skin periosteal reaction on x-ray Ewing’s sarcoma
Oral pigmentation and intestinal polyps Peutz-Jegher syndrome
Osteophytes Osteoarthritis
Owl-eye appearance Cryptococcus neoformans
p16 oncogene Malignant melanoma
Pannus formation Rheumatoid Arthritis
Philadelphia chromosome Chronic Myelogenous Leukemia
Post-coital bleeding Carcinoma of the cervix
Post-menopausal bleeding Endometrial cancer
Prostatic Specific Antigen Prostatic carcinoma
Red and gray hepatization in lung Pneumonia
Red blood cell casts in urine Glomerulonephritis
Recurrent peptic ulcers Zollinger-Ellison syndrome
Rib notching on chest x-ray Coarctation of the aorta
Reed-Sternberg cells Hodgkin’s lymphoma
Rheumatoid factor RA, SLE
Rokitansky-Ashoff sinuses Cholecystitis
Soap-bubble appearance on x-ray Giant cell tumor
Spaghetti and meatballs appearance Malassezia furfur
Splenomegaly and eyethema nodosum Sarcoidosis
Starry sky appearance in lymph node Burkitt’s lymphoma
Stunted small intestinal villi due to gluten sensitivity Celiac disease
Thymic and parathyroid aplasia DiGeorge syndrome
Thyroglobulin antibodies Hashimoto’s disease
Vanilyl mandelic acid in the urine Pheochromocytoma
Virchow’s triad-vessel damage, stasis, hypercoagulability Deep vein thrombosis
Vomiting blood after protracted vomiting and retching Mallory-Weiss syndrome
Wallerian degeneration Nerve damage
White blood cell casts in urine Pyelonephritis
XO chromosomal disease Turner’s disease
XXY chromosomal disease Klinefelter’s syndrome
Zenker’s degeneration Skeletal muscle damage

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KEY MICROBIOLOGY WORD ASSOCIATIONS

Description Pathogen
All viruses are RNA except 6 HHAPPY ones which are DNA
3 enveloped DNA viruses HepaDNA, Herpes and Pox
2 naked DNA viruses Adeno and Papova
1 single stranded DNA virus Parvo B17
All RNA viruses are single stranded EXCEPT Rota virus of the REO virus family
All RNA single stranded viruses are + EXCEPT 6 PROFAB group
Paramyxo, Rhabo, Orthomyxo, Filo, Arena and Buynya PROFAB group
All hepatitis viruses are RNA EXDCEPT Hepatitis B [hepaDNA group]
All hepatitis viruses are spread by the orofecal route EXCEPT Hepatitis B and C [sex and blood]
Single stranded retro virus Human Immune Deficiency virus
All ARBO viruses are flavi viruses EXCEPT California encephalitis [Bunya virus]
Parotitis, pancreatritis and painful orchitis Paramyxo virus [Mumps]
Common cold with runny nose and sore throat Corona virus
Hand, foot and mouth lesions Coxsackie virus
Bacteria without cell walls Rickettsiae, Chlamydia and Bartonella
Flexible bacteria Borrleia, Leptospira and Treponema
Gram stain resistant Mycobacteria
Infection in bird keepers Chlamydia psittaci
Lung infection in wool sorters Bacillus anthracis
Rheumatic fever and glomerulonephritis Streptococcus pyogenes
Previously damaged heart valves Streptococcus viridans
Infected previously healthy heart valves Staphylococcus aureus
Causes lockjaw [trismus] Clostridium tetani
Transmitted by contaminated honey and causing paralysis Clostridium botulinum
Causes muscle necrosis with gas formation Clostridium perfringens
Grey psuedomenbrane in the throat Corynebacterium diphtheriae
Paroxysmal bouts of coughing with a whoop in a child Bordetella pertussis
Fever from handling infected rabbit skin Francisella tularensis
Lung infection from infected air conditioners Legionella pneumophilia
Infected burns with blue green burns Pseudomonas aeroginosa
Gram negative coccus which ferments glucose Neisseria gonorrhea
Gram negative coccus which ferments maltose Neisseria meningitidis
Causes severe diarrhea with rice water stool Vibrio cholera
Obligate intracellular parasitic bacteria Chlamydia
Causes peptic ulcer and some forms of stomach cancer Helicobacteria pylori
Gram resistant bacteria with thick waxy wall Mycobacterium tuberculosis
Commonest cause of urinary tract infections Escherichia coli
Causes Hemolytic Uremic Syndrome E. coli subtype O157 H7
Rose colored spots and step ladder fever Salmonella typhi
Spread by bat doppings Histoplasma capsulatum
Causes meningitis spread by pigeon poop Cryptococcus neoformans
Causes pneumonia in an immune compromised patient Pneumocystis jiroveci [carinii]
Fatal encephalitis in warm waters Naegleria fowleri
Diarrhea more common in hikers Gardia lamblia
Causes megaoesophagus and spread by sand fly bites Trypanosoma cruzi
Sleeping sickness spread by tsetse fly bites Trypanosoma gambiense
Frothy vaginal discharge caused by flagellate protozoan Trichomonas vaginitis
Recurrent or chronic diarrhea in immune compromised Crpptosporidium parvum
Most dealy form of malaria Plasmodium falciparum
Intestinal parasite associated with iron deficiency Necator americanus
Most common intestinal nematode in the USA Enterobius vermicularis
Associated with rectal prolapse Trichuris trichuria
River blindness spread by the simulium blackfly Onchocerca volulus
Elephantiasis spread by Culex filariasis Wuchereria bancrofti
Intestinal parasite associated with vitamin B12 deficiency Diphyllobothrium latum
Bladder parasite causing blood in the urine Schistosoma hematobium

230
Spread by eating undercooked contaminated beef Taenia saginatum
Smallest tapeworm Hymenolepis nana
Ames test Mutagenic potential
Armadillo Mycobacterium leprae
Ascoli test Anthrax
ASOT Recent streptococcal infection
Bordet-Gegnou medium Bordetella pertussis
Catalase test Staphylococcus [+] from streptococcus[-]
Chocolate agar Neisseria and Hemophilus
Coagulase test Staphylococcus aureus from other Staph.
Coombs test Hemolytic anemia
Darkfield microscopy Syphilis
Dick test Scarlet fever
Eaton agar Mycoplasma pneumoniae
ELISA HIV and Lyme
FTA-Abs Syphilis
Heaf skin test Tuberculosis
Hektoen agar Salmonella
Indian ink stain Cryptococcus neoformans
Kviem skin test Sarcoidosis
Lowenstein-Jensen culture medium Mycobacterium tuberculosis
MacConkey agar Promotes growth of Gram negative rods
Mantoux skin test Tuberculosis
Middlebrook medium Tuberculosis
Mitsuda test Mycobacterium leprae
Paul Bunnel test Mononucleosis
Regan-Lowe agar Bordetella pertussis
Quellung reaction Bacteria with capsules-Strep pneumoniae
Sabouraud medium Fungal organisms
Schick test Corynebacterium diphtheria
Schultz Carlton reaction Scarlet fever
Telluritie agar Corynebacterium diphtheria
Thayer-Martin medium Neisseria organisms
Thiosulfate-Citrate-Bile salts-Sucrose Vibrio cholera
Tine skin test Tuberculosis
VDRL test Syphilis
Weil-Felix test Rickettsiae
Wood’s light Fungal organisms
Wright-Giemsa stain Parasites and syphilis
Ziehl-Neelsen stain Mycobacterium tuberculosis
Test to exclude a disease if test is negative [SnOUT] Sensitivity
Test to include a diagnosis if test is positive [SpIN] Specificty
Sudden increase in the number with a disease locally Epidemic
Normal occurrence of a disease in a particular locality Endemic
Sudden increase in the number with a disease worldwide Pandemic
Number of people with the disease at a given time Prevalence
Number of new cases in the population at a given time Incidence
Number of people who die from a particular disease Mortality rate
Number of people who have a particular disease Morbidity rate
Epidemiology or Disease Triangle Host, Agent [microbe] and Environment
Antigenic shift [virus], spores [bacteria/fungus]cysts [protozoa] Microbial adaptations
Disease that has newly appeared Emergin disease
Previously known disease that has increased or spread Re-emerging disease
Bacteria and fungi form spores and protozoa form cysts Pathogen adapatations to environment
Viral adaptation to the environment and host Antigenic shift
Exposure of milk to progressively higher temperatures Pasteurization
Use of chemicals or heat to destroy all life Sterilization
Use of chemicals to destroy most pathogens Disinection
Use of aluminum to precipitate material from water Flocculation

231
KEY CHEMISTRY WORD ASSOCIATIONS

FEATURE KEY WORD

Process in which there is a loss of hydrogen electrons Oxidation
Process in which there is a gain of hydrogen electrons Reduction
Replacement of hydrogen by a carboxyl group [-COOH] Carboxylation
Enzyme that catalyzes the addition of a carboxyl group Carboxylase
Removal of the carboxyl group [-COOH] Decarboxylation
An enzyme that catalyzes the release of CO2 from compounds Decarboxylase
Reaction that combines H2O with a salt to produce acid and base Hydrolysis
An enzyme that causes hydrolysis Hydrolase
Movement of a phosphate [PO4] from one molecule to another Phosphorylation
An enzyme that removes a phosphate to an organic compound Phosphatase
An enzyme that adds a phosphate to an organic compound Kinase
An enzyme that catalyzes the transfer of one group to another Transferase
A substance which speeds up the rate of a chemical reaction Enzyme
Inactive precursor protein with an additional peptide attached Pro-enzyme
Maximum velocity of a reaction Vmax
The amount of substrate required to reach ½ of the Vmax Kmax
A substance which slows down the rate of an enzyme reaction Inhibitor
Competition and Allosterism Enzymatic regulation
Actively competes with substrate for the active site Competition
Chemical bond between two amino acids Peptide bond
Chemical bond between the base bases found in DNA Hydrogen bond
Chemical bond between glycerol and fatty acids Ester bond
Chemical bond between two sugars Glycosidic bind
Chemical bond between nucleotides Phosphodiester
Constituents of starch Amylose and amylopectin
Long, unbranched chains of glucose linked at C1 and C4-α 1,4 link Amylose
Fewer branches of glucose with α 1,4 and 1,6 linked branches Amylopectin
Comprised of glucose and fructose; found in table sugar and fruit Sucrose
Contains galactose linked to glucose; found in milk; β 1,4 link Lactose
Form in which excess glucose is stored in skeletal muscle Glycogen
Aldopentose [5 Carbon] sugar Ribose
Ketohexose [6 Carbon] sugar Fructose
A crucial step that controls how fast or slow the pathway goes Rate limiting step
The most important control point-rate limiting step in glycolysis Phosphofructokinase
Number of pyruvate produced from one glucose in glycolysis 2
Number of ATP produced from the breakdown of one glucose molecule 4 ATP
Number of NADH produced from the breakdown of one glucose 2 NADH
Net ATP gain from the breakdown of one glucose molecule 2 ATP
Main fate of pyruvate Converted to Acetyl CoA
Alternate fates of pyruvate Lactate and Alanine
Process of creating new glucose from the end-products of glycolysis Gluconeogenesis
Irreversible steps in glycolysis that are replaced in gluconeogenesis Steps 1, 3 and 10
Location of gluconeogenesis Mitochondria and cytoplasm
Lactate is converted to pyruvate which is converted to Glucose Sequence of events
Causes Pyruvate to build up; results in excess lactic acid production Biotin deficiency
Rate limiting step in gluconeogenesis F1,6 bisphosphatase
Hormone which inhibits gluconeogenesis Insulin
Location of Krebs cycle Mitochondrial matrix
Destination of the energy harvested from the Krebs cycle Electron Transport Chain
Number of ATPs generated from 1 NADH 3 ATP
Number of ATPs generated from 1 FADH2 2 ATP
Total ATP generated by the breakdown of one molecule of glucose 38 ATP
Alternate fuel types for the Krebs cycle Proteins and fat
Succinyl CoA, Oxaloacetate, Fumarate and α-ketoglutarate Sites at which proteins enter
α-ketoglutarate and Succinyl CoA Sites at which fats can enter
Location of Electron Transport Chain Inner mitochondrial matrix

232
Role of Electron Transport Chain Transfer electrons to O2
A compound which has both reduce and oxidized form of a molecule Redox pair
NAD [oxidized] and NADH [reduced] Redox pair example
Drop-off point for NADH Complex I
Drop-off point for FADH2 Complex II
Alternate name for CoQ10 Ubiquinone
Heme containing compounds that receive electrons from CoQH2 Cytochromes
Other metal which is important to the electron Transport Chain Copper
Purpose of the Cori cycle Prevents lactic acidosis
Purpose of the hexose monophosphate shunt Produce NADPH, ribose
Location of the pentose phosphate pathway Cytosol
Rate limiting enzyme G6P dehydrogenase
Site of glycogen metabolism Cytosol
RATE LIMITING enzyme; used to lengthen the glycogen chain Glycogen Synthase
Chemical bonds between glucose molecules: mainly 1-4 links Glycosidic bond
Rate Limiting enzyme in glycogenolysis, activated by ATP Glycogen phosphorylase
Sites for glycogenolysis Heart, liver and muscle
Name of enzyme that changes G1P to G6P Phosphoglucomutase
Group consisting of Carbon with Oxygen and a hydroxyl attached Carboxyl group
One with no double bond between the carbon atoms [C-C] Saturated fatty acid
One with one or more double bonds between the carbon atoms Unsaturated fatty acid
Linoleic acid [vegetable oil Ω-6] and linolenic acid [fish oil- Ω 3] Essential fatty acids
Location of lipolysis Mitochondria
Site of lipogenesis Cytosol
Rate limiting step in cholesterol synthesis and target for statins HMG CoA reductase
Starting point for steroid hormone synthesis Cholesterol
Phe, Val, Thr, Trp, Ile, Met, His, Leu and Lys Essential amino acids
Pro, Try, Gly, Ala, Glu, Asp, Gln, Arg, Ser and Cys Non-essential amino acids
Removal of the amine NH2 group Deamination
Source of nitrogen for the urea cycle Glutamate and alanine
Location of the urea cycle Mitochondrion then cytosol
Rate limiting enzyme in the urea cycle Carbamoyl PO4 synthase
Purine or Pyrimidine base PLUS sugar Nucleoside
Purine or Pyrimidine base PLUS sugar AND phosphate Nucleotide
Adenine and Guanine; used to make nucleosides and nucleotides Purine bases
Cytosine, Uracil and Thymine Pyrimidine bases
Adenine & Thymine; Cytosine & Guanine; Adenine & Uracil Base pairs
Converts xanthine into uric acid Xanthine oxidase
Process by which RNA template for protein synthesis is made from DNA Transcription
Process by which RNA codon begins to make an protein Translation
Water-soluble vitamins D, A, K and E
Fat soluble vitamins B and C
Anti-oxidants Vitamin A,C, E and selenium
Used to make rhodopsin, helps in the differentiation of epithelial tissue Vitamin A
Used in carboxylation of glutamate residue in making clotting factors Vitamin K
Powerful antioxidant which mops free radicals; lipid antioxidant Vitamin E
Cofactor in Pyruvate kinase and α-ketoglutarate dehydrogenase Vitamin B1 [Thiamine]
Precursor for FMN and FAD in the ETC and Redox reactions Vitamin B2 [Riboflavin]
Precursor for NAD and NADP in the Electron Transport Chain Vitamin B3 [Niacin]
Acyl carrier as part of Coenzyme A; Pantene ProV [V=Five] Vitamin B5 [Pantothenic acid]
Cofactor for several transaminase and decarboxylation reactions Vitamin B6 [Pyridoxin]
Used in carboxylation reactions; deficiency causes lactic acidosis Vitamin B7 [Biotin]
Used in the transfer of 1-Carbon units and make methionine and purines Vitamin B9 [folic acid]
Cofactor for methionine and succinyl CoA manufacture Vitamin B12 [cobalamin]
Cofactor in hydroxylation in the synthesis of collagen Vitamin C [ascorbic acid]
Necessary in the Electron Transport Chain and found in prunes Copper
Cofactor of carbonic anhydrase found in seafood, meat and whole grain Zinc
Forms complexes with ATP and found in nuts Magnesium
Helps with glucose transport into cells and found in oysters Chromium

233
234
INDE X
Amphiarthrosis, 37
A Ampulla of uterine tube, 50
Abdominal aorta, 25 Ampulla of Vater, 58
Abdominal Aortic Aneurysm, 142 Amylase, 111, 112, 197
Abducens nerve, 82, 84 Amylose, 197
ABO blood groups, 112 Amylopectin, 197
Abscess, 135 Amyotrophic Lateral Sclerosis, 154
Acanthosis nigricans, 140 Anal canal, 36
Accessory nerve, 82, 87 Anal sphincter, 36
Accessory pancreatic duct, 30 Anaerobic bacteria
Accessory hemiazygos vein, 54 facultative, 179
Acetylcholine, 101, 119 strict, 179
Acetylcholinesterase, 119 Anaplasia, 136
Achalasia, 147, 156 Anatomical position, 9
Achondroplasia, 149 Anatomical snuffbox, 16
Acid-Base Balance, 126 Anatomical terms, 9
Acidosis Aneurysm, 142
metabolic, 126 Aneurysmal Bone Cyst, 149
respiratory, 128 Angina pectoris, 142
Acne vulgaris, 166 Angiotensin, 125
Aconitase, 203 Ankle joint, 44
Acoustic neuroma, 154 Ankylosing Spondylitis, 150
Acromegaly, 144 Anoxia, 136
Acrosome, 128 Anterior abdominal wall, 32
ACTH, 108 Anterior cervical triangle, 11
Actin, 118 Anterior pituitary lobe, 108
Action Potential, 121 Anterior tibial artery, 26
Acute Lymphoblastic Leukemia, 140 Anterolateral system, 76
Acute Myelogenous Leukemia, 140 Anthracosis, 162
Acyanotic Heart Disease, 141 Antibiotic targets, 181
Adaptations to survive, 171 Antibodies, 116
Addison’s disease, 145 Anti-diuretic Hormone, 109, 125
Adductor canal, 17 Antigenic shift, 192
Adenine, 217 Anulus fibrosus, 71
Adenohypophysis, 108 Aortic valve, 22
Adeno viruses, 172, 174 Aplasia, 136
Adrenal Appendicitis, 147
cortex, 30. 109 Appendix, 35
gland, 30, 109 Arachnoid mater, 76
medulla, 30, 110 ARBO viruses, 174
ADH, 109 Arachidonic acid, 211
Adrenocorticotropin Hormone, 108 Arginine, 215
Aeration, 192 Arnold-Chiari deformity, 153
Aerobic, 178 Arteriosclerosis, 141
Agenesis, 136 Artery
Alanine, 215, 216 anterior cerebral, 81, 82
Aldolase, 198 anterior communicating, 81, 82
Aldosterone, 109, 125 anterior inferior cerebellar, 81, 82
Alkalosis anterior tibial, 26
metabolic, 126 axillary, 25
alkalosis, 127 basilar, 81, 82
Alkaptonuria, 138 brachial, 27
Allosteric regulation, 195 dorsalis pedis, 26
Alpha Fetal Protein, 140 external iliac, 25
Alpha 1-antitrypsin deficiency, 161 femoral, 25
Alpha ketoglutarate, 203 great radicular, 79
Alpha ketoglutarate dehydrogenase, 203 inferior thyroid, 29
Alzheimer’s disease, 154 internal iliac, 25
Amino acids, middle cerebral, 81
essential, 215 popliteal, 25
non-essential, 215 posterior cerebral, 81, 82

235
 posterior communicating, 81, 82 Beri beri, 217
posterior inferior cerebellar, 81, 82 Berry aneurysm, 142, 153
posterior tibial, 25 Biliary tree, 34
radial, 27 Bilirubin metabolism, 113
superior thyroid, 29 Biotin, 218
ulnar, 27 Bird fancier’s disease, 176
vertebral, 81, 82, 90 1, 3 Bisphosphoglycerate, 198
Arthritis Bitemporal hemianopia, 84
psoriatic, 150 Bitot’s spots, 217
rheumatoid, 150 Black simulium fly, 187
Arytenoid Bladder, 65
oblique, 95 Blastomyces dermatitis, 184
transverse, 95 Blood
Asbestosis, 162 brain barrier, 90, 130
Arginine, 215, 216 cell production, 114
Ascaris lumbricoides, 186 clotting, 115
Ascending colon, 35 composition, 114
Ascorbic acid, 219 flow, 107
Asparagine, 215 groups, 112
Aspartate, 215, 216 Blood pressure control, 107
Aspergillus fumigatus, 184 Blue bloaters, 161
Association fibers, 81 Bohr effect, 129
Asterion, 92 Bond
Asthma, 161 ester, 196
Astrocytes, 80 glycosidic, 196
Atelectasis, 161 hydrogen, 196
Atherosclerosis, 141 phosphodiester, 196
Atlas, 70 Bone
Atrial Septal Defect, 141 classification, 37
Atresia, 136 histology, 39
Atrioventricular node, 24 Bordetella pertussis, 178
Atrium Borrelia burgdorferi, 176
left, 22 Bowman’s capsule, 124
right, 21 Brachial artery, 27
Atrophic gastritis, 147 Brachial plexus, 96
Atrophy, 136 Brain abscess, 154
Auer rods, 140 Branchial arches, 95
Autonomic Nervous System, 100 Breast, 62
Autosomal Breathing
dominant, 137 Biot, 130
recessive, 137 Cheyne-Stokes, 130
Autosome, 137 Kussmaul, 130
Axilla, 14 Bregma, 92
Axillary artery, 27 Bronchopulmonary segment, 51
Axis, 70 Bronchiectasis, 161
Azygos vein, 54 Bronchogenic carcinoma, 162
Bronchopneumonia, 161
B Bronchus, 52
Bacillus anthracis, 177 Broad ligament, 50
Bacterial Brucella abortus, 179
characteristics, 176 Brucellosis, 179
growth phases, 171 Bruton’s agammaglobulinemia, 136
Bagassosis, 162 Buck’s fascia, 32, 49
B cells, 114 Buerger’s disease, 143
β-HCG, 140 Bulbourethral gland, 66
Baroreceptors, 107 Bundle of His, 24
Barrett’s esophagus, 147 Burkitt’s lymphoma, 139
Barteonella henselae, 176 Burning feet syndrome, 218
Bat droppings, 184 Byssinosis, 162
Basophils, 114
Beck’s triad, 142 C
Benign tumors, 139 Calcium, 220

236
Calcitonin, 109 Cervical cancer, 165
Callot’s triangle, 34 Cervical plexus, 96
cAMP, 210 Cervical triangle
Camper’s fascia, 32 anterior, 11
Campylobacter jejuni, 178 posterior, 12
Canal Cervicitis, 165
adductor, 17 Chagas disease, 186
femoral, 17 Chancre, 164
Guyon, 16 Chancroid, 164
inguinal, 17 Charcot’s joint, 149
spinal, 72 Charcot-Leyden crystals, 161
Candida albicans, 183, 184 Charcot-Marie-Tooth disease, 152
Candidiasis, 166 Chediak-Higashi syndrome, 136
Capacitation, 127 Chemical reactions, 195
Caplan’s lung, 162 Chemoreceptors, 130
Carbohydrate metabolism, 197 Chemotaxis, 135
Carbon monoxide poisoning, 155 Cheiralgia paresthetica, 155
Carbonic anhydrase, 127 Chickenpox virus, 166, 173
Carboxylation, 195 Chlamydia
Carcinoembryonic antigen, 140 psittaci, 176
Carcinogens, 140 urethritis, 164
Carcinoma Chlorination, 192
basal cell, 166 Cholecystitis, 148
squamous cell, 166 Cholecystokinin, 111
Cardiac chambers, 20 Cholelithiasis, 148
Cardiac conduction system, 24 Chronic bronchitis, 161
Cardiac cycle, 106 Chronic Lymphocytic Leukemia, 140
Cardiac muscle, 105 Chronic Myelogenous Leukemia, 140
Cardiac muscle contraction, 105 Chronic Obstruction Pulmonary Disease, 161
Cardiac plexus, 24 Chrysops biting fly, 187
Cardiac tamponade, 142 Chylomicrons, 211
Cardiomyopathy, 142 Circle of Willis, 81
Carotid body, 130 Cirrhosis, 148
Carotid sheath, 11 Citrate, 203
Carotid sinus, 107 Citrate synthase, 203
Carotid triangle, 11 Clonorchis sinensis, 188
Carpal tunnel, 16 Clostridium
Carpal Tunnel Syndrome, 155 botulinum, 177
Carpometacarpal joint, 42 difficile, 177
Cartilage, 39 perfringens, 178
Casal’s necklace, 218 tetani, 177
Cat scratch disease, 175 Colles fascia, 32
Caudate nucleus, 89 Coccidioides immitis, 184
CCK, 111, 113 Coccidiomycosis, 184
Cecum, 35 Coenzyme Q, 207
Celiac disease, 147 Cohort, 191
Celiac trunk, 25, 31 Cold sores, 166
Cells Colon, 35
B lymphocytes, 114 Commensal, 171
plasma, 114 Commissural fibers, 81
red blood, 114 Common bile duct, 34
T lymphocytes, 114 Common cold virus, 174
white blood, 114 Complex 1, 207
Cellulose, 197 Complex II, 107
Center Complex III, 207
apneustic, 130 Complex IV, 207
expiratory, 130 Complex V, 207
inspiratory, 130 Complex Regional Pain Syndrome, 156
pneumotaxic, 130 Compliment activation, 116
Cerebellum, 89 Condyloma accuminata, 165
Cerebral palsy, 153 Congenital Heart Disease, 141
Cerebrovascular accident, 153 Congenital Pyloric Stenosis, 147

237
Congestive Heart Failure, 142 Dehydroepiandrosterone, 213
Conn’s disease, 145 Deltoid, 45
Contrecoup injury, 153 Dengue fever virus, 174
Contraction of muscle Dens, 70
concentric, 119 Dermatome, 69, 99
eccentric, 119 Dermatomyositis, 152
isokinetic, 119 Dermis, 59
isometric, 119 Descending colon, 35
isotonic, 119 Development
Control of blood pressure, 107 brain, 80
Control of respiration, 130 diaphragm, 55
COPD, 161 gut, 31
Copper, 220 heart, 20
Co Q, 207 kidney, 64
Cori cycle, 208 lungs, 52
Coronary artery ovum, 127
left, 23 sperm, 127
right, 23 spinal cord, 76
Coronary blood supply, 23 urinary bladder, 65
Coronary sinus, 23 vertebral, 69
Cor pulmonale, 142 DHAP, 198
Corpuscle Diabetes insipidus, 144
Meissner, 59 Diabetes mellitus, 146, 155
Merkel, 59 Diabetic nephropathy, 159
Pacinian, 59 Diapedesis, 135
Corynebacterium diphtheriae, 178 Diarthrosis, 37
Coxsackie viruses, 174 Diencephalon, 80
Cranial Nerves 1-XII, 82 Diffusion of gases, 129
Craniosacral outflow, 100 Digastric triangle, 11
CREST syndrome, 143 DiGeorge’s syndrome, 136
Cretinism, 158 Dihydroacetone phosphate, 198
Creutzfeldt-Jakob disease, 154 Dihydroxycholecalciferol, 125
Cricoarytenoid Diphyllobothrium latum, 188
lateral, 95 Dimorphic fungi, 188
posterior, 95 Diphtheria, 178
Cricothyroid, 95 Disc, intervertebral, 71
Crohn’s disease, 147 Disinfection, 192
Cryptococcus neoformans, 184 Distal convoluted tubule, 124
CSF circulation, 91 Diverticulitis, 147
Cubital fossa, 15 Diverticulosis, 147
Curschmann spirals, 161 Dorsal columns, 76
Cushing’s disease, 144 Down’s syndrome, 137
Cushing’s syndrome, 144 Duchenne’s muscular dystrophy, 138
Cutaneous larva migrans, 166 Ductus deferens, 48
Cyanotic Heart Disease, 141 Duodenum, 33
Cycle Dura mater, 76
cardiac, 106 Dural sac, 76
menstrual, 128 Dural venous sinuses, 91
Cysteine, 214 Dwarfism
Cystic artery, 34 achondroplasia, 149
Cystic duct, 34 pituitary, 144
Cystic Fibrosis, 138 Dysentery
Cysts, 192 amebic, 180
Cytochrome, 207 bacillary, 180
Cytosine, 216 Dysplasia, 135
Dystrophy
D Becker’s, 151
Dandy-Walker syndrome, 153 Duchenne’s, 151
Darkfield microscopy, 189
Decarboxylation, 195 E
Deep palmar arch, 28 Eastern Equine Encephalitis, 174
Deep Vein Thrombosis, 142 Ebola, 172

238
ECG, 106 transversalis, 32
Echinococcus granulosus, 188 Fasciola hepatica, 188
Ectoderm derivatives, 10 Fat metabolism, 211
Edinger-Westphal nucleus, 85 Fatty acid
Endotoxin, 179 activation, 212
Ehlers-Danlos syndrome, 137 beta oxidation, 212
Ehrlich, Paul, 169 essential, 211
Elbow joint, 41 non-essential, 211
Electrocardiogram, 106 saturated, 211
Electron Transport Chain, 206 transport, 212
Elephantiasis, 187 unsaturated, 211
Embolism, 141, 154 Female genitalia, 50
Emerging diseases, 192 Femoral artery, 25
Emphysema, 161 Femoral canal, 17
Empyema, 163 Femoral triangle, 13
Encephalitis, 154 Fertilization, 128
Endemic, 192 Fetal Alcohol Syndrome, 155
Endoderm derivatives, 10 Fever
Endotoxin, 179 beaver, 186
Enolase, 199 blackwater, 187
Entameba histolytica, 186 Q, 180
Enteric brain, 102 rabbit, 178, 180
Enterobius vermicularis, 187 Rocky Mountain Spotted, 176
Eosinophils, 114 recurrent fever, 180
Epidemic, 192 rheumatic, 180
Epidermis, 59 scarlet fever, 180
Epidermophyton infection, 183 trench, 179
Epididymis, 48 Fibers
Epilepsy, 155 association, 81
Epinephrine, 110 commissural, 81
Epistropheus, 70 fast twitch, 119
Epithelioid cells, 135 projection, 81
Epstein Barr virus, 139, 173 slow twitch, 119
Erb-Duchenne palsy, 97, 155 Fibrin, 115
Erythrocytes, 114 Fibrinogen, 115
Erythropoietin, 124 Fibrous joint, 37
Escherichia coli, 178 Filariasis, 187, 189
Esophageal cancer, 147 Filtration, 192
Esophageal varices, 147 Filum terminale, 76
Espundia, 187 Fistula, 135
Estrogen, 110, 127, 213 Flavin-linked dehydrogenase, 206
Ewing’s sarcoma, 150 Flavi virus, 174
Exercise, vascular response, 107 Fleming, Alexander, 169
Exotoxin, 179 Flocculation, 192
Expiratory Reserve Volume, 130, 131 Flukes, 188
External bladder sphincter, 65 Follicle Stimulating Hormone, 108
External iliac artery, 25 Foramen
Enzyme, 195 cecum, 93
cribriform, 93
F ethmoidal, 93
Facet joint, 73 hypoglossal, 93
Facet joint orientation, 73 intervertebral, 71
Facial nerve, 82, 85 jugular, 93
Fallopian tube, 50 lacerum, 93
Fallot’s tetralogy, 21, 141 ovale, 93
Farmer’s lung, 117,162 rotundum, 93
Fascia transverse, 70
Buck, 32 Forced Expiratory Volume, 130, 131
Camper, 32 Fracastoro, Lazzaro, 169
Colles, 32 Francisella tularensis, 178
Scarpa, 32 Friedreich’s ataxia, 155
Sibson, 54 FSH, 108, 127

239
Functional Reserve Capacity, 130, 131 Gram, Hans Christian, 169
Fructose 1,6 Bisphosphate, 198 Gram stain, 169
Fructose 6-Phosphate, 198 Granulocyte, 114
Fumarase, 204, 205 Granuloma, 135, 162
Fumarate, 204, 205 Granuloma inguinale, 164
Graves disease, 145
G Grawitz tumor, 160
Galactose, 111 Growth Hormone, 108
Gallbladder, 33, 113 Guanine, 216
Gallstones, 148 Guarneri bodies, 173
Gaseous exchange, 130 Guillain-Barré Syndrome, 156
Gas gangrene, 178 Gut embryology, 31
Gastroesophageal reflex disease, 147 Guyon’s canal, 16
Gastric carcinoma, 147
Gastric Inhibitory Peptide, 113 H
Gastrin, 113 Haldane effect, 130
Gastrinoma, 146 Hashimoto’s thyroiditis, 145
Gaucher’s disease, 137 Haversian canal, 39
Genitalia Heart rate control, 107
female, 49 Heart valves, 22
male, 48 Helicobacter pylori, 178
GERD, 147 Hemangioma, 143
Gestational Diabetes, 146 Hemiazygos vein, 54
Giardia lamblia, 186 Hemochromatosis, 158
Giant cell tumor, 149 Hemophilia, 138
Gigantism, 144 Hematoma
Glabella, 92 extradural, 153
Gland subdural, 153
adrenal, 30 Hemolytic Uremic syndrome, 177
Brunner’s, 111 Hemophilus
bulbourethral, 66 aegypti, 179
parathyroid, 30, 109 ducreyi, 179
pituitary, 27 influenzae, 179
sebaceous, 59 Hemorrhagic disease of newborn, 158
sweat, 59 Hepatitis, 148
thyroid, 29, 109 Hepatitis A virus, 148, 174
Globus pallidus, 89 Hepatitis B virus, 148, 173
Glioblastoma multiforme, 154 Hepatitis C virus, 148, 174
Glomerular Filtration Rate, 123 Hepatitis D virus, 174
Glomerulonephritis, 159 Hepatitis E virus, 174
Glomerulus, 123 Hepatocellular carcinoma, 148
Glossopharyngeal nerve, 82, 86 Hepatolenticular disease, 158
Glucagon, 110 Hering-Breuer reflex, 130
Glucagon-like peptide 1, 113 Herpes simplex virus, 166, 173
Glucokinase, 198, 199 Herpes zoster, 156, 173
Gluconeogenesis, 201 Hexokinase, 198
Glucose 6-Phosphate, 198 Hexose monophosphate shunt, 209
GLUT 1-4, 110, 205 HGPRT deficiency, 138
Glutamic acid, 215 Hilton’s law, 39
Glutamine, 215 Hip joint, 42
Glutathione peroxidase, 220 Hirano bodies, 154
Glyceraldehyde 3-Phosphate, 198 Histidine, 214
Glycerol 3-phosphate shuttle, 206 Hirschsprung’s disease, 148, 156
Glycogenesis, 209 Histoplasma capsulatum, 184
Glycogen metabolism, 209 Histoplasmosis, 184
Glycogenolysis, 210 HIV, 172, 174
Glycogen Phosphorylase, 210 HLA-B27 arthritis, 150
Glycolysis, 197 Hodgkin’s lymphoma, 139
Gomphosis, 35 Homonymous hemianopia, 84
Gonalgia paresthetica, 155 Hook, Robert, 169
Gonococcal urethritis, 164, 177 Hookworm, 187
Gout, 151, 216 Horner’s syndrome, 156, 163

240
Hormone production, 213 Insulinoma, 146
Host Intercostal space, 61
primary, 186 Internal acoustic meatus, 86, 93
secondary, 186 Internal bladder sphincter, 64, 65
Human Immune Deficiency virus, 174 Internal capsule, 88
Human Papilloma virus, 173 Intracerebral hemorrhage, 154
Hunter’s canal, 17 Internal iliac artery, 25
Huntington’s chorea, 154 Interphalangeal joint, 42
Hutchinson’s teeth, 154 Interstitial cystitis, 159
Hyaluronidase, 128 Interstitial pneumonia, 162
Hydatid cysts, 188 Intervertebral disc, 71
Hydrolysis, 195 Invasion, 170
Hymenolepis nana, 188 Iodine, 220
Hyperparathyroidism, 145 Iodine deficiency, 158
Hyperplasia, 136 Iron, 220
Hyperprolactinemia, 144 Iron deficiency, 158
Hypersensitivity reactions, 117 Irritable Bowel Syndrome, 148
Hypertension, 142 Ischemia, 136
Hyperthyroidism, 145 Ischemic Heart Disease, 142
Hypertrophy, 136 Ischium, 51
Hypoglossal nerve, 82, 87 Islet cells, 110
Hypoparathyroidism, 145 Isocitrate, 203
Hypothyroidism, 144 Isocitrate dehydrogenase, 203
Hypoxia, 136 Isoleucine, 214
Ivanowski, Dimitri, 169
I
Iatrogenic, 170 J
Ileum, 33 Jejunum, 35
Ilium, 51 Jenner, Edward, 169
Immunoglobulins, 116 Joint classification, 37
Immunity Joint
acquired, 117 ankle, 44
artificial, 117 atlantoaxial, 38, 73
cell-mediated, 117 atlanto-occipital, 73
humoral, 117 carpometacarpal, 42
innate, 117 condyloid, 38
natural, 117 costochondral, 74
non-specific, 117 costotransverse, 74
passive, 117 costovertebral, 74
specific, 117 elbow, 41
Implantation, 128 ginglymus, 38
Incidence, 192 hip, 42
Indian ink preparation, 184, 189 interphalangeal, 42
Infection control, 192 knee, 43
Inferior colliculus, 86 manubriosternal, 74
Inferior mesenteric artery, 25, 35 planar, 38
Inferior salivary nucleus, 87 sacroiliac, 74
Inferior thyroid artery, 27, 29 sellar, 38
Inflammation shoulder, 40
acute, 135 spheroidal, 38
cardinal signs, 135 sternochondral, 74
chronic, 135 sternoclavicular, 41
Influenza virus, 174 temporomandibular, 40
Inhibition trochoid, 38
competitive, 195 wrist, 41
non-competitive, 195 xiphisternal, 74
Inguinal canal, 17 zygapophyseal, 73
Inguinal triangle, 13 Juxtaglomerular apparatus, 125
Inosine, 216
Intrinsic Factor, 112, 219 K
Intussusception, 147 Kala-azar, 187
Insulin, 110 Kaposi sarcoma, 143, 166, 173

241
Kartagener’s syndrome, 161 pulmonary, 53
Karyolysis, 136 supraspinous, 70
Karyorrhexis, 136 transforaminal, 71
Kayser-Fleisher rings, 158 Treitz, 33
Keto acids, 214 Ligamentum flavum, 70, 71
Keloid, 135 Ligase, 195
Kenshan’s disease, 220 Linoleic acid, 211
Kidney, 64 Lipogenesis, 213
Kinase, 195 Lipolysis, 212
Kissing bug, 186 Lipoprotein, 211
Klebsiella pneumoniae, 178 high density, 211
Klumpke’s palsy, 97, 155 intermediate density, 211
Kmax, 195 low density, 211
Knee joint, 43 very low density, 211
Koch, Robert, 169 Listeria monocytogenes, 178
Koch-Weeks bacillus, 179 Listeriosis, 178
Korsakoff’s psychosis, 154 Liver, 57
Krebs cycle, 203 Liver fluke, 188
Kuru, 154 Lobe
Kussmaul’s breathing, 130 frontal, 81
Kwashiorkor, 157 limbic, 81
occipital, 81
L parietal, 81
Lactase, 113 temporal, 81
Lactation, 128 Loop of Henle, 123
Lactic acid, 201 Looser’s zone, 158
Lactose, 113, 197 Lou Gehrig’s disease, 154
Lambert-Eaton syndrome, 151 Lowenstein-Jensen medium, 177, 189
Langhan’s cells, 135 Lumbar plexus, 97, 98
Lao lao, 187 Lumbar triangle, 12
Large intestine, 35, 112 Lumbosacral plexus, 98, 99
Lateral corticospinal, 76 Lung, 53
Lateral geniculate body, 84 Lung abscess, 162
Law Lung compliance, 131
Boyle, 129 Lung volumes, 131
Charles, 129 Lupus vulgaris, 166
Fick, 129 Luteinizing Hormone, 108, 127
Frank-Starling, 105 Lyme disease, 151, 176
Hilton, 39 Lymph node, 56
La Place, 107 Lymphocytes, 114
Lead poisoning, 155 Lymphogranuloma venereum, 164, 176
Legg-Calvé-Perthes disease, 152 Lymphoid cell line, 114
Legionella pneumophila, 179 Lysine, 214
Leishmania
brasilliensis, 187 M
donovani, 187 Macrophages, 114, 115
Leprosy, 156, 166, 177 Madurella grisea/mycetomastis, 184
Leptospira interrogans, 176 Magnesium, 220
Lesch Nyhan syndrome, 138 Main pancreatic duct, 34
Leucine, 214 Malaria, 187
Libman Sacks endocarditis, 141 Malassezia furfur, 183
Life exp[ectancy, 192 Malate, 204, 205
Ligament Malate-aspartate shuttle, 206
anterior longitudinal, 70 Malate dehydrogenase, 204, 205
broad, 50 Male genitalia, 48
cruciate, 70 Malignant pustule, 177
dentate, 76 Malignant melanoma, 166
inguinal, 15 Malignant tumors, 139
interspinous, 70 Mallory-Weiss syndrome, 147
intertransverse, 70 Maltase, 111
nuchal, 70 Maltose, 111
posterior longitudinal, 70 Marasmus, 157

242
Marfan’s syndrome, 137 anopheles, 187
Margination, 135 culex filiriasis, 187
Marie-Strumpell’s disease, 150 culex pipiens, 187
McArdle disease, 137 aedes aegypti, 174
McBurney’s point, 35 Mouth, 111
Measles, 166, 174 Mullerian duct, 48
Meckel’s diverticulum, 31, 147 Multiple myeloma, 139, 150
Medial geniculate body, 86 Multiple sclerosis, 154
Mediastinum, 62 Mumps, 174
Medium Muscle
chocolate agar, 189 biceps brachii, 45
Hektoen enteric agar, 189 brachioradialis, 46
Loeffler’s medium, 189 cardiac, 105
Lowenstein-Jensen, 189 contraction, 120
MacConkey’s agar, 189 deltoid, 45
Middlebrook, 189 diaphragm, 55
Purified Chick Embryo Culture, 189 erector spinae, 75
Regan-Lowe agar, 189 extensor hallucis longus, 47
Sabouraud, 189 facial expression, 94
Thiosulfate-Citrate-Bile salts-Sucrose, 189 frontalis, 94
Meningitis, 154, 177, 181 gastrocnemius, 47
Meningocele, 153 gluteus maximus, 47
Menstrual cycle, 127 infraspinatus, 46
MEN Type 1, 146 inferior oblique, 84
MEN Type II, 146 interspinales, 75
MEN Type III, 146 intertransversarii, 75
Meralgia paresthetica, 155 lateral cricoarytenoid, 95
Mesencephalon, 80 lateral rectus, 84
Mesoderm derivatives, 10 latissimus dorsi, 45
Mesophile, 178 levator scapulae, 45
Mesothelioma, 163 medial rectus, 84
Metabolism multifidus, 75
acidosis, 126 oblique arytenoid, 95
alkalosis, 126 orbicularis oculi, 94, 94
bilirubin, 113 orbicularis, oris, 94
carbohydrate, 197 palatoglossus, 87
lipid, 212 pectoralis major, 45
protein, 215 peroneus longus, 47
Metaplasia, 135 posterior cricoarytenoid, 95
Metencephalon, 80 psoas major, 46
Methionine, 214 quadratus femoris, 47
Microsporum infection, 183 scalenus anterior, 45
Midgut derivatives, 31 scalenus medius, 45
Minamato disease, 155 serratus anterior, 45
Minerals, skeletal, 119
calcium, 220 stapedius, 86
copper, 220 sternocleidomastoid, 45
iodine, 220 stylopharyngeus, 86, 95
iron, 220 subscapularis, 46
magnesium, 220 superior oblique, 84
selenium, 220 superior rectus, 84
zinc, 220 teres major, 46
Mitral valve, 22 teres minor, 46
MODY [Mature Onset Diabetes in Young], 146 tibialis anterior, 47
Mold, 182 tibialis posterior, 47
Molluscum contagiosum, 173 triceps, 46
Monocytes, 115 supraspinatus, 46
Mononucleosis, 173 trapezius, 45
Mons pubis, 49 Muscle types, 39
Morbidity, 192 Muscular triangle, 12
Mortality, 192 Myasthenia gravis, 151
Mosquito Mycobacterium leprae, 177

243
Mycobacterium tuberculosis, 177 oculomotor, 82. 84
Mycoplasma pneumoniae, 176 optic, 82, 84
Myelencephalon, 80 phrenic, 96
Myeloid cell line, 114 pudendal, 98
Myelomeningocele, 153 radial, 96
Myocardial Infarction, 142 sciatic, 98
Myopathies, 151 spinal accessory, 82, 87
Myosin, 118, 119 subscapular, 97
Myotome, 69 superficial peroneal, 99
Myxedema, 158 superior gluteal, 98
supraclavicular, 96
N suprascapular, 97
NAD, 198, 206 thoracodorsal, 97
NADH, 198, 204, 206 tibial, 99
NADP, 206 transverse cervical, 96
Nasion, 92 trochlear. 82, 84
Necator americanus, 187 ulnar, 96
Necrosis vestibulocochlear, 82, 86
caseous, 136 Nerve conduction, 121
coagulative, 136 Nerve ending types, 123
enzymatic, 136 Nerve fiber type, 123
fatty, 136 Nervus intermedius, 93
liquefactive, 136 Neural crest cells, 76
Negri bodies, 174 Neuroblastoma, 145
Neisseria Neurofibromatosis, 154
gonorrhoea, 177 Neurohypophysis, 109
meningitis, 177 Neuromuscular junction, 119
Nematodes, 187 Neurulation, 76
Neoplasia, 139 Neutrophils, 11
Nephritic syndrome, 159 Niemann-Pick disease, 137
Nephron, 123 Night blindness, 217
Nephrotic syndrome, 159 Nitrogen removal
Nerve ammonia formation, 215
abducens, 82, 84 deamination, 215
accessory, 87 transamination, 215
ansa cervicalis, 96 urea formation, 215
axillary, 96 Nociceptor classification, 122
chorda tympani, 86 Nodes,
common fibular [peroneal], 99 Bouchard’s, 150, 151
cranial accessory, 82, 87 Heberden’s, 151
deep peroneal, 99 Haygarth’s, 150
dorsal scapular, 97 Ranvier, 121
facial, 82, 86 Nor-epinephrine, 101, 110
femoral, 97 Nosocomial, 171
genitofemoral, 97 Notochord, 69
glossopharyngeal, 82, 87 Nucleus
great auricular, 96 ambiguus, 87
greater splanchnic, 100 paraventricular, 109
hypoglossal, 82, 87 pulposus, 71
iliohypogastric, 97 solitarius, 86, 87
ilioinguinal, 97 supraoptic, 109
inferior gluteal, 98 Nyctalopia, 217
lateral femoral cutaneous, 97
lateral pectoral, 97 O
least splanchnic, 100 Obturator nerve, 97
lesser occipital, 96 Oculomotor nerve, 82, 84
lesser splanchnic, 100 Odontoid process, 70
long thoracic, 97 Ohio Valley fever, 184
medial pectoral, 97 Olfactory nerve, 82, 83
median, 96 Oligodendrocytes, 80
musculocutaneous, 96 Onchocerca volvulus, 186
obturator, 97 Oncogenes, 140

244
Optic chiasm, 84 Phlebotomous sand flies, 187
Optic nerve, 82, 84 Phosphoenolpyruvate, 199
Optic radiation, 84 Phosphoenolpyruvate carboxykinase, 201
Orthomyxo virus, 172, 174 Phosphofructokinase, 198, 199
Osteochondroma, 149 Phosphoglucomutase, 209
Osteogenesis imperfecta, 137, 149 Phosphoglycerate kinase, 199
Osteoma, 150 Phosphoglycerate mutase, 199
Osteitis fibrosa cystica, 149 Phosphorylation, 195
Osteoarthritis, 151 Phrenoderma, 217
Osteomalacia, 149, 158, 217 Pia mater, 76
Osteomyelitis, 149 Pico RNA virus, 174
Osteoporosis, 149 PID, 165
Osteosarcoma, 139, 150 Piedra hortae, 183
Ovary, 50 Pigeon poop, 184
Owl-eye appearance, 184, 189 Pink puffers, 161
Oxaloacetate, 203, 206 Pin worm, 187
Oxidation, 195 Piriformis syndrome, 155
Oxidative phosphorylation, 206 Pituitary gland, 29, 108
Oxytocin, 109, 128 Pityriasis versicolor, 166, 183
Pityrosporum orbiculare, 183
P Plate
Paget’s disease, 149 alar, 76
Palmitic acid, 211 basal, 76
Pancoast tumor, 163 Plasmodium
Pancreas, 30, 110 falciparum, 187
Pancreatic cancer, 148 malariae, 187
Pancreatitis, 148 ovale, 187
Pandemic, 192 vivax, 187
Paul Bunnel test, 173, 190 Pleura
Paracoccidioides brasiliensis, 184 effusion, 163
Paragonimus westermani, 188 parietal, 53
Paramesonephric duct, 48 visceral, 53
Paramyxo virus, 172, 174 Plexus
Paranasal sinuses, 95 Auerbach, 102
Parasites, 185 brachial, 95
Parasympathetic nervous system, 100, 101 cervical, 95
Parathyroid gland, 30 lumbar, 97
Pars interarticularis, 69 lumbosacral, 98
Parvo virus, 172, 173 Meissner, 102
Pasteurization, 169, 192 vertebral venous, 66
Pasteur, Louis, 169 Plumbism, 155
Patent Ductus Arteriosus, 141 Plummer-Vinson syndrome, 158
Pathogenicity, 170 Pneumocytes
Pavementation, 135 Type I, 129
Pectinate line, 36 Type II, 129
Pellagra, 218 Pneumoconioses, 162
Pelvic Inflammatory Disease, 165 Pneumocystis
Pelvis, 51 carinii, 184
Penis, 49 jiroveci, 184
Pentose Phosphate Pathway, 208 pneumonia, 162
Peptic Ulcer Disease, 147, 178 Pneumonia, 161, 162
Perfusion, 129 Pneumothorax
Peripheral Arterial Disease, 143 secondary, 163
Peripheral resistance, 107 spontaneous, 163
Peritoneum, 32 tension, 163
Peutz-Jegher syndrome, 148 Podagra, 151
Pfeiffer’s bacillus, 179 Poisoning
Phagocytosis, 114, 116 carbon monoxide, 155
Pharyngeal arches, 95 lead, 156
Phenylalanine, 214 mercury, 156
Phenylketonuria, 138 Poliomyelitis, 154, 174
Pheochromocytoma, 139, 145, 146 Polio virus, 174

245
Polyarteritis nodosa, 143 R
Polymyalgia rheumatica, 152 Rabbit fever, 180
Pompe disease, 137 Rabies, 174
Popliteal artery, 25, 26 Radial artery, 25
Popliteal fossa, 18 Randomized Controlled Trial, 191
Posterolateral sclerosis, 154 Raphespinal tract, 76, 77
Posterior columns, 76 Rathke’s pouch, 29
Posterior pituitary lobe, 109 Raynaud’s disease, 143
Posterior tibial artery, 25 Raynaud’s phenomenon, 143
Pox virus, 173 Receptors
Prevalence, 192 adrenergic, 122
Prinz Metal angina, 142 cholinergic, 122
Process muscarinic, 122
accessory, 70 nicotinic, 122
mammillary, 70 Rectum, 35
odontoid, 70 Rectus abdominis, 32
Proenzyme, 195 Rectus sheath contents, 32
Progesterone, 108, 110, 127, 128 Rectus sheath formation, 32
Projection fibers, 81 Recurrent fever, 180
Prolactin, 109 Recurrent laryngeal nerve, 29
Proliferative phase, 127, 128 Red blood cells, 114
Proline, 214 Red currant jelly sputum, 178
Prosencephalon, 80 Reduction, 195
Prostatic Specific Antigen, 140 Reed, Walter, 169
Protein Calorie Deficiency, 157 Re-emerging diseases, 192
Protein structure Reflex
primary, 214 deep tendon, 120
quaternary, 214 Hering-Breuer, 130
secondary, 214 pain withdrawal, 120
tertiary, 214 somatosomatic, 120
Proteus mirabilis, 178, 190 somatovisceral, 102
Prothrombin, 116 sympathetic dystrophy, 156
Protozoa, 185 viscerosomatic, 102
Proximal Convoluted Tube, 123 viscerovisceral, 102
Prusiner, Stanley, 169 Regions of the abdomen, 31
Pseudomembranous colitis, 177 Reiter’s syndrome 150, 176
Pseudomonas aeruginosa, 179 Relapsing fever, 180
Psittacosis, 176 Renal blood flow, 123
Psoriasis, 166 Renal calculi, 160
Psychrophile, 179 Renal Cell Carcinoma, 160
Pterion, 92 Renal function, 123
Pubic bone, 51 Renal stones, 160
Pulmonary Renin, 124
embolism, 143 Respiratory
ligament, 53 acidosis, 126
Purine metabolism, 216 alkalosis, 126
Purkinje fibers, 24 Reticulospinal tract, 76, 77
Putamen, 89 Rexed laminae, 79
Pyelonephritis, 159 Reye’s syndrome, 148
Pyknosis, 136 Rhagades, 154
Pyridine-linked dehydrogenase, 206 Rheumatic Fever, 141, 180
Pyrimidine metabolism, 216 Rheumatoid Arthritis, 117, 150
Pyruvate carboxylase, 201 Rhino virus, 172, 174
Pyruvate kinase, 199 Rhombencephalon. 80
Ribs
Q atypical, 61
Quadrangular space, 15 false, 60
Quadrants of the abdomen, 31 true, 60
Quadratus lumborum, 64 typical, 60
Quinones, 206 Rice water stool, 179
Rickets, 149, 158, 217
Rickettsia

246
 prowazekii, 176 Siderosis, 162
rickettsii, 176 Silicosis, 162
tsutsugamishi, 176 Sinu-atrial node, 23, 24
typhi, 176 Sinus, 135
Riedel’s thyroiditis, 145 Sipple’s syndrome, 146
Ringworm, 166, 183 Silo-filler’s lung, 162
River blindness, 187 Sjörgen’s syndrome, 150
Root of the lung, 53 Skeletal muscle, 39
Roseola, 166 Skin layers, 59
Roundworm, 187 Skull, 92
Rubella, 172, 174 Slapped cheek syndrome, 173
Rubeola, 172, 174 Slipped capital femoral epiphysis, 152
Rubrospinal tract, 76, 77 Sludge digestion, 192
Ruska, Ernst, 169 Small cell lung cancer, 163
Small intestine, 35, 111
S Smallpox virus, 173
Sabin, Albert, 169 Smooth muscle, 39
Salk, Jonas, 169 Solitary nucleus, 87
Salmonella Somatostatin, 112, 113
enterides, 178, 180 Sorbitol, 200
typhi, 178, 180 Space
Salpingitis, 165 quadrangular, 14
Sand filtration, 192 triangular, 15
San Joaquin Valley fever, 184 Specificity, 191
Sarcoidosis, 162 Spelunker’s disease, 184
Sarcolemma, 118 Spermatic cord, 49
Sarcomere, 118 Sperm development, 127
Sacroplasmic reticulum, 118 Sphincter of Oddi, 30, 34, 112
Sarcoptes scabiei, 166 Spina bifida, 153
Scabies, 166 Spinal canal, 72
Scalp, 92 Spinal cord
Scar, 135 structure, 76
Scarlet fever, 166 organization, 76
Schistosoma blood supply, 79
hematobium, 188 Spinothalamic tract, 77
japonicum, 188 Spleen, 56
mansoni, 188 Spores, 192
Schwann cells, 80 Sporothricosis, 166, 184
Sclerotome, 69 Sporothrix schenckii, 166, 182, 184
Schultz-Carlton test, 189 Stain
Scurvy, 220 Eosin-Methylene blue, 189
Secretin, 113 Gram, 169
Secretory phase, 127 Indian ink, 184, 189
Selenium, 220 Wright-Giemsa, 189
Sella turcica, 29 Ziehl-Neelsen, 189
Semmelweiss, Ignazio, 169 Staphylococcus
Sensitivity, 191 aureus, 176
Septal development, 21 saprophyticus, 176
Serine, 214 Starch metabolism, 197
Seronegative, arthritis, 150 Stearic acid, 211
Seropositive arthritis, 150 Sterilization, 192
Serratia marcescens, 178 Sternoclavicular joint, 41
Severe Combined Immunodeficiency, 136 Still’s disease, 150
Sheehan’s syndrome, 144 Stomach, 33, 111
Shigella Stratum
dysenteriae, 178 basale, 59
flexneri, 178 corneum, 59
sonnei, 178 granulosum, 59
Shoulder joint, 40 lucidum, 59
SIADH, 163 spinosum, 59
Sickle Cell Disease, 138 Streptococcus
Sickle Cell Trait, 138 pneumoniae, 177

247
 pyogenes, 177 Sipple, 146
viridans, 177 Sjörgen, 150
Strongyloides stercoralis, 187 Slapped Cheek, 166
Study population, 191 Turner, 137
Subarachoid hemorrhage, 153 Tarsal tunnel, 155
Subarachnoid space, Waterhouse-Friderichsen, 145
Subclavian artery, 27 Wermer, 146
Submental triangle, 12 Wernicke, 154, 218
Suboccipital triangle, 11 Wiskott-Aldrich, 136
Subsartorial canal, 17 Zollinger-Ellison, 146
Substantia gelatinosa, 78 Synergism, 170
Succinate, 204 Synovial joint, 38
Succinate dehydrogenase, 204 Syphilis, 164, 176
Succinate thiokinase, 203 congenital, 154
Succinyl CoA, 203 primary, 164
Sucrase, 111 secondary, 164
Sucrose, 111, 197 tertiary, 164
Sudeck’s atrophy, 156 Syringomyelia, 155
Surface markings of the heart, 21 Systemic Lupus Erythematosus, 117, 151
Surfactant, 129
Superficial palmar arch, 28 T
Superior laryngeal nerve, 29 Tabes dorsalis, 164
Superior mesenteric artery, 31, 35 Taenia
Superior thoracic aperture, 14 saginatum, 188
Superior thyroid artery, 29 solium, 188
Suprapleural membrane, 54 Takayasu’s arteritis, 143
Symphysis, 37 Tapeworm, 188
Synchondrosis, 37 Tarsal tunnel, 19
Swimmer’s itch, 188 Tarsal Tunnel Syndrome, 155
Symbiosis, 171 Tay-Sachs disease, 137
Sympathetic nervous system, 100 T cells, 114
Synaptic conduction, 121 Tectospinal tract, 76, 77
Synchondrosis, 37 Temporal arteritis, 143
Syndesmosis, 37 Temporomandibular joint, 40
Syndrome. Test
Addison, 144 Ascoli, 189
Bruton’s agammaglobulinemia, 136 Ames, 189
Carpal tunnel, 155 Anti-Streptolysin, 190
Chediak-Higashi, 136 Bordet-Gengou, 189
Chronic Regional Pain, 156 Catalase, 189
Conn, 145 Coagulase, 189
Cushing, 145 Coombs, 190
DiGeorge, 136 Dick, 189
Down, 137 ELISA, 190
Ehlers-Danlos, 137 Heaf, 190
Elbow tunnel, 155 Kvein, 190
Felty, 150 Mantoux, 190
Goodpasture, 160 Paul Bunnel, 190
Horner, 156, 163 Quellung, 191
Inappropriate ADH secretion, 163 Schultz Carlton reaction, 189
Kartagener, 161 Tine, 190
Klinefelter, 137 RPR, 190
Lambert-Eaton, 151 VDRL, 190
Lesch-Nyhan, 138 Weil-Felix, 190
Mallory-Weiss, 147 Western Blot, 190
Marfan, 137 Widal, 190
Peutz-Jegher, 148 Testis, 48
Piriformis, 155 Testosterone, 111, 213
Plummer-Vinson, 158 Tetanus, 177
Reiter, 151 Thalassemia, 138
Reye, 148 Thermophile, 179
Sheehan, 144 Thoracic aorta, 25

248
Thoracic cage, 60 Trigeminal nerve, 82, 85
Thoracic duct, 58 Triglyceride, 211
Thoracic outlet, 14 Triose phosphate isomerase, 198
Thoracolumbar outflow, 100 Trochlear nerve, 82, 84
Threadworm, 187 Troisier’s sign, 147
Threonine, 214 Tropical sprue, 147
Thromboangitis obliterans, 143 Troponin, 118, 119
Thrombosis, 141, 154 Tropomyosin, 118
Thrombophlebitis, 143 Truncus arteriosus, 20
Thymine, 218 Trypanosoma
Thymoma, 151 cruzi, 186
Thymus, 58 gambiense, 186
Thyroarytenoid, 95 rhodensiense, 186
Thyroid gland, 29 Tryptophan, 215
Thyroid Stimulating Hormone, 108, 109 Tuberculosis, 162, 177
Thyroxin, 109 Tumor markers, 140
Tidal Volume, 130, 131 Tunnel
Tinea carpal, 16
capitis, 183 ulnar, 16
corporis, 183 Type I pneumocytes, 130
cruris, 183 Type II pneumocytes, 130
versicolor, 183 Types of joints, 36
Toga virus, 172 Typhoid fever, 178, 180
TORCHeS infections, 165 Typhus
Total Lung Capacity, 130, 131 edemic, 176, 180
Toxoplasma gondii, 187 epidemic, 176, 180
Toxoplasmosis, 165, 187 murine, 176, 180
Trachea, 52 scrub, 176, 180
Tract Tyrosine, 214
dorsal columns, 76,
dorsal spinocerebellar, 76 U
lateral corticospinal, 76 Ubiquinone, 206
raphespinal, 76 Ulcerative colitis, 148
reticulospinal, 76 Ulnar artery, 27, 28
rubrospinal, 76 Ulnar tunnel, 16
spinothalamic, 76 Ulnar tunnel syndrome, 155
tectospinal, 76 Undulant fever, 180
ventral corticospinal, 76 Uracil, 216
ventral spinocerebellar, 76 Urea cycle, 215
vestibulospinal, 76 Urea-splitting bacteria, 190
Transferase, 195 Ureter, 65
Transient Ischemic Attack, 154 Urethra, 66
Transmigration, 135 Urethritis
Transposition of the great vessels, 141 chlamydia, 164
Transverse colon, 35 gonococcal, 164
Treponema pallidum, 177 Uric acid, 216
Triacylglycerols, 211 Urinary bladder, 65
Triangle US Health Agencies, 192
Auscultation, 12 Uterine tube, 50
Callot, 34 Uterus, 50
inguinal, 13
lumbar, 12 V
Petit, 12 Vagina, 47
suboccipital, 11 Vagus, 82, 87
Triangular space, 15 Valine, 214
Trichinella spiralis, 187 Van Leeuwenhoek, 169
Trichinosis, 187 Varicose vein, 143
Trichomonas vaginalis, 185 Vascular response to exercise, 107
Trichomoniasis, 165 Venous drainage of the heart, 23, 24
Trichophyton infection, 183 Valves
Trichuris trichuria, 187 aortic, 22
Tricuspid valve, 22 mitral, 22

249
 pulmonary, 22 Von Recklinghausen disease, 154
tricuspid, 22 VSD, 141
VDRL false positive, 190
Vector, 186 W
Vein Wallerian degeneration, 136
accessory azygos, 54 Waterhouse-Friderichsen syndrome, 145
accessory hemiazygos, 54 Water purification, 192
azygos, 54 WEE, 172, 174
brachiocephalic, 54 Weil disease, 175
cardiac, 23 Wermer’s syndrome, 146
femoral, 13 Wernicke’s syndrome, 154, 218
Ventilation, 129 Wernicke-Korsakoff psychosis, 218
Ventilation/Perfusion ration, 129 Western Equine Encephalitis, 172, 174
Ventral corticospinal tract, 76, 77 West Nile virus, 174
Ventricle Whipple’s disease, 147
right, 22 Whipworm, 187
left, 22 White blood cells, 114
Ventricular septal defect, 141 Whooping cough, 178
Vertebra Wilms tumor, 159
cervical, 70 Wilson’s disease, 158
lumbar, 70 Wiskott-Aldrich syndrome, 136
prominens, 70 Wood’s light, 189
regional characteristics, 70 Wool sorter’s disease, 176
thoracic, 70 Worms
typical, 69 eye, 187
Vertebral development, 69 hook, 187
Vertebral end plate, 71 pin, 187
Vertebral venous plexus, 66 round, 187
Vestibulocochlear nerve, 82, 86 tape, 188
Vestibulospinal tract, 76, 77 thread, 187
Vibrio cholerae, 179 whip, 187
Virchow’s triad, 142 Wuchereria bancrofti, 187
Virulence, 170
Viruses, 172 X
Vital capacity, 131, 132 Xanthine, 216
Vitamin A, 157, 217 Xanthine oxidase, 216
Vitamin B1, 157, 218 Xerophthalmia, 217
Vitamin B2, 157, 218 Xiphoid process, 60
Vitamin B6, 157, 218
Vitamin B7, 157, 219 Y
Vitamin B9, 157, 219 Yeast, 183
Vitamin B12, 157, 219 Yellow fever virus, 172, 174
Vitamin D, 158, 217 Yersinia pestis, 178
Vitamin E, 158, 217
Vitamin K, 158, 217
Vmax, 197 Z
Vocalis, 95 Zenker’s degeneration, 136
Volvulus, 148 Ziehl-Neelsen stain, 177, 189
Von Gierke disease, 137 Zollinger-Ellison syndrome, 146

250