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USMLE STEP 1

PLATINUM NOTES
The Complete Preparatory Guide
Second Edition

Ashfaq UI Hassan

MBBS MS
Consultant Anatomy
SKIMS Medical College
Bemina, Srinagar, Jammu and Kashmir, India

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USMLE Step 1 Platinum Notes
First Edition: 2013
Second Edition: 2016
ISBN: 978-93-5250-171-7
Printed at

Contributors
Ashfaq UI Hassan
MBBS MS

ConsultantAnatomy
SKIMS Medical College
Bemina, Srinagar, Jammu and Kashmir, India

Prof. Showkat A Zargar


MD DM (Gastroenterology)

Director and Principal


Sher-i-Kashmir Institute of Medical Sciences (SKIMS)
Srinagar, Jammu and Kashmir, India

Prof. Naseer Mir


MS (Orthopedics)

Professor and Head Orthopedics


Sher-i-Kashmir Institute of Medical Sciences (SKIMS)
Srinagar, Jammu and Kashmir, India

Dr Sheikh Manzoor Ahamed


MD (Dermatology)

Associate Professor and HeadDermatology


Sher-i-Kashmir Institute of Medical Sciences (SKIMS)
Srinagar, Jammu and Kashmir, India

Preface to the Second Edition


I am extremely obliged to the Almighty Allah and no words would be enough to express my thanks to his holiness for
guiding me.
This book USMLE Step 1 Platinum Notes consists of complete revision material for the preparation of the USMLE
examinations with important latest questions asked in these examinations and most of the students do not fare well with
these questions, thus significantly lowering their scores.
The book is for complete revision with special focus on the most common and most important cases asked. It covers
special and important topics which are most frequently asked by the examiners.
The prime focus for the students to go through the most important points and recapitulating these at the end is
important for any examination and special focus for the same has been given for their benefit.
Like the other series of books for the USMLE examinations being authored by me, which have had a tremendous
success, I hope this effort of mine again would be helpful for the students throughout the world in their pursuit of academic
excellence along with the important fact of getting a very good score in the examinations.
I hope the book proves to be useful for our students to the fullest.
I would encourage any aspiring student to join me for his/her contribution.

Ashfaq Ul Hassan
ashhassan@rediffmail.com

Preface to the First Edition


It gives me a great pleasure to introduce Platinum Notes for USMLE Step 1 and Step 2.
A need was felt by most of the students for a comprehensive book for USMLE for preparing extensively and
simultaneously getting a very good score.
My efforts are directed to benefit the students to the maximum.
For a student preparing, revising, forgetting and consulting different books is a part of the game. In this journey some
students tend to get nervous and anxious and I thought of putting all my best efforts into one book which would make the
preparation simpler, interesting, more lucid and palatable.
High yield points, important topics, clinical correlations, in-depth focus on subjects, easy retention and quick revision
are the points on which I have focused taking into account the latest trends of the examinations.
The matter in the book is highly concentrated, needs multiple revisions and deep concentration for retention.
The book has been framed to simulate the study pattern of USMLE examinations to its best.
The questions in the text and after every subject are almost similar to the questions put in the actual USMLE examination
which gives a student a good chance to understand the standard of USMLE as well as to prepare for the examinations in a
better way.
I feel that the students would be benefitted through my effort and a feedback from the students would be highly
appreciated at ashhassan@rediffmail.com
I wish you good luck for your academic pursuits.

Ashfaq Ul Hassan
ashhassan@rediffmail.com

Acknowledgments
No words would be enough to express my regards to Prof. Showkat A Zargar, Director, Sher-i-Kashmir Institute of Medical
Sciences (SKIMS), Srinagar, Jammu and Kashmir, India for his constant encouragement.
I am also thankful to my father Prof. Ghulam Hassan for his constant encouragement in all my academic pursuits and
guiding me throughout the process of the completion of this book.
I convey my sincere thanks to Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India for their efforts and
suggestions, especially Shri Jitendar P Vij (Group Chairman), Ms Chetna Vohra (Associate Director), and Ms Payal Bharti
(Project Manager) for helping me through my idea.

Abbreviations
1

Primary

bid

Twice a day

Secondary

BMR

Basal metabolic rate

Fracture

BP

Blood pressure

ACE

Angiotensin converting enzyme

BPH

Benign prostatic hypertrophy

ACE-I

Angiotensin converting enzyme inhibitor

BUN

Blood urea nitrogen

ACTH

Adrenocorticotropic hormone

B/L

Bilateral

ACh Acetylcholine

BM

Bone marrow, basement membrane

Adr Adrenaline

b/n or b/w

Between

AD

Autosomal dominant

C/S

Culture and sensitivity

ADH

Anti-diuretic hormone

Ca Calcium

AF

Atrial fibrillation

CABG

Coronary artery bypass graft

AFB

Acid-fast bacilli

CAD

Coronary artery disease

AFP Alpha-fetoprotein

CCF

Congestive cardiac failure

A.k.a

Also known as

CT

Computerized tomography

ALL

Acute lymphocytic leukemia

CHF

Congestive heart failure

AML

Acute myelogenous leukemia

CHO Carbohydrate

ANA

Antinuclear antibody

CML

ANS

Autonomic nervous system

CMV Cytomegalovirus

2+

Chronic myelogenous leukemia

AP Anteroposterior

CN

Cranial nerves

AR

Autosomal recessive

CNS

Central nervous system

ARDS

Acute respiratory distress syndrome

CO

Cardiac output

ARF

Acute renal failure

C/O

Complaining of

AS

Aortic stenosis

COLD

Chronic obstructive lung disease

ATP

Adenosine triphosphate

COPD

Chronic obstructive pulmonary disease

ASD

Atrial septal defect

CPK

Creatine phosphokinase

AV Atrioventricular

CRF

Chronic renal failure

A/E

All except

CRP

C-reactive protein

Acc/ to

According to

CSF

Cerebrospinal fluid

Ad/E, ad/e

Adverse effects

CVA

Cerebrovascular accident

A/W or a/w

Associated with

CVP

Central venous pressure

BBB

Bundle branch block

CVS

Cardiovascular system

xii

USMLE Step 1 Platinum Notes


FTT

Failure to thrive

Ca Carcinoma/Cancer

FVC

Forced vital capacity

C/c

Complication

FA

Fatty acid

CT

Chemotherapy

FFA

Free fatty acid

C/I

Contraindication

GFR

Glomerular filtration rate

CI/f

Clinical features

GH

Growth hormone

CTD

Connective tissue disease

GIT

Gastrointestinal tract

Cont./L

Contralateral

GTT

Glucose tolerance test

Cx

Cervix

GU Genitourinary

D and C

Dilation and curettage

HAV

Hepatitis A virus

DI

Diabetes insipidus

HCG

Human chorionic gonadotropin

DIC

Disseminated intravascular coagulopathy

HDL

High density lipoprotein

DIP

Distal interphalangeal joint

Hb Hemoglobin

DKA

Diabetic ketoacidosis

HIV

Human immunodeficiency virus

dL Deciliter

HLA

Histocompatibility locus antigen

DM

Diabetes mellitus

H/O

History of

DTR

Deep tendon reflexes

HR

Heart rate

DVT

Deep venous thrombosis

HSV

Herpes simplex virus

d/to

Due to

HTN Hypertension

D/g

Diagnosis

HS

Hereditary spherocytosis

DOC

Drug of choice

HCC

Hepato cellular carcinoma

Ds, d/s

Disease, disease

HD

Hodgkins disease

DM

Diabetes mellitus

I and D

Incision and drainage

ECG Electrocardiogram

IDDM

Insulin dependent diabetes mellitus

ECT

Ig Immunoglobulin

CXR

Chest X-ray

Electroconvulsive therapy

ECHO Echocardiography

IM Intramuscular

EMG Electromyogram

INR

International normalized ratio

EOM

Extraocular muscles

ITP

Idiopathic thrombocytopenic purpura

ESR

Erythrocyte sedimentation rate

IV Intravenous

ERCP

Endoscopic retrograde cholangioPancreatography

IVP

Intravenous pyelogram

IVU

Intravenous urogram

EUA

Examination under anesthesia

ICT

Intracranial tension

FBS

Fasting blood sugar

IOC

Investigation of choice

FEV

Forced expiratory volume

ILD

Interstitial lung disease

FFP

Fresh frozen plasma

IOT

Intraocular tension

FRC

Functional residual capacity

Ipsi/L

Ipsilateral

Abbreviations
JVP

Jugular venous pressure

K Potassium
+

xiii

PT

Prothrombin time, or physical therapy

PTCA

Percutaenous transluminal coronary


angioplasty

K/as

Known as

LAE

Left atrial enlargement

PTH

Parathyroid hormone

LBBB

Left bundle branch block

PTT

Partial thromboplastin time

LDH

Lactate dehydrogenase

P/g

Prognosis

LMN

Lower motor neuron

Px

Prophylaxis

LE

Lupus erythematosus

PBC

Primary bilary cirrhosis

LP

Lumbar puncture

RA

Rheumatoid arthritis

LV

Left ventricle

RBBB

Right bundle branch block

LVH

Left ventricular hypertrophy

RBC

Red blood cell

LN

Lymph node

RIA Radioimmunoassay

MAO

Monoamine oxidase

RNA

Ribonucleic acid

MEN

Multiple endocrine neoplasia

RTA

Renal tubular acidosis

MI

Myocardial infarction or mitral


insufficiency

RVH

Right ventricular hypertrophy

Rx Treatment

mL Milliliter

R, or T/t

Treatment

MMR

Measles, mumps, rubella

RT

Radiotherapy

MRI

Magnetic resonance imaging

SBE

Subacute bacterial endocarditis

MRSA

Methicillin resistant staph aureus

SGOT

Serum glutamic-oxaloacetic transaminase

MG

Myasthenia gravis

SGPT

Serum glutamic-pyruvic transaminase

Mc or MC

Most common

SIADH

MN

Malnutrition

Syndrome of inappropriate antidiuretic


hormone

M/m

Management

SLE

Systemic lupus erythematous

Ms, m/s

Muscle

SCLC

Small cell lung carcinoma

Na Sodium

SM

Smooth muscle

NIDDM

Non-insulin dependent diabetes mellitus

Supf.

Superficial

NSAID

Non-steroidal anti-inflammatory drugs

SqCC

Squamous cell carcinoma

n.or nv

Nerve

TIBC

Total iron binding capacity

NHL

Non-Hodgkins lymphoma

tid

Three times a day

OCG

Oral cholecystogram

TSH

Thyroid stimulating hormone

PA Posteroanterior

TT

Thrombin time

PDA

Patent ductus arteriosus

TTP

Thrombotic thrombocytopenic purpura

PMN

Polymorphonuclear leukocyte
(neutrophil)

TURP

Transurethral resection of prostate

TOC

Treatment of choice

Patient profile

UC

Ulcerative colitis

PP

xiv

USMLE Step 1 Platinum Notes

UMN

Upper motor neuron

V/s

Vessel

URI

Upper respiratory infection

Vs

Versus (= against)

US, U/S Ultrasound

WBC

White blood cell

UTI

Urinary tract infection

WPW Wolff-Parkinson-White

UVA

Ultraviolet A light

WG

Wegners granulomatosis

U/L

Unilateral

WT

Wilms tumor

VF

Ventricular fibrillation

XLR

X linked recessive

VDRL

Venereal disease research laboratory

Yr Year

(test for syphilis)

Zn Zinc

V/Q Ventrilation-perfusion

ZES

Zollinger Ellison Syndrome

VT

Ventricular tachycardia

Reaction block by, inhibited by

vWD

von Willebrands virus

Denotes heading

VZV

Varicella zoster virus

! Increase

Contents
1. Anatomy

2. Physiology

115

3. Biochemistry

183

4. Microbiology

237

5. Pathology

333

6. Pharmacology

451

7. Biostatistics

549

ANATOMY

Anatomy

EMBRYOGENESIS
Important Events and Their Time Sequence: (Days)
Implantation occurs at

6 days

Uteroplacental circulation establishes at

1112 days

Primitive streak appears on


Formed from: ectoderm

1315th day

Angiogenesis

15th day

Closure of anterior neuropore

24 days

Embryo develops by

8 week

Fetus is

> 8 weeks

Common Signaling Pathways Used during Development


The differentiation of many different cell types is regulated through a relatively restricted set of molecular signaling pathways:
Morphogens: These are diffusible molecules that specify which cell type will be generated at a specific anatomic location and
direct the migration of cells and their processes to their final destination
These Include
Retinoic acid
Transforming growth factor bone morphogenetic proteins (BMPs) and
The hedgehog and the Wnt family proteins
Notch/Delta: This pathway often specifies which cell fate precursor cells will adopt
Transcription factors: This set of evolutionarily conserved proteins activates or represses downstream genes that are essential
for many different cellular processes. Many transcription factors are members of the homeobox or helix-loop-helix (HLH) families.
Their activity can be regulated by all of the other pathways described in this chapter
Receptor tyrosine kinases (RTKs): Many growth factors signal by binding to and activating membrane-bound RTKs. These
kinases are essential for the regulation of cellular proliferation, apoptosis and migration as well as processes such as the growth of
new blood vessels and axonal processes in the nervous system.

Fetal Landmarks (Weeks)


Within 1 week

Implantation

Within 2 week

Bilaminar disk

Within 3 week

Trilaminar disk Gastrulation

Within 3 week

Primitive streak begins to form


Notochord forms

Within 38 week

Organogenesis
Teratogen susceptibility maximum

Week 10

Genitalia with male and female characters

USMLE Step 1 Platinum Notes

Stem Cells (USMLE Favorite)


Stem cells must be able to:
Divide to produce sufficient cells
Differentiate into the cell types needed
Survive after transplant
Mesh into the surrounding tissues
Function properly for long enough to extend the recipients life or to improve it significantly
Avoid harming the recipient

Karyotyping
In 1961 an international meeting was held at the University of Colorado Medical School in Denver, Colorado to standardize the format for
a normal human karyotype. The format that evolved is known as the Denver System.
Each chromosome has its own individuality as shown by its size, shape, and position of its kinetochore. Using the Denver System, the
chromosomes are put into similar groups designated by letters. Then numbers are used to subdivide the chromosomes within the groups
designated by numbers based on the position of the kinetochore and the length of the chromatids. The homologous chromosomes are
paired based on their banding.

X Chromosome belongs to group C


Y Chromosome belongs to group G
Group A

Ch 1, 2, 3

Group B

Ch 4, 5

Group C

Ch 6, 7, 8, 9, 10, 11, 12, X

Group D

Ch 13, 14, 15

Group E

Ch 16, 17, 18

Group F

Ch 19, 20

Group G

Ch 21, 22, Y

Important Embryological Structures: High Yield Points for USMLE


Meckels Diverticulum
This true diverticulum is a remnant of the vitelline duct and often contains ectopic gastric mucosa which can cause bleeding and
perforation.
The Ductus Venosus
It is a shunt that bypasses the liver and carries blood from the umbilical vein directly to the IVC. Its remnant is the ligamentum
venosum.
The Ductus Arteriosus
It is a shunt that bypasses the lungs to carry blood from the pulmonary artery to the aortic arch. Its remnant is the ligamentum
arteriosum.
The Urachus
Becomes the Median umbilical ligament
The 2 umbilical arteries becomes the Medial umbilical ligaments
Urachal fistula from persistent allantois
The Vitelline Duct
It is a connection with the yolk stalk and bowel, but normally obliterates during week 7 of development.

Anatomy
Fetal Structure

Adult Remnant

Right and left umbilical artery

Medial umbilical ligament

Left umbilical vein

Ligamentum teres

Ductus venosus

Ligamentum venosum

Foramen ovale

Fossa ovalis

Ductus arteriosus

Ligamentum arteriosum

Embryology of Umbilical Cord: (USMLE Favorite )


Connects fetus and placenta
It is rich in Whartons jelly
Has Two arteries and one vein
Rt umbilical vein disappears, left is left
In case of single artery only, congenital anomalies should be excluded
Umbilical arteries carry deoxygenated blood
Umbilical arteries do not possess internal elastic lamina
Vas vasorum are absent in cases of umbilical vessels

Female Gametogenesis
Oogonia are derived from yolk sac
Germ cells are derived from yolk sac
Polar bodies are formed during oogenesis
Polar bodies are extruded 24 hours prior to ovulation

Male Gametogenesis
Spermatogenesis occurs at temperature lower than body temperature
Y chromosome is ACROCENTRIC
In absence of Y chromosome ovaries develop
Sperms are stored in epididymis
Length of mature human sperm is 5060 microns

Chromosomal Configuration of Important Cells in Gonads


Number of Chromosomes in Cells During Gametogenesis
Primordial germ cell, oogonia, spermatogonia

46, 2N

Primary oocyte, primary spermatocyte

46, 4N

Secondary oocyte, secondary spermatocyte

23, 2N

Oocyte, spermatid, sperm

23, 1N

Placentation: (USMLE Favorite)


Abnormalities of Placenta
Biscoidal placenta: Placenta has two disks
Lobed placenta: Placenta divides into lobes
Diffuse placenta: Chorionic villi persist all around the blastocys.
Placenta succenturiate: Small part of placenta separated from the rest

USMLE Step 1 Platinum Notes

Fenestrated: Placenta has hole in center


Circumvallate: Edge of placenta covered by circular fold of deciduous
According to umbilical cord attachment:
Marginal: Marginal as well as battledore placenta refers to placenta with cord attached to margins
Furcate: Blood vessels divide before reaching the placenta
Velemantous insertion: Blood vessels are attached to amnion where they ramify before reaching the placenta
Oligohydramnios: Low level of amniotic fluid (< 400 ml) in renal agenesis
Polyhydramnios: High level of amniotic fluid (>2000 ml)
In the fourth intrauterine month the fetus begins to swallow amniotic fluid (25 to 40% of the volume) and absorbs the fluid from
the upper gastrointestinal tract
The fluid is urinated back out into the amniotic pool by the fetal kidneys and a functioning bladder. Although there are maternal
causes of polyhydramnios (cardiac failure, renal failure, other causes of fluid retention) and some idiopathic cases, many instances
are related to the presence of fetal anomalies. These include:
Central nervous system problems such as anencephaly, which prevents normal swallowing, and any high alimentary tract
obstruction that blocks the passage of the amniotic fluid and prevents its absorption such as:
Esophageal atresia
Pyloric atresia
Duodenal atresia
Maternal diabetes
Amniotic band syndrome: When bands of amniotic membrane encircle and constrict parts of fetus causing limb amputations
and Craniofacial anomalies

USMLE Case Scenario


Polyhydramnios is not seen in one of the following conditions:
1. Esophageal atresia
2. Duodenal atresia
3. Pyloric atresia
4. Hirschsprungs disease
5. Congenital diaphragmatic hernia
Ans. 4. Hirschsprungs disease

Derivatives of Germ Layers: (USMLE Favorite)


Derivatives of Ectoderm

Skin and most of appendages


Lens of eye
Epithelial linning of Lower half of anal canal
Epithelial lining of external auditory meatus
Epithelial lining of distal part of male urethra
Adenohypophysis

Derivatives of Mesoderm

Musculoskeletal system
Cardiovascular system
Kidney, ureter
Trigone of bladder (mesonephric duct absorption)

Anatomy

Posterior wall of female urethra


Posterior wall of prostatic part of male urethra
Reproductive tract except labia majora, minora and major part of prostate
Mesothelium of pleural, pericardial and peritoneal cavities
Dentine of teeth
Cornea, sclera, choroid, ciliary body and iris of eye
Somites from paraxial mesoderm

Derivatives of Endoderm

Epithelial lining of GIT


Epithelial lining of Biliary tract
Epithelial lining of Respiratory tract
Epithelial lining of vagina
Epithelial lining of auditory tube, middle ear

Development of Lungs

Glandular stage
Cannalicular stage
Terminal sac stage
Alveolar stage

517 weeks
1625 weeks
24 Weeksbirth
Birth-8 years

Respiration not possible


Respiratory bronchioles and terminal sacs form
Type I and II Pneumocytes present
Respiratory bronchioles, terminal sacs, alveolar duct, alveoli

Embryology of Heart: (USMLE Favorite)


Embryonic Structure

Adult Structure

Truncus arteriosus

Aorta
Pulmonary trunk

Bulbus cordis

Smooth part of R ventricle


Smooth part of L ventricle

Development of heart

USMLE Step 1 Platinum Notes

Primitive ventricle

Rough part of R ventricle


Rough part of L ventricle

Primitive atrium

Rough part of R ventricle


Rough part of Latrium

Sinus venosus

Smooth part of Ratrium


Coronary sinus (Lt horn of sinus venosus)
Oblique vein of left atrium

Embryology of Thoracic Vessels


Embryonic Structure

Adult Structure

Aortic arch 1
Aortic arch 2
Aortic arch 3

Common carotid artery


Internal carotid artery (proximal part)

Aortic arch 4

Rt. Subclavian artery (proximal part)


Part of aortic arch
Persistence leads to double aortic arch

Aortic arch 5

Regresses

Aortic arch 6

Pulmonary artery
Ductus arteriosus

Remember
Ventral mesogastrium

Lesser omentum, hepatoduodenal, hepatogastric, falciform, coronary and triangular


ligament of liver

Dorsal mesogastrium

Greater omentum, mesentry of small intestine, mesoappendix, sigmoid mesocolon,


transverse mesocolon

Embryology of Urinary Tract: (USMLE Favorite)


Embryo

Adult structure

Ureteric Bud

Collecting duct
Major/Minor Calyx
Renal pelvis
Ureter
Epithelium of ureter from mesonephros

Metanephric Mesoderm

Renal glomerulus
Bowmans capsule
PCT
DCT
Loop of Henle
Connecting tubule

Anatomy

Embryology of Genital Tract


Gonads

Ovary

Testis

Paramesonephric duct or Mullerian duct

Appendix testis

Mesonephric duct or Wollfian duct

Appendix vesiculosa
Duct of Garnier

Epididymis
ductus deferens
Seminal vesicles
Ejaculatory ducts
Appendix epididymis

Mesonephric tubules

Epoophoron
Paroophoron

Efferent ductules
Paradidymis

Phallus

Clitoris

Glans penis

Urethral folds

Labia minora

Genital swellings

Labia majora

Uterine tubes
Uterus
Cervix
Hydatid of morgagni

Scrotum

USMLE Favorite
Embryonic Structure

Genital ridge
Genital swelling
Genital fold
Genital tubercle

Female

Male

Ovary
L majora
L minora
Clitoris

Testis
Scrotum
Ventral aspect of penis
Glans penis

Testicular Descent
Iliac fossa

3rd month

Deep inguinal ring

7th month

Pass through inguinal canal

7th month

At superficial inguinal ring

8th month

Enter scrotum

9th month

Derivatives of Neural Crest


Neurons of spinal posterior nerve root ganglia
Neurons of sensory ganglia
Neurons of autonomic ganglia (sympathetic ganglia)
Schwann cells
Melanocytes
Piamater and arachnoid matter
Mesenchyme of dental papillae
Cartilage cells of branchial arches
Chromaffin tissue

10

USMLE Step 1 Platinum Notes

Defective Migration of Neural Crest Cells Results in

Albinism
Melanoma
Hirschsprungs disease
Oropharyngeal teratoma
Neurocristopathies (Cleft Lip, Cleft palate, Digeorges syndrome, Waarden burgs syndrome, Charge syndrome

Tumors of Neural Crest Origin

Neuroblastoma
Pheochromacytoma
Carcinoid tumor
Neurofibromatosis
Medullary carcinoma thyroid

USMLE Case Scenario


A newborn boy does not pass meconium until 45 hours after his birth. Several weeks later his well educated mother complains
that he has not been passing stool regularly. Anorectal manometry reveals increased internal anal sphincter pressure on
rectal distention with a balloon. The patients disorder maybe attributed to distention with a balloon. The patients disorder
maybe attributed to:
1. Defective recanalization of the colon
2. Failure of neural crest cells to migrate
3. Herniation of abdominal contents into the umbilical cord
4. Persistence of the proximal end of the yolk stalk
5. Persistence of processus vaginalis
6. Failure of gastrulation
Ans. 2. Failure of neural crest cells to migrate

Pharyngeal Apparatus (USMLE Favorite)


Pharyngeal Arches are derived from Mesoderm
Pharyngeal clefts are derived from Ectoderm
Pharyngeal Pouches are derived from Endoderm

Five pharyngeal arches

Anatomy

Pharyngeal Arch 1 Derivatives


Meckels Cartilage:
Mandible
Malleus
Incus
Sphenomandibular ligament
Muscles: Muscles of mastication (Medial pterygoid and lateral pterygoid, masseter, temporalis)
Two Tensors (Tensor tympani, tensor palati)
Mylohyoid, anterior belly of digastrics

Pharyngeal Arch 2 Derivatives (Word S)


Reicherts Cartilage:
Stapes
Styloid process
Smaller cornu of Hyoid Bone
Superior surface of Hyoid Bone
Stylohyoid ligament
Muscles of facial expression, Stapedius, Stylohyoid, Posterior Belly of Digastric
Platysma

Pharyngeal Arch 3 Derivatives


Greater cornu of Hyoid Bone
Stylopharyngeus muscle
Think of Stylopharyngeus when thinking about Glossopharyngeal Nerve

Pharyngeal arch 4 and 6 Derivatives


Cartilages of larynx
Intrinsic muscles of larynx and pharynx

PHARYNGEAL ARCH 5 DOES NOT CONTRIBUTE TO DEVELOPMENT


Nerve Supply of Pharyngeal arches is: My Father gave me Some Rupees

Mandibular nerve Ist arch


Facial nerve 2nd arch
Glossopharyngeal nerve 3rd arch
Superior laryngeal nerve 4th arch
Reccurent laryngeal nerve 6th arch

Treacher-Collins syndrome/Mandibulofacial dysostosis


Abnormal formation of pharyngeal arch
Faulty migration of neural crest cells

11

12

USMLE Step 1 Platinum Notes

Patients are mostly characterized by the following abnormalities


Hypoplasia of the facial bones: An underdeveloped mandibular and zygomatic bone leading to a small and malformed jaw
Ear anomalies: Consist small, rotated or even absent ears with or without bilateral stenosis or atresia of the external auditory
canals
Eye problems: Varying from colobomata of the lower eyelids and aplasia of lid lashes to short, downslanting palpebral fissures and
missing eyelashes. Vision loss can occur and is associated with strabismus, refractive errors, and anisometropia
Cleft palate
Airway problems: Which are often results of mandibular hypoplasia
Dental anomalies: Consist in tooth agenesis, enamel disformaties and malplacement of the maxillary first molars.

Less Frequent Defects


Nasal deformity
High-arched palate
Coloboma of the upper lid
Ocular hypertelorism
Choanal atresia
Macrostomia
Preauricular hair displacement
Pharyngeal Pouch

Adult Structure

Pharyngeal Pouch 1

Epithelial linning of Auditory tube/Middle ear

Pharyngeal Pouch 2

Palatine tonsil

Pharyngeal Pouch 3

Inferior parathyroid and Thymus

Pharyngeal Pouch 4

Superior parathyroid and Ultimobranchial body


Para follicular cells are derived from ultimobranchial body

Pharyngeal Cleft/Groove

Adult Structure

External linning of External auditory meatus

2, 3, 4

Obliterated

Cleft Lip and Cleft Palate: (USMLE Favorite)


Cleft Lip:
Failure of Fusion of Maxillary and Medial Nasal Process
Usually associated with cleft palate. (Commonest)
Midline cleft lip is due to failure of fusion of two medial nasal processes
Cleft Palate: Failure of fusion of lateral palatine process, nasal septum and median palatine process (occasional)

Cleft Lip and Cleft Palate (Detailed Overview)


Unilateral cleft lip. Also called Harelip

Failure of fusion of medial nasal process with maxillary process

Midline defect of upper lip

Defect in development of lowermost part of frontonasal process

Midline defect of lower lip

Defective fusion of mandibular processes

Anatomy
Microstomia

Excessive fusion of maxillary and mandibular processes

Macrostomia

Inadequate fusion of maxillary and mandibular processes

Oblique facial cleft

Non fusion of maxillary and lateral nasal process

Tongue Development
1st pharyngeal arch forms ant 2/3
3 rd and 4 th arch forms post 1/3
Muscles of tongue develop from occipital myotomes
Muscles of tongue are both smooth and skeletal muscles
Muscles of tongue are supplied by hypoglossal nerve
Safety muscle of tongue is genioglossus

Genioglossus

Tip of tongue drains to submental lymph nodes


Posterior 1/3 of tongue is supplied by glossopharyngeal nerve
Pain of cancer base of tongue is also reffered to ear through glossopharyngeal nerve
Circumvallate pappilae of tongue are supplied by glossopharyngeal nerve

Development of tongue

13

14

USMLE Step 1 Platinum Notes

General Features of Tongue

Anterior 2/3 of tongue develops from lingual swellings and tuberculum impar
Anterior 2/3 of tongue is supplied by chorda tympani (FACIAL) (taste)
Anterior 2/3 of tongue is supplied by lingual nerve (general)
Anterior 2/3 of tongue drains into submandibular lymph nodes
Posterior 1/3 of tongue develops from hypobranchial eminence
Posterior 1/3 of tongue is supplied by glossopharyngeal nerve (taste)
Posterior 1/3 of tongue is supplied by glossopharyngeal nerve (general)
Posterior 1/3 of tongue drains into jugulo omohyoid lymph nodes
Tip drains into submental lymph nodes

Tonsil: (USMLE Favorite)

Has nonkeratinized squamous epithelium


It is an endodermal structure
Rests on superior constrictor muscle of pharynx
Vagus supplies tonsil
Main nerve supply is the glossopharyngeal nerve
Lymph drains into jugulo digastric nodes
Arterial supply:
Ascending palatine
Descending palatine and
Ascending pharyngeal artery supply tonsils

Diaphragm Development

Septum transversum
Pleuroperitoneal folds
Body wall
Dorsal mesentry of esophagus

Development of Intra-abdominal Organs Frequently Asked


Spleen
It is unique in respect to its development within the gut. While most of the gut viscera are endodermally derived (with the exception
of the neural-crest derived suprarenal gland), the spleen is derived from mesenchymal tissue. Specifically, the spleen forms within,
and from, the dorsal mesentery.
Pancreas
The pancreas develops between the layers of the mesentery from dorsal and ventral pancreatic buds of endodermal cells, which
arise from the caudal or dorsal part of the foregut. Most of the pancreas is derived from the dorsal pancreatic bud. The larger dorsal
pancreatic bud appears first and develops a slight distance cranial to the ventral bud.
The liver, gallbladder and the biliary duct system arise as a ventral outgrowth (hepatic diverticulum) from the caudal foregut in the
4th week
This hepatic diverticulum extends into septum transversum, a mass of splanchnic mesoderm between the developing heart and
the midgut
The septum transversum forms the ventral mesentery in this region. This double-layered membrane gives rise to the lesser
omentum and the falciform ligament
The superior layers of the coronary and left triangular ligaments meet and continue as a ventral mesentery attached to the
ventrosuperior aspect of the liver
Gallbladder arises from pars cystica (from the hepatic bud)

Anatomy

15

Embryology of Nervous System


The nervous system develops from the neural plate which appears at the beginning of the third week as thickening of the
ectoderm
Its lateral edges soon elevate to form the neural folds
With further development, the neural folds continue to elevate, and form a tube known as neural tube
The neural tube has an enlarged cranial part that forms the brain, and a narrow caudal part that becomes the spinal cord
The wall of the neural tube at first has a single layer of cells. They multiply and form three layers- ependymal, mantle and marginal
layer
Neural tube closure begins at cephalic end
The mantle layer divides into a
Ventral part, the basal lamina and
Dorsal part, the alar lamina, separated by a groove, the sulcus limitans
Alar plate gives rise to sensory areas of the spinal cord and the sensory nuclei
Basal plate forms the motor areas of the spinal cord and motor nuclei
The cerebellum and its nuclei develop from the dorsal parts of the alar plate
Inferior olivary and Substantia nigra are sensory nuclei and thus derived from the alar plate
Hypoglossal is a motor nuclei and develops from the basal plate

The Wall of the Spinal Cord


Neuroepithelial Layer

Mantle Layer

Marginal Layer

These cells extend over the Once the neural tube closes,
entire thickness of the wall and
neuroepithelial cells begin to give rise
form a thick PSEUDOSTRATIFIED
to another cell type.
EPITHELIUM

The outermost layer of the spinal cord,


the marginal layer, contains nerve
fibers emerging from neuroblasts in the
mantle layer.

Junctional complexes at the These cells are characterized by


lumen connect them
a large round nucleus with pale
nucleoplasm and a dark- staining
nucleolus. These are primitive nerve
cells, or NEUROBLASTS.

As a result of myelination of nerve fibers,


this layer takes on a white appearance
and therefore is called the white matter
of the spinal cord.

After closure of neural tube,


they divide rapidly, producing
more and more neuroepithelial
cells

They form the mantle layer, a zone


around the neuroepithelial layer.
The mantle layer later forms the gray
matter of the spinal cord.

Remember
Forebrain
(Prosencephalon)

Telencephalon

Cerebral hemispheres

Diencephalon

Thalamus
Hypothalamus
Posterior Pituitary
Pineal body

No division

Tectum

Metancephalon
Cerebellum

Pons

Myelencephalon

Medulla

No division

Spinal cord

Midbrain
(Mesencephalon)
Hindbrain
(Rhombencephalon)

Remainder of neural tube

16

USMLE Step 1 Platinum Notes

Development of brain
3rd ventricle develops from diencephalon
4th ventricle develops from rhombencephalon

Myelination
Myelin is formed in the central nervous system by oligodendrocytes
There are no myelinated fibers in the CNS before the end of the fifth fetal month
There is no myelination of the forebrain until the seventh fetal month. Most myelination in the telencephalon occurs in the third
trimester and postnatally
The first neurones to acquire myelin sheaths are the olfactory, optic and acoustic cortical areas and the motor cortex
(pyramidal cells)
The last to be myelinated are the projection commissure and association neurons of the cerebral hemispheres
Myelination is a critical process for the development of the brain because it enhances the speed of neural communication. It occurs
most rapidly during the first 2 years of life, but continues until early adulthood

In CNS Myelin is produced by Oligodendrocyte


A single oligodendrocyte myelinates as many as 20 or 30 different CNS axonal segments, each over a length of 1 mm or less
Oligodendrocyte membrane extensions wrap around the axons in a concentric fashion to form the myelin sheath. Myelin proteins
include proteolipid protein, myelin basic protein, myelin-associated glycoprotein, and a number of less abundant proteins detectable
by electrophoretic separation
Active myelin synthesis starts in utero and continues for the first 2 years of life; slower synthesis continues during childhood and
adolescence.

High Yield USMLE Points Lately Asked


Developmental Anomalies of Lungs
Lobe of Azygos Vein: This lobe appears especially in the right lung in approximately 1% of people. It develops when the apical
bronchus grows superiorly, medial to the arch of the azygos vein and produces a linear marking on a radiograph of the lungs
Sequestration of lung: Lung tissue getting trapped in the core of a lobe is called as intralobar sequestration. Lung tissue
completely separated from tracheobronchial tree replacing complete lobe is lobar sequestration
Potters Syndrome: It is pulmonary Hypoplasia with renal agenesis.

Anatomy

17

Developmental Anomalies of Thyroid


Thyroglossal Duct Cysts and Sinus: Normally, the thyroglossal duct atrophies and disappears, but a remnant of it may persist and
form a cyst in the tongue or in the anterior part of the neck, usually just inferior to the hyoid bone.
Most thyroglossal duct cysts are observed by the age of 5 years. The swelling produced by a thyroglossal duct cyst usually develops
as a painless, progressively enlarging, movable mass. The cyst may contain some thyroid tissue.
After infection of a cyst, a perforation of the skin occurs, forming a thyroglossal duct sinus that usually opens in the median plane
of the neck, anterior to the laryngeal cartilages.
Ectopic Thyroid Gland: An ectopic thyroid gland is usually located along the course of the thyroglossal duct. Lingual thyroid
tissue is the most common of ectopic thyroid tissues. Other sites:
Larynx
Trachea
Esophagus
Pericardium
Pleura
Ovaries
Struma Ovary:
It is a rare ovarian tumor defined by the presence of thyroid tissue
Most commonly, they occur as part of a teratoma, but may occasionally be encountered with serous or mucinous cystadenomas
Benign strumosis is a rare version of mature thyroid tissue implants throughout the peritoneal cavity

Teratoma (ovary)
A 10-year-old girl with round 1 cm mass in midline of neck moving with Throglossal duct cyst
movement of tongue
A 15-year-old girl with round 1 cm on side of neck beneath and in front of Branchial cyst
sternocleidomastoid.
A 6-year-old with fluid filled translucent mass in supraclavicular area

Cystic hygroma

Developmental Anomalies of Tongue


Ankyloglossia: The lingual frenulum normally connects the inferior surface of the tongue to the floor of the mouth. Sometimes
the frenulum is short and extends to the tip of the tongue. This interferes with its free protrusion and may make breastfeeding
difficult. A short frenulum usually stretches with time, making surgical correction of the anomaly unnecessary.
Macroglossia: An excessively large tongue is not common. Amyloidosis is associated with Macroglossia
Microglossia: An abnormally small tongue is extremely rare and is usually associated with micrognathia (underdeveloped
mandible and recession of the chin) and limb defects (Hanharts syndrome)
Bifid Tongue
Fissured tongue

18

USMLE Step 1 Platinum Notes

Developmental Anomalies of Larynx


Laryngeal Atresia: This anomaly results from failure of recanalization of the larynx, which causes obstruction of the upper fetal
airway. Distal to the region of atresia (blockage) or stenosis (narrowing), the airways become dilated, the lungs are enlarged and
echogenic
Laryngeal web: Results from incomplete recanalization of the larynx during the 10th week. A membranous web forms at the level
of the vocal folds, partially obstructing the airway
Laryngoptosis: Larynx is situated lower down in neck
Laryngeocele: Excessive enlargement of saccule of larynx.

Developmental Anomalies of Trachea


Tracheoesophageal Fistula:
A fistula between the trachea and esophagus
Most affected infants are males
In more than 85% of cases, the tracheoesophageal fistula (TEF) is associated with esophageal atresia
A TEF results from incomplete division of the cranial part of the foregut into respiratory and esophageal parts during the
fourth week
Incomplete fusion of the tracheoesophageal folds results in a defective tracheoesophageal septum and a TEF between the
trachea and esophagus
Polyhydramnios is often associated with esophageal atresia. The excess amniotic fluid develops because fluid cannot pass to the
stomach and intestines for absorption and subsequent transfer through the placenta to the mothers blood

Developmental Anomalies of Cardiovascular System


Ectopia cordis: Non union of sternal plates exposing the heart to surface
Dextrocardia: If the heart tube bends to the left instead of to the right, the heart is displaced to the right and there is transposition
the heart and its vessels are reversed left to right as in a mirror image. Dextrocardia is the most frequent positional abnormality
of the heart. In isolated dextrocardia, the abnormal position of the heart is not accompanied by displacement of other viscera
Maybe associated with
Situs Inversus/ Kartageners Syndrome/Immotile Cilia Syndrome
Atrial Septal Defects: An atrial septal defect (ASD) is a common congenital heart anomaly and occurs more frequently in females
than in males. The most common form of ASD is patent oval foramen. A small isolated patent oval foramen is of no hemodynamic
significance; however, if there are other defects (e.g. pulmonary stenosis or atresia), blood is shunted through the oval foramen
into the left atrium and produces cyanosis.
Ventricular Septal Defects: VSDs are the most common type of CHD, accounting for approximately 25% of defects. VSDs occur
more frequently in males than in females. VSDs may occur in any part of the IV septum but membranous VSD is the most common
type frequently, small VSDs close spontaneously. Most people with a large VSD have massive left-to-right shunting of blood.
Muscular VSD is a less common type of defect and may appear anywhere in the muscular part of the interventricular septum.
Sometimes there are multiple small defects, producing what is sometimes called the Swiss cheese VSD.
Cor biloculare: Two chambered heart
Cor Triloculare: Three chambered heart
L. Cor triloculare biatriatum: (Two atria, one ventricle): Absence of the IV septum-single ventricle or common ventricle-resulting
from failure of the IV septum to form is extremely rare and results in a three-chambered heart (L. cor triloculare biatriatum).
Transposition of the Great Arteries: TGA is the most common cause of cyanotic heart disease in newborn infants. TGA is often
associated with other cardiac anomalies (e.g. ASD and VSD).
In typical cases, the aorta lies anterior and to the right of the pulmonary trunk and arises from the morphologic right ventricle, whereas
the pulmonary trunk arises from the morphologic left ventricle. The aorticopulmonary septum fails to pursue a spiral course during
partitioning of the bulbus cordis and TA
This defect is thought to result from failure of the conus arteriosus to develop normally during incorporation of the bulbus cordis into
the ventricles
Recent studies suggest that defective migration of neural crest cells may also be involved.

Anatomy

19

Tetralogy of Fallot: This classic group of four cardiac defects


Pulmonary stenosis (Obstruction of right ventricular outflow)
VSD
Dextroposition of aorta (Overriding or straddling aorta)
Right ventricular hypertrophy
Coarctation of the Aorta: Aortic coarctation (constriction) occurs in approximately 10% of children and an adult with CHDs.
Coarctation is characterized by an aortic constriction of varying length. Most coarctations occur distal to the origin of the left
subclavian artery at the entrance of the DA (juxtaductal coarctation). The classification into preductal and postductal coarctations
is commonly used. Coarctation of the aorta occurs twice as often in males as in females and is associated with a bicuspid aortic
valve in 70% of cases.

Developmental Anomalies of Lymphatic System


Cystic hygroma: Large swellings usually appear in the inferolateral part of the neck and consist of large single or multilocular,
fluid-filled cavities. Hygromas maybe present at birth, but they often enlarge and become evident during infancy. Most hygromas
appear to be derived from abnormal transformation of the jugular lymph sacs
Represents lymphatic venous anastamotic failure
Located usually in the neck at lower in posterior triangle
Brilliantly translucent

Developmental Anomalies of GIT


Esophageal Atresia: Esophageal atresia is associated with tracheoesophageal fistula in more than 85% of cases. Atresia may
occur as a separate anomaly, but this is less common. Esophageal atresia results from deviation of the tracheoesophageal septum
in a posterior direction as a result there is incomplete separation of the esophagus from the laryngotracheal tube. A fetus with
esophageal atresia is unable to swallow amniotic fluid; consequently, this fluid cannot pass to the intestine for absorption and
transfer through the placenta to the maternal blood for disposal. This results in polyhydramnios

Tracheoesophageal fistula
Esophageal Stenosis: Narrowing of the lumen of the esophagus can be anywhere along the esophagus, but it usually occurs in its
distal third, either as a web or as a long segment of esophagus with a thread like lumen. Stenosis usually results from incomplete
recanalization of the esophagus.
Short Esophagus (Congenital Hiatal Hernia): Initially the esophagus is very short. Its failure to elongate sufficiently as the neck
and thorax develop results in displacement of part of the stomach superiorly through the esophageal hiatus into the thoraxcongenital hiatal hernia. Most hiatal hernias occur long after birth, usually in middle-aged people.

20

USMLE Step 1 Platinum Notes

Dysphagia Lusoria: Abberant vessels compressing esophagus leading to dysphagia. Usually Abnormal right subclavian artery is
implicated.
Duodenal Atresia: Complete occlusion of the lumen of the duodenum. If recanalization of the lumen fails to occur a short segment
of the duodenum is occluded. The blockage occurs nearly always at the junction of the bile and pancreatic ducts (hepatopancreatic
ampulla) but occasionally involves the horizontal (third) part of the duodenum.
In infants with duodenal atresia, vomiting begins a few hours after birth. The vomitus almost always contains bile; duodenal
atresia may occur as an isolated anomaly, but other congenital anomalies are often associated with it, e.g. anular pancreas
cardiovascular abnormalities, anorectal anomalies, and malrotation. Importantly, approximately one third of affected infants
have Down syndrome and an additional 20% are premature. Duodenal atresia is associated with bilious emesis (vomiting of bile)
because the blockage occurs distal to the opening of the bile duct. Polyhydramnios also occurs because duodenal atresia prevents
normal intestinal absorption of swallowed amniotic fluid. The diagnosis of duodenal atresia is suggested by the presence of a
double bubble sign on plain radiographs or ultrasound scans. This appearance is caused by a distended, gas-filled stomach and
proximal duodenum.
Riedels Lobe: A tongue like extension of right lobe of liver.
Phrygian cap: Fundus of the gallbladder folded upon itself giving rise to an appearance of cap worn by people of an ancient
Asian community of Phrygia.
Moynihans Hump: Normally the arterial supply of gallbladder is from cystic artery which is a branch of Right hepatic artery.
Sometimes an accessory cystic artery is also seen to arise from either Gastroduodenal or right hepatic artery
The Right hepatic artery takes a tortuous course called caterpillar turn or Moynihans hump. This can be a source of profuse
bleeding.
Intrahepatic gallbladder is one of the ectopic locations of the gallbladder. The gallbladder is usually intrahepatic during
its embryologic period and becomes extrahepatic later on in its development. In adults approximately 60% of intrahepatic
gallbladders are associated with gallstones
Double and Triple gallbladders have been reported, the latter being extremely rare. Double gallbladders may share a common
cystic duct and be completely separated, or they maybe divided by a septum. When they do not share a common outlet, the cystic
ducts of double or triple gallbladders open separately into the common bile duct or, less commonly, into the right hepatic duct
Choledochal Cyst: Choledochal cysts are congenital cystic dilatations of the extrahepatic and/or intrahepatic biliary tree. They
are rare. Originally, they were described as cystic dilatations of the extrahepatic duct system. Subsequently this classification was
extended to include the frequent association with cystic dilatation of the duct system within the liver, a condition described in
1958 and now known as Carolis disease.
Extrahepatic Biliary Atresia: This is the most serious anomaly of the extrahepatic biliary system and occurs in one in 10,000 to
15,000 live births
The most common form of extrahepatic biliary atresia is obliteration of the bile ducts at or superior to the porta hepatis
Biliary atresia could result from a failure of the remodeling process at the hepatic hilum or from infections or immunologic reactions
during late fetal development
Jaundice occurs soon after birth and stools are acholic (clay colored).
Accessory Pancreatic Tissue: Accessory pancreatic tissue is most often located in
The wall of the stomach
Wall of duodenum
In an ileal diverticulum a/Meckel diverticulum
Anular Pancreas:
May cause duodenal obstruction
The ring like or anular part of the pancreas consists of a thin, flat band of pancreatic tissue surrounding the descending or
second part of the duodenum.
An anular pancreas may cause obstruction of the duodenum either shortly after birth or later. Infants present with symptoms
of complete or partial bowel obstruction. An anular pancreas maybe associated with
Down syndrome
Intestinal atresia
Imperforate anus
Pancreatitis
Malrotation

Anatomy

21

Congenital Omphalocele: This anomaly is a persistence of the herniation of abdominal contents into the proximal part of the
umbilical cord. Herniation of intestines and herniation of liver and intestines occurs
Infants with these large omphaloceles often suffer from pulmonary and thoracic hypoplasia and a delayed closure is a better
clinical decision. The covering of the omphalocele is by amnion and peritoneum.
Umbilical Hernia: When the intestines return to the abdominal cavity during the 10th week and then herniate through an
imperfectly closed umbilicus, an umbilical hernia forms. This common type of hernia is different from an omphalocele. In an
umbilical hernia, the protruding mass (usually the greater omentum and part of the small intestine) is covered by subcutaneous
tissue and skin. The defect through which the hernia occurs is in the linea alba. The hernia protrudes during crying, straining, or
coughing and can be easily reduced through the fibrous ring at the umbilicus. Surgery is not usually performed unless the hernia
persists to the age of 3 to 5 years.
Gastroschisis: This anomaly is a relatively uncommon congenital abdominal wall defect. Gastroschisis results from a defect lateral
to the median plane of the anterior abdominal wall. The linear defect permits extrusion of the abdominal viscera without
involving the umbilical cord. The viscera protrude into the amniotic cavity and are bathed by amniotic fluid.

Anomalies of the Midgut


Nonrotation occurs when the intestine does not rotate as it re-enters the abdomen. As a result, the caudal limb of the midgut loop
returns to the abdomen first and the small intestines lie on the right side of the abdomen and the entire large intestine is on the left
and the cecum lies just inferior to the pylorus of the stomach. The cecum is fixed to the posterolateral abdominal wall by peritoneal
bands that pass over the duodenum. These bands and the volvulus (twisting) of the intestines cause duodenal obstruction.
When midgut volvulus occurs, the superior mesenteric artery maybe obstructed, resulting in infarction and gangrene of
the intestine supplied by it. Infants with intestinal malrotation are prone to volvulus and present with bilious emesis.
Reversed Rotation: In very unusual cases, the midgut loop rotates in a clockwise rather than a counterclockwise direction. As
a result, the duodenum lies anterior to the superior mesenteric artery rather than posterior to it, and the transverse colon lies
posterior instead of anterior to it. In these infants, the transverse colon maybe obstructed by pressure from the superior mesenteric
artery.

Development of gut
Congenital Megacolon or Hirschsprung Disease:
Infants with congenital megacolon or Hirschsprungs disease lack autonomic ganglion cells in the myenteric plexus distal to the
dilated segment of colon
(Hirschsprungs disease is the congenital absence of enteric neurons in the submucosal and myenteric plexuses, due to an
arrest of the embryonic caudal migration of the enteric neurons along the gut. The aganglionic segment remains contracted,
dilating the proximal normal bowel
The severity of symptoms and the age at diagnosis are related to the length of the aganglionic segment. Involvement of the
rectum or additional parts of the colon results in constipation or obstipation in infancy, requiring emergent resection of the a
ganglionic bowel and a pull-through anastomosis to the anus.)

22

USMLE Step 1 Platinum Notes

Imperforate Anus and Anorectal Anomalies: Imperforate anus occurs approximately once in every 5000 newborn infants
and is more common in males. Most anorectal anomalies result from abnormal development of the urorectal septum, resulting
in incomplete separation of the cloaca into urogenital and anorectal portions. There is normally a temporary communication
between the rectum and anal canal dorsally from the bladder and urethra ventrally but it closes when the urorectal septum fuses
with the cloacal membrane.
Anal Agenesis, with or without a Fistula: The anal canal may end blindly or there maybe an ectopic anus or an anoperineal fistula
that opens into the perineum. The abnormal canal may, however, open into the vagina in females or the urethra in males.
Anal Stenosis: The anus is in the normal position, but the anus and anal canal are narrow. This anomaly is probably caused by a
slight dorsal deviation of the urorectal septum as it grows caudally to fuse with the cloacal membrane. As a result, the anal canal
and anal membrane are small.

USMLE Case Scenario


Embryologically, The Gut rotates and the rotation occurs in a way that:
1. The large intestine rotates in a clockwise manner around the axis of the celiac trunk
2. The large intestine rotates in a clockwise manner around the axis of the superior mesenteric artery
3. The large intestine rotates in a clockwise manner around the axis of the inferior mesenteric artery
4. The large intestine rotates in a counterclockwise manner around the axis of the celiac trunk
5. The large intestine rotates in a counterclockwise manner around the axis of the superior mesenteric artery
6. The large intestine rotates in a counterclockwise manner around the axis of the inferior mesenteric artery
Ans. 5. The large intestine rotates in a counterclockwise manner around the axis of the superior mesenteric artery

Derivatives of fore, mid and hindgut

Developmental Anomalies of Urinary Tract


Horseshoe Kidney: In 0. 2% of the populations, the poles of the kidneys are fused; usually the inferior poles fuse. The large
U-shaped kidney usually lies in the hypogastrium, anterior to the inferior lumbar vertebrae. Normal Persons with Turners
syndrome have horseshoe kidneys.
Ectopic Ureter: An ectopic ureter does not enter the urinary bladder. In males, ectopic ureters usually open into the neck of the
bladder or into the prostatic part of the urethra, but they may enter the ductus deferens, prostatic utricle, or seminal gland. In
females, ectopic ureters may open into the
Bladder neck
Urethra
Vagina
Vestibule of the vagina

Anatomy

23

An ectopic ureter: Results when the ureter is not incorporated into the trigone in the posterior part of the urinary bladder. Instead
it is carried caudally with the mesonephric duct and is incorporated into the middle pelvic portion of the vesical part of the
urogenital sinus.
Cystic Kidney Diseases
In autosomal recessive polycystic kidney disease, diagnosed at birth or in utero by ultrasonography, both kidneys contain
many hundreds of small cysts which result in renal insufficiency.
Multicystic dysplastic kidney disease results from dysmorphology during development of the renal system. The outcome for
children with multicystic dysplastic kidney disease is generally good because the disease is unilateral in 75% of the cases. In
multicystic dysplastic kidney disease, fewer cysts are seen than in autosomal recessive polycystic kidney disease and they range in
size from a few millimeters to many centimeters in the same kidney.
Congenital Adrenal Hyperplasia (CAH): An abnormal increase in the cells of the suprarenal cortex results in excessive androgen
production during the fetal period. In females, this usually causes masculinization of the external genitalia. Affected male infants
have normal external genitalia, and the syndrome may go undetected in early infancy. Later in childhood in both sexes, androgen
excess leads to rapid growth and accelerated skeletal maturation. CAH is a group of autosomal recessive disorders that result in
virilization of female fetuses.

Developmental Anomalies of Genital System


Mesonephric Duct Remnants in Males
The cranial end of the mesonephric duct may persist as an appendix of the epididymis, which is usually attached to the head of the
epididymis Caudal to the efferent ductules, some mesonephric tubules may persist as a small body, the paradidymis. It forms
Epididymis
Ductus deferens
Seminal vesicles
Ejaculatory ducts
Appendix epididymis
Mesonephric Duct Remnants in Females
The cranial end of the mesonephric duct may persist as an appendix vesiculosa. A few blind tubules and a duct, the epoophoron,
correspond to the efferent ductules and duct of the epididymis in the male. The epoophoron may persist in the mesovarium between
the ovary and uterine tube. Closer to the uterus, some rudimentary tubules may persist as the paroophoron. Parts of the mesonephric
duct, corresponding to the ductus deferens and ejaculatory duct, may persist as Gartners duct cysts between the layers of the broad
ligament along the lateral wall of the uterus and in the wall of the vagina.
Paramesonephric Duct Remnants in Males
The cranial end of the paramesonephric duct may persist as a vesicular appendix of the testis, which is attached to the superior pole
of the testis
The prostatic utricle, a small saclike structure that opens into the prostatic urethra, is homologous to the vagina.
Paramesonephric Duct Remnants in Females
Part of the cranial end of the paramesonephric duct that does not contribute to the infundibulum of the uterine tube may persist
as a vesicular appendage it forms
Uterus
Cervix
Uterine tubes
Hydatid of morgagni

24

USMLE Step 1 Platinum Notes

Appendages around testis


Cryptorchidism or Undescended Testes
The term cryptorchidism (Greek cryptos = hidden, orchis = testis) should be reserved for impalpable, usually abdominal, testes
There is a higher incidence of undescended testes in premature than in full-term babies
Two-thirds of undescended testes in newborn infants will descend, usually by 6 weeks in term and 3 months in preterm babies
There is an increased incidence of cryptorchidism in anencephalics and other cerebral anomalies.
Ectopic Testes: After traversing the inguinal canal, the testis may deviate from its usual path of descent and lodge in various
abnormal locations
Interstitial (external to aponeurosis of external oblique muscle)
In the proximal part of the medial thigh
Dorsal to the Penis
On the opposite side (crossed ectopia)
Exstrophy of the bladder results from a rare ventral body wall defect through which the posterior wall of the urinary bladder
protrudes onto the abdominal wall. Epispadias is a common associated anomaly in males; the urethra opens on the dorsum
of the penis.

Developmental Anomalies of CNS


Spina Bifida: The original defect lies in the vertebrae when their laminae fail to cover the spinal cord dorsally. Spina bifida maybe
simple or complicated. Complicated Spina bifida is associated with involvement of the cord and its membranes
Rarely do the two halves of the vertebral body fail to fuse and the spinal cord protrudes anteriorly through the gap. This rarity is
called as anterior spina bifida
Spina bifida occulta: Here the spinal cord is normal. The defect is not manifest externally and usually a tuft of hair is present
on the skin over the affected area
Meningocele: The Arachnoid and the Piamater covering the spinal cord protrude through the opening of the bifid spine and
form a cystic swelling
Meningomyelocele: Here the spinal cord along with its meninges and the spinal nerves are seen to protrude. It is a more
serious condition owing to development of infection of the cord itself
This condition is associated with displacement of medulla and a part of cerebellum which cause obstruction of the
foramen magnum producing hydrocephalus. An association of hydrocephalus and Meningomyelocele is called Arnold Chiari
malformation
Syringomyelia: Once the central canal of the spinal cord is distended with excessive fluid it is called Syringomyelia
Myelomalacia: Abnormal softening of spinal cord. Usually seen after trauma to spinal cord

Anatomy

25

Syringomyelia
In Syringomyelia there is softening of the spinal cord and the central canal becomes very wide at lesion in this position will
interrupt the pain and temperature fibers which pass in front of the central canal as they cross from one side to another
Syringomyelia usually occurs in the lower cervical and the upper thoracic regions of the spinal cord and the loss of pain and
temperature
Only the fibers of the pain and temperature which pass in front of the central canal are injured: the lateral spinothalamic tracts
themselves remain normal and there is no loss of pain and temperature in the lower limbs
Touch can be felt in the area of the skin in which pain and temperature are lost: this condition in which pain and temperature is lost
while touch is nearly normal called Dissociated sensory loss.

USMLE Case Scenario


Which of the following embryonic structures gives rise to the adrenal cortex?
1. Ectoderm
2. Endoderm
3. Mesoderm
4. Mesonephros
Ans. 3. Mesoderm

Types of Neurons Based on Poles


Unipolar Neurons
They have only one pole
Both Axon and Dendrons arise by a common stem.

Present in
Fetal life
Posterior root ganglion
Sensory nucleus of the fifth cranial nerve

Bipolar Neurons
They have two poles
Axon and Dendron lie at opposite poles

Present in

Cochlear ganglion of the eight nerves


Vestibular ganglion of the eight nerves
Retina
Olfactory nerve

Multipolar Neurons
They have multiple poles
The Axon and all other Dendrons form multiple poles

Present in
The spinal cord
Cerebral cortex
Cortex of cerebellum

26

USMLE Step 1 Platinum Notes

Important Changes in Phases of Cell Cycle

Leptotene: Chromosomes become visible


Zygotene: Pairing of chromosomes
Pachytene: Tetrad formation, crossing over, chiasmata formation
Diplotene: Chromosomes break
Metaphase: Spindle formation
Anaphase: Chromosomes move from equator to poles
Telophase: Chromosomes move completely to opposite sides

Sex Chromatin or Barr body


Of the two X-chromosomes in a Female only one is functionally active. The other (Inactive) X-chromosome forms a mass
of heterochromatin that lies just under the nuclear membrane. This mass of heterochromatin can be identified in suitable
preparations and can be useful in determining whether a particular tissue belongs to a male or a female. Because of this
association with sex this mass of heterochromatin is called the SEX CHROMATING. It is also called a BARR-BODY after the name
of the scientist who first discovered it.

Sex chromatin
In NEURONS it forms a rounded mass lying very close to the nucleolus and is therefore called a NUCLEOLAR SATELLITE.
In NEUTROPHIL LEUCOCYTES it may appear as an isolated round mass attached to the rest of the nucleus by a narrow band, thus
resembling the appearance of a DRUM-STICK. Rarely, some individuals may have more than two X-chromosomes. In these cases
only one X-chromosome is active (and hence euchromatic) while others are represented by masses of heterochromatin.
In normal females XX

There is one barr body

In normal males XY

There is no barr body

In Turners Syndrome XO

There is no barr body

In males with Klienfilters syndrome XXY

There is one barr body

In super female XXX

There are two barr bodies

The number of Barr bodies is (X-1)

Cell Division
The number of chromosomes found in somatic cells is constant and is termed the diploid (2n) number. Each gamete, however, has only
half the diploid number and is said to be haploid (n). In order to maintain this regularity, two types of cell division occur: mitosis, which
is the cell division occurring in somatic tissues during growth and repair, and meiosis, which is the specialized form of cell division
occurring when gametes form.

Mitosis
The function of mitosis is to distribute and maintain the continuity of the genetic material in every cell of the body. This process
consists of a number of different phases, which results in an equal distribution of the chromosomes to the two daughter cells. The cell
cycle has four stages: mitosis (M), gap1 (G1), synthesis (S), and gap2 (G2). The G1 phase follows mitosis, during which RNA and
protein synthesis occurs. S is the period during which DNA replication takes place and the DNA content of the cell doubles, and G2 is
the period during which energy requirements for cell division are built-up and any repair of errors in DNA synthesis takes place.

Anatomy

27

Meiosis
This process occurs only during the formation of the gametes and results in four daughter cells, each with the haploid number of
chromosomes. In males each primary spermatocyte forms four functional spermatids that develop into sperm, while in females each
oocyte forms only one ovum, the remaining products of meiosis being nonfunctional polar bodies.
Lyonization
In females, the sex chromosomes are identical in size and are genetically homologous chromosomes (as in the case of autosomes);
however, in the normal diploid interphase cell, one of the Xs forms a condensed heterochromatic body called the Barr body. These
condensations, together with evidence from coat color pattern in mice, led Lyon to hypothesize X-inactivation.
She Stated
In each somatic cell there is inactivation of all but one of the X-chromosomes;
This process occurs early in development and is random with respect to maternally or paternally derived X-chromosomes in
different cells; and
Once a particular X is inactive, it is inactive in all daughter cells.

Important Points about Skin

1.
2.
3.
4.

The Skin has stratified squamous epithelium


Classically epidermis has four layers
Normal turn over of epidermis is 4 weeks
Skin doubling time is 4 weeks
Stratum Germinativium composed of stratum Basale and Stratum Spinosum
Stratum Granulosum (Granular cell layer)
Stratum Lucidum (Clear cell layer)
Stratum Corneum (horny cell layer)

1. Stratum Germinativium is also called as Malphigian layer composed of


(a) Basal cell layer
(b) Prickle cell layer (stratum spinosum)
The Basal cell layer is composed of single layer of columnar cells resting on a clear wavy basement membrane From the basal borders
of these cells Cytoplasmic processes extend anchoring the epidermis to dermis Melanocytes are present here.
Acantholytic cells are present here
Dermatophytes are present here
It is underdeveloped in VLBW infants
The prickle cell layer (stratum spinosum) consists of 46 layers of cells which are polygonal and connected together by tonofilaments
giving them a prickly appearance.
2. Stratum Granulosum
Consists of 34 layers of flattened cells rich in keratohyaline granules
The keratohyaline granules eventually fill much of the cell, and it is these granules which give the cells of the stratum
Granulosum its granular appearance
The keratohyaline granules contain a protein called filaggrin, the function of which appears to be to bind the tonofibrils
together, converting them into keratin
3. Stratum Lucidum
Consists of few layers of dead, non nucleated cells without cell boundaries
These cells are rich in Eleidin granules
4. Stratum Corneum
It is the most superficial layer of epidermis
It is made of flat, dead cornified cells which have horny scales
They are continuously shed from the surface and replaced by newer cells

28

USMLE Step 1 Platinum Notes

The Dermis is formed of CT present beneath the epidermis. It is made of two layers continuous with each other
The Papillary layer or the loose connective tissue layer
The Reticular layer or the deeper layer
The Hypodermis is continuous with the dermis. It is formed of loose CT rich in blood vessels, loose CT, nerve endings.

Cells in Skin are


Langerhans Cells
Are located primarily in the stratum spinosum
They function in the immune system as antigen presenting cells
They stain selectively with gold chloride and contain numerous rod like or racket-shaped Cytoplasmic granules (Birbecks
granules)

Merkel Cells
Are located in the stratum basale
They contain granules which contain catecholamines
The base of a Merkel cell makes contact with the expanded terminal disk of a nerve fiber, forming a special receptor which functions
as a mechanoreceptor (detection of touch)

Dendritic Cells
Are found throughout the epidermis
They are antigen presenting cells

EPITHELIUM
Simple Squamous Epithelium
Alveoli of lungs
Mesothelium of pleura, peritoneum and pericardium
Endothelium of heart and blood vessels

Simple Cuboidal Epithelium


Lining of the thyroid follicles
Germinal epithelium of ovary
Anterior surface of lens of eye

Simple Columnar Epithelium


The lining of stomach
Intestines
Gallbladder

Simple Columnar Ciliated


Fallopian tubes and the uterus
Central canal of spinal cord
Osseous part of eustachian tube

Anatomy

29

Pseudostratified Columnar (Pseudo: False, Stratified: Layered)


It is a simple type of columnar cells resting on a clear wavy basement membrane. The cells are crowded over each other and appear
multilayered. The nuclei are arranged at different levels, some situated basal and others centrally as a result of which a false impression
of multilayered cells is created. However, most of the cells reach the basement membrane. The cells maybe ciliated or nonciliated
With cilia
Nasal cavity, nasal air sinuses, nasopharynx, larynx, trachea and bronchi
Eustachian tube in its cartilaginous parts
Without cilia
Vas deferens
Part of male urethra

Stratified Squamous Epithelium


The surface of the cells maybe keratinized (Protective function) as in case of
Epidermis of skin
External ear
External nose
The surface of the cells maybe without keratin called Nonkeratinized as in case of
Esophagus
Tongue
True vocal cords
Cornea
Tonsil

Stratified Columnar Epithelium


Conjunctival fornicies
Penile part of male urethra
Anorectal junction

Transitional Epithelium

It is a type of epithelium composed of multiple cell layers


They have extra reserve of cell membrane
The top cell layers are broader
The intermediate cell layers are polyhedral without intercellular bridges separated by mucus like substance. The cells can
undergo transition in relaxed and contracted state. In the relaxed state the number of layers is 68 while as in the contracted state
it is 23 layers
The basal cell layers are cuboidal.

It is present in

Calyces
Ureter
Urinary bladder
UV junction
Male urethra

30

USMLE Step 1 Platinum Notes

Salivary Glands
Gland

Duct

Type of Gland

Duct opening

Parotid

Stensens duct

Serous

Vestibule of mouth opposite second upper molar

S u b m a n d i - Whartons duct
bular

Mixed but
predominantly serous

On the floor of mouth on summit of sublingual papilla


at the side of frenulum of tongue

Sublingual

Mixed but
predominantly mucus

On the floor of mouth on summit of sublingual papilla

Bartholins duct

Structures within Parotid Gland


External carotid artery
Retromandibular vein
Facial nerve

Questions Frequenly asked from Histology of Liver


Classic Hepatic Lobule: This model is based on the direction of blood flow. In sections, liver substructure exhibits a pattern of
interlocking hexagons; each of these is a classic lobule. Whereas lobules in pigs are defined by a sheath of connective tissue, there
is less connective tissue in humans and the lobule boundaries are indistinct. The central vein at its center and the alternating
hepatocyte plates and sinusoids that lie between them.
Portal Canal/triad: One triad occupies a potential space (portal space) at each of the 6 corners of the lobule. Each triad contains
3 main elements surrounded by connective tissue: a portal venule (a branch of the portal vein), a hepatic arteriole (a branch of
the hepatic artery) and a bile ductule (a tributary of the larger bile ducts). A lymphatic vessel may also be seen. In the portal canal
blood vessels and bile ductules are separated by a space called as Space of Mall
Portallobule: This model is based mainly on the direction of bile flow, which is opposite to that of blood. From this perspective,
the liver parenchyma is divided into interlocking triangles, each of which has a portal triad at the center and a central vein at each
of its 3 comers
Hepatic lobule: It is the structural unit of liver. It has a central vein. A single vein marks the center of each lobule. This vessel is easily
distinguished from those in the portal triad by its larger opening and lack of a connective tissue investment.
Kuffercells are Reticuloendothelial cells of liver
Itto cells are fat storing cells in liver
'Space of Dissie and Space of Mall are seen in Liver

Important Histological Features: (USMLE Favorite)


Hassals corpuscles

Thymus

Corpora amaylacea

Prostate

Corpora atretica

Ovary

Germinal center

Lymph node

Corpora aranacea

Pineal gland

Herring bodies

Pituitary gland

Cords of Billiroth

Spleen

Cells of Stomach
The Mucus neck cells
Called so as they are present in the necks of glands
They secrete mucin which serves as a protective layer against HCL

Anatomy

31

They appear pale because of dissolved mucin


They are low columnar with basal flat nuclei
The Chief cells (The Peptic cells or the Zymogen cells)
Called as chief because they line the main part of the body of the gland
They are low columnar with basal round nuclei
They secrete pepsinogen
Oxyntic Cells (Parietal Cells)
They are scattered in between peptic cells
They are highly acidophilic
Intrinsic factor of Castle is secreted by parietal cells
They secrete HCL
They contain secretory canaliculi and are rounded
The Argentaffin Cells
They are chromaffin positive and stain positive with Silver salts
They also contain acidophilic granules and are oval in shape

Cells of Intestine
Simple Columnar Cells
Line the villi and crypts
Have free brush border due to presence of microvilli to increase surface area
Goblet Cells
Are also present in the villi and crypts
They are unicellular glands
They are flask shaped
They secrete mucin
Paneth Cells
Are acidophilic
Secrete intestinal enzymes
Rich in Rough ER
Argentaffin cells
These are cells with silver staining properties
They secrete serotonin

Diffuse Lymphatic Tissue, Isolated Lymphatic Nodules


The diffuse lymphatic tissue is a collection of lymphatic tissue in:
Alimentary tract
Respiratory tract
Genitourinary tract
The lymphoid tissue is deposited randomly in the subepithelial layers and placed strategically so as to detect and destroy the
pathogenic agents instantaneously and effectively. Located in adventitia
Functioning in close collaboration is other set of localized concretions of lymphocytes in the form of follicles and nodules such as:
Pharyngeal tonsils
Palatine tonsils
Lingual tonsils
Peyers patches in the small intestine especially in the ileum
Lymphoid follicles in appendix/abdominal tonsil

32

USMLE Step 1 Platinum Notes

In the alimentary canal the diffuse and the local lymphatic systems combine synergistically to form the GUT ASSOCIATED LYMPHOID
TISSUE (GALT). The main function of this system is to act along with the main lymphatic organs.

Remember frequently asked Terms in USMLE


Eponyms

Description

Bowmans capsule

Glomerular capsule of the kidney seen on histology slides

Bowmans membrane

Layer in the cornea below epithelium seen on histology slides

Brunners glands

Glands in the duodenum seen on histology slides

Bundle of His

Atrioventricular bundle

Cords of Billroth

Splenic cords of the spleen seen on histology slides

Crypts of Lieberkuhn

Epithelial glands in the small intestine seen on histology slides

Descemets membrane

Limiting layer of the cornea seen on histology slides

Ducts of Bellini

Papillary duct of the kidney seen on histology slides

Ducts of Luschka

Small ducts found in the connective tissue between the gallbladder and the liver

Golgi aparatus

Intracellular organelle

Golgi tendon organ

Sensory nerve ending embedded in a tendon for proprioception

Graafian follicle

Tertiary follicle of an ovary seen on a histology slide

Haversian canal

Central canal of an osteon of bone seen on a histology slide

Haversian system

Osteon of bone seen on a histology slide

Islets of Langerhans

Pancreatic islets of the pancreas seen on histology slides

Leydig cells

Interstitial cells of the testis

Loop of Henle

U shaped loop in the nephron of the kidney

Krause end bulbs

Cylindrical/oval sensory receptor

Malpighian corpuscle

Renal corpuscle of the kidney seen on histology slides

Meissners corpuscle

Mechanoreceptor

Meissner s plexus

Submucosal plexus

Merkels disk

Tactile receptor

Molls gland

Glands of the conjunctiva

Nissl bodies

Rough endoplasmic reticulum of a neuron

Node of Ranvier

Area between two Schwann cells covering nerve fibers with axon which is not covered
by myelin

Organ of Corti

Small organ of sound transduction; spiral organ

Pacinian corpuscle

Lamellar corpuscle

Peyers patches

Aggregates of lymphatic tissue in the ileum seen on histology slides

Purkinje fibers

Part of the conducting system of the heart

Renal columns of Bertin

Renal columns seen on histology slides

Ruffinis corpuscle

Sensory receptor

Space of Disse

Perisinosoidal space of the liver seen on histology slides

Volkmanns canals

Perforating canals of bone

Whartons jelly

Mucous connective tissue seen in umbilical cord

Anatomy

HIGH YIELD CLINICAL ANATOMY


Upper Limb
Brachial Plexus
C5 and C6 roots join to form the upper trunk
C7 root alone forms the middle trunk
C8 and T1 roots join to form the lower trunk
Each trunk divides into an anterior and posterior division:
All the posterior divisions join to form the posterior cord
The upper two anterior divisions join to form the lateral cord
The lowest anterior division alone forms the medial cord

Branches of the Brachial Plexus


Branches from the roots
Nerve to serratus anterior (C5,C6,C7)
Dorsal scapular nerve (C5)
Muscular branches to the 3 scalene muscles
Branches from the trunks
Suprascapular nerve (C5,C6)
Subclavius nerve (C5,C6)
Branches from the cords
Medial cord
Medial head of median nerve (C8, T1)
Medial pectoral (C8, T1)
Ulnar nerve (C8, T1)
Median cutaneous nerve of forearm (C8, T1)
Medial cutaneous nerve of arm (T1)
Lateral cord
Lateral pectoral (C5, C6, C7)
Lateral head of median (C5, C6, C7)
Musculocutaneous (C5, C6, C7)
Posterior cord

Radial (C5, C6, C7, C8, T1)


Axillary (C5, C6)
Nerve to latissimus dorsi (C6, C7, C8)
Subscapular Upper (C5, C6)
Subscapular lower

Upper trunk deformity is called


Erbs palsy or policemans
Waiters tip
Porter tip deformity
Lower trunk deformity is called Klumpkes palsy

33

34

USMLE Step 1 Platinum Notes

Questions frequently asked from Nerves of Upper Limb


Ulnar nerve Musicians Nerve
Ulnar nerve supplies medial 1/3 of palm. (Hypothenar area)
Ulnar nerve in hand supplies:
3, 4 Lumbricals
Palmar and dorsal interosei
Adductor pollicis
Hypothenar muscles
Ulnar nerve in hand supplies flexor carpi ulnaris and medial half of flexor digitorum profundus
Lesion of ulnar nerve causes:
Weakness of ulnar deviation
Weakness of wrist flexion
Adductor pollicis paralysis with loss of thumb adduction

In Ulnar Nerve Palsy there is


Positive card test
Positive book test/Froment sign
Positive Egawas test
Ulnar claw hand

Median nerve: Laborers nerve, Eye of hand


Does not supply arm
Supplies all flexors except flexor carpi ulnaris and medial half of flexor digitorum profundus in forearm
Supplies thenar eminence
Lumbrical 1 and 2
Opponens pollicis
Abductor pollicis brevis
Flexor pollicis brevis in hand. (LOAF)
Implicated in:
Lunate dislocation
Ape thumb deformity
Carpal tunnel syndrome
Pointing index
Pen test is positive in median nerve injury
Loss of opposition and abduction of thumb

Carpal Tunnel Syndrome


Affects the median nerve. Patients often note a tingling, a loss of sensation, or diminished sensation in the digits. There is also often
a loss of coordination and strength in the thumb, because the median nerve also sends fibers to the abductor pollicis brevis, flexor
pollicis brevis, and the opponens pollicis. A final function of the median nerve distal to the carpal tunnel is control of the first and
second lumbricals which function to flex digits two and three at the metacarpophalangeal joints and extend interphalangeal joints of
the same digits.

Anatomy

35

Radial Nerve
Supplies:
Extensor compartment of arm, forearm
Triceps
Anconeus and extensors of forearm. Extension of MCP joint
Injury to RN Causes
Wrist drop
Saturday night palsy/crutch palsy
Commonly injured in Radial groove

USMLE Case Scenario


A 43-year-old man suffered an injury in his left upper limb. His radial nerve was injured. The radial nerve is at greatest risk for
injury with:
1. Fracture of the surgical neck of the humerus
2. Fracture of the shaft of the humerus
3. Supracondylar fracture of the humerus
4. Olecranon fractures
Ans. 2. Fracture of the shaft of the humerus

Remember
The radial nerve lies in proximity to the humerus as it courses laterally at the junction of the middle and distal thirds of the shaft
of the humerus. Therefore, it is at greatest risk of injury in shaft fractures.

Common Questions in Surgical Anatomy (Hot Questions)


In supracondylar fracture of humerus triangular relationship of three bony prominences is not disturbed. In elbow
dislocation it is disturbed
The shoulder joint is the most commonly dislocated major joint in the body
MC dislocation is inferior
In subacromial bursitis, person feels pain when arm is abducted. Dawbarns sign is seen in subacromial bursitis
PIN (Posterior interosseous nerve) is a branch of radial nerve. No wrist drop is seen in injury to PIN
If posterior medial aspect of elbow is banged against a hard object, it mat cause temporary ulnar nerve damage. This may result in
painful tingling sensations along ulnar aspect of forearm and hand. Because of these sensations, this area of elbow is called Funny
bone/Crazy bone
Eye of hand: median nerve. Enables the individual to feelthinness and texture of cloth
Pronator syndrome: compression of Median nerve between two heads of pronator teres
Infection of pulp spaces is Felon/Whitlow

REMEMBER
USMLE Favorite
Important Nerves Involved in

Wrist drop
Foot drop
Meralgia parasthetica
Winging of scapula
Erbs Palsy
Klumpkes palsy
Sluders neuralgia

Radial nerve palsy


Common peroneal nerve palsy
Lateral cutaneous nerve of thigh
Long thoracic nerve of bell
Upper trunk of brachial plexus
Lower trunk of brachial plexus
Middle turbinate pressing anterior ethmoidal nerve

36

USMLE Step 1 Platinum Notes

The Axillary Nerve


The Axillary nerve is a branch of the posterior cord of the brachial plexus
It is particularly susceptible to the injury in shoulder dislocations that displace the humeral head or in fracture of the surgical neck
of the humerus
A poorly placed crutch (Crutch Palsy) may also damage this nerve causing paralysis of the Teres minor and Deltoid muscles
Arm abduction is impaired and there is associated loss of sensation over the lower half of the deltoid
When the head of the humerus dislocates from the glenohumeral joint, it exits inferiorly, where the joint capsule is the
weakest. Immediately inferior to the glenohumeral joint, the axillary nerve exits from the axilla by passing through the
quadrangular space. At this location, the downward movement of the head of the humerus can stretch the axillary nerve.
The axillary nerve innervates the deltoid muscle after leaving the axilla.
The Lower Subscapular nerve innervates the Teres major, which is responsible for adducting and medially rotating the arm, it
is a branch of the posterior chord (C5 C6) of the brachial plexus.
The Suprascapular nerve innervates the Supraspinatus and Infraspinatus muscle that are responsible for abduction and
lateral rotation of the arm. The nerve is derivated from the C5 and C6 nerve roots
In shoulder abduction:
Humerus elevates
Clavicle rotates
Lateral rotation of scapula occurs along with acromioclavicular joint movement.
The Throacodorsal nerve innervates the latissimus dorsi muscle that is responsible from adduction and extension of the arm.
The nerve arises from the posterior chord (C5, C6, C7) of the brachial plexus
Musculocutaneous nerve supplies (BBC) biceps, bracialis and corocabrachialis.
Brachioradialis is supplied by radial nerve.

Effects caused by Injuries of Important Nerves of Upper Limb


Musculocutaneous
nerve

Muscles of anterior compartment of arm

Median nerve

Muscles of anterior compartment of forearm

Supplies Biceps, corocabrachialis, brachialis


Injury causes loss of elbow flexion and weakness in
supination.
Injury to median nerve at wrist causes:
Ape thumb deformity
Pen test for abductor pollicis brevis
Inability to count on fingers with thumb

Axillary nerve

Deltoid and teres minor


Injury causes
Loss of abduction of shoulder
Rounded contour of shoulder is lost
Sensory loss over lower half of deltoid

Radial nerve

Posterior muscles of arm and forearm


Injury causes
Saturday night palsy
Crutch palsy
Wrist drop

Fracture surgical neck of humerus


dislocation of shoulder

Fracture of humeral shaft

Anatomy

37

USMLE Case Scenario


Deltoid is a thick muscle. It arises from the anterior border and superior surface of the lateral third of the clavicle. Which of the
following nerves innervates the deltoid?
1. Radial
2. Musculocutaneous
3. Ulnar
4. Anterior interosseous c nerve
5. Cranial nerve XI
6. Subscapular
7. Axillary
Ans. 7. Axillary Nerve

Action of Various Muscles of Upper Limb


Flexors of forearm: Biceps, brachialis, brachioradialis
Extensors of arm: Triceps, Anconeus
Muscles attached to greater tubercle: Supraspinatus, infraspinatus, teres minor
Muscles attached to lesser tubercle: subscapularis
Muscles attached to coracoid process: biceps, short head of biceps
Abductors of shoulder joint: Deltoid, serratus anterior, trapezius
Adductors of shoulder joint: pectoralis major, lattismus dorsi

Cleidocranial Dysostosis
Defective intramembranous ossification
Agenesis of clavicle and deformity of skull cap

Four Rotator Cuff Muscles are


Supraspinatus
Infraspinatus
Teres minor
Subscapularis

Remember: Clinical Anatomy (USMLE Favorite)

Frozen shoulder
Dropped shoulder
Chronic supraspinatus tendinitis
Tennis elbow
Golfers elbow
Base pitchers elbow
De quevarians disease
Trigger finger
Mallet finger

Is adhesive capsulitis or periarthritis


Paralysis of trapezius
Is painful arc syndrome
Is lateral epicondylitis
Is medial epicondylitis
Is damage to soft tissues/bones around elbow
Is tenosynovitis of Extensor pollicis brevis and abductor pollicis longus
Is thickening of tendon sheaths at metacarpophalyngeal joint
Is avulsion of extensor tendon of distal interphalangeal joint

38

USMLE Step 1 Platinum Notes

The Anatomical Snuffbox


Triangular depression formed on the posterolateral side of the wrist and metacarpal I by the extensor tendons passing into the
thumb
Historically, ground tobacco (snuff ) was placed in this depression before being inhaled into the nose
The base of the triangle is at the wrist and the apex is directed into the thumb. The impression is most apparent when the thumb
is extended:
The lateral border is formed by the tendons of the abductor pollicis longus and extensor pollicis brevis;
The medial border is formed by the tendon of the extensor pollicis longus;
The floor of the impression is formed by the scaphoid and trapezium and distal ends of the tendons of the extensor carpi radialis
longus and extensor carpi radialis brevis. Structures inside:
Remember essentially:
The radial artery passes obliquely through the anatomical snuffbox
Terminal parts of the superficial branch of the radial nerve pass subcutaneously over the snuffbox
Origin of the cephalic vein from the dorsal venous arch of the hand

Volkmans Ischemic Contracture (Features) (P)

Pallor
Pain (Most important sign)
Paralysis
Parasthesias
Pulselessness

Median nerve mostly involved with Deformity: Flexion of wrist, Extension of Fingers at MCP, Flexion at IP and Pronation of forearm.
Flexor digitorum profundus and Flexor Pollicis Longus are muscles damaged.

Dupuytrens contracture
Progressive, Painless, Puckeringor fibrosis of skin of Palmar Fascia with flexion of MCP joints of ring and little fingers

Colles Fracture
Fall on outstretched hands, Common in elderly women
Distal fragment displaced dorsally, Angulated dorsally, supinated and is also called as Dinner Fork Deformity

De Quervain syndrome
Also known as washerwomans sprain or mothers wrist is a tendinosis of the sheath or tunnel that surrounds two tendons that
control movement of the thumb. (Extensor pollicis brevis and abductor pollicis longus muscles). De Quervain is potentially more
common in women; the speculative rationale for this is that women have a greater styloid process angle of the radius. Symptoms are
pain, tenderness, and swelling over the thumb side of the wrist, and difficulty gripping. Finkelsteins test is used to diagnose
de Quervain syndrome in people who have wrist pain.

Scaphoid Fracture
Scaphoid is one of the Carpal bones which undergo fracture commonly as well as avascular necrosis. Avascular necrosis of
proximal fragment is seen
Injury occurs by fall on outstretched hands. MC site of injury is Waist
Tenderness in Anatomical snuff box maybe seen. Best Radiological view is Oblique view
In absence of Radiological findings, suspect scaphoid fracture. Most common site is between proximal 1/3 and distal 2/3.

Anatomy

39

Action of Various Muscles of Lower Limb


Hip joint
Medial rotator of thigh:
Gracilis
Lateral rotators of femur are:
Obturator internus, Obturator externus
Sartorius, Pyriformis
Superior gemellus, inferior gemellus
Abductors of the hip include the gluteus medius and gluteus maximus
Adductors of the hip include the adductors longus, brevis and magnus
Extensors of hip include gluteus maximus
Internal (medial) rotators of the hip include gluteus medius, minimus, Tensor facia lata
Lateral rotators: quadriceps femoris (rectus femoris, vastus lateralis, medialis and intermedius)
Iliopsoas is flexor of hip
Remember:
Tensor fascia lata is extensor of knee, Abductor and medial rotator of hip. (Imp) TEAM
Ilio tibial tract is flexor, external rotator, abductor of hip. (Imp)
Knee Joint
Extensor of knee: quadriceps femoris
Flexion of knee: long head of biceps femoris. Semimembranosus, semitendonosus, ischial head of adductor magnus
Medial rotation: Semimembranosus, semitendonosus, popliteus
Lateral rotation: biceps femoris

Important Points: (USMLE Favorite)


Meralgia Parasthetica Lateral cutaneous nerve of thigh
Anterior Tarsal Tunnel Syndrome: Deep peroneal nerve
Tarsal Tunnel syndrome: Tibial nerve
Joggers Foot: Medial plantar nerve
Hip Pointer: Iliac Crest
Tennis Leg: Gastrocnemius Soleus strain

Hip Joint

Ileo femoral ligament is ligament of Bigelow


It is the strongest ligament
It prevents hyperextension of hip
Pain of hip is referred to knee joint

Knee

Coronary ligament is present between menisci and tibial condyle


There is other Coronary ligament in liver
Posterior dislocation of Femur is prevented by anterior cruciate ligament
Posterior cruciate ligament prevents posterior dislocation of Tibia
Ligament of Humphery and Wrisberg are anterior and posterior meniscofemoral ligaments

40

USMLE Step 1 Platinum Notes

MENISCAL TEAR
Medial meniscus is 20 times more prone to injury than lateral meniscus. The medial meniscus is firmly adherent to the
deep part of tibial collateral ligament. In forceful strains (adduction and lateral rotation of the femur over the tibia with
the foot firmly placed on the ground) the medial meniscus gets torn. It is because:
The medial collateral ligament does not allow the meniscus to move away from under the femoral condyle
It gets compressed crushed between femoral and tibial condyles that are moving with great force
Part of torn cartilage may get displaced. This small piece floats in the joint cavity. It may get lodged between femoral and
tibial condyles causing locking of knee joint in flexed position

Arterial Supply of Hip Joint

Obturator artery
Medial circumflex artery
Lateral circumflex artery
Superior gluteal artery
Inferior gluteal artery

In Fracture Neck of femur, Blood supply is from these vessels.

USMLE Case Scenario


A 88-year-old osteoporotic female who was a chronic smoker stumbled and fell. The right leg is shortened and externally
rotated with marked loss of range of movements at hip joint
The most likely cause is: Fracture Neck of femur

Nerve Supply of Hip Joint

Femoral nerve through nerve to rectus femoris


Anterior division of obturator nerve
Nerve to quadrates femoris
Superior gluteal nerve

Arterial Supply of Knee Joint

Genicular branches of popliteal artery


Genicular branches of femoral artery
Genicular branches of lateral circumflex femoral artery
Branches of anterior tibial artery
Branches of posterior tibial artery

Nerve Supply of Knee Joint


Femoral nerve through nerve to vasti
Posterior division of obturator nerve
Sciatic nerve through tibial and common peroneal nerves

Nerves Related to Lower Limb Compartments: (USMLE Favorite)

Adductor compartment of thigh: Obturator nerve


Flexor compartment of thigh: Femoral nerve
Posterior compartment of thigh (hamstrings); tibial part of sciatic nerve
Gluteal region: superior and inferior gluteal nerves

Anatomy

41

Anterior compartment of leg: Deep peroneal nerve


Lateral compartment of leg: Superficial peroneal nerve
Posterior compartment of leg: Tibial nerve

Nerves of Lower Limb


Femoral nerve (posterior division of L2, L3, L4)

Anterior compartment of high

Obturator nerve (anterior division of L2, L3, L4)

Medial compartment of thigh

Tibial nerve

Posterior compartment of thigh


Posterior compartment of leg

Common peroneal nerve

Short head of biceps femoris

Superficial peroneal nerve

Lateral compartment of leg


Injury causes loss of eversion of foot

Deep peroneal nerve

Anterior compartment of leg


Injury causes foot drop

Superior gluteal nerve


(Very Important)

Gluteus minimus, gluteus medius, tensor fascia lata NOT Gluteus maximus. Injury Causes
loss of abduction of limb
Impairment of gait
Patient cannot keep pelvis level when standing on one leg. Tredlenburgs sign +

Inferior gluteal nerve

Gluteus maximus. Injury causes:


Weakened hip flexion
Difficulty rising from sitting position.

Q angle: Quadriceps angle is formed by line of pull of quadriceps femoris muscle and that of ligamentum patellae as they intersect
at center of patella. more pronunced in females
Genu valgum (knock knee) angle < 165
Genu varum (bow legs) angle > 180
The Common Peroneal Nerve
Branches into the superficial and deep peroneal nerves, which supply the muscles of the anterior compartment of the leg and
cutaneous areas of the distal anterior leg, dorsum of the foot, and most of the digit
The Tibial Nerve
Supplies all the muscles in the posterior compartment of the leg (e.g. tibialis posterior, flexor digitorum longus, gastrocnemius, and
soleus)

Movements at Different Joints


Ankle: Dorsiflexion, Plantar flexion
Subtalar joint: Inversion, eversion
Mid tarsal joint: Forefoot adduction and abduction

Muscles Involved in Various Movements


Plantar flexion

Gastrocnemius, soleus

Dorsiflexion

Tibialis anterior

Inversion

Tibialis anterior, tibialis posterior

Eversion

Peroneus longus, peroneus brevis

42

USMLE Step 1 Platinum Notes

Common Peroneal Nerve


It is related to the neck of fibula and winds around it
It is the smaller terminal branch of Sciatic nerve
It pierces peroneus longus
It divides into superficial and deep peroneal nerves and supplies the anterior and lateral compartments of leg
Injury to CPN produces foot drop
It is subcutaneous
It is the most common nerve in lower limb to get injured

Ankle Joint
Dorsiflexion

Tibialis anterior
Extensor digitorum longus
Extensor hallucis longus
Peroneus tertius

Plantar flexion

Gastrocneimus
Soleus
Plantaris
Tibialis posterior
Flexor hallucis longus
Flexor digitorum longus

Inversion

Tibialis posterior
Flexor hallucis longus
Flexor digitorum longus

Eversion

Peroneus longus
Peroneus brevis
Peroneus tertius

Reflexes
Biceps

C5, C6

Supinator

C5, C6

Pronator

C5, C6

Triceps

C6, C7

Cremaster

L1, L2

Knee

L2, L3, L4

Plantar

L5 S1

Ankle

S1, S2

Anal, Bulbocavernous

S3, S4

Important Points about Anatomy of Breast


The protuberant part of the human breast is generally described as overlying the 2nd to the 6th ribs, and extending from the
lateral border of the sternum to the anterior axillary line. Actually, a thin layer of mammary tissue extends considerably farther
from the clavicle above to the 7th or 8th ribs below, and from the midline to the edge of latissimus dorsi posteriorly.
The Axillary tail of Spence in the breast is of considerable surgical importance. In some normal cases it is palpable, and in a few it
can be seen premenstrually or during lactation. A well-developed axillary tail is sometimes mistaken for a mass of enlarged lymph
nodes or a lipoma.

Anatomy

43

Axillary tail
The lobule is the basic structural unit of the mammary gland. The number and size of the lobules vary enormously: they are
most numerous in young women. From 10 to over 100 lobules empty via ductules into a lactiferous duct of which there are
from 15 to 20. Each lactiferous duct is lined by a spiral arrangement of contractile myoepithelial cells and is provided with a
terminal ampulla a reservoir for milk or abnormal discharges.
The ligaments of Cooper are hollow conical projections of fibrous tissue filled with breast tissue, the apices of the cones being
attached firmly to the superficial fascia and thereby to the skin overlying the breast. These ligaments account for the dimpling of
the skin overlying a carcinoma.
The areola contains involuntary muscle arranged in concentric rings as well as radially in the subcutaneous tissue. The areolar
epithelium contains numerous sweat glands and sebaceous glands, the latter of which enlarge during pregnancy and serve to
lubricate the nipple during lactation (Montgomerys tubercles).
The nipple is covered by thick skin with corrugations. Near its apex lie the orifices of the lactiferous ducts. The nipple contains
smooth muscle fibers arranged concentrically and longitudinally; thus is an erectile structure which points outwards. Lymphatics
of the breast drain predominantly into the axillary and internal mammary lymph nodes. The axillary nodes receive approximately
75 percent of the drainage and are arranged in the following groups.

Blood Supply is via


Internal thoracic artery
Intercostal artery
Lateral thoracic artery

Lymph nodes of Breast


Lateral, along the axillary vein
Anterior, along the lateral thoracic vessels
Posterior, along the subscapular vessels
Central embedded in fat in the center of the axilla
Interpectoral, a few nodes lying between the pectoralis major and minor muscles
Apical, which lie above the level of the pectoralis minor tendon in continuity with the lateral nodes and receive the efferents of all
the other groups
The apical nodes are also in continuity with the supraclavicular nodes and drain into the subclavian lymph trunk which enters the
great veins directly or via the thoracic duct or jugular trunk. The sentinal node is that lymph node designated as the first axillary node
draining the breast.
The internal mammary nodes are fewer in number and lie along the internal mammary vessels deep to the plane of the costal cartilages
Mondors disease is thrombophlebitis of the superficial veins of the breast and anterior chest wall (although it has also been
encountered in the arm).
Familial breast cancer Recent developments in molecular genetics and the identification of a number of breast cancer predisposition
genes (BRCA1, BRCA2 and TPS3). These women have a risk of developing breast cancer two to 10 times above baseline.

44

USMLE Step 1 Platinum Notes

Lymph nodes below Pectoralis Minor Level 1


Lymph nodes behind Pectoralis Minor Level 2
Lymph nodes above Pectoralis Minor Level 3
The principal nodes which drain the breast are: Axillary Group of Lymph nodes
About 70 -75% of lymph from breast drains into Axillary group of Lymph nodes, 20% into internal mammary group of Lymph
nodes and 5% into posterior intercostal group of lymph nodes
Among the Axillary Group Chief is the Anterior group
Rotters nodes are interpectoral nodes
Absence of sternal head of pectoralis major: Polands syndrome

Openings of Diaphragm: (USMLE Favorite)


Vena caval opening:
Thoracic 8 level
Inferior vena cava
Rt phrenic nerve
Esophageal opening:
Thoracic 10 level
Esophagus
Vagus nerves
Esophageal branch of it gastric artery
Aortic opening:
Thoracic 12 level
Aorta
Thoracic duct
Azygous vein

CONTENTS OF IMPORTANT STRUCTURES


Contents of Spermatic Cord: (USMLE Favorite)

The ducts deferens


Testicular and cremastric arteries
Artery of vas
The pampiniform plexus of veins
Lymph vessels from testis
Genital branch of Genitofemoral nerve
Remains of processus vaginalis

Contents of Rectus Sheath: (USMLE Favorite)

Rectus abdominis and pyramidalis muscle


Superior epigastric artery and inferior epigastric artery
Superior epigastric vein and inferior epigastric vein
Lower five intercostal nerves and subcostal nerve

Contents of Broad Ligament: (USMLE Favorite)

Uterine tube
Round ligament of uterus, ligament of ovary
Uterine vessels, ovarian diseases
Uterovaginal, ovarian nerve plexus
Epoophoron, Paroophoron
Lymph vessels, lymph nodes

Anatomy

Contents of Ischiorectal Fossa: (USMLE Favorite)

Perianal space
Ischiorectal space
Lunate fascia
Pudendal canal

Contents of Adductor Canal are: (USMLE Favorite)


Femoral artery
Saphanous nerve
Nerve to vastus medialis

Esophageal opening lies in muscular part of diaphragm


Vena caval lies in central tendon of diaphragm
Aortic opening is not a true opening but an osseo aponeurotic opening
Greater and lesser splanchnic nerves pierces each crus of diaphragm
Lt crus is also pierced by hemi azygous vein
Sympathetic chain passes behind medial arcuate ligament
Subcostal nerves vessels pass behind lateral arcuate ligament
Superior epigastric vessels and lymphatics pass through Foramen of Morgagni (Larrys space)
Musculophrenic vessels pierce the diaphragm
Hernia does not occur through vena caval opening
Bochaldeks hernia occurs through posterolateral part of diaphragm
Morgagni hernia occurs anteriorly on right usually
Remember Accessory phrenic nerve is commonly a branch from the nerve to subclavius

Sites of Esophageal Constrictions


Distance from Incisor

Landmark

6 inches

Pharyngoesophageal junction

9 inches

Aortic arch crossing

11 inches

Left bronchus

15 inches

Pierces diaphragm

Esophagus

Length 25 cm
Commences at lower end of cricoid
Has squamous epithelium
Toughest layer is muscularis
No serosa

THORAX
Heart
Right coronary artery arises from anterior aortic cusp
Left coronary arises from posterior aortic cusp
Posterior interventricular artery determines coronary dominance

45

46

USMLE Step 1 Platinum Notes

In case it arises from right coronary artery, right dominance


In case it arises from left coronary, left dominance
Right Coronary artery mostly supplies SA node, AV node, AV bundle
The SA node is usually supplied by Right coronary artery and Right Vagus
The AV node is usually supplied by Right coronary artery and Left vagus
Sympathetic innervation is by T2-T6
Maximum (90%) of venous drainage of Heart goes to Coronary Sinus
In fetal life left sided svc drains into coronary sinus
Great Cardiac Vein follows Anterior Interventricular artery
Middle Cardiac Vein follows Posterior Interventricular artery
Small Cardiac Vein follows Rt Marginal artery
Inferior surface of heart is formed by Rt and Lt ventricle
Base of heart is formed by Rt and Lt atrium
Part of heart lying close to esophagus: Lt atrium
Structures Present In:
Musculi pectinati: Atria of heart
Trabeculae cornea: Rt ventricle of heart
Moderator band/Septomarginal trabeculae: right ventricle
Coronary sinus, SVC, IVC: open in Right atrium
SA node is located in: Rt Atrium
Whole of conducting system is mostly supplied by rt coronary artery except Right bundle branch (supplied by left coronary
artery)
Holmes heart: single ventricle

Coronary Sinus
It is the largest venous channel of the heart about 3 cms. It located in left posterior coronary sulcus
It is a remnant of left horn of sinus venosus = while the right horn gets incorporated into right atrium
It opens into the right atrium of the heart through an orifice of coronary sinus and has a valve called the Thebesian valve. It receives:
Great cardiac vein
Middle cardiac vein
Small cardiac vein
Right marginal vein
Oblique vein of left atrium
Right marginal vein

Thoracic Duct

Also called as Pecquets duct


Beaded in appearance
18 inches in length
It is the largest lymphatic pathway in body
The duct commences in the abdomen as an elongated lymph sac of the cisterna chylli is: Thoracic duct
Begins from cisterna chyli at the level of T12 vertebrae
Injury to thoracic duct by trauma leads to chylothorax

Anatomy

47

LUNGS
Bronchopulmonary Segment

Vascular segment
Independent
Bronchial artery supplies till respiratory bronchiole
Largest subdivision of lobe

Remember
Because the right main bronchus is wider and more vertical than the left, foreign objects are more likely to be aspirated into the
right main bronchus. The superior segmental bronchus of the lower lobar bronchus is the only segmental bronchus that exits from
the posterior wall of the lobar bronchi. Therefore, if a patient is supine at the time of aspiration, the object is most likely to enter the
superior segmental bronchus of the lower lobe.

Peculiarities of Blood Supply of Lung


Smallest functional unit of lung is lobule
Blood supply of lung tissue proper is by Bronchial arteries
Bronchial arteries are branches of descending: Thoracic Aorta
They supply nutrition to bronchial tree and pulmonary tissue up to respiratory bronchiole
Segments distal to respiratory bronchiole are supplied by branches from pulmonary vessels
On the right side there is only one BA arising indirectly from descending Thoracic Aorta
On the Left side there are two BA arising directly from descending Thoracic Aorta
Bronchial arteries are responsible for Hemoptysis
Pulmonary arteries carry deoxygenated blood
Pulmonary veins carry oxygenated blood
Sequestered segments are supplied by systemic circulation

AZYGOS Lobe of Lung


Azygos means unpaired. Azygos lobe maybe seen on the right lung
It is seen as a result of developmental anomaly related to lung bud and posterior cardinal vein
The posterior cardinal vein (future azygos vein) gets embedded in the substance of lung which passes as lung bud below the arch
formed by posterior cardinal vein
The part of lung medial to the vein forms the azygos lobe

GEMS ABOUT INTRA-ABDOMINAL ORGANS


The Spleen
It is a hemolymphatic organ:
The second largest organ of the reticuloendothelial system
It is located in the posterior left upper quadrant of the abdomen (left hypochondrium) where its relationships to the diaphragm,
stomach, pancreas, left kidney, and splenic flexure of the colon are maintained by suspensory ligaments. The splenophrenic,
splenorenal, and splenocolic ligaments are usually relatively avascular and their transection allows the spleen to be displaced
medially and anteriorly
The Gastrosplenic ligament extends from the greater curvature of the body and fundus of the stomach to the spleen, contains
the short gastric arteries and veins
The Splenorenal ligament (Lienorenal) and attached to the spleen at the hilum: Splenic artery and vein, lymphatic structures,
and often the tail of the pancreas

48

USMLE Step 1 Platinum Notes

The arterial supply to the spleen is derived from the celiac artery from both the splenic artery and the short gastric arteries,
which usually arise as branches of the gastroepiploic or the splenic arteries
The splenic vein is formed by a coalescence of polar veins in the splenic hilum and courses with the splenic artery along the dorsal
surface of the pancreas to enter the portal system.

The Stomach
Starts from gastroesophageal junction to the pylorus
It is bounded on the left by the spleen and on the right by the liver
The blood supply to the stomach is extensive
Left gastric artery, which supplies the upper lesser curvature of the stomach from celiac trunk
The right gastric artery branches off the hepatic artery, which originates from the celiac axis; it supplies blood to the distal lesser
curvature
The left gastroepiploic artery is a branch off the short gastric vessels; it comes from the splenic and therefore originally from the
celiac axis
The right gastroepiploic artery branches off the gastroduodenal artery, which comes originally from the hepatic artery and
therefore from the celiac axis
The venous drainage of the stomach empties in a variety of directions, including venous tributaries along the esophagus, veins that
flow with the short gastrics to the splenic vein, and venous drainage that is carried toward the duodenum and toward the portal vein
Nerve supply is predominantly by the vagus
An anterior (left) and posterior (right) vagus nerve courses with the esophagus until the gastroesophageal junction
The criminal nerve of Grassi is the first branch of the posterior vagal nerve innervating the greater curvature fundus. At the junction
of the fundus and the antrum of the stomach, the vagal nerves branch and innervate the antrum. This vagal branch point is called the
crows foot
The lesser sac is bounded ventrally by the stomach and is an important location during operation, in that it is a frequent space for
fluid collection and is an important plane for the exposure of gastric anatomy.

Duodenum
The duodenum extends from the pylorus about 20 to 30 cm and ends at the ligament of Treitz, which is where the jejunum
begins. This is marked by adhesive bands between the duodenal-jejunal junction and the retroperitoneum on the left side of the
abdomen
The duodenum is divided into four anatomic regions:
The first portion, or the cap or bulb
The second portion, or the descending duodenum
The third, or transverse, portion; and the
Fourth, or ascending, portion

Gems about Duodenum


The duodenal cap lies just beyond the pylorus. Ninety percent of ulcers occur in the duodenal cap region.
The gastroduodenal artery lies directly behind the duodenal cap, and penetrating ulcers into the pancreas initially erode through
the gastroduodenal artery, accounting for the massive bleeding that occurs with these ulcers.
The second (descending) portion of the duodenum: The ampulla of Vater and the minor papilla both enter into the duodenum
in this portion. The second portion of the duodenum is approximately 10 cm in length.
The third and fourth portions of the duodenum (transverse and ascending portions) are mostly retroperitoneal.
The third portion is attached to the uncinate process and crosses the abdomen and over the aorta.
Compression of the junction of the third and fourth portions of the duodenum by the angle of the SMA and the aorta is called
the SMA syndrome.

Anatomy

49

The fourth portion of the duodenum blends into the jejunum at the ligament of Treitz, which attaches this junction to the
retroperitoneum. Mobilization of the ligament of Treitz is necessary in duodenal resections. The ligament is often composed of small
strands of striated muscle that eventually extend to the crus of the diaphragm.
Kerckrings folds The mucosal surface of the small intestine contains numerous circular mucosal folds called the plicae
circulares (valvulae conniventes, or valves of Kerckring) of the duodenum begin just beyond the cap and continue throughout
the duodenum. The concentric folds of Kerckring are approximately 1 to 2 mm thick and 2 to 4 mm high. They are taller and more
numerous in the distal duodenum and proximal jejunum, becoming shorter and fewer distally.

Difference between Small and Large Intestine


Small intestine

Large intestine

About 6 -7 meters in length

About 180 cms in length

Small diameter

Larger diameter

Mucosa has villi and crypts

Mucosa hascrypts but no villi

Paneth cells present

Paneth cells absent

Less goblet cells

More goblet cells

Brunners glands in duodenum present


Peyers patches in ileum present

Both absent

Sacculations absent

Sacculations present

Appendices epiploicae absent

Appendices epiploicae present

Tenia absent

Tenia present

Celiac Trunk
LEFT GASTRIC ARTERY Esophageal branch, gastric branch
COMMON HEPATIC ARTERY Right hepatic, left hepatic, Gastroduodenal artery supraduodenal, right gastroepiploic, superior
pancreaticoduodenal artery
SPLEENIC ARTERY Short gastric, left gastroepiploic, pancreatic branches

Meckels Diverticulum
A Meckels diverticulum, a true congenital diverticulum
It is a vestigial remnant of the omphalomesenteric duct (also called the vitelline duct) and is the most frequent malformation
of the gastrointestinal tract
Meckels diverticulum is located in the distal ileum, usually within about 60-100 cm of the ileocecal valve
It is typically 3-5 cm long, runs antimesenterically and has its own blood supply
It is a remnant of the connection from the umbilical cord to the small intestine present during embryonic development

A Memory Aid is the Rule of 2s


2% (of the population)
2 feet (from the ileocecal valve)
2 inches (in length)
2% are symptomatic
2 types of common ectopic tissue (gastric and pancreatic)
Most common age at clinical presentation is 2
Males are 2 times as likely to be affected

50

USMLE Step 1 Platinum Notes

Anal canal above Dentate Line

Anal Canal Below Dentate Line

Endodermal

Ectodermal

Cuboidal epithelium

Stratified squamous

Superior Rectal Artery

Inferior Rectal Artery

Superior Rectal Vein

Inferior Rectal Vein

Internal Iliac group of lymph nodes

Superficial inguinal group of lymph nodes

Pain insensitive

Pain sensitive

The liver
Lies in the right upper quadrant of the abdomen
It is the largest gland in the body, it weighs approximately 1500 gm
The gallbladder lies on the dorsal surface of the liver in a transpyloric plane
A peritoneal membrane (Glissons capsule) covers the liver
The superior surface of the liver conforms to the undersurface of the right diaphragm. The relations of the inferior surface of
the liver are the duodenum, colon, kidney, adrenal gland, esophagus, and stomach. Peritoneum invests the entire liver except for a
bare area under the diaphragm on the posterosuperior surface adjacent to the inferior vena cava and hepatic vein.

Ligaments of Liver
The falciform ligament, which attaches the liver to the anterior abdominal wall from the diaphragm to umbilicus and incorporates
the ligamentum teres hepaticus
The anterior and posterior right and left coronary ligaments, which in continuity with the falciform ligament connect the
diaphragm to the liver. The lateral aspects of the anterior and posterior leaves of the coronary ligaments fuse to form the right and
left triangular ligaments
The gastrohepatic and hepatoduodenal ligaments, which consist of the anterior layer of lesser omentum and are continuous
with the left triangular ligament. The hepatoduodenal ligament contains the hepatic arteries, portal vein, and extrahepatic bile
ducts. It forms the anterior boundary of the epiploic foramen of Winslow and the communication between the greater and lesser
peritoneal cavities.

Four Lobes of the Liver are Commonly Described

Right
Left
Quadrate
Caudate

Portal Vein
The portal vein provides about three fourths of the livers blood supply
The combination of the superior mesenteric and splenic veins forms the portal vein, behind the neck of the pancreas
The portal vein then passes superiorly, posterior to the first part of the duodenum at the level of the second lumbar vertebra
Portal vein is 1 to 3 cm in diameter and 5 to 8 cm in length before dividing into right and left branches at the portal hepatis
The portal vein usually passes behind the bile duct and hepatic artery in the hepatoduodenal ligament
The portal trunk divides into left and right hepatic branches in the portal fissure. The left branch of the portal vein is longer
The portal vein divides into small veins and venules, which finally enter hepatic sinusoids
The portal vein has no valves

Anatomy

51

Portocaval Anastomosis
Numerous tributaries of the portal vein connect outside the liver with the systemic venous system. Under normal circumstances
these communications have little physiologic significance. However, if portal hypertension develops, these rudimentary
portosystemic communications develop into large channels with increased collateral flow.

Sites of Portosystemic Anastomoses Include


The submucosal veins of the proximal stomach and distal esophagus, which can receive blood from the coronary and short gastric
veins to drain into the azygous veins (high blood flow through this pathway produces gastric varices, esophageal varices, or
both)
Umbilical and periumbilical veins, recanalized from the obliterated umbilical vein in the ligamentum teres hepaticus, and which
may cause caput medusae or the loud Cruveilhier-Baumgarten bruit
Tributaries of the inferior mesenteric vein, which include the superior hemorrhoidal veins that communicate with the middle and
inferior hemorrhoidal veins of the systemic circulation and may cause large hemorrhoids; and
Other retroperitoneal communications, including connections to the renal and adrenal veins.

Sphincter of Oddi
The circular smooth muscle fibers in the ampulla of Vater area constitute the sphincter of Oddi, which regulates the flow of bile from
the liver into the duodenum
The three principal parts of the sphincter of Oddi are:
1. The sphincter of the choledochus (i.e. the circular muscle fibers surrounding the intramural and submucosal bile duct);
2. The pancreatic sphincter, which consists of a muscular septum between the bile and pancreatic ducts;
3. Ampullary sphincter: The ampullary sphincter, the most important component of the sphincter of Oddi, includes a layer of
longitudinal muscle fibers that help prevent reflux of intestinal contents into the ampulla
Relaxation of the ampullary sphincter may promote reflux into the pancreatic duct.

Gallbladder
The gallbladder, a pear-shaped (pyriform), distensible appendage of the extrahepatic biliary system
Capacity: 30 to 50 ml of bile
Parts: It has a fundus, body, and neck
The duct of gallbladder cystic duct varies in length and usually contains spiral valves of Heister that regulate bile flow
Enlargement of the neck of the gallbladder such as from a stone may form a pouch (Hartmanns pouch)
The triangle bounded by the cystic duct, common hepatic duct, and inferior border of the liver is the Triangle of Calot
The gallbladder receives its blood supply from the cystic artery, which originates from the right hepatic artery
Venous drainage of the gallbladder enters principally into the portal vein
The lymphatics drain into cystic duct nodes near the superior aspect of the cystic duct. (Cystic Lymph node of Lund)

The Triangle of Calot


It is a surgical landmark used to identify important structures during cholecystectomy, is bounded by the cystic duct, the
common hepatic duct, and the inferior border of the liver
The right hepatic and cystic arteries are located within it and anomalous structures often pass through it
Moynihans Hump: An abnormal bend in the course of the right hepatic artery, throwing it into the configuration of a caterpillar
hump, (Moynihans hump) invites injury unless it is carefully dissected free

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USMLE Step 1 Platinum Notes

The Pancreas (Pan: All creas Flesh)


It is a retroperitoneal organ, lying posterior to the stomach and lesser omentum
It extends from the duodenal C loop to the hilum of the spleen
The gland has a distinctive yellow/tan/pink color and is multilobulated
The pancreas is covered by peritoneum anteriorly and posteriorly it lies in proximity to the inferior vena cava, right renal vein, aorta
at the level of the first lumbar vertebra, superior mesenteric vessels, and splenic vein.
The gland is divided into four portions:
a. The head (which includes the uncinate process)
b. The neck
c. The body and
d. The tail
The head of the gland extends to the right of the neck, lying within the confines of the duodenal C loop; it includes the posteroinferior
extension arising from the ventral primordium, designated the uncinate process. The uncinate process extends posterior to the
superior mesenteric vein, ending at the right margin of the superior mesenteric artery. The body of the pancreas lies immediately
to the left of the neck; the tail of the pancreas extends to the left of the body into the splenic hilum.
The head of the pancreas is intimately associated with the second portion of the duodenum, and these two structures are jointly
supplied by two arterial arcades known as the anterior and posterior pancreaticoduodenal arteries. These arteries originate
from the superior and inferior pancreaticoduodenal vessels as branches of the celiac axis and superior mesenteric artery,
respectively. The distal body and tail of the pancreas are supplied by short branches of the splenic and left gastroepiploic arteries.
Within the posterosuperior and posteroinferior aspects of the body of the pancreas lie the superior and inferior pancreatic arteries,
respectively.
Veins draining the pancreatic parenchyma eventually terminate in the portal vein, which arises posterior to the neck of the
pancreas at the junction of the splenic and superior mesenteric veins
Multiple lymph node groups drain the pancreas
From the head of the gland, nodes in the pancreaticoduodenal groove communicate with subpyloric, portal, mesocolic,
mesenteric, and aortocaval nodes
Lymphatics in the body and tail of the pancreas drain to retroperitoneal nodes in the splenic hilum or to celiac, aortocaval,
mesocolic or mesenteric nodes

The Kidneys
Bean shaped
Retroperitoneal
Right kidney is lower than left (but right suprarenal is higher than left.)
Each kidney is 9 to 15 cm long, 4 to 5 cm wide and approximately 3 cm thick. They are located on each side of the vertebral
column between the parietal perineum and the fascia and musculature of the posterior abdominal wall and are embedded in a
variable amount of fat and surrounded by a layer of fascia (Gerotas fascia)
They lie on the side of the psoas muscle
They are not parallel, with the upper poles being approximately 2 cm from the midline and the lower poles approximately 3.5 cm
from the midline
Coverings of Kidney (From inside to out)
Fibrous capsule
Perinephric fat
Renal fascia with 2 layers
-- Anterior layer of Toldts Fascia
-- Posterior layer of fascia of Zuckerkandl
Pararenal Fat

Anatomy

53

Posterior Relations of Kidney

3 parts of diaphragm: Medial arcuate ligament, Lateral arcuate ligament, Diaphragm


3 muscles: Psoas major, quadrates lumborum, transverses abdominis
3 nerves: Subcostal, iliohypogastric, ilioinguinal nerves
Right kidney: 12th rib
Left kidney: 11th and 12th rib

Ureter
25 cm long (PGI)
Totally retroperitoneal
It enters true pelvis after crossing iliac vessel

Important Points about Ureter

Starts at the hilum


Changes its direction at the ischial spine
Penetrates the bladder wall without any valve
Enters the bladder at the lateral angle of the trigone
Enters pelvis in front of bifurcation of common iliac artery

The Suprarenals or the Adrenal Glands


Are bilateral retroperitoneal organs located on the superior medial aspect of the upper pole of each kidney
Each gland weighs approximately 4 gm. The left adrenal is larger and flatter
The normal adrenal cortex is bright yellow and thicker than the red-brown medulla.

Blood Supply of Suprarenals


Superior suprarenal artery: branch of inferior phrenic artery
Middle suprarenal artery: branch of abdominal aorta
Inferior suprarenal artery: branch of renal artery

Venous Drainage
The left adrenal vein empties primarily into the left renal vein but may occasionally drain directly to the vena cava
Lymphatic plexuses within the subcapsular portion of the adrenal cortex and the adrenal medulla drain to the adjacent para-aortic
subdiaphragmatic and renal lymph nodes.

Important Anatomical Relations


Relations at hilum of kidney (Anterior to Posterior) VAP
Renal vein
Renal artery
Renal pelvis
Relations at Femoral Triangle (From Medial to Lateral) 'VAN
Femoral vein
Femoral artery
Femoral nerve

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USMLE Step 1 Platinum Notes

Intercostal space (From Above Downwards) VAN


Intercostal vein
Intercostal artery
Intercostal nerve
Cubital Fossa (From Medial to lateral side). MBBR
Median nerve (Medial aspect)
Brachial artery
Biceps tendon
Radial nerve
Lateral boundary by brachioradialis muscle.

MALE REPRODUCTIVE TRACT


Testes

It is male gonad
Two oval structures are average 4 to 5 cm in length and 2.5 to 3.5 cm in width in the normal adult male
1015 gms in weight (Indians average)
Testis arises from the genital ridge

Covered by
Tunica vaginalis
Tunica albugenia
Tunica vasculosa
Blood supply is by testicular artery which is a branch of abdominal aorta
Venous drainage of the testis is through the pampiniform plexus to the spermatic vein, which is usually single and emerges
from the upper end of the cord and then follows the internal spermatic artery through the retroperitoneum. On the right the
spermatic vein empties into the vena cava below the right renal vein, whereas on the left the spermatic vein empties into
the main renal vein. Increased hydrostatic pressure, particularly on the left, may result in dilatation of the pampiniform venous
plexus, producing a varicocele
The lymphatic drainage of the testis is through the spermatic cord and the inguinal canal and then to the common iliac and
preaortic and paraortic nodes, with the latter communicating across the midline at the level of the kidneys and also with the
mediastinal and supraclavicular chains
Histologically, there are two principal portions of the testis: The seminiferous tubules, which are responsible along with the
Sertoli cells for spermatogenesis, and the interstitial or Leydig cells, which elaborate androgenic hormones, predominantly
testosterone

Testicular Descent
Iliac Fossa: 3rd month
Deep Inguinal Ring: 7th month
Pass through Inguinal Canal: 7th month
At Superficial Inguinal ring: 8th month
Enter Scrotum: 9th month

Anatomy

55

Epididymis
Are coiled structures each containing a single epididymal tubule 12 to 19 feet long and attached to the posterolateral surface of each testis
Remember:
From the tails of the epididymi sperm are transmitted into the vasa deferentia, which are direct continuations of the duct of the
epididymi passing up the spermatic cord, across the inguinal canal, and then retroperitoneally to the ampulla of the seminal vesicles,
with which they conjoin to form an ejaculatory duct on each side. The ejaculatory duct then empties directly into the prostatic
urethra.
The principal blood supply for the epididymis is from the internal spermatic artery. Venous drainage corresponds to the arterial supply,
and the lymphatic drainage of the epididymis parallels that of the testis. The prime function of the epididymis is not only as a conduit
for spermatozoa but also for biochemical and functional maturation and ultimate storage.
Ductus deferens/Vas Deferens
It is 18 inches in length. The vas deferens is an easily discernible structure within the scrotum and spermatic cord because it is a
heavily muscled tubular structure
Spermatic Cord
The spermatic cord, suspending each testis and its attached epididymis, is composed of the vas deferens, the internal spermatic
artery, the external spermatic artery, the pampiniform plexus of veins, the lymphatic drainage system of the contents of the
scrotum, and the autonomic nerve supply to the testis. In addition, the cord is surrounded by fibers of the cremasteric muscle,
which assist by contraction and relaxation in the maintenance of optimal testicular temperature and provide for testicular
retraction with sexual excitation or in the primitive fright reaction.

Contents of Spermatic Cord

The ducts deferens


Testicular and cremastric arteries
Artery of vas
The pampiniform plexus of veins
Lymph vessels from testis
Genital branch of genitofemoral nerve
Remains of processus vaginalis

Scrotum
The scrotal sac, consisting of two lateral compartments fused in the midline encloses the testes, epididymi, and terminal
portions of the spermatic cords. The dartos, consisting of elastic fibers, connective tissue, and smooth muscle fibers, is attached
to the corrugated skin of the scrotum, rich in sebaceous glands, and provides for muscular contraction of the scrotal sac in response
to temperature changes or sexual excitation. The principal function of the scrotum is to aid in temperature control of the testes
for optimal spermatogenesis, which takes place at temperatures several degrees lower than those in the intra-abdominal cavity
The blood supply of the scrotum comes from the deep pudendal branches of the femoral artery and branches of the internal
pudendal artery
The lymphatics of the scrotal halves anastomose freely, surround the penis, and drain to the inguinal and femoral nodes. There are
no connections between the lymphatics of the scrotum and the testes; the scrotal lymphatics do not accompany the pudendal
vessels.

Seminal Vesicles
Are paired, monotubular, convoluted structures lying beneath the base of the bladder and trigone. Posteriorly they are
invested by Denonvilliers fascia, which separates them from the anterior wall of the rectum
The two seminal vesicles fuse immediately with the ampullae of the vasa, forming the ejaculatory ducts, which open into
the prostatic urethra at the level of the verumontanum. The seminal vesicles secrete a mucoid vehicle for the spermatozoa and
also elaborate the bodys only source of fructose, which is used as an essential nutrient for maintenance of spermatozoal viability.

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USMLE Step 1 Platinum Notes

Prostate Gland
It is a fibromuscular, glandular organ that surrounds the neck of the urinary bladder and the proximal portion of the male
urethra. The gland is supported anteriorly by the puboprostatic ligaments, inferiorly by the genitourinary diaphragm (external
urinary sphincter), and posteriorly by the rectal wall, which is separated from the prostate by an obliterated pelvic reflection of
the peritoneum called Denonvilliers fascia.
The prostate consisting of two portions: an anterior (inner) group of glands intimately associated with the urethra and a posterior
(outer) portion of more fibromuscular character
Arterial supply: The inferior vesical and internal pudendal arteries provide the blood supply to the prostate, entering the gland
posterolaterally at the vesical neck
Venous drainage of the prostate is complex and diffuse, with plexuses over the anterior and lateral portions of the gland that
drain into the internal iliac veins
Intercommunicating lymphatics of the prostate, bladder, seminal vesicles, vasa deferentia, and rectum provide drainage into
both the internal and external iliac systems as well as the sacral promontory nodes
Zones of Prostate:
These zones have physiologic and surgical significance because Benign enlargement of the prostate (BHP) occurs in the
transition or periurethral zone and Malignancy develops in the majority of cases in the Peripheral zone.

Urethra
18-20 cms in length with 3 parts
Prostatic (3 cms semilunar)
Membranous (2 cms stellate)
Spongy/penile (15 cms slit shaped)
Prostatic part is widest and more dilatable part
Contains:
Veru montanum (urethral crest)
Colliculus seminalis
Prostatic sinuses
Prostatic utricle (analogous to uterus/vagina of females)
Cowpers Glands: (Bulbourethral glands of Cowper) are small, paired glands lying between the layers of the urogenital diaphragm at
the junction of the bulbous and membranous portions of the urethra. The ducts of the glands empty distally into the bulbous urethra
traversing the corpus spongiosum. The secretions from this gland not only act as a lubricant but may also have factors that aid in
seminal fluid coagulation after ejaculation.

Penile Tissue
Organ of copulation and excretion of urine
It consists of two parallel erectile tissues as the corpora cavernosa, which are situated dorsolaterally, and the corpus spongiosum,
which invests the urethra ventrally, terminating distally in the erectile glans penis
Each corpus cavernosum and the corpus spongiosum are enveloped in fascial sheaths, and all three corpora are surrounded by
Bucks fascia
The blood supply of the penis is through the dorsal arteries derived from the internal pudendal arteries, which are branches
of the internal iliac artery
The venous drainage is through the dorsal veins, with the superficial dorsal vein emptying into the saphenous vein, and the
deep dorsal vein emptying into the prostatic plexus known as the plexus of Santorini
Penile erection is induced by the engorgement of the erectile tissues of the corpora, principally the corpora cavernosa
Lymphatic drainage of the penis is abundant. The lymphatics from the shaft of the penis, the corpora cavernosa, and the skin pass
through the superficial and deep inguinal nodes, communicating with the iliac nodes.

Anatomy

57

Lymphatic drainage of the glans penis drains into deep inguinal nodes and rest of the penis drains into superficial inguinal
nodes
The skin of the penis differs considerably from other skin of the body in its paucity of sebaceous glands, its elasticity, and its
extensive blood supply.

REMEMBER
High Yield Points

The bulbourethral glands secrete mucus for lubrication


The epididymis concentrates and stores sperm for ejaculation
The prostate gland secretes alkaline fluid to neutralize vaginal pH and induces clotting of the semen
The seminal vesicles produce fructose, citric acid, prostaglandins, and fibrinogen. These comprise about 60% of the volume of
semen
The ampulla is the end of the vas deferens
The bulbourethral glands secrete mucus for lubrication
The epididymis concentrates and stores sperm for ejaculation
The prostate gland secretes alkaline fluid to neutralize vaginal pH and induces clotting of the semen

The seminal vesicles produce fructose, citric acid, prostaglandins, and fibrinogen. These comprise about 60% of the volume of semen.

FEMALE REPRODUCTIVE TRACT


The Vagina
The vagina is a female copulatory organ. It is a muscular tube lined with stratified squamous epithelium. The adult vagina measures
12 to 13 cm in-depth. In virgin lower end of vagina is closed partially by annular fold of mucus membrane called hymen which gets
distorted after intercourse forming rounded elevations called caruncle hymenale.

The Cervix
It is the lower cylindrical portion of the uterus
The cervix, is a fibromuscular organ covered with stratified squamous epithelium. The walls of cervix show mucosal folds called
arbor vitae
The squamocolumnar junction is the most common site of origin of squamous cell carcinoma
The endocervical canal is lined by columnar epithelium, and racemose glands, lined with similar epithelium, are found in the
fibromuscular stroma. Such glands, if obstructed, may form nabothian cysts on the cervical surface
The nulliparous cervical os is round.

The Uterus
The uterus is a hollow, fibromuscular-walled organ between the bladder
The normal position of uterus is anteverted and anteflexed
Angle of anteversion is 90
Angle of anteflexion is 120
The organ is pear shaped and in nonpregnant women measures approximately 8 cm in length and weighs 30 to 100 gm
The fallopian tubes and the cervical canal communicate with the uterine cavity, which is lined by the endometrium
The uterine fundus is covered by peritoneum except in the lower anterior portion, where the bladder is contiguous with the lower
uterine segment and the peritoneum is reflected, and laterally where the folds of the broad ligament are attached. The uterus is
supported by condensations of endopelvic fascia and fibromuscular tissue laterally at the base of the broad ligaments
Blood supply of uterus is by uterine artery which is tortuous and branch of anterior division of internal iliac artery lying on the
lateral aspect of uterus in the broad ligament.

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USMLE Step 1 Platinum Notes

Uterine Prolapse, or Procidentia and Uterine Descensus


Occurs when the uterus and its adjoining structures herniate through the vaginal canal
Prolapse is described as first, second, or third degree in severity, the last being protrusion of the entire uterus from the vagina, with
the entire vagina everted as a consequence.
Although congenital weakness of the supporting tissues may occasionally cause uterine prolapse, the most frequent cause is
childbirth. The signs of uterine prolapse are protrusion of the cervix or uterus through the introitus. Prolapse is frequently associated
with cystocele or rectocele, and these defects may cause presenting symptoms. Symptoms include backache, significant pelvic
pressure, and ulceration or bleeding of the prolapsed structures.

The Fallopian Tubes


Tortous ducts about 10 cms in length:
Arise from the superior portion of the lateral borders of the uterus, superior to the attachment of the round ligaments, and are
patent. The distal ends, the fimbriae, open into the abdominal cavity and the proximal ends open into the uterine cavity. It is
divided into interstitial, isthmic, ampullar, and fimbriated portions
The wall is thin with two muscular layers and an outer layer of peritoneum within the upper borders of the broad ligament.

The Ovaries
Lie in the ovarian fossa. Ovaries are almond-shaped structure measuring 2 3 3 cm and is located on the posterior surface of
the broad ligament and inferior to the fallopian tube. The ovary has a cortex and a medulla. Germinal epithelium, a single layer
of cuboidal cells, covers condensed fibrous tissue called the tunica albuginea. Follicles originate within the ovarian cortex and are
composed of the basic embryonic complement; no new follicles are formed after birth
Mesovarium is a fold of peritoneum by which ovary is connected to the broad ligament
The Arterial blood supply is predominantly by ovarian artery a branch of Abdominal aorta
Venous drainage is by Pampiniform plexus. The left ovarian vein empties into the left renal vein; the right ovarian vein empties
into the vena cava just inferior to the renal vein.

The Adult Inguinal Canal


It is approximately 4 cm in length
Extends between the internal (deep inguinal) ring and the external (superficial inguinal) ring opening
The inguinal canal contains either the spermatic cord or the round ligament of the uterus
The inguinal canal is bounded superficially by the external oblique aponeurosis
The superior wall is composed of internal oblique muscle, transversus abdominis muscle, and the aponeuroses of these muscles
The inferior wall of the inguinal canal is formed by the inguinal ligament and lacunar ligament
The posterior wall (floor) of the inguinal canal is formed by the transversalis fascia and the aponeurosis of the transversus
abdominis muscle
Hesselbachs triangle: The inferior epigastric vessels serve as the superolateral border of Hesselbachs triangle. The medial border
of the triangle is formed by the rectus sheath, and the inguinal ligament serves as its inferior border
Hernias occurring within Hesselbachs triangle are considered direct hernias, whereas hernias occurring lateral to the triangle are
indirect hernias.

THE HEAD AND NECK AND CNS


The Scalp
The SCALP has five layers:
S Skin
C Connective tissue

Anatomy

59

A Aponeurosis -galea aponeurotica


L Loose connective tissue
P Pericranium
The scalp receives a rich vascular supply. This arises from both the external and internal carotid arteries with the vessels lying in the
dense connective tissue layer.
The anterior part of the scalp is supplied by the supratrochlear and supraorbital arteries, and branches of the internal carotid via the
ophthalmic artery
The lateral and posterior part of the scalp is supplied by the superficial temporal, posterior auricular and occipital arteries, and
branches of the external carotid
The sensory nerves run with the arteries and are derived from the trigeminal nerve at the front and sides
The posterior aspect is supplied by the greater and lesser occipital nerves with motor supply to the occipitofrontalis muscle by the
facial nerve
Venous drainage of the face and anterior scalp is via the facial vein. The lateral and posterior aspects are drained by the external
jugular vein and the vertebral venous plexus, respectively. The veins of the scalp and face communicate directly with the intracranial
venous sinuses via emissary veins, hence infections in the nasal region have the potential to cause cavernous sinus thrombosis
Lymph drainage from the scalp is to the preauricular and occipital lymph nodes
The loose areolar tissue under the galea aponeurotica is a Dangerous zone for infections. Pus can spread freely in this layer and
reach the intracranial sinuses through the emissary veins
Abscesses and hematomas under the pericranium are limited to the area of one bone because the pericranium is firmly adherent to
the sutures between the skull bones
Osteomyelitis of the skull is associated with a subperiosteal swelling and edema of the scalp referred to as Ports puffy tumor

Fractures of Facial Skeleton


The Le Fort I fracture separates the alveolus and palate from the facial skeleton above
The fracture line runs through points of weakness from the pyriform aperture, through the lateral and medial wall of the maxillary
sinus running posteriorly to include the lower part of the pterygoid plates
The Le Fort II fracture is pyramidal in shape. The fracture involves the orbit, running through the bridge of the nose, and the ethmoids
whose cribriform plate maybe fractured, leading to a dural tear and CSF leak. It continues to the medial part of the infraorbital rim,
through the infraorbital foramen and through the infraorbital fissure. The orbital floor is always involved
The Le Fort III fracture effectively separates the facial skeleton from the base of the skull The fracture lines run high through the
nasal bridge, septum and ethmoids, again with the potential for dural tear and CSF leak, and irregularly through the bones of the orbit
to the frontozygomatic suture. The zygomatic arch fractures, and the facial skeleton is separated from the bones above at a high level
through the lateral wall of the maxillary sinus and the pterygoid plates.

Various Important Areas of Cerebrum

Motor area
Premotor area
Brocas area
Sensory area
Visual area
Werneckies area

Precentral gyrus
Anterior to motor area
Motor speech area (Inferior frontal gyrus)
Postcentral gyrus
Occipital lobe
Superior temporal lobe

Important Points about Functional Anatomy of Cerebral Cortex


Frontal
lobe

Primary motor area


(concerned with initiation of
Precentral cortex voluntary movements and speech)
(Post Part)
Premotor area

Supplementary motor area

Area 4 center for movement


Area 4S suppressor area. Inhibits movements initiated by
area 4.
Area 6 concerned with coordination of movements
initiated by area 4.
Area 8 frontal eye field.
Area 44 and 45 (brocas area) motor area for speech.
Concerned with coordinated skilled movements.

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USMLE Step 1 Platinum Notes


Prefrontal cortex Silent area or association area
(Ant Part)
Center for higher functions
emotion, learning, memory

Area 1 concerned with sensory perception


Area 2 and 3 integration of these sensations. Spatial
recognition. Recognition of intensity, similarities and diff.
B/W stimuli
Concerned with perception of sensation.

Somesthetic area I
Parizetal
lobe

Somesthetic area II
Somesthetic association area

Synthesis of various sensations perceived by S. Area-I.


Stereognosis

Primary auditory area

Area 41, 42 and wernickes area concerned with


perception of auditory impulses, analysis of pitch,
determination of intensity and source of sound
Superior part of temporal gyrus.

Auditopsychic area
Area of equilibrium
Primary visual area

Area 22 Interpretation of auditory sensation


Maintenance of equilibrium
Area 17 Perception of visual impulse
Lines of Gernari seen.
Area 18 - Interpretation of visual impulses
Area 19 - Movements of eye

Temporal
lobe

Occipital
lobe

Area 9 to 14, 23, 24, 29 and 32. Center for planned action
Seat of intelligence. Personality of individual

Visual association area


Occipital eye field

Lemniscus
Lemniscus, tract and sensation

Thalamic nucleus

Part of the internal capsule Sensory areas of the cerebral


cortex

Medial lemniscus
(Proprioception and fine touch)
Spinal lemniscus
(Pain, temperature and crude touch)

PLVNT

SENSORY RADIATION

Trigeminal lemniscus
(Pain, temperature, touch and
proprioception from the head, taste)

PMVNT

In posterior of postlimb of Lower 1/3 of sensory area in


internal capsule (IC)
post-central gyrus (Face region).

Lateral lemniscus
(hearing)

Medial geniculate body AUDITORY RADIATION


[MGB]
in sublentiform part of IC

Upper 1/3 of sensory area in


post-central gyrus (Arm and leg
region).

Auditory area in Heschls gyrus in


temporal lobe (area 41 and 42).

Internal Capsule
Part of internal capsule

Types of fibers in it

Anterior limb

Fibers from and to the prefrontal area of the cortex

Genu (MOTOR)

Corticobulbar fibers
Sensory fibers from thalamus to brain

Ant of posterior limb (MOTOR)

Corticospinal fibers

Post of posterior limb (SENSORY)

SENSORY radiation
(From PLVNT and PMVNT to main sensory area in post central gyrus)

Retrolentiform part (VISION)

OPTIC radiation
(From LGB to visual sensory area 17)

Sublentiform part (HEARING)

AUDITORY radiation
(From MGB to auditory area in temporal lobe)

Anatomy

61

Remember: M-M (medial geniculate body/hearing (music)


Lateral L-L Lateral geniculate body/light)

Arrows show geniculate bodies


A small lesion at the level of internal capsule can result in a clinical scenario with widespread manifestations and most of them lethal
depending on what part of internal capsule is damaged.
The internal capsule maybe damaged by a cerebrovascular lesion mostly by Hemorrhage (rupture of Charcots artery) leading to
Hemiplegia on the opposite side of the body.
In this type of Hemiplegia motor functions are effected mostly and sensory functions later or not at all because motor fibers lie laterally
and the arterial supply is more laterally as a result of which are motor fibers likely to be effected more.

Summary of the Lesion in Brown Sequard Syndrome


On the same side of the lesion
Pyramidal tract damage results in: UMNL and motor paralysis below the injury (spastic paralysis, hyperactive reflexes, loss of
superficial reflexes and Babinski sign)
Proprioceptive tracts damage (gracile and cuneate) results in: loss of sense of position, sense of passive movement, sense of
vibration and touch discrimination below the injury. These are the signs of sensory ataxia.
On the opposite side of the lesion:
Lateral spinothalamic tract damage results in: loss of pain and temperature sensation beginning one or two dermatomes below
the lesion
Ventral spinothalamic tract damage results in: little or No change in the sense of simple touch.

Remember
Midbrain: Usually the fibers of the third (oculomotor) nerve are affected alternating oculomotor hemiplegia, this means;
Hemiplegia on opposite half of the body (UMNL)
Signs of oculomotor nerve paralysis on the same side (LMNL)
Pons: Usually the fibers of the sixth (abducent) nerve are affected alternating abducent hemiplegia, this means:
Hemiplegia on opposite half of the body (UMNL)
Signs of abducent nerve paralysis on the same side (LMN)
Medulla: Usually the fibers of the hypoglossal nerve are affected alternating hypoglossal hemiplegia, this means
Hemiplegia on opposite half of the body (UMNL)
Signs of hypoglossal nerve paralysis on the same side (LMNL)

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USMLE Step 1 Platinum Notes

Brown sequard syndrome

Arterial Territories and Important Points in Blood Supply of Brain


Left middle cerebral artery: Blockage of this vessel would cause, among other effects, right-sided hemiplegia and sensory deficits
mainly of the face and arms, a right visual field defect with inability to gaze to the right, and aphasia.

Anatomy

63

Right middle cerebral artery: Blockage of this vessel would cause, among other things, left-sided hemiplegia and sensory deficits
mainly of the face and arms and left visual field neglect with inability to gaze to the left. In addition, there maybe neglect of the
left side.
Left anterior cerebral artery: This vessel supplies the medial aspects of the left hemisphere. Blockage may cause a weak, numb
right leg (and possibly arm symptoms in milder forms). The face is typically spared.
Right anterior cerebral artery: This vessel supplies the medial aspects of the right hemisphere. Blockage may cause a weak,
numb left leg (and possibly arm symptoms in milder forms). The face is typically spared.
Left posterior cerebral artery: This lesion presents as a right-sided visual field deficit, alexia without agraphia (if the corpus
callosum is spared), and possible defects in naming colors.
Right posterior cerebral artery: This lesion typically presents as a left-sided visual field deficit along with left-sided sensory loss
if the thalamus is affected. There may also be left-sided neglect
Visual cortex is supplied by posterior + middle cerebral artery.
Left posterior inferior cerebellar artery: This lesion would cause infarction of the lateral medulla and inferior cerebellar surface,
causing vertigo with vomiting, dysphagia, and dysarthria. In addition, there would be nystagmus looking toward the left, leftsided
Horners syndrome, and loss of pinprick sensation on the left side of the face and on the right side of the trunk and extremities. This
condition is also known as Wallenbergs syndrome.

Blood supply of brain


Right posterior inferior cerebellar artery: This lesion would cause infarction of the lateral medulla and inferior cerebellar
surface, causing vertigo with vomiting, dysphagia, and dysarthria. In addition, there would be nystagmus looking toward the
right, rightsided Horners syndrome, and loss of pinprick sensation on the right side of the face and on the left side of the trunk
and extremities. This condition is also known as Wallenbergs syndrome.

64

USMLE Step 1 Platinum Notes

MOVEMENT DISORDERS AND THEIR NUCLEI


Cranial Nerves: (USMLE Favorite)

Optic nerve is not only a cranial nerve. It is a tract and direct extension of CNS
This nerve is about 4 cm long
The optic nerve is enclosed in 3 sheaths covering with meninges
It is crossed by ophthalmic artery
Trigeminal nerve is the largest cranial nerve
Abducent nerve has the longest course
Trochlear nerve has the longest intracranial course. Thinnest as well
Cranial nerve 3 and 4 have their nuclei in midbrain
Cranial nerve 5, 6, 7, 8 have their nuclei in pons
Cranial nerve 9, 10, 11, 12 have their nuclei in medulla

Cranial nerve emerging from dorsal aspect of brain: Trochlear


MC nerve involved in intracranial aneurysms: Occulomotor
Common nucleus for VII, IX, X nerves is Nucleus Tractus Solitarius. (NTS)
Trochlear nerve has the longest intracranial course

Summary of Distribution of Cranial Nerves: (USMLE Favorite)


No.

Nerve

Type

Function

1.

Olfactory

Sensory

smell

2.

Optic

Sensory

vision

3.

Oculomotor

Motor

To all muscles of the eye except two: (superior oblique and lateral rectus)

4.

Trochlear

Motor

To one eye muscle (superior oblique)

5.

Trigeminal

Mixed
Sensory to
mainly sensory with small
Mouth
motor part
Face
Ant of scalp

6.

Abducent

Motor

To one eye muscle (lateral rectus)

7.

Facial

Mixed
Motor Sensory
Parasympathetic

(a) Motor to muscles of the face


(b) Sensory: taste to anterior 2/3 of tongue
(c) Parasym
(d) Pathetic to certain glands.

8.

Vestibulocochlear

Sensory

(a) Hearing (cochlear part)


(b) Equilibrium (Vestibular part)

9.

Glossopharyngeal

Mixed
Motor Sensory
Parasympathetic

Sensory for pharynx and tongue


Motor to: One muscle of pharynx (stylophar ngeus)
Parasympathetic to parotid gland

10.

Vagus
(Including Cranial
accessory)

Mixed
Motor Sensory
Parasympathetic

Motor to: Muscles of pharynx, larynx and palate


Parasympathetic and sensory to:
The structures in the thorax and abdomen

11.

Spinal Accessory

Motor

To two important muscles of the neck:


1. Sternomastoid
2. Trapezius

12

Hypoglossal

Motor

To all muscles of the tongue (except one)

Anatomy

65

Cranial Nerve
The First (Olfactory) Nerve Palsy
The chief function of the 1st cranial nerve (olfactory nerve) is concerned with the sense of smell. Cells of origin are located in the nasal
mucosa. Nerve filaments group and pass through the cranium at cribriform plate and end in olfactory bulb. The olfactory nerve is
composed exclusively of somatic afferent fibers.
The olfactory nerve branches penetrate through the cribriform plate, and collect in the olfactory bulb and nerve which passes under
the frontal lobe to the temporal lobe and other centers
EXAMINATION
Each nostril is examined separately. One nostril is closed while the patient sniffs with the other. Mild aromatic substances such as
orange, coffee, or tobacco should be used as strong irritant smells stimulate the sensory endings of the fifth nerve. The result of
affection will be loss of smell or anosmia.

The Third (Oculomotor) Nerve Palsy


It supplies all extraocular muscles except the superior oblique and the lateral rectus
Complete paralysis results in:
External ophthalmoplegia: In a complete lesion inability to move the eye upward, inward and downward
External Squint: The eye is deviated laterally and downwards due to the unopposed action of the lateral rectus and superior
oblique
Diplopia: A person sees double
Ptosis: Drooping of the upper eyelids due to paralysis of levator palpabrea superioris
Dilated nonreactive pupil due to paralysis of the sphincter pupillae. The pupil also shows no reaction to light (direct or consensual),
or to accommodation.

The Fourth (Trochlear) Nerve Palsy


There is weakness or paralysis of the superior oblique muscle which normally moves the eye downwards and inwards
Result: Defective depression of the adducted eye. The patient is unable to look at his shoulder
Symptom presentation: DIPLOPIA (double vision), when looking downwards, e.g. when reading or descending the stairs. The
head may tilt to the opposite side to minimize the diplopia.

The Sixth (Abducent) Nerve Palsy


The sixth nerve supplies the lateral rectus which normally rotates the eye laterally. Its paralysis causes:
Internal Squint: The eyeball is turned inwards due to unopposed adduction of the medial rectus
Diplopia, which is maximum on looking outwards.

The Fifth (Trigeminal) Nerve Palsy


The sensory fibers are divided into three divisions:
1. Ophthalmic Division
2. Maxillary Division
3. Mandibular Division
Sensation
Sensation is tested in the distribution of the 3 divisions of the nerve. Routinely, it is sufficient to test the sensation at three Sites: on the
forehead, the cheek and over the lower jaw, together with anterior two-thirds of the tongue
Motor Functions
A. Masseters And Temporalis:
Any wasting of the temporalis
The degree of contraction of the temporalis and masseter by palpation while asking the patient to bite hard.

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USMLE Step 1 Platinum Notes

The Seventh (Facial) Nerve Palsy


Weakness in the facial muscles may result from:
Upper motor neuron lesion:
Here only the muscles of the lower part of face are affected. The eye closure is normal
This is because the muscles of the lower part (unlike those of the lower part) are activated through the upper motor neuron fibers of
both sides
Spontaneous emotional expression is unaffected
Lower motor neuron lesion:
All the muscles of the face (upper and lower) are affected on the same side
Facial nerve passes through parotid gland but does not supply it
Facial nerve supplies submandibular and lacrimal glands
Arterial supply to facial nerve: ascending pharyngeal artery.
Facial Nerve has:
The longest intraosseous course
It is the Mc paralyzed cranial nerve
Muscles supplied by facial nerve:
Platysma
Stylohyoid
Muscles of facial expression
Buccinator
Stapedius
Posterior belly of digastric
Submandibular, Lacrimal, nasal gland
Supplies gustatory sensation to soft palate
Kindly never forget that despite the fact that facial nerve traverses the substance of parotid but does not supply it. (keeps
it high and dry)
Facial nerve is related to
Pterygopalatine ganglion
Geniculate ganglion submandibular ganglion
Submandibular

The Eight (Vestibulocochlear) Nerve Palsy


The eighth nerve consists of two parts which have different functions Cochlear and vestibular nerves
The cochlear part is concerned with hearing. An affection results is tinnitus and deafness
The vestibular part is concerned with equilibrium. Its affection may result in vertigo.

The Ninth (Glossopharyngeal) Nerve Palsy


Paralysis of Glossopharyngeal nerve causes:
Anesthesia of the pharynx
Loss of taste on the posterior third of the tongue
Glossopharyngeal nerve is involved in:
Jugular foramen syndrome: Involving IX, X, XI cranial nerves
Collet Sicard Syndrome: Involving IX, X, XI, XII cranial nerves (Extracranially)
Villaret Synrome: Lesion in retropharyngeal space involving IX, X, XI, XII cranial nerves

Anatomy

67

The Tenth (Vagus) Nerve Palsy


Paralysis of vagus nerve causes:
Ipsilateral paralysis of the palate,
Ipsilateral paralysis of the pharynx and
Ipsilateral paralysis of the larynx with anesthesia of the larynx on the affected side
Remember: The Recurrent Laryngeal nerve arises from vagus. On the Right side it winds around the subclavian artery and on
the Left side it winds around the aortic arch behind ligamentum arteriosum.

The Eleventh (Accessory) Nerve Palsy


As a Result of damage to the Accessory nerve
Sternomastoids
Unilateral
Apparent wasting
The muscle does not stand out on testing
Bilateral
Wasting of the neck which appears like that of a chicken
Falling of head backwards
Trapezius
Unilateral paralysis
Drooping of the shoulder when arm is hanging
Weak movements on testing
Supplies all palatal muscles except Tensor palate
Spasmodic torticollis is due to central irritation of this nerve (cranial part)

The Twelfth (Hypoglossal) Nerve Palsy


Lesion of one hypoglossal nerve results in deviation of the tongue towards the paralyzed side. If you ask the patient to
protrude his tongue the muscles of the same side of the lesion become paralyzed and begin to atrophy (lower motor neuron lesion)
Safety muscle of tongue is geniglossus supplied by hypoglossal nerve.

GEMS NEVER TO BE FORGOTTEN


The Pituitary Gland
Also known as Hypophysis cerebri. Pineal is Epiphysis cerebri
The average adult pituitary measures 11 15 5 mm
The gland is oval, bilaterally symmetrical, and brownish red
The pituitary is approximately 20% larger in females than in males and it enlarges about in females during pregnancy
It lies within the sella turcica (Turkish saddle)
This fossa is bordered anteriorly, posteriorly, and inferiorly by the sphenoid bone and laterally by the cavernous sinus
The floor of the sella forms the roof of the sphenoidal sinus
The diaphragma sellae, a thick reflection of dura mater, covers the roof of the sella and closely encircles the pituitary stalk in 50% of
individuals
The arterial supply to the hypothalamic-pituitary region is complex and arises from three sources
a. The inferior hypophyseal artery, a branch of the carotid artery, supplies the posterior pituitary.
b. The superior hypophyseal arteries branch from the circle of Willis to supply the median eminence
c. The middle hypophyseal arteries are of variable origin and supply the pituitary stalk
Capillary portions of the superior hypophyseal arteries drain from the hypothalamus, the median eminence, and the superior portions
of the pituitary stalk. These vessels drain into the hypophyseal portal system, which forms a secondary venous plexus in the anterior
pituitary and ultimately empties into the cavernous sinus. This portal venous system constitutes the principal blood supply to the
anterior pituitary and serves as the medium through which releasing hormones from the hypothalamus reach the pituitary.

68

USMLE Step 1 Platinum Notes

The pituitary has dual embryonic origin


The Anterior pituitary arises from embryonic ectoderm (Rathkes pouch) and includes the pars distalis, pars intermedia
(vestigial in humans), and pars tuberalis
The Posterior pituitary of the gland arises from the diencephalon and includes the neural stalk, infundibulum, and posterior lobe
Embryonic defects in invagination and obliteration of the pharyngeal extent of Rathkes pouch may lead to craniopharyngiomas
or hormonally active ectopic pituitary adenomas.

Cavernous Sinus

Paralysis of 3, 4, 6 cranial nerves indicates lesion of cavernous sinus


Occulomotor, trochlear and ophthalmic nerves lie in lateral wall of cavernous sinus
Abducent nerve is a direct content of cavernous sinus
Infections from dangerous area of face can spread to cavernous sinus

Remember
The pituitary gland is located in the pituitary fossa within the skull. The floor of this fossa is formed by the sella turcica. The
lateral walls of the fossa are formed by the cavernous sinuses. The abducens nerve passes through the cavernous sinus along
with the internal carotid artery. As the tumor expands laterally, the first nerve that will be encountered is the abducens nerve,
producing lateral rectus palsy.

Sympathetic and Parasympathetic Systems


Organ

Sympathetic

Parasympathetic

Pupil

Dilates

Constricts

Lacrimal and salivary glands

Stops secretion

Produces secretion

Heart

Accelerates

Slows

Bronchioles

Dilates

Constricts

Alimentary canal

Dilates

Contracts

Urinary bladder

Dilates

Contracts

Penis

Causes erection
[For this reason the pelvic nerve was called the nervus erigens].

Limbic System

Subcallosal Gyri
Cingulate Gyri
Hippocampal formation comprising of Hippocampal Gyrus, Parahippocampal Gyrus and Dentate gyrus
Amygdaloidal nucleus
Mammillary bodies
Anterior thalamic nucleus

Briefly Functions of the Limbic System can be summarized by Five Fs

Feeding
Flight
Feeling
Fighting and
Fun {sex}

Anatomy

69

SKULL FORAMINA AND CONTENTS (USMLE FAVORITE)


What Passes through What
Foramen

Contents

Optic canal

Optic (II) Nerve and ophthalmic artery

Superior orbital fissure

III, IV, VI and ophthalmic division of V cranial nerves, sympathetic nerves and ophthalmic veins

Stylomastoid foramen

VII cranial nerve

Foramen Rotundum

Maxillary division of V

Foramen ovale

Mandibular division of V and accessory meningeal artery

Foramen spinosum

Middle meningeal artery, meningeal branch of the mandibular nerve

Foramen magnum

Accessory (XI) nerve, vertebral and spinal arteries. NOT SPINAL CORD

Foramen lacerum

Internal carotid artery, lesser petrosal


Nerve (branch of IX), greater petrosal
Nerve (branch of VII), deep petrosal

Jugular foramen

Inferior petrosal sinus (anterior part)


Internal jugular vein and IX, X, XI cranial nerves

Hypoglossal foramen

XII cranial nerve, meningeal branch of ascending pharyngeal artery

Internal auditory meatus


Dorellos canal

VII and VIII cranial nerves, labyrinthine (internal auditory) artery


Abducent nerve.

Cerebrospinal Fluid (CSF)


Clear fluid
Colorless fluid
Choroid Plexus (formed by)
Chloride content
Cells minimal
Cushions the brain

Circulus arteriosus (branches) supply choroids plexus


CSF is principally secreted by choroid plexus
Choroid plexus is absent in anterior horn of lateral ventricle
Total volume of CSF 150 ml
Normal adult CSF pressure: 6 12 mm Hg
pH of CSF is: 7.33
Epidural space is devoid of CSF
Rate of CSF absorption is the main factor controlling CSF Pressure
Persistent leakage can cause headache
No neutrophils in normal state seen

ARTERIAL TERITORIES IN HEAD AND NECK AND CLINICAL CORRELATION


(USMLE Favorite)
* Occlusion of the vertebral artery may cause Medial Medullary Syndrome which is characterized by:
Paralysis or atrophy of tongue on the side of lesion (XII nerve involvement)
Paralysis of arm and leg on opposite side
Impaired tactile and proprioceptive sense on opposite side. (Involvement of pyramidal tract and medial lemniscus)

70

USMLE Step 1 Platinum Notes

* The posterior inferior cerebellar artery:


It is the largest and main branch of the vertebral artery
It has a tortuous S-shaped course. Immediately after it arises from the vertebral artery, it runs backwards around the lower
end of the olive passing through the rootless of the hypoglossal nerve, it then turns round the inferior cerebellar peduncle
and finally divides into two terminal branches which supply: (a) the inferior vermis (b) the posterior part of the inferior
surface of the cerebellum.
Impaired pain and temperature sense on opposite side
Nystagmus (involvement of vestibular nucleus)
Dysphagia (involvement of nucleus ambigus)
Nystagmus (involvement of cerebellum)
Horners syndrome (involvement of sympathetic pathway)

Occlusion of the Anterior Spinal Artery May Cause

Loss of motor function below the level of the lesion (due to damage to the corticospinal tracts)
Loss of pain and temperature Sensation below the level of the lesion (due to damage to the spinothalamic tracts)
Weakness of limbs (due to damage of the anterior grey horns in the cervical or lumbar regions of the cord)
Loss of bowel and bladder control (due to damage of the descending autonomic tracts)

Occlusion of the Posterior Spinal Artery May Cause


Loss of position sense, vibration sense and light touch due to damage of the posterior white columns

Larynx
Larynx has three paired and three unpaired cartilages
Extends from C3-C6
Anatomic basis of stridor is in larynx
The larynx serves as the sounding source for speech. A fundamental tone is produced by the movement of the vocal cords, which is
brought about by the flow of exhaled air past lightly approximated vocal cords
The internal laryngeal nerve is sensory to larynx above vocal cords
The recurrent laryngeal nerve is sensory to larynx below vocal cords
All muscles of larynx except cricothyroid are supplied by recurrent laryngeal nerve
Cricothyroid supplied by External laryngeal nerve

Muscles of Larynx and their Action


Abductor of vocal cords: Posterior Cricoarytenoid
Adductor of vocal cords:
Lateral cricoarytenoid
Transverse arytenoids
Cricothyroid
Thyroarytenoid
Tensor of vocal cords: Cricothyroid
Relaxor of vocal cords:
Thyroarytenoids
Vocalis

Anatomy

71

Muscles Acting at Temporomandibular Joint

Depression: Lateral Pterygoid


Elevation: Temporalis, Massetter, Medial Pterygoid
Protrusion: Pterygoids
Retraction: Posterior fibers of Temporalis
Lateral movements: Pterygoids
Buccinator: Nota muscle of mastication

In Simple Terms

The backward movement step is accomplished by the posterior fibers of the temporalis muscle
The digastric helps to depress the lower jaw during chewing
The lateral pterygoid helps to move the lower jaw forward during chewing
The medial pterygoid helps to elevate the lower jaw during chewing
The mylohyoid helps to depress the lower jaw during chewing

Ansa Cervicalis
Ansa cervicalis is a thin nerve loop that lies in the anterior wall of carotid sheath
Superior root is a continuation of descending branch of hypoglossal (XII) Cranial nerve. Superior root supplies Superior belly of
omohyoid. Its fibers are derived from first cervical nerve
Inferior root is derived from spinal nerves C2 and C3
Loop of Ansa supplies:
Inferior belly of omohyoid
Sternothyroid
Sternohyoid

Dangerous Areas: (USMLE Favorite)


Dangerous area of face: Lowerpart of nose and upper lip
Dangerous area of scalp: Loose areolar tissue layer of scalp
Dangerous zone of eye: Ciliary body

Commonest Sites

Commonest site of BHP: Periurethral zone


Commonest site of cancer prostate: peripheral zone
Commonest site of varicocele: Left side
Commonest position of appendix: Retrocecal
Commonest site of internal hemorrhoids: 3, 7 and 11 Oclock

Superficial Cutaneous Reflexes


Center spinal
segment involved

Reflex

Stimulus

Response

Scapular

Irritation of skin at the interscapular space

Contraction of scapular muscles and C5 to T1


drawing in of scapula

Upper
abdominal

Stroking the abdominal wall below the Ipsilateral contraction of abdominal T6 to T9


costal margin
muscle and movement of umbilicus
towards the site of stroke

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USMLE Step 1 Platinum Notes

Lower abdominal Stroking the abdominal wall at umbilical Ipsilateral contraction of abdominal T10 to T12
and iliac level
muscle and movement of umbilicus
towards the site of stroke
Cremasteric

Stroking the skin at upper and inner aspect Elevation of testicles


of thigh

L1, L2

Gluteal

Stroking the skin over glutei

Contraction of glutei

L4 to S1, S2

Plantar

Stroking the sole

Plantar flexion and adduction of toes

L5 to S2

Bulbocavernous

Stroking the dorsum of glans penis

Contraction of bulbocavernous

S3, S4

Anal

Stroking the perianal region

Contraction of anal sphincter

S4, S5

Functions of Limbic System


Emotion
Memory
Higher functions
Consolidation of long-term memory occurs in hippocampus
Processing of short term memory to long term occurs in hippocampus
Amygdala is the window of limbic system
Damage to amygdala causes Kluver Bluck syndrome
Reward center is in medial forebrain bundle.

Herniations
Uncal or transtentorial herniation. The herniated uncus will compress the oculomotor nerve, the posterior cerebral artery, and
the brainstem. The pathophysiologic consequences include oculomotor paralysis (manifesting with fixed and dilated pupil on
the same side), ipsilateral infarction of the occipital lobe, and hemorrhages within the midbrain and pons. The latter may result in
respiratory paralysis and death
Cerebellar tonsillar herniation refers to downward displacement of the cerebellar tonsils through the foramen of magnum. This
results from space-occupying lesions in the infratentorial compartment, such as bleeding and tumors. It leads to compression of
the medulla and death by cardiorespiratory arrest
Subfalcine (cingulate) herniation describes the lateral displacement of the cingulate gyrus beneath the falx cerebri. This
event is caused by space-occupying masses in the cerebral hemisphere. It leads to compression of the anterior cerebral artery and
infarction of dependent cerebral territories (mostly the medial portion of the frontal and parietal lobes)
Reverse cerebellar herniation is a rare form of herniation due to midbrain lesions (again, hemorrhages and tumors) that push
the midbrain upward through the incisura of the tentorium
Transcalvarial herniation may develop in open (i.e. accompanied by calvarial bone fractures) head injuries if brain
parenchyma is displaced outside the cranial cavity through a calvarial defect
Split brain syndrome: Disconnection syndrome of cerebral cortex resulting from transection or congenital absence of cerebral
cortex.

Types of Fibers in CNS


Association fibers: Connecting different areas of same cerebral hemisphere
Superior longitudinal fasiculus
Inferior longitudinal fasiculus
Cingulum
Uncinate fasiculus

Anatomy

73

Projection fibers: Connecting cerebral cortex to other parts of CNS


Corticospinal tract
Internal capsule
Commisural fibers: connecting corresponding parts of two cerebral hemispheres
Corpus callosum
Anterior commisure
Posterior commisure
Hippocampal commisure
Habenular commisure
Hypothalmic commisure

Clinical
observation

Effects

Upper motor neuron

Lower motor neuron lesion

Muscle tone

Hypertonic

Hypotonic

Paralysis

Spastic type of paralysis

Flaccid type of paralysis

Wastage of muscle

No wastage

Present

Superficial reflexes

Lost

Lost

Plantar reflex

Abnormal babinskis sign

Absent

Deep reflexes

Exaggerated

Lost

Clonus

Present

Lost

Anatomy of Eye: (USMLE Favorite)


The Extroter of Eye ball is Inferior Oblique and Inferior Rectus
The Introter of Eye ball is Superior Oblique and Superior Rectus.
Action of Superior oblique is Abduction, Intorsion and depression
Dilator Pupillae dilates pupil and is supplied by Sympathetics
Sphincter Pupillae constricts pupil and is supplied by Parasympathetics
LR6S04
Lateral rectus is supplied by 6th Cranial Nerve (Abducent)
Superior oblique is supplied by 4th Cranial Nerve (Trochlear)
Rest other ocular muscles are supplied by 3rd Cranial Nerve (Occulomotor)
Muscle attached to posterior tarsal margin: Mullers muscle
Ligament of Lockwood is found in Orbit.

Structures passing through Superior Orbital Fissure are


Live Free To See No Insult at All
Lacrimal Nerve
Frontal Nerve
Trochlear Nerve
Superior Ophthalmic Vein
Nasociliary Nerve
Inferior Ophthlamic Vein
Abducent Nerve

74

USMLE Step 1 Platinum Notes

Structures Passing Through Inferior Orbital Fissure are

Maxillary nerve
Zygomatic nerve
Infraorbital vessels
Orbital branch of pterygoplatine ganglion

Lesions and Effects of (Visual Pathway)

Central scotoma ~ macula


Ipsilateral blindness ~ optic nerve
Bitemporal hemianopia ~ optic chiasm
Homonymous hemianopia ~ optic tract
Upper homonymous quadrantanopia ~ temporal optic radiations
Lower homonymous quadrantanopia ~ parietal optic radiations
Also, cortical lesions produce defects similar to those of the optic radiations, but may spare the macula.

Spinal Cord

Spinal cord in adults ends at L1- L2


Spinal cord in infant sends at L3
Thoracic and sacral curves are concave anteriorly
Subarachnoid space/Subdural space ends at S2
Dural sheath ends at S2
Filum terminale and piamater extend up to tip of coccyx
Number of spinal nerve pairs: 31.

Cauda Equina Syndrome


It is a serious neurologic condition in which there is acute loss of function of the lumbar plexus, neurologic elements (nerve roots)
of the spinal canal below the conus of the spinal cord
After the conus, the canal contains a mass of nerves (the cauda equina or horse-tail) that branches off the lower end of the spinal
cord and contains the nerve roots from L1-5 and S1-5. The nerve roots from L4-S4 join in the sacral plexus which affects the sciatic
nerve, which travels caudally (toward the feet)

End of spinal cord

Anatomy

75

Vertebrae and Corresponding Spinal Level


Cervical region

C1-C7 Add1

Upper Thoracic Lesion

T1 T6 Add 2

Lower Thoracic Lesion

T7-T9 Add 3

T 10

Corresponds to L1-L2

T12-L1

Corresponds to L5-S1

Ascending Tracts of Spinal Cord


Situation

Tract

Function

Anterior white funiculus

Anterior spinothalamic tract

Crude touch sensation

Lateral spinothalamic tract

Pain and temperature sensation

Ventral spinocerebellar tract

Subconscious kinesthetic sensations

Dorsal spinocerebellar tract

Subconscious kinesthetic sensations

Spinotectal tract

Concerned with spinovisual reflex

Fasiculus dorsolateralis

Pain and temperature sensations

Spinoreticular tract

Conciousness and awareness

Spino olivary tract

Proprioception

Spinovestibular tract

Proprioception

Fasciculus gracilis

Tactile sensation

Fasciculus cuneatus

Tactile localization
Tactile discrimination
Vibratory sensation
Conscious kinesthetic sensation
Stereognosis

Lateral white funiculus

Posterior white funiculus

Descending Tracts of Spinal Cord


Situation

Tract

Function

Pyramidal
tracts

Anterior corticospinal tract

Control voluntary, skilled movements

Lateral corticospinal tract

Forms upper motor neurons

Medial longitudinal fasciculus

Coordination of reflex ocular movement


Integration of movements of eyes and neck

Extra
Pyramidal
tracts

Anterior vestibulospinal tract

Maintenance of muscle tone and posture

Lateral vestibulospinal tract

Maintenance of position of head and body during acceleration

Reticulospinal tract

Coordination of voluntary and reflex movements


Control of muscle tone
Control of respiration and blood vessels

Tectospinal tract

Control of movement of head in response to visual and auditory impulses

Rubrospinal tract

Facilitatory influence on flexor muscle tone

Olivospinal tract

Control of movements due to proprioception

76

USMLE Step 1 Platinum Notes

Important Stains used in Histology


Hand E Stain (Hematoxylin and Eosin): Hematoxylin, a natural dye product, acts as a basic dye that stains blue or black. Nuclear
heterochromatin stains blue and the cytoplasm of cells rich in ribonucleoprotein also stains blue
The aniline dye, Eosin, is an acid dye that stains cytoplasm, muscle, and connective tissues various shades of pink and orange. This
difference in staining intensity is useful in differentiating one tissue from another
Vital Stain: Such as Neutral red, Trypan blue are used for staining living cells such as Reticuloendothelial cells
Metachromatic Stains are used for staining mast cells with Toluidine blue. The stains react with granules of mast cells
(metachromasia) to give a new color to the cells
Periodic Acid-Schiff Method (PAS): Principally used to demonstrate structures rich in carbohydrate macromolecules such as
glycogen, glycoprotein, and proteoglycans found in ground substance of connective tissues, basement membranes and mucus
Phosphotungstic Acid Hematoxylin (PTAH): This is an ideal stain for the demonstration of striated muscle fibers and
mitochondria, which stain blue
Silver Stains: Certain tissue components called Argyrophilic have a natural affinity for silver salts. Reticular fibers and the
granules in diffuse endocrine cells are argyrophilic
Sudan Stains: Sudan dyes are used to stain lipids. The Sudan dyes, e.g. Sudan IV, dissolve in droplets containing triglycerides and
color them intensely.

Important Points about Vessels: (USMLE Favorite)

Umbilical arteries carry venous blood


Pulmonary vasculature also follows reverse pattern
Coronary arteries have three elastic lamina: Internal, middle and external
Umbilical arteries have no elastic lamina
The arteries of lower limb have more developed muscular tissue than those of upperlimb

IMPORTANT POINTS ABOUT SKULL BONES Skull


Scaphocephaly

Boat shaped skull due to premature union of saggital suture

Acrocephaly/Oxycephaly

Pointed skull due to premature union of coronal suture

Plagiocephaly

Twisted skull due to assymetrical union of sutures

Trigonocephaly

Triangular prominence of forehead due to premature fusion of metopic suture

Brachycephaly

Short and broad skull


Seen in Cleidocranial dysostosis
Seen in Downs Syndrome
Seen in Achondroplasia

Dolicocephaly

Long and thin skull


Seen in Marfans syndrome

Anencephaly

Vault of skull not developed resulting in the absence of a major portion of the brain, skull, and scalp

Pneumatic Bones: (USMLE Favorite)


Contain air spaces. Usually present in skull
Make the skull light in weight
Act as air conditioners
Maxilla
Sphenoid
Ethmoid
Mastoid Bones

Anatomy

Sesamoid Bones
Patella
Pisiform
Fabella

Bones Ossified at Birth


Lower end of femur
Upper end of tibia
Calcaneum

Important Points about Muscles


Anti rape muscle/muscle virgineous: Gracilis
Cheating muscle: Superior oblique of eye
Safety muscle of tongue: Genioglossus
Tailors muscle: Sartorius
Thermostat of testis cremaster
Bladder muscles in whorls detrusor

Hybrid/Composite Muscles

Adductor magnus
Biceps Femoris
Pectineus
Digastric
Flexor digitorum superficialis

Digastric Muscles
Digastric: Anterior belly, posterior belly
Omohyoid: Superior belly, inferior belly
Occipitofrontalis: Occipital belly, frontal belly
Gastrocnemius: Lateral head, medial head
Ligament of Treitz: Skeletal part, smooth part

Important Lymph Nodes (USMLE Favorite)


Glans Penis and clitoris

Cloquets node

Rest of Penis

Superficial inguinal node

Labium majus
Testis
Ovaries
Palatine tonsil

Superficial inguinal node


Preaortic/Para aortic nodes
Preaortic/Para aortic nodes
Jugulo digastric nodes

Tip of Tongue

Submental nodes

Anal canal above pectinate line

Internal iliac nodes

Anal canal below pectinate line

Superficial inguinal nodes

Delphic nodes

Pretracheal

Spongiform urethra

Deep inguinal nodes

77

78

USMLE Step 1 Platinum Notes

Lymph node of lund: cystic lymph node of gallbladder


Cloquets node/Rossenmullers node
Mucocutaneous lymph node syndrome
Sister mary josephs node
Virchows node
Rotters lymph nodes are small interpectoral lymph nodes located between the pectoralis major and pectoralis minor muscles.
They receive lymphatic fluid from the muscles and the mammary gland, and deliver lymphatic fluid to the axillary lymphatic plexus.

Thoracic duct

Thoracic duct starts as continuation of cisterna chylii


Crosses from right to left at four level
Passes through aortic opening of diaphragm
The right lymphatic duct drains the right arm, the right side of the chest, and the right side of the head. The thoracic duct drains
the rest of the body. Both the right lymphatic duct and the thoracic duct dump into the large venous channels at the base of the
neck. Occlusion of this drainage cans produce intractable edema in sites feeding these ducts.

Primary lymphoid organs are Thymus and Bone marrow

Lymphatics are absent in

Epidermis
Eye
Cornea
Lens
Articular cartilage
Placenta
Bone marrow
Glottis

Eponym Nerves: (USMLE Favorite)


Arnolds nerve/Aldermans nerve auricular branch of vagus
Nerve of Bell long thoracic nerve

Buffer nerve carotid sinus and vagal fibers from aortic arch
Saphenous nerve longest/largest cutaneous branch of femoral nerve
Herrings nerve branch of glossopharyngeal nerve to carotid sinus
Exners nerve from pharyngeal plexus to cricothyroid membrane
Vidian nerve Greater pertrosal + deep pertrosal nerve (N of Pterygoid canal)
Nerve of Wrisberg: (2 nerves) Nervus intermedius (branch of Facial nerve), medial cutaneous nerve of forearm

Freys syndrome/Baillargers Syndrome


Due to abnormal and inappropriate regeneration Auriculotemporal branch of trigeminal nerve there is rednesss, sweating especially
on cheeks while eating, talking (gustatory sweating)

Important Points about Veins

Great cerebral vein of Galen is formed by union of internal cerebral veins


Great cerebral vein of Galendrains into straight sinus
Facial vein communicates to cavernous sinus via: Superior ophthalmic vein, inferior ophthalmic vein, deep facial vein
Long saphenous vein is the largest and longest superficial vein of lower limb formed on medial side of dorsal venous arch
Injury to great saphenous vein corresponds to area of femoral nerve distribution.

Anatomy

79

The portal vein begins at the level of the second lumbar vertebra and is formed from the convergence of the superior
mesenteric and splenic veins. It is 3. 8 cm long and lies anterior to the inferior vena cava and posterior to the neck of the
pancreas. It lies obliquely to the right and ascends behind the first part of the duodenum, the common bile duct and
gastroduodenal artery. At this point it is directly anterior to the inferior vena cava. It enters the right border of the lesser
omentum, and ascends anterior to the epiploic foramen to reach the right end of the porta hepatis. It then divides into
right and left main branches which accompany the corresponding branches of the hepatic artery into the liver
Portal vein is formed behind the neck of pancreas by union of superior mesentric and spleenic vein
Normal pressure is 510 mm Hg
Portal venous system is valveless.

Left suprarenal drains into left renal vein


Left testicular vein drains into left renal vein
Left ovarian vein drains into left renal vein
Batesons vertebral venous plexus is valveless

Varicose Veins
Are dilated, tortuous veins and are very common; they may either give no symptoms or cause aching and discomfort in the legs.
Varices are recognized as tortuous dilated veins in the leg, a varicose vein is one which permits reverse flow through its faulty valves.
Occasionally complications of varicose veins may develop. These include:
Thrombosis: Which is referred to as superficial thrombophlebitis
Sometimes thrombosis extends into the deep venous system to cause Deep vein thrombosis, although this is infrequent
Hemorrhage: Can occur when large superficial varices are damaged
The most serious problem is venous ulceration which complicates varicose veins.

Excepts in Anatomy
All muscles are mesodermal in origin except muscles of Iris (Sphincter pupillae and dilator pupillae) which are ectodermal
All Pharyngeal arches persist except fifth which disappears
All intrinsic muscles of Larynx are supplied by recurrent laryngeal nerve except cricothyroid which is supplied by external laryngeal
nerve
All major salivary gland are supplied by facial nerve except Parotid gland (Although passes through the substance of parotid)
All divisions of Trigeminal nerve except Mandibular division lie in lateral wall of Cavernous sinus
All muscles of pharynx are supplied by pharyngeal plexus except stylopharyngeus which is supplied by Glossopharyngeal nerve.
All muscles of soft palate are supplied by pharyngeal plexus except tensor palate which is supplied by Nerve to medial pterygoid
All muscles of tongue are supplied by hypoglossal nerve except palatoglossus which is supplied by pharyngeal plexus.

Important Vessels and Source of Bleeding: (USMLE Favorite )

Hemoptysis: Bronchial artery


Duodenal ulcer: Gastroduodenal artery
Gastric ulcer: Left Gastric artery
SDH: Bridging veins
EDH: Middle meningeal artery
Tonsillectomy: Paratonsillar vein
Menstruation: Spiral arteries

Duodenal ulcer: The duodenal cap lies just beyond the pylorus. Externally, the cap has attachments to the hepatoduodenal
ligament in the pancreatic head. Most of the ulcers occur in the duodenal cap region. The gastroduodenal artery lies directly
behind the duodenal cap, and penetrating ulcers into the pancreas initially erode through the gastroduodenal artery,
accounting for the massive bleeding that occurs with these ulcers
Extradural hemorrhage: Usually follows arterial hemorrhage between the skull and the dura. Most frequently, acute epidural
hematomas occur in the temporal or temporoparietal region as a consequence of hemorrhage from one of the branches of
the middle meningeal artery.

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USMLE Step 1 Platinum Notes

Eponym Ducts
Parotid duct: Stensons duct
Submandibular duct: Whartons duct
Pancreatic duct: Wirsungs duct
Accessory pancreatic duct: Santoniris duct
Gartners duct: Remanant of Mesonephric duct (WOLLFIAN)
Thoracic duct: Pecquet duct

Important Membranes in Body: (USMLE Favorite)


Huxles Membrane

Inner layer of cells of root sheath of hair

Henles Membrane

Outer layer of cells of root sheath of hair

Bowmans Membrane

'Anterior limiting membrane of Cornea

Decemets Membrane

Posterior limiting membrane of Cornea

Bruchs Membrane

Pigment membrane in Retina

Elschings Membrane

Astroglial membrane covering Optic Disk

Heusers Membrane

Exocelomic Membrane

Sharpnells Membrane

Pars Flaccida of the tympanic membrane

Important Cells in Histology (USMLE Favorite)


Bergmann Cells

Glial cells of Cerebellum

Gitter Cells

Microglia

Interstitial Cells of Cajal

Nerve cells of superficial layers of cerebral cortex

Supporting Cells of Claudius

Cells in floor of Cochlear canal of inner ear

Dieters Cells

Outer hair cells of organ of Corti

Hensens Cells

Supporting cells in organ of Corti external to Dieters cells

Houfbauers Cells

Ellipsoidal cells in chorionic villi of placenta

JG Cells

Smooth muscle cells of afferent arteriole. (kidney)

Ito Cells

Stellate cells in liver

Langerhans Cells

Antigen presenting epithelial dendritic cells

Langhans Cells

Cytotrophoblastic cells of chorionic villi

Basket Cells

Myoepithelial cells in salivary/mammary/sweat glands

Gitter Cells

Microglia of brain

Basket Cells of Cerebellum

Neurons of molecular layer of Cerebellum

Merkel Cells

Sensory nerve endings

Mullers Cells

Neuroglial cells in Retina

Hilus Cells

Rare cells found in Medulla of Ovary at Hilum of Ovary

Lacis Cells

Extra glomerular Mesengial Cells outside Glomerulus

Peg Cells

Secretory cells in mucosa of uterine tube

Glomus Cells

Present in Carotid Bodies

Anatomy

81

Abnormal cells
Reed Sternberg cell
These cells characteristically are neoplastic giant cells with a bilobed mirror-image nucleus that may have large (owl-eyes)
nucleoli surrounded by a clear halo. Most commonly, these cells are associated with Hodgkins disease.
The Langhans cell
It is a giant cell with peripherally arranged nuclei found in granulomas
The LE cell
It is a degenerating neutrophil seen in lupus erythematosus in in vitro preparations
The Mott cell
It is a constipated plasma cell filled with immunoglobulins, producing a grape-cluster appearance to the cell. Mott cells are
seen in multiple myeloma and some parasitic infestations
The Touton giant cell
Has distributed nuclei and is found in tumors other than Hodgkins lymphoma

Diaphragms of Body (USMLE Favorite)


Diaphragm of oral cavity: Mylohyoid
Diaphragm of Superior thoracic aperture: Sibsons Fascia

Sibsons fascia
Pelvic diaphragm: Levator ani and coccygeus
Urogenital diaphragm: Deep transverse perinea and sphincter urethrae, perineal mermbrane
Diaphragm sella: Fold of duramater overlying pituitary fossa
Iris diaphragm: In eye

Eponym Fascias (USMLE Favorite)


Toldts fascia

Anterior renal fascia

Zuckerland fascia

Posterior renal fascia

Bucks fascia

Deep fascia of penis

Denonvillers fascia

Fascia separating rectum from prostate

Waldeyers fascia

Fascia separating rectum from coccyx

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USMLE Step 1 Platinum Notes

Campers fascia

Fatty layer of superficial fascia

Scarpas fascia

Deep membranous layer of Superficial fascia

Fascia Colli

Investing layer of deep cervical fascia of neck

Fascia transversalis

Forms anterior wall of femoral sheath

Fascia iliaca

Forms posterior wall of femoral sheath

Pelvic fascia

Forms hypogastric sheath

USMLE Case Scenario


The Fascial layer separating the rectum from the coccyx is:
1. Waldeyers Fascia
2. Fascia Coli
3. Denonveliers Fascia
4. Gerotas Fascia
5. Cruveilhiers Fascia
6. Campers Fascia
7. Colles Fascia
8. Scarpas Fascia
Ans. 1. Waldeyers Fascia

Bursitis
Bursitis is inflammation of a bursa, which is a thin-walled sac lined with synovial tissue
The function of the bursa is to facilitate movement of tendons and muscles over bony prominences:
Subacromial bursitis (subdeltoid bursitis) is the most common form of bursitis. Trochanteric bursitis involves the bursa around
the insertion of the gluteus medius onto the greater trochanter of the femur.
Olecranon bursitis occurs over the posterior elbow, and when the area is acutely inflamed, infection should be excluded by
aspirating and culturing fluid from the bursa. Achilles bursitis involves the bursa located above the insertion of the tendon to the
calcaneus and results from overuse and wearing tight shoes.
Retrocalcaneal bursitis involves the bursa that is located between the calcaneus and posterior surface of the Achilles tendon.
Ischial bursitis (weavers bottom) affects the bursa separating the gluteus medius from the ischial tuberosity and develops from
prolonged sitting and pivoting on hard surfaces.
Iliopsoas bursitis affects the bursa that lies between the iliopsoas muscle and hip joint and is lateral to the femoral vessels.
Anserine bursitis is an inflammation of the sartorius bursa located over the medial side of the tibia just below the knee and under
the conjoint tendon and is manifested by pain on climbing stairs.
Prepatellarbursitis (housemaids knee) occurs in the bursa situated between the patella and overlying skin and is caused by
kneeling on hard surfaces. Treatment of bursitis consists of prevention of the aggravating situation, rest of the involved part,
administration of a nonsteroidal anti-inflammatory drug (NSAID), or local glucocorticoid injection.

Bursitis of Knee Joint


Housemaids knee is the result of inflammation of Prepatellar bursa
Miners beat knee is the result of inflammation of Prepatellar bursa
Clergymans knee is the result of inflammation of subcutaneous infrapatellar bursa

Important Nutrient Arteries


Nutrient artery of clavicle

Suprascapular artery

Nutrient artery of humerus

Profunda brachii artery

Anatomy

83

Nutrient artery of femur

Second perforating artery. Sometimes by first and third perforating arteries

Nutrient artery of tibia. Largestin body

Posterior tibial artery

Nutrient artery of fibula

Peroneal artery

Axis Arteries
Axis artery of upper limb: seventh cervical intersemental artery persisting as:
Axillary
Brachial
Anterior interosseous artery and
Deep palmar arch
Axis artery of lower limb: fifth lumbar intersemental artery persisting as:
Inferior gluteal artery
Companion artery of sciatic nerve
Popliteal artery
Peroneal artery and
Plantar arch

Important Vessels (USMLE Favorite)


The Marginal artery of Drummond is also known as the Marginal artery of the colon.
The anastomoses of the terminal branches of the ileocolic, right colic and middle colic arteries of the continuous arterial circle or
arcade along the inner border of the colon known as the marginal artery of Drummond.
Components
Ileocolic artery - colic branch
Right colic artery ascending and descending branches
Middle colic artery right and left branches
Left colic artery ascending and descending branches
Sigmoid arteries unnamed terminal branches
From this marginal artery, straight vessels (known as vasa recta) pass to the colon
The marginal artery is an important connection between the SMA and IMA, and provides collateral flow in the event of
occlusion or significant stenosis. The junction of the SMA and IMA territories is at the:
-- Superior mesentric artery (SMA), and of the left colic and sigmoid branches of the IMA, form a splenic flexure. Anastomoses
here are often weak or absent, hence the marginal artery at this point (known as Griffiths point) is often focally small or
discontinuous. For this reason, the splenic flexure is a watershed area prone to ischemia and infarction
-- One of the commonest area of colonic ischemia is called Sudecks point.

Charcots Artery
Charcots Artery: lenticulostriate arteries which arise at the commencement of the middle cerebral artery supply blood to part of
the basal ganglia and posterior limb of the internal capsule. The lenticulostriate perforators are end arteries. The name of these arteries
is derived from some of the structures it supplies: the lenticular nucleus and the striatum.

Heubners Artery
Heubners artery: A branch of anterior Cerebral artery, supplies the anteromedial part of the head of the caudate and anteroinferior
internal capsule Its vascular territory is the anteromedial section of the caudate nucleus and the anteroinferior section of the internal capsule.

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USMLE Step 1 Platinum Notes

Artery of Adamkiewicz
Artery of Adamkiewicz: Arteria Radicularis Magna, Great radicular artery of Adamkiewicz. Provides the major blood supply to the
lumbar and sacral cord. When damaged or obstructed, it can result in anterior spinal artery syndrome, with loss of urinary and fecal
continence and impaired motor function of the legs; sensory function is often preserved to a degree. It is important to identify the
location of the artery when treating a thoracic aortic aneurysm or a thoracoabdominal aortic aneurysm.

The Dorsalis Pedis Artery


The dorsalis pedis artery is the continuation of the anterior tibial artery after the artery anterior tibial artery crosses the ankle
to reach the dorsum of the foot
Its pulse is the most distal palpable pulse in the lower limb and therefore is useful for evaluating the arterial supply to the limb
On the dorsum of the foot, the pulse maybe felt as the artery passes over the navicular bone between the extensor hallucis longus
tendon and the extensor digitorum longus tendon.

Batsons Vertebral Venous Plexus


Batsons vertebral venous plexus: The valveless vertebral venous veins that communicate with the prostatic venous plexus and
explain the readiness with which carcinoma of the prostate spreads to the pelvic bones and vertebrae.
Tortuous Arteries
Facial artery
Splenic artery
Uterine artery
Vaginal artery
Ophthalmic artery
Lingual artery
PICA (Post Inferior Cerebellar Artery)

USMLE Case Scenario


A 66-year-old male patient from Florida complains of loss of pain and temperature sensation over the left side body ipsilateral
dysphagia, hoarseness, and diminished gag reflex with vertigo and diplopia of two months duration. Most likely tortuous
vessel affected is:
1. AICA
2. PICA
3. Common carotid
4. Internal carotid
5. Arch of aorta
Ans. 2. PICA: The condition itself is Lateral Medullary (Wallenburgs Syndrome)

End Arteries

Central artery of retina


Central branches of cerebral artery
Coronary artery
Segmental branches of renal/splenic artery

Important Arteries and Their Branches: (USMLE Favorite)


Axillary Artery
It is continuation of subclavian artery
Pectoralis minor divides it into three Branches

Anatomy

Ist part:
Superior thoracic artery
2nd part:
Thoracoacromial artery
Lateral thoracic artery
3rd part:
Subscapular artery
Anterior circumflex humeral artery
Posterior circumflex humeral artery

Internal Carotid Artery


No Branches in Neck
Caroticotympanic
Pterygoid

Cavernous branch to trigeminal ganglion


Superior and inferior hypophyseal
Ophthalmic
Anterior cerebral
Middle cerebral
Posterior communicating
Anterior choridal

External Carotid Artery

Superior thyroid
Lingual
Facial
Occipital
Posterior auricular
Ascending pharyngeal
Maxillary
Superficial temporal

Subclavian Artery

Vertebral artery
Internal thoracic artery
Thyrocervical trunk (Inferior thyroid, suprascapular, superficial cervical)
Costocervical trunk (Superior intercostal, Deep cervical)

Vertebral Artery

Spinal
Muscular
Meningeal
Anterior spinal
Posterior spinal
Posterior inferior cerebellar
Medullary

85

86

USMLE Step 1 Platinum Notes

Basilar Artery

Formed by Union of Two Vertebral Arteries:


Posterior cerebral arteries
Superior cerebellar
Pontine
Labyrinthine
Anteroinferior cerebellar

Internal Iliac Artery


It is smaller terminal branch of common iliac artery
It is about one and half inches long (33.5 cn)
It begins in front of sacroiliac joint
It divides into ant and post Divisions at upper margin of greater sciatic notch
Branches from Anterior Division: (Six in males and seven in females.)
Superior vesical artery
Inf vesical
Obturator
Middle rectal
Inf Gluteal
Internal pudendal
In females, inferior vesical is replaced by vaginal artery
Uterine artery is the 7th branch in females
Branches from Posterior Division
Superior gluteal
IIio lumbar
Lateral sacral

Questions asked in USMLE Examinations


Inferior thyroid artery is a branch of: Thyrocervical trunk
Ascending pharyngeal artery is a branch of external carotid artery
Internal pudendal artery in females is a branch of internal iliac artery
Left gastroepiploic artery is a branch of splenic artery
Splenic artery is a branch of celiac trunk
Uterine artery is a branch of internal iliac artery
Cystic artery is a branch of right hepatic artery
Cilio retinal artery is a branch of choridal artery
Middle meningeal artery is a branch of maxillary artery
Anterior spinal artery is a branch of vertebral artery
Ophthalmic artery is a branch of internal carotid artery

Structures Pasing between/Piercing


Structure passing between two heads of gastrocnemius: Sural nerve
Structure passing between two heads of lateral pterygoid: Maxillary artery
Structure passing between pronator teres: Median nerve

Anatomy

87

Structure passing between two plains of fibers of supinator: Posterior interosseous nerve
Structure passing through tarsal tunnel: Posterior tibial nerve
Structure passing through choroid fissure of eye: Hyaloids artery
Structure passing through foramen of Vesalius: Emissary vein
Structure passing through carotid sheath: Internal carotid/common carotid artery, internal jugular vein, vagus nerve. External
carotid is External to sheath
Structure piercing corocabrachialis: Musculocutaneous nerve
Structure piercing clavipectoral fascia (encloses subclavius): Lateral pectoral nerve, thoracoacromial vesses Cephalic vein
Structure piercing thyrohyoid membrane: Internal laryngeal nerve

Important Structures Accompanying (USMLE Favorite)


Axillary nerve accompanies posterior humeral circumflex artery
Radial nerve accompanies profunda brachii vessels
Short saphenous vein accompanies sural nerve
Great saphenous vein accompanies saphenous nerve
Superior thyroid vessels accompany external laryngeal nerve
Superior laryngeal vessels accompany internal laryngeal nerve
Inferior laryngeal vessels accompany recurrent laryngeal nerve

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USMLE Step 1 Platinum Notes

USMLE Case Scenario


Stroking the skin of the medial side of the thigh evokes a reflex contraction of the muscle, the cremasteric reflex, which
is most, pronounced in children. It may represent a protective reflex, and the cremaster may also have a role in testicular
thermoregulation. Cremaster consists of loosely arranged muscle fasciculi lying along the spermatic cord. It is variable in
thickness and is thickest in young men. It may form an incomplete coating around the cord, known as the cremasteric fascia,
which extends around the testis but lies within the external spermatic fascia. Cremaster is innervated by:
1. The terminal branches of the subcostal nerve
2. The terminal branches of the iliohypogastric nerve
3. The terminal branches of the ilioinguinal nerve
4. The genital branch of the genitofemoral nerve
5. The femoral branch of the genitofemoral nerve
Ans. 4. The genital branch of the genitofemoral nerve

USMLE Case Scenario


A 45-year-old man is evaluated by a neurologist because of a gait disorder. When the physician passively moves the patients
right great toe upward or downward, the patient cannot accurately report the direction of motion. This finding can best be
explained by a lesion of which of the following structures?
1. Right fasciculus cuneatus
2. Right fasciculus gracilis
3. Right lateral lemniscus
4. Right medial lemniscus
Ans: 2. Right fasciculus gracilis

USMLE Case Scenario


As part of a complete neurological examination, a medical student takes a cotton-tipped applicator and touches the patients
left eye with a thin wisp of cotton as the patient looks to the right. The patient closes both of his eyelids in response. Which of
the following cranial nerves is responsible for the motor limb of this reflex?
1. Abducens
2. Facial
3. Optic
4. Trigeminal
Ans. 2. Facial

USMLE Case Scenario


The Epithelium of the Bronchi contains:
1. Simple ciliated columnar cells, basal cells, and goblet cells
2. Simple ciliated columnar cells, basal cells, but not goblet cells
3. Non ciliated columnar cells, basal cells, and goblet cells
4. Stratified ciliated columnar cells, basal cells, and goblet cells
Ans. 4. Stratified ciliated columnar cells, basal cells, and goblet cells

USMLE Case Scenario


The Dandy-Walker malformation is a developmental abnormality in which:
1. In which the roof of the third ventricle fails to perforate with concomitant hyperplasia of the cerebellar vermis
2. In which the roof of the fourth ventricle fails to perforate with concomitant hyperplasia of the cerebellar vermis
3. In which the roof of the third ventricle fails to perforate with concomitant hypoplasia of the cerebellar vermis
4. In which the roof of the fourth ventricle fails to perforate with concomitant hypoplasia of the cerebellar vermis
Ans. 4. In which the roof of the fourth ventricle fails to perforate with concomitant hypoplasia of the cerebellar vermis.

Anatomy

89

The Dandy-Walker malformation is a developmental abnormality in which the roof of the fourth ventricle fails to perforate to form the
foramen of Magendie. The resultant cystic dilatation of the fourth ventricle expands the posterior fossa, elevating the tentorium and
causing hydrocephalus because of obstruction of the aqueduct of Sylvius, with concomitant hypoplasia of the cerebellar vermis.

USMLE Case Scenario


The kidneys and ureter arise from:
1. The pronephros and a diverticulum from the wolffian duct
2. The mesonephros and a diverticulum from the wolffian duct
3. The metanephros and a diverticulum from the wolffian duct
4. The pronephros and a diverticulum from the gartners duct
5. The mesonephros and a diverticulum from the gartners duct
6. The metanephros and a diverticulum from the gartners duct
Ans. 2. The mesonephros and a diverticulum from the wolffian duct.

USMLE Case Scenario


From its origin, the uterine artery crosses the ureter anteriorly in the broad ligament before branching at the level of the
uterus. One major branch ascends the uterus tortuously within the broad ligament until it reaches the region of the ovarian
hilum where it anastomoses with branches of the ovarian artery. The uterine artery arises as a branch of:
1. The anterior division of the internal iliac artery
2. The anterior division of the external iliac artery
3. The posterior division of the internal iliac artery
4. The posterior division of the external iliac artery
5. The common iliac artery
Ans. 1. The anterior division of the internal iliac artery

USMLE Case Scenario


A 34-year-old patient arrives in the emergency room after having suffered severe head trauma in a accident. Radiographic
studies of the head reveal a basilar skull fracture in the region of the foramen ovale. Which of the following nerve passes
through this foramen:
1. Maxillary
2. Mandibular
3. Ophthalmic
4. Occulomotor
Ans. 2. Mandibular

90

USMLE Step 1 Platinum Notes

USMLE Case Scenario


A Lecturer in Florida is demonstrating a thick fibrous band that runs on the visceral surface of the liver. It is attached on one
end to the inferior vena cava and on the other end to the left branch of the portal vein. In the Adult the structure corresponds to:
1. Ductus venosus
2. Ligamentum teres
3. Ligamentum venosum
4. Umbilical arteries
5. Ligamentum arteriosum
6. Ligamentum nucha
7. Ligament of Treitz
Ans. 3. Ligamentum venosum

USMLE Case Scenario


A Lecturer in Florida is demonstrating a fibrous band that runs on the visceral surface of the liver. It is attached on one end
to the inferior vena cava and on the other end to the left branch of the portal vein. In the embryo structure corresponds to:
1. Ductus venosus
2. Ligamentum teres
3. Ligamentum venosum
4. Umbilical arteries
Ans. 1. Ductus venosus

USMLE Case Scenario


A 66-year-old driver suffers a stroke while driving on highway. He has a history of hypertension, is a heavy smoker, and drinks
beer every weekend A right upper motor neuron paralysis of the facial nerve is noted; the other cranial nerves are normal. He
has a hemiplegia on the right side, with equal paralysis of the arm and leg. His lesion most likely involves the:
1. Left internal capsule
2. Left midbrain
3. Left pons
4. Left medulla
Ans. 1. Left internal capsule
Remember:
The anterior limb of the internal capsule conveys frontopontine fibers, the genu conducts corticobulbar fibers, and the posterior limb
of the internal capsule conveys corticospinal fibers to the contralateral arm and leg. Hemorrhage of the left internal capsule results in
right-sided dense hemiplegia in which paralysis of the arm and leg are of the same intensity.

USMLE Case Scenario


A structure is caused by failure of obliteration of the vitellointestinal duct. It is classically located in the distal ileum within 30
cm of the ileocecal valve, and the structure is a true diverticulum. The anatomist is talking about:
1. Ligament of Trietz
2. Meckels diverticulum
3. Appendicis epiploicae
4. Sacculations
Ans. 2. Meckels diverticulum

USMLE Case Scenario


A newborn boy does not pass meconium until 48 hours after his birth. Several weeks later his mother complains that he has not
been passing stool regularly. Anorectal manometry reveals increased internal anal sphincter pressure on rectal distention with
a balloon. The patients disorder maybe attributed to distention with a balloon. The patients disorder maybe attributed to:
1. Defective recanalization of the colon

Anatomy

91

2. Failure of neural crest cells to migrate


3. Herniation of abdominal contents into the umbilical cord
4. Persistence of the proximal end of the yolk stalk
Ans. 2. Failure of neural crest cells to migrate

USMLE Case Scenario


The vagina is a muscular tube lined with:
1. Non stratified squamous epithelium that is histologically similar to the mucosa of the cervix and vulva
2. Stratified squamous epithelium that is histologically similar to the mucosa of the cervix and vulva
3. Stratified cuboidal epithelium that is not histologically similar to the mucosa of the cervix and vulva
4. Stratified cuboidal epithelium that is histologically similar to the mucosa of the cervix and vulva
Ans. 2. Stratified squamous epithelium that is histologically similar to the mucosa of the cervix and vulva.

USMLE Case Scenario


A 5-year-old child aspirates a peanut. Following bronchopulmonary segments would this foreign object most likely enter.
1. Superior segment of the right lower lobes
2. Inferior segment of the right lower lobe
3. Superior segment of the left lower lobe
4. Superior segment of the left lower lobe
Ans. 1. Superior segment of the right lower lobe
Because the right main bronchus is wider and more vertical than the left, foreign objects are more likely to be aspirated into the
right main bronchus. The superior segmental bronchus of the lower lobar bronchus is the only segmental bronchus that exits from
the posterior wall of the lobar bronchi. Therefore, if a patient is supine at the time of aspiration, the object is most likely to enter the
superior segmental bronchus of the lower lobe.

USMLE Case Scenario


Fracture of neck of Fibula produces foot drop due to injury of:
1. Common peroneal nerve
2. Tibial nerve
3. Obturator nerve
4. Femoral nerve
Ans: 1. Common peroneal nerv

USMLE Case Scenario


Which of the following embryonic structures gives rise to the adrenal cortex?
1. Ectoderm
2. Endoderm
3. Mesoderm
4. Mesonephros
Ans. 3. Mesoderm

USMLE Case Scenario


The modified structures at the border of the epithelium are villi which are immotile in a patient. Which of the following would
be a consequence of this lack of motility?
1. Implantation failure
2. Kartageners syndrome

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USMLE Step 1 Platinum Notes

3. Increased gut motility


4. Decreased protein absorption
Ans. 2. Kartageners syndrome

USMLE Case Scenario


The arterial blood supply to the palatine tonsil is derived from branches of the external carotid artery. The principal artery is
the tonsillar artery, which is a branch of the:
1. Facial artery
2. Lingual artery
3. Superficial temporal artery
4. Maxillary artery
5. Superior thyroid artery
Ans. 1. Facial artery

USMLE Case Scenario


Occlusion of which artery would result in insufficient perfusion of the urinary bladder:
1. Internal iliac
2. External iliac
3. Renal
4. Suprarenal
Ans. 1. Internal iliac

USMLE Case Scenario


Statement True about Esophagus is:
1. The upper 2/3 of the esophagus contains striated muscle and is innervated by the vagus nerve (CNX). The lower 1/3 contains
smooth muscle from splanchnic mesoderm and is innervated by the splanchnic plexus
2. The lower 2/3 of the esophagus contains striated muscle and is innervated by the vagus nerve (CNX). The upper 1/3 contains
smooth muscle from splanchnic mesoderm and is innervated by the splanchnic plexus
3. The upper 2/3 of the esophagus contains smooth muscle and is innervated by the vagus nerve (CNX). The lower 1/3 contains
skeletal muscle from splanchnic mesoderm and is innervated by the splanchnic plexus
4. The upper 2/3 of the esophagus contains striated muscle and is innervated by the splanchnic plexus. The lower 1/3 contains
smooth muscle from splanchnic mesoderm and is innervated by the vagus nerve
Ans. 1. The upper 2/3 of the esophagus contains striated muscle and is innervated by the vagus nerve (CNX). The lower 1/3
contains smooth muscle from splanchnic mesoderm and is innervated by the splanchnic plexus.

USMLE Case Scenario


The mesentery, a large fold of peritoneum, suspends the small intestine from the posterior abdominal wall. The base of the
mesentery attaches to the posterior abdominal wall:
1. To the right of the third lumbar vertebra and passes obliquely to the left and inferiorly to the right sacroiliac joint
2. To the left of the third lumbar vertebra and passes obliquely to the left and inferiorly to the right sacroiliac joint
3. To the right of the second lumbar vertebra and passes obliquely to the left and inferiorly to the right sacroiliac joint
4. To the left of the second lumbar vertebra and passes obliquely to the right and inferiorly to the right sacroiliac joint
Ans. 4. To the left of the second lumbar vertebra and passes obliquely to the right and inferiorly to the right sacroiliac joint.
The mesentery contains blood vessels, nerves, lymphatics, and lymph nodes, as well as considerable fat. It attaches to the small
intestine along the length of one side, the mesenteric border, leaving the remainder of the surface of the bowel covered by its visceral
peritoneum, the serosa. The broad-based attachment of the mesenteric base stabilizes the small bowel and prevents it from twisting
upon its blood supply.

Anatomy

93

USMLE Case Scenario


A 33-year-old person from Toledo is hit by a car has been said to develop extradural hematom1. Most likely vessel to bleed is:
1. Ophthalmic artery
2. Subdural veins
3. Occipital artery
4. Middle meningeal artery
Ans. 4. Middle meningeal artery

USMLE Case Scenario


During an abdomino pelvic surgery a big, tortuous vessel was seen by a gynecologist on the lateral side of uterus. The vessel
was found to be a branch of internal iliac artery. Most likely the vessel found by the gynecologists was:
1. Splenic artery
2. Ovarian artery
3. Vaginal artery
4. Uterine artery
Ans. 4. Uterine artery

USMLE Case Scenario


A surgeon wishes to perform a splenectomy on a 77-year-old patient who has been in an automobile accident. Before
removing the spleen, the splenic artery and splenic vein are ligated. Within which of the following peritoneal structures are
the splenic artery and vein found?
1. Gastrocolic ligament
2. Gastrosplenic ligament
3. Lesser omentum
4. Splenorenal ligament
Ans. 4. Splenorenal ligament

USMLE Case Scenario


A 44-year-old has a normal thyroid gland which normally moves with swallowing because the thyroid gland is enclosed by
which of the following fascia?
1. Carotid sheath
2. Investing layer of the deep cervical fascia
3. Pretracheal fascia
4. Prevertebral fascia
Ans. 3. Pretracheal fascia

USMLE Case Scenario


A 15-year-old typist from ilinos comes to the health clinic because of recurrent episodes of wheezing during basketball
practices. His activity has been hampered by shortness of breath shortly after beginning practice and during games. The
symptoms are accompanied by a nonproductive cough and chest tightness. He denies any symptoms at rest. The symptoms
occur whether the practices are indoors or outdoors. On physical examination, he is comfortable and denies any symptoms.
His physical examination is unremarkable. Which of the following cells are most likely to mediate his symptoms?
1. Eosinophils
2. Lymphocytes
3. Mast cells
4. Monocytes

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USMLE Step 1 Platinum Notes

5. Neutrophils
Ans. 3. Mast cells
This patient has symptoms of exercise-induced asthma. The symptoms of exercise-induced asthma are due to mast cell release of
histamines, which degranulate with the initiation of exercise.

USMLE Case Scenario


Carotid Sheath is an important structure. It contains a cranial nerve. The cranial nerve is:
1. IX
2. X
3. XI
4. XII
Ans. 2. X

USMLE Case Scenario


The cranial nerve passing through the substance of parotid gland is:
1. Abducens
2. Facial
3. Optic
4. Trigeminal
5. Glossopharyngeal
6. Vagus
Ans. 2. Facial

USMLE Case Scenario


A feature of Sharipos Syndrome is agenesis of:
1. Corpus callosum
2. Anterior commisure
3. Posterior commisure
4. Hippocampal commisure
Ans. 1. Corpus callosum

USMLE Case Scenario


During cranial nerve examination, a neurologist asks her 33-year-old patient to protrude his tongue. On doing so, her tongue
deviates to the right side. This finding results from paralysis of tongue muscle namely:
1. Genioglossus
2. Styloglossus
3. Palatoglossus
4. Hyoglossus
Ans. 1. Genioglossus
The genioglossus muscle is innervated by the hypoglossal nerve. The function of the genioglossus muscle is to pull the tongue
forward (protrude) and toward the opposite side. When the right genioglossus muscle is paralyzed, the left genioglossus muscle pulls
the tongue forward and to the right.

USMLE Case Scenario


Bells Palsy is a LMNL of a cranial nerve. The cranial nerve most commonly involved is:
1. Abducens
2. Facial
3. Optic
4. Trigeminal
Ans. 2. Facial

Anatomy

95

USMLE Case Scenario


An inflammatory process in the temporal bone has resulted in a swelling of the facial nerve within the facial canal. Which
muscle maybe paralyzed as a result of this compression?
1. Anterior belly of the digastrics
2. Geniohyoid
3. Stapedius
4. Stylopharyngeus
Ans. 3. Stapedius
The stapedius muscle is innervated by the facial nerve. This muscle is located in the middle ear and attaches to the neck of the stapes.
Contraction of the Stapedius reduces the amplitude of oscillation of the stapes and thus reduces the perceived loudness of a sound.
Paralysis of this muscle may result in hyperacusis.

USMLE Case Scenario


A 34-year-old male smoker notices loss of taste sensation in his anterior part of tongue. He reports to a physician who tells him
that one of his nerves maybe damaged which supplies taste sensation to this part of his tongue. The nerve specifically most
likely to be damaged is:
1. Glossopharyngeal
2. Lingual
3. Chorda tympani
4. Vagus
Ans. 3. Chorda tympani

USMLE Case Scenario


The neck of the pancreas links the head and body. It is often the most anterior portion of the gland. The lower part of the
neck lies anterior to the superior mesenteric vein. This is important during surgery for pancreatic cancer since malignant
involvement of these vessels may make resection impossible. The anterior surface of the neck is covered with peritoneum. The
posterior surface of neck is closely related to:
1. Pylorus of stomach
2. Aorta
3. Internal iliac vein
4. External iliac vein
5. Common iliac vein
6. Portal vein
Ans. 6. Portal vein
The neck of the pancreas is defined as that portion of the pancreas which lies anterior to the portal vein, and is closely related to the upper
posterior surface. The lower part of the neck lies anterior to the superior mesenteric vein just before the formation of the portal vein.

USMLE Case Scenario


An ENT surgeon plainly tells his patient from North Carolina that he has got hyperacusis and that one of his important nerve
is damaged. The nerve most likely to be damaged is:
1. Auriculotemporal
2. Greater Auricular
3. Auricular branch of Vagus
4. Nerve to Stapedius
Ans. 4. Nerve to Stapedius

USMLE Case Scenario


A 66-year-old patient from Ohio has a large meningioma involving the parasagittal region and falx cerebri neurologic deficits
expected to be produced by mass lesion in this region is:
1. Lower limb paralysis

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USMLE Step 1 Platinum Notes

2. Upper limb paralysis


3. Motor aphasia
4. Sensory aphasia
Ans. 1. Lower limb paralysis
A meningioma of the parasagittal region and the falx cerebri would be located superiorly, between the two hemispheres. In this
position, it could compress the sensory (postcentral gyrus) or motor cortex (precentral gyrus) supplying the lower extremities and
cause lower limb paralysis.

USMLE Case Scenario


A 66-year-old man working in a bar complains of trouble swallowing and hoarseness. On physical exam, he is noted to have
ptosis and a constricted pupil on the left, and a diminished gag reflex. Neurological examination shows decreased pain and
temperature sensation on the left side of his face and on the right side of his body. Which vessel is most likely occluded?
1. Spinal artery
2. PICA
3. AICA
4. Vertebral artery
Ans. 2. PICA
The signs and symptoms in this patient are consistent with occlusion of the posterior inferior cerebellar artery (PICA). PICA
is a branch of the vertebral artery (which is itself a branch of the subclavian artery). Occlusion of PICA causes a lateral medullary
syndrome characterized by deficits in pain and temperature sensation over the contralateral body (spinothalamic tract dysfunction);
ipsilateral dysphagia, hoarseness, and diminished gag reflex (interruption of the vagal and glossopharyngeal pathways);
vertigo, diplopia, nystagmus and vomiting (vestibular dysfunction); ipsilateral Horners syndrome (disruption of descending
sympathetic fibers); and ipsilateral loss of pain and temperature sensation of the face (lesion of the spinal tract and nucleus of the
trigeminal nerve).

USMLE Case Scenario


Vessel lying within cavernous sinus is:
1. Internal carotid
2. External carotid
3. Common carotid
4. External jugular vein
Ans. 1. Internal carotid

USMLE Case Scenario


A 55-year-old male received a hit on left hypochondriac region. Spleen was found to be lacerated. On operation, a large
tortuous vessel was found to be seen. Doctor reported it as splenic artery. It is a branch of:
1. Celiac trunk
2. Superior mesenteric artery
3. Inferior mesenteric artery
4. Thoracic aorta
Ans. 1. Celiac trunk

USMLE Case Scenario


A 55-year-old male had a surgery. His leino renal ligament was seen to contain an artery. Most likely the artery was:
1. Short gastric artery
2. Splenic artery
3. Pancreatic artery
4. Renal artery
Ans. 2. Splenic artery

Anatomy

97

USMLE Case Scenario


A 55-year-old is to be operated for inguinal hernia. An antomist while discussing the hernia describes one artery as a land
mark for differentiating direct and indirect inguinal hernias. The artery most likely is:
1. Superior epigastric artery
2. Inferior epigastric artery
3. Umbilical artery
4. Obliterated umbilical artery
Ans. 2. Inferior epigastric artery
Remember:
Indirect inguinal hernias lie lateral to the inferior epigastric artery, whereas direct inguinal hernias lie medial to these vessels.

USMLE Case Scenario


The superficial perineal fascia is a continuation into the perineum of the membranous fascia from the anterior abdominal
wall. The superficial perineal fascia is called as:
1. Colles fascia
2. Fascia colli
3. Campers fascia
4. Waldeyers fascia
5. Thoraco lumbar fascia
Ans. 1. Colles fascia

USMLE Case Scenario


An aneurysm of the axillary artery within the axilla is most likely to compress which of the following neural structures?
1. Axillary nerve
2. Long thoracic nerve
3. Lower trunk of the brachial plexus
4. Medial cord of the brachial plexus
Ans. 4. Medial cord of the brachial plexus
Remember:
Within the axilla, the axillary artery is within the axillary sheath and is surrounded by the three cords of the brachial plexus, which are
also within the axillary sheath. An aneurysm of the axillary artery may compress any of the three cords.

USMLE Case Scenario


Physical examination of 32-year-old medical graduate from kansas reveals a winged left scapula and an inability to raise his
left arm above the horizontal. Which of the following nerves is most likely affected?
1. Axillary nerve
2. Long thoracic nerve
3. Lower subscapular
4. Suprascapular nerve
Ans. 2. Long thoracic nerve
Remember:
The serratus anterior, innervated by the long thoracic nerve, is responsible for stabilization of the scapula during abduction of the arm
from 90 to 180 degrees. When the long thoracic nerve is damaged, it is difficult to elevate the arm above the horizontal. This nerve
arises from C5, 6, and 7. Remember: winged scapula is a classic clue for long thoracic nerve injury.

USMLE Case Scenario


Waldeyers ring is a circumpharyngeal ring of mucosa-associated lymphoid tissue which surrounds the openings into the
digestive and respiratory tracts. It is made-up:
1. Posterosuperiorly by the lingual tonsil

98

USMLE Step 1 Platinum Notes

2. Anterosuperiorly by the lingual tonsil


3. Posteroinferiorly by the lingual tonsil
4. Anteroinferiorly by the lingual tonsil
Ans. 4. Anteroinferiorly by the lingual tonsil
Waldeyers Ring: Anteroinferiorly by the lingual tonsil, laterally by the palatine and tubal tonsils, and posterosuperiorly by the
nasopharyngeal tonsil

USMLE Case Scenario


A 33-year-old female engineer complains to her orthopedician that her thumb does not work right. The physician notes
weakness of the thumb in extension, although rotation, flexion, abduction, adduction, and opposition are normal. Which of
the following nerves is most likely involved?
1. Ulnar
2. Radial
3. Median
4. Axillary
Ans. 2. Radial
Redial extension is provided by the extensors pollicis longus and brevis, which are innervated by the radial nerve
The median nerve supplies the thenar group, which allows the thumb to oppose, flex, abduct, and rotate
The ulnar nerve supplies the adductor pollicis, which adducts the thumb
Axillary nerve supplies Teres Minor and Deltoid.

USMLE Case Scenario


A branch of the posterior cord of the brachial plexus particularly susceptible to injury in shoulder dislocations that displace
the humeral head with impaired Arm abduction and loss of sensation over the lower half of the deltoid. The nerve involved is:
1. Ulnar
2. Radial
3. Median
4. Axillary
Ans. 4. Axillary

USMLE Case Scenario


A nerve innervates the muscle of the anterior compartment of the arm but does not innervate any muscle in the hand is:
1. Ulnar
2. Radial
3. Musculocutaneous
4. Median
Ans. 3. Musculocutaneous

USMLE Case Scenario


A 36-year-old Acromegaly patient complains of a tingling sensation in the 1st, 2nd, and 3rd digits of the right hand and loss
of coordination and strength of the right thumb. The condition is most likely to be:
1. Claw hand
2. Carpal tunnel syndrome
3. Ape hand deformity
4. Dupynterns contracture
Ans. 2. Carpal tunnel syndrome
Overgrowth in the wrist area has compressed the carpal tunnel, thereby impinging on the median nerve. The median nerve (root C5T1) provides motor innervation to the forearm flexors, thenar muscles, and radial lumbricals. It provides sensory innervation to the
radial 2/3 of the palm, volar surfaces of the thumb, 2nd and 3rd digits, and radial 1/2 of the 4th digit.

Anatomy

99

USMLE Case Scenario


A 55-year-old suffered trauma to his penis. His Dorsal artery of penis got damaged. The said vessel is a branch of:
1. Anterior division of internal iliac artery
2. Posterior division of internal iliac artery
3. Anterior division of external iliac artery
4. Posterior division of external iliac artery
Ans. 1. Anterior division of internal iliac artery
The internal pudendal is a branch of the anterior division of the internal iliac artery. It gives rise to the inferior rectal artery, perineal
artery, artery of the bulb in men, urethral artery, deep artery of the penis and dorsal artery of the penis.

USMLE Case Scenario


A 66-year-old reports pain in his left upper extremity and tingling and numbness in his 4th and 5th digits of his left hand.
There is mild swelling of the left hand. The man reports most of his pain and numbness occurs when he is doing electric work
with his arms overhead. X-ray reveals the presence of a cervical rib. The artery liable to be compressed is:
1. Axillary
2. Radial
3. Brachial
4. Subclavian
Ans. 4. Subclavian
The subclavian artery passes laterally over the upper surface of the first rib and lies posterior to the scalenus anterior. In the case of
thoracic outlet syndrome, this artery is usually compressed between the scalenus anterior and a cervical rib. Thoracic outlet syndrome
is a broad term for a group of disorders in which there is compression of certain neurovascular bundles. The presence of a cervical rib
adds to the compression, and repetitive motion and poor posture are other predisposing factors. When the neurovascular bundle is
entrapped, the patient presents with neurological and/or circulatory changes in the upper extremity on the involved side.

USMLE Case Scenario


A 44-year-old complains of Galactorrhea and Amonorrhea. CT Scan was done. Image shows a pituitary tumor compressing
optic chiasma. Hemianopia produced would be of type:
1. Bitemporal hemianopia
2. Binasal hemianopia
3. Unilateral hemianopia
4. Superior quadrant unilateral hemianopia
Ans. 1. Bitemporal hemianopia

100

USMLE Step 1 Platinum Notes

Parkinsons disease

USMLE Case Scenario


The person shown in figure has features as identified in figure. Most likely he is suffering from a disease that affects which
part of CNS.
1. Cerebellum
2. Substantia nigra
3. Nucleus basalis
4. Frontal lobe
Ans. 2. Substantia nigra

Midbrain

Anatomy

101

USMLE Case Scenario


The chorda tympani nerve of is a branch of cranial nerve. The cranial nerve is:
1. Abducens
2. Facial
3. Optic
4. Trigeminal
Ans. 2. Facial

USMLE Case Scenario


A 45-year-old from India notices swelling in his groin. He is reported to have an abscess after further investigations reveal
tuberculosis of spine. The abscess is found along sheath of a muscle whose function is: to flex the thigh at the hip. The muscle
involved is:
1. Gluteus maximus
2. Psoas
3. Gluteus minimus
4. Sartorius
Ans. 2. Psoas

USMLE Case Scenario


Pyramidalis is a triangular muscle that lies in front of the lower part of rectus abdominis within the rectus sheath. It is attached
by tendinous fibers to the front of the pubis and to the ligamentous fibers in front of the symphysis. The muscle diminishes
in size as it runs upwards, and ends in a pointed apex that is attached medially to the linea alba. This attachment usually lies
midway between the umbilicus and pubis, but may occur higher. The pyramidalis is supplied by:
1. The terminal branches of the subcostal nerve
2. The terminal branches of the iliohypogastric nerve
3. The terminal branches of the ilioinguinal nerve
4. The terminal branches of the genitofemoral nerve
Ans. 1. The terminal branches of the subcostal nerve

USMLE Case Scenario


The muscles of the pharynx with the exception of one muscle are supplied from the pharyngeal plexus by the pharyngeal
branch of the vagus. The exception is:
1. Palatopharyngeus
2. Stylopharyngeus
3. Salpingopharyngeus
4. Inferior constrictor
Ans. 2. Stylopharyngeus
The muscles of the pharynx-with the exception of stylopharyngeus, which is supplied by the glossopharyngeal nerve are supplied
from the pharyngeal plexus by the pharyngeal branch of the vagus. This branch emerges from the upper part of the inferior vagal
ganglion.

USMLE Case Scenario


The paired renal arteries supply the kidneys through a number of subdivisions described sequentially as segmental, lobar,
interlobar, and arcuate arteries. These are end arteries with no anastomoses. The renal arteries branch laterally from the:
1. Iliac vessels just below the origin of the superior mesenteric artery
2. Iliac vessels just above the origin of the superior mesenteric artery
3. Aorta just below the origin of the superior mesenteric artery

102

USMLE Step 1 Platinum Notes

4. Aorta just above the origin of the superior mesenteric artery


Ans. 3. Aorta just below the origin of the superior mesenteric artery
The renal arteries branch laterally from the aorta just below the origin of the superior mesenteric artery. Both cross the corresponding
crus of the diaphragm at right angles to the aorta. The right renal artery is longer and often higher, passing posterior to the inferior
vena cava, right renal vein, head of the pancreas and descending part of the duodenum. The left renal artery is a little lower and passes
behind the left renal vein, the body of the pancreas and splenic vein.

USMLE Case Scenario


The aortic aperture is the lowest and most posterior of the large openings. It is at the level of the lower border of the twelfth
thoracic vertebra and the thoracolumbar intervertebral disk, slightly to the left of the midline. It is an osseoaponeurotic
opening defined by the diaphragmatic crura laterally, the vertebral column posteriorly and the diaphragm anteriorly. Strictly
speaking, it lies behind the diaphragm and its median arcuate ligament. The aortic opening transmits:
1. The aorta, thoracic duct, azygos veins
2. The inferior vena cava, thoracic duct, azygos veins
3. Esophagus, thoracic duct, azygos veins
4. The phrenic nerve, thoracic duct, azygos veins
Ans. 1. The aorta, thoracic duct, azygos veins

USMLE Case Scenario


The epithelial lining of the trachea is composed of:
1. Pseudostratified columnar nonciliated cells, goblet cells and basal cells
2. Pseudostratified columnar ciliated cells, goblet cells and basal cells
3. Stratified columnar nonciliated cells, goblet cells and basal cells
4. Stratified noncolumnar ciliated cells, goblet cells and basal cells
Ans. 2. Pseudostratified columnar ciliated cells, goblet cells and basal cells

USMLE Case Scenario


Kidney is surrounded by a special layer of fascia called:
1. Waldeyers fascia
2. Fascia coli
3. Denonveliers fascia
4. Gerotas fascia
5. Cruveilhiers fascia
6. Campers fascia
7. Colles fascia
8. Scarpas fascia
Ans. 4. Gerotas fascia

USMLE Case Scenario


The ovarian vessels follow a downward course and pass between the layers of the infundibulopelvic ligament and the broad
ligament to reach the ovary. The true statement regarding blood supply of ovary is:
1. The ovarian arteries arise from aorta, the left ovarian vein and the right ovarian vein empties into the vena cava
2. The ovarian arteries arise from aorta and the left ovarian vein empties into the left renal vein; the right ovarian vein empties
into the vena cava
3. The ovarian arteries arise from uterine artery and the right ovarian vein empties into the left renal vein; the left ovarian vein
empties into the vena cava
4. The ovarian arteries arise from uterine artery and the left ovarian vein empties into the left renal vein; the right ovarian vein
empties into the vena cava
Ans. 2. The ovarian arteries arise from aorta and the left ovarian vein empties into the left renal vein; the right ovarian vein
empties into the vena cava.

Anatomy

103

USMLE Case Scenario


A 44-year-old suffers fracture of surgical neck of humerus. Most likely effected nerve is:
1. Radial
2. Musculocutaneous
3. Ulnar
4. Anterior interosseous c nerve
5. Cranial nerve XI
6. Subscapular
7. Axillary nerve
Ans. 7. Axillary nerve

USMLE Case Scenario


Valves of Kerckring are seen in:
1. Appendix
2. Small intestine
3. Cecum
4. Sigmoid colon
5. Rectum
6. Anal canal
Ans. 2. Small intestine
The mucosal surface of the small intestine contains numerous circular mucosal folds called the plicae circulares (valvulae conniventes,
or valves of Kerckring). These folds are 3 to 10 mm in height; they are taller and more numerous in the distal duodenum and proximal
jejunum, becoming shorter and fewer distally. Intestinal villi barely visible to the naked eye resemble tiny finger-like processes
projecting into the intestinal lumen.

USMLE Case Scenario


A nerve innervates the anconeus muscle of the arm. Most likely nerve supply of anconeus is:
1. Ulnar
2. Radial nerve
3. Musculocutaneous
4. Median
Ans. 2. Radial nerve

USMLE Case Scenario


The cranial nerves lying in the cavernous sinus are:
1. VII , IX
2. X , XI
3. XII, VI
4. Divisions of V nerve
5. Divisions of VII nerve
Ans. 4. Divisions of V nerve

USMLE Case Scenario


Annular bronchial cartilage is congenitally absent, leading to bronchomalacia and Bronchiectasis is termed as:
1. Cystic fibrosis syndrome
2. Ehlers-Danlos syndrome
3. Mounier-Kuhn syndrome
4. Kartageners syndrome
5. Immotile cilia syndrome
6. Williams-Campbell syndrome
Ans. 6. Williams-Campbell syndrome

104

USMLE Step 1 Platinum Notes

USMLE Case Scenario


Fold of serous pericardium surrounding right and left pulmonary veins are connected by an irregular pericardial reflection
creates a space termed the:
1. Oblique sinus
2. Transverse sinus
3. Coronary sinus
Ans. 1. Oblique sinus

USMLE Case Scenario


After a fight a sharp instrument passed through the superior orbital fissure of a 45-year-old man. It would most likely damage the:
1. Abducens nerve
2. Facial nerve
3. Mandibular nerve
4. Maxillary nerve
5. Middle meningeal artery
6. Ophthalmic artery
7. Optic nerve
Ans. 1. Abducens nerve
Almost everything that innervates the eye, other than the optic nerve, passes through this fissure. This includes the oculomotor nerve
(CN III), the trochlear nerve (CN IV), the ophthalmic nerve (V1), and the abducens nerve (CN VI).

USMLE Case Scenario


Meckels Diverticulitis is persistence of:
1. Portion of the vitelline duct on the mesenteric border of the distal ileum, may produce bleeding, intestinal obstruction
2. Portion of the vitelline duct on the mesenteric border of the proximal ileum, may produce bleeding, intestinal obstruction
3. Portion of the vitelline duct on the antimesenteric border of the proximal ileum, may produce bleeding, intestinal obstruction
4. Portion of the vitelline duct on the antimesenteric border of the distal ileum, may produce bleeding, intestinal obstruction
Ans. 4. Portion of the vitelline duct on the antimesenteric border of the distal ileum, may produce bleeding, intestinal
obstruction

USMLE Case Scenario


A 27-year-old woman presents with hyperthyroidism, and subtotal thyroidectomy is successfully performed, but following
the surgery, the woman is extremely hoarse, and can barely speak above a whisper. This hoarseness is most probably related
to damage to a nerve which is a branch of CRANIAL NERVE:
1. IX
2. X
3. XI
4. XII
Ans. 2. X

USMLE Case Scenario


A physician is performing a cranial nerve examination on a patient. While testing the gag reflex, it is noted that when the
right side of the pharyngeal mucosa is touched, the patients uvula deviates to the right. When the left side of the pharyngeal
mucosa is touched, the patient does not gag. Which of the following is the most likely location of his lesion?
1. Left glossopharyngeal nerve and left vagus nerve
2. Right glossopharyngeal nerve and left vagus nerve
3. Left glossopharyngeal nerve and Right vagus nerve
4. Right glossopharyngeal nerve and Right vagus nerve
Ans. 1. Left glossopharyngeal nerve and left vagus nerve

Anatomy

105

USMLE Case Scenario


A cranial nerve innervates the stylopharyngeus muscle and the parotid gland. Visceral afferents supply the carotid sinus
baroreceptors and carotid body chemoreceptors, and mediate taste from the posterior one-third of the tongue. Somatosensory
fibers supply pain, temperature, and touch information from the posterior one-third of the tongue, upper pharynx, middle
ear and eustachian tube. The cranial nerve mentioned is:
1. IX
2. X
3. XI
4. XII
Ans. 1. IX

USMLE Case Scenario


An injury to the lateral portion of the dorsal columns would most likely damage:
1. Fine motor control of fingers
2. Motor control of the contralateral foot
3. Sweating of the ipsilateral face
4. Proprioception from the ipsilateral leg
5. Vibratory sense from the ipsilateral arm
6. Vibratory sense from the contralateral arm
7. Sensory control of the contralateral foot
Ans. 5. Vibratory sense from the ipsilateral arm

USMLE Case Scenario


Atresia (blockage) of this canal results from failure of the meatal plug to canalize. Usually the deep part of the meatus is open,
but the superficial part is blocked by bone or fibrous tissue. Most cases are associated with the:
1. First arch syndrome
2. Second arch syndrome
3. Third arch syndrome
4. Fifth arch syndrome
Ans. 1. First arch syndrome

USMLE Case Scenario


The tensor tympani muscle, attached to the malleus, is derived from mesenchyme in the first pharyngeal arch and is innervated by:
1. CN V, the nerve of this arch
2. CN VI, the nerve of this arch
3. CN VII, the nerve of this arch
4. CN VIII, the nerve of this arch
Ans. 1.CN V, the nerve of this arch

USMLE Case Scenario


Fine motor control of the fingers would be carried principally by the:
1. Contralateral lateral corticospinal tract
2. Ipsilateral lateral corticospinal tract
3. Ipsilateral rubrospinal tract
4. Ipsilateral Tectospinal tract
5. Ipsilateral vestibulospinal tract
Ans. 2. Ipsilateral lateral corticospinal tract

106

USMLE Step 1 Platinum Notes

USMLE Case Scenario


The rectum is separated from the prostate by:
1. Waldeyers fascia
2. Fascia coli
3. Denonveliers fascia
4. Gerotas fascia
5. Cruveilhiers fascia
6. Campers fascia
7. Colles fascia
8. Scarpas fascia
Ans. 3. Denonveliers fascia

USMLE Case Scenario


An 89 years old elderly patient suffering from Picks disease also had multiple small strokes. During her stay in the nursing
home on multiple occasions she aspirated food, and neurological examination reveals that her gag reflex is absent. These
findings suggest involvement of the nucleus of which of the following cranial nerves?
1. Facial (VII)
2. Glossopharyngeal (IX)
3. Hypoglossal (XII)
4. Spinal accessory (XI)
5. Vestibulocochlear (VIII)
Ans. 2. Glossopharyngeal (IX)
Cranial nerve IX is the glossopharyngeal nerve, which has a nucleus in the medulla and is necessary for the gag reflex

USMLE Case Scenario


The esophagus begins at the lower border of the cricoid cartilage at the level of C6 vertebra. It is about 25 cm (10 inches) long.
The intra-abdominal part of the esophagus varies in length according to the tone of its muscle and the degree of distension
of the stomach. It passes through the diaphragm at the level of:
1. T6 vertebra
2. T8 vertebra
3. T10 vertebra
4. T12 vertebra
Ans. 3. T10 vertebra

USMLE Case Scenario


The upper part of the anal canal above the pectinate line is endodermal, and the lower part is derived from the ectoderm.
The upper half of the canal is lined by columnar epithelium and the lower half with stratified squamous epithelium. True
statement would be:
1. A carcinoma of the lower canal is usually an adenocarcinoma, while that arising from the upper part would be a squamous cell
carcinoma
2. A carcinoma of the upper canal is usually an adenocarcinoma, while that arising from the lower part would also be an
adenocarcinoma
3. A carcinoma of the upper canal is usually a squamous cell carcinoma, while that arising from the lower part would also be a
squamous cell carcinoma
4. A carcinoma of the upper canal is usually an adenocarcinoma, while that arising from the lower part would be a squamous cell
carcinoma
Ans. 4. A carcinoma of the upper canal is usually an adenocarcinoma, while that arising from the lower part would be a
squamous cell carcinoma

Anatomy

107

USMLE Case Scenario


The cranial nerve carrying the pain sensations from tip of tongue is:
1. VI
2. V2
3. V3
4. VII
5. IX
6. X
7. XI
8. XII
Ans. 3. V3
The mandibular division of the trigeminal nerve (V3) carries general somatic sensation from the anterior two-thirds of the
tongue.

USMLE Case Scenario


Which of the following eye muscles rotates the eye downward and away from midline?
1. Inferior oblique
2. Superior oblique
3. Inferior rectus
4. Superior rectus
Ans. 2. Superior oblique

USMLE Case Scenario


A 44-year-old engineer noticed that he has an eye that is persistent directed toward his nose. A lesion of which of the following
nerves could produce this finding?
1. CN II
2. CN IV
3. CN V
4. CN VI
Ans. 4. CN VI

USMLE Case Scenario


The Fascial layer separating the rectum from the coccyx is:
1. Waldeyers fascia
2. Fascia coli
3. Denonveliers fascia
4. Gerotas fascia
5. Cruveilhiers fascia
6. Campers fascia
7. Colles fascia
8. Scarpas fascia
Ans. 1. Waldeyers fascia

USMLE Case Scenario


Carotid Sheath is an important structure. It contains:
1. Facial nerve and internal carotid artery
2. Facial nerve and external carotid artery
3. Facial artery and external carotid artery
4. Vagus nerve and external carotid artery
5. Vagus nerve and internal carotid artery
Ans. 5. Vagus nerve and internal carotid artery

108

USMLE Step 1 Platinum Notes

USMLE Case Scenario


Meckels ganglion is related to a cranial nerve. The cranial nerve is:
1. Abducens
2. Facial
3. Optic
4. Trigeminal
Ans. 4. Trigeminal

USMLE Case Scenario


The cranial nerve supplying the Trapezius muscle is:
1. VII
2. IX
3. X
4. XI
5. XII
Ans. 4. XI

USMLE Case Scenario


A Nerve innervating the muscles of the Posterior compartment of the arm is:
1. Ulnar
2. Radial
3. Musculocutaneous
4. Median
Ans. 2. Radial

USMLE Case Scenario


Physical examination of 36-year-old medical graduate from Texas reveals a winged left scapula and an inability to raise his left
arm above the horizontal. Which of the following muscles is most likely affected?
1. Serratus posterior
2. Serratus anterior
3. Deltoid
4. Scalenus anterior
5. Scalenus medius
6. Scalenus posterior
7. Levator scapulae
8. Sternomastoid
9. Rhombidius minor
Ans. 2. Serratus anterior
Remember:
The serratus anterior, innervated by the long thoracic nerve, is responsible for stabilization of the scapula during abduction of the arm
from 90 to 180 degree.

USMLE Case Scenario


A Newborn boy does not pass meconium until 55 hours after his birth. Several weeks later his mother complains that he has
not been passing stool regularly. Anorectal manometry reveals increased internal anal sphincter pressure on rectal distention
with a balloon. The patients disorder is:
1. Intussusception
2. Hirschsprungs disease
3. Exomphalos
4. Dysphagia lusoria

Anatomy

109

5. Anal atresia
6. Malrotation of gut
Ans. 2. Hirschsprungs disease

USMLE Case Scenario


A physician during cranial nerve examination asks her patient to protrude his tongue. On doing so, her tongue deviates to the
right side. This finding results from paralysis of tongue muscle. The likely nerve paralyzed is:
1. Facial
2. Vagus
3. Hypoglossal
4. Glossopharyngeal
5. Chorda tympani
6. Lingual
Ans. 3. Hypoglossal
The genioglossus muscle is innervated by the hypoglossal nerve. The function of the genioglossus muscle is to pull the tongue
forward (protrude) and toward the opposite side. When the right genioglossus muscle is paralyzed, the left genioglossus muscle pulls
the tongue forward and to the right.

Tongue deviation

USMLE Case Scenario


As part of a complete neurological examination, a medical student takes a cotton-tipped applicator and touches the patients
left eye with a thin wisp of cotton as the patient looks to the right. The patient closes both of his eyelids in response. Which of
the following cranial nerves is responsible for the sensory limb of this reflex?
1. Abducens
2. Facial
3. Optic
4. Trigeminal
Ans. 4. Trigeminal

USMLE Case Scenario


A 34-year-old patient arrives in the emergency room after having suffered severe head trauma in a accident. Radiographic
studies of the head reveal a basilar skull fracture in the region of the foramen ovale. Which of the following nerve passes
through this foramen:
1. Maxillary

110

USMLE Step 1 Platinum Notes

2. Mandibular
3. Ophthalmic
4. Occulomotor
Ans. 2. Mandibular

USMLE Case Scenario


Annular pancreas is a condition that results when normal pancreatic tissue completely or partially encircles the duodenum.
Annular pancreas is thought to arise from failure of normal clockwise rotation of the ventral pancreatic bud. In children,
there is a common association with other serious congenital anomalies such as intracardiac defects, Downs syndrome, and
intestinal malrotation. It commonly encircles:
1. First part of duodenum
2. Second part of duodenum
3. Third part of duodenum
4. Fourth part of duodenum
5. Jujenum
6. Ileum
Ans. 2. Second part of duodenum

USMLE Case Scenario


Pancreas is a mixed gland divided into four portions: the head, the neck, the body, and the tail. It is a retroperitoneal organ.
The structure related to the head of the pancreas is:
1. Hilum of spleen
2. Uncinate process
3. Portal vein
4. Tuber omentale
5. Pappilary process
6. Foramen of Winslow
7. Ligament of Treitz
8. Linea semilunaris
Ans. 2. Uncinate process

USMLE Case Scenario


The Distal portion of the gallbladder has the appearance of a diverticulum, which is called:
1. Morrisons pouch
2. Zenkers diverticulum
3. Meckels diverticulum
4. Spiral valve of Heister
5. Hartmanns pouch
6. Uncinate process
7. Tuber omentale
8. Pappilary process
9. Foramen of Winslow
Ans. 5. Hartmanns pouch

USMLE Case Scenario


Pancreas is a mixed gland divided into four portions: the head, the neck, the body, and the tail. It is a retroperitoneal organ.
The endocrine portion of pancreatic function is served by the structures termed the islets of Langerhans. The islets are nearly
spherical collections of cells scattered throughout the pancreatic parenchyma and is composed of several distinctive cell
types. True statement is:
1. The insulin-producing alpha cells compose the majority of the islet population
2. The insulin-producing beta cells compose the minority of the islet population

Anatomy

111

3. The insulin-producing beta cells compose the majority of the islet population
4. The insulin-producing alpha cells compose the minority of the islet population
Ans. 3. The insulin-producing beta cells compose the majority of the islet population

USMLE Case Scenario


Embryologically, the gut rotates and the rotation occurs in a way that:
1. The large intestine rotates in a clockwise manner around the axis of the celiac trunk
2. The large intestine rotates in a clockwise manner around the axis of the superior mesenteric artery
3. The large intestine rotates in a clockwise manner around the axis of the inferior mesenteric artery
4. The large intestine rotates in a counterclockwise manner around the axis of the celiac trunk
5. The large intestine rotates in a counterclockwise manner around the axis of the superior mesenteric artery
6. The large intestine rotates in a counterclockwise manner around the axis of the inferior mesenteric artery
Ans. 5. The large intestine rotates in a counterclockwise manner around the axis of the superior mesenteric artery

USMLE Case Scenario


The ligaments that should be carefully considered during mobilization of the splenic flexure to avoid injury to the spleen are:
1. Leinorenal and splenocolic attachments
2. Phrenocolic and leinorenal attachments
3. Phrenocolic and splenocolic attachments
4. Greater omentum and splenocolic attachments
5. Lesser omentum and leinorenal attachments
Ans. 3. Phrenocolic and splenocolic attachments
The large intestine rotates in a counterclockwise manner around the axis of the superior mesenteric artery

USMLE Case Scenario


The anastomosis between the superior and inferior mesenteric vessels is known as the:
1. Marginal artery of Drumond
2. Sudecks point
3. Batesons Plexus
4. Vasa recta
5. Anastomosis of Riolan
Ans. 5. Anastomosis of Riolan

USMLE Case Scenario


As Per the anatomical knowledge of a student, which is not true about pain:
1. A sudden burning pain in the epigastric region suggests a perforated viscus
2. Severe intermittent cramping pain with short pain-free intervals favors small bowel obstruction
3. Sudden excruciating tearing pain maybe associated with a ruptured aneurysm
4. Pain of acute cholecystitis frequently radiates around the right costal margin to the right scapula and to the shoulder
5. Pain in acute pancreatitis is usually epigastric in origin, with subsequent radiation along both costal margins to the back
6. Ureteral calculi causes pain radiating to the groin
7. Pain of stomach is referred to perineum
Ans. 7. Pain of stomach is referred to perineum

USMLE Case Scenario


Maximal tenderness in the right lower quadrant over Mcburneys point is suggestive of an inflammation of an organ. The
characteristic feature of the organ implicated is:
1. It is rich in blood supply with rich anastomosis

112

USMLE Step 1 Platinum Notes

2. It is not covered by peritoneum


3. It is rich in lymphatic tissue
4. It is a derivative of foregut
5. It has a fixed location
6. It has a wide lumen
Ans. 3. It is rich in lymphatic tissue

USMLE Case Scenario


The arterial supply to the hypothalamic-pituitary region is complex and arises from three sources. The inferior hypophyseal
artery, the superior hypophyseal arteries and the middle hypophyseal arteries. These vessels drain into the hypophyseal
portal system, which forms a secondary venous plexus in the anterior pituitary and ultimately empties into the cavernous
sinus. The inferior hypophyseal artery is:
1. A branch of the internal carotid artery
2. A branch of the external carotid artery
3. A branch of the common carotid artery
4. A branch of the vertebral artery
5. A branch of the subclavian artery
Ans. 1. A branch of the internal carotid artery

USMLE Case Scenario


Oxyphil cells are a feature of:
1. Spleen
2. Pituitary
3. Adrenals
4. Prostate
5. Lens of eye
6. Cochlea
7. Thymus
8. Thyroid
9. Parathyroid
Ans. 9. Parathyroid

USMLE Case Scenario


The superior parathyroid glands are usually located on the posterior surface of the upper portion of the thyroid lobe. The lower
parathyroid glands are more ventral, close to the lower pole of the thyroid gland. True statement about the development of
parathyroids is:
1. The superior parathyroids arise from the second pharyngeal pouch and the inferior parathyroids arise from the third
pharyngeal pouch
2. The superior parathyroids arise from the second pharyngeal pouch and the inferior parathyroids arise from the fourth
pharyngeal pouch
3. The superior parathyroids arise from the third pharyngeal pouch and the inferior parathyroids arise from the fourth
pharyngeal pouch
4. The superior parathyroids arise from the fourth pharyngeal pouch and the inferior parathyroids arise from the third
pharyngeal pouch
Ans. 4. The superior parathyroids arise from the fourth pharyngeal pouch and the inferior parathyroids arise from the third
pharyngeal pouch

USMLE Case Scenario


The transition between the oblique fibers of the thyropharyngeus muscle and the transverse fibers of the cricopharyngeus
muscle creates a point of potential weakness in the pharyngoesophageal segment, which is the site of origin of:
1. Rathkes pouch

Anatomy

113

2. Foramen of morgagni
3. Pharyngoesophageal diverticulum
4. Laryngocele
Ans. 3. Pharyngoesophageal diverticulum

USMLE Case Scenario


The esophagus is a hollow tube of muscle that is approximately 25 cm in length and extends from the pharynx to the stomach.
It is arbitrarily divided into four segments: pharyngoesophageal, cervical, thoracic, and abdominal.
True statement about esophagus is that:
1. The esophagus is a nonmucosal-lined muscular tube that has a serosa
2. The esophagus is a nonmucosal-lined muscular tube that lacks a serosa
3. The esophagus is a mucosal-lined muscular tube that has a serosa
4. The esophagus is a mucosal-lined muscular tube that lacks a serosa
Ans. 4. The esophagus is a mucosal-lined muscular tube that lacks a serosa

USMLE Case Scenario


Throughout the fat of the breast, coursing from the overlying skin to the underlying deep fascia, strands of dense connective
tissue provide shape and hold the breast upward. These strands, devoid of epithelial elements, are called:
1. Montogmerys tubercles
2. Sappys Plexus
3. Axillary tail of spence
4. Coopers ligaments
5. Milk line
6. Pectoral fascia
Ans. 4. Coopers ligaments

USMLE Case Scenario


Retropubic space is named after:
1. Fallopius
2. Meckel
3. Camillo golgi
4. Hunter
5. Scarpa
6. Retzius
7. Tredlenburg
Ans. 6. Retzius

USMLE Case Scenario


In the cochlear pathway, the axons terminate in the dorsal and ventral cochlear nuclei in the medulla and the pathway to the
auditory cortex consists of at least four orders of neurons and includes the superior olivary complexes, the lateral lemnisci,
the inferior colliculi, and the medial geniculate bodies. The auditory cortex:
1. Lies in the posterior portion of the Inferior temporal gyrus
2. Lies in the posterior portion of the superior temporal gyrus
3. Lies in the posterior portion of the superior frontal gyrus
4. Lies in the posterior portion of the middle frontal gyrus
5. Lies in the posterior portion of the inferior frontal gyrus
Ans. 2. Lies in the posterior portion of the superior temporal gyrus

114

USMLE Step 1 Platinum Notes

USMLE Case Scenario


The primordia of the principal respiratory organs appear as a medial longitudinal groove in the ventral wall of the pharynx by
the fourth week of gestation. True statement is:
1. The tube is lined with ectoderm, from which the epithelium of the respiratory tract develops
2. The tube is lined with mesoderm, from which the epithelium of the respiratory tract develops
3. The tube is lined with endoderm, from which the epithelium of the respiratory tract develops
4. The tube is lined with endothelium, from which the epithelium of the respiratory tract develops
5. The tube is lined with mesothelium, from which the epithelium of the respiratory tract develops
Ans. 3. The tube is lined with endoderm, from which the epithelium of the respiratory tract develops

USMLE Case Scenario


Folds of serous pericardium surrounding the entrance of the right and left pulmonary veins are connected by an irregular
pericardial reflection that creates a space called as:
1. Transverse sinus
2. Oblique sinus
3. Occipital sinus
4. Maxillary sinus
5. Coronary sinus
6. Sinus of morgagni
7. Sinus venosus
Ans. 2. Oblique sinus

USMLE Case Scenario


The Mullerian ducts develop into the:
1. Ovaries, uterus, cervix, and lower vagina
2. Ovaries, uterus, cervix, and upper vagina
3. Cervix, and upper vagina only
4. Uterus, cervix, and upper vagina
5. Fallopian tubes, uterus, cervix, and upper vagina
6. Ovaries, fallopian tubes, uterus, cervix, and upper vagina
Ans. 5. Fallopian tubes, uterus, cervix, and upper vagina

USMLE Case Scenario


A semicircular line which is about halfway between the umbilicus and pubic symphysis is named as line of:
1. Mc Burney
2. Nelaton
3. Rion
4. Douglas
5. Waldeyer
6. Morrison
7. Heister
8. Scarpa
9. Zuckderkand
Ans. 4. Douglas

USMLE Case Scenario


Lymphatics from the gallbladder drain into the lymph node, located near the superior aspect of the junction of the
infundibulum of the gallbladder and the cystic duct. It is known as:
1. Lymph node of Rossenmller
2. Lymph node of Cloquet
3. Delphic node
4. Lymph node of lund
Ans. 4. Lymph node of lund

PHYSIOLOGY

Physiology

Basics of Physiology
Na+ K+ ATPase Pump
Two ions are responsible: sodium (Na+) and potassium (K+). An unequal distribution of these two ions occurs on the two
sides of a nerve cell membrane because carriers actively transport these two ions: sodium from the inside to the outside and
potassium from the outside to the inside. As a result of this active transport mechanism (commonly referred to as the sodiumpotassium pump), there is a higher concentration of sodium on the outside than the inside and a higher concentration of
potassium on the inside than the outside.
Na K ATPase Pump is an active, electrogenic pump moving three sodium ions outside and in place two potassium ions inside
utilizing ATP. It helps in intrusion of K+
It accounts for 20% of energy utilized by cells
Thus its coupling ratio is 3:2
Extracellular binding site is Ouabain
Its activity is inhibited by Ouabain and related cardiac glycosides
It is a P type ATPase (super family of cation transporters)
Also called E1/E2 Type ATPase responsible for carrying ions across cell membranes
Type: Heterodimer Heterogeneous
It is an example of active transport
RMP (Resting Membrane Potential)
Resting membrane potential of a skeletal muscle is 90 mV
Resting membrane potential of a smooth muscle is 50 to 75 mV
Resting membrane potential of a cardiac muscle is 85 to 95 mV
The resting membrane potential in the nerve fiber is 70 mV
The resting membrane potential in the rods is 40 mV
The resting membrane potential of inner ear cell is 60 mV

The Action Potential

Neurons transmit information as action potentials


An action potential is a temporary change in the membrane potential
Usually initiated in the cell body
Travels in one direction normally
Action potential is conducted in an all-or-none fashion
If the stimulus is too low there is no action potential
If the stimulus is above a threshold the action potential is always the same size

118

USMLE Step 1 Platinum Notes

Action potential
Electrical changes during action potential
Membrane potential depolarizes (becomes more positive)
After the peak of the spike the membrane repolarises (becomes more negative)
The potential becomes more negative than the resting potential (negative after potential)
It then returns to normal
The action potentials of most nerves last 510 milli seconds
Action potentials are initiated by many different types of stimuli
Sensory nerves respond to stimuli of many types including chemicals, light, electricity, pressure, touch and stretch
In the central nervous system most nerves are stimulated by chemical activity at synapses
Stimuli must be above a threshold level to initiate an action potential
After a nerve has fired there is a period of time during which it cannot be stimulated again
This is known as the refractory period

Concepts
Resting Membrane Potential is due to: K+
Resting Membrane Potential is close to isoelectric potential of: Cl
IPSP is due to Cl influx
EPSP is due to K+ influx
For action potential; threshold stimulus is required
Nerve conduction follows All or None phenomenon
Axon has the lowest threshold potential in a nerve fiber
Nerve impulse travels in one direction only at synapse

Physiology

RMP is close to isoelectric potential of chloride


RMP is due to pottasium
IPSP is due to chloride
Amplitude is due to chloride

Most of pottasium is intracellular


Mx pottasium is found in skeletal muscles
In response to tissue injury intracellular pottasium shifts to extracellular space

The Cell Membrane: (USMLE Favorite)

Main constituent is the protein


Lipids are regular but assymetrically arranged
Membrane lipids are amphiphatic
Are arranged as a bilayer
Signal transduction and enzyme activation are the functions of phospholipid part
The fluidity of cell membrane is increased by Polyunsaturated fatty acids
Lipids and proteins intract by hydrogen bonds
RBC Membrane is specially having spectrin (maintains integrity) and glycophyrin
Lipid bilayer is most permeable to urea
Lipid bilayer acts as a gel
Protein: lipid ratio is 2:1

Basement Membrane

Contains laminin
Nidogenin
Enactin
Type IV collagen
Degeneration mediated by metalloproteineases

Functions of Organalles Commonly Asked: (USMLE Favorite)

Synthesis of lipids occurs in Agranular Endoplasmic Reticulum


Synthesis of proteins occurs in Rough ER
Intracellular sorting and packing is done in Golgi complex
Cell shape and motility are a function of Microtubules
Catabolism of H2O2 is a function of Peroxisomes
Site of ATP synthesis is Mitochondria

Marker of
Plasma membrane: adenyl cyclase, 5 nucleotidase
Golgi bodies: galactosyl transferase
Mitochondria: Glutamic dehydrogenase

Fluids and Electrolytes: (USMLE Favorite)


Water constitutes between 50% and 70% of total body weight
The water of the body is divided into three functional compartments

119

120

USMLE Step 1 Platinum Notes

The intracellular water, represents between 30% and 40% of body weight
The extracellular water represents approximately 20% of body weight and is divided between intravascular fluid, or plasma (5%
of body weight), and interstitial, or extravascular, extracellular fluid (15% of body weight)
Intracellular Fluid: Measurement of intracellular fluid (ICF) is determined indirectly by subtraction of the measured extracellular
fluid (ECF) from the measured total body water. The intracellular water is between 30% and 40% of body weight, with the
largest proportion in the skeletal muscle mass. Because of the smaller muscle mass in the female, the percentage of intracellular
water is lower than in the male. The chemical composition of ICF with potassium and magnesium the principal cations, and
phosphates and proteins the principal anions
Extracellular Fluid: The total ECF volume represents approximately 20% of body weight. The ECF compartment has two major
subdivisions. The plasma volume is approximately 5% of body weight in the normal adult. The interstitial, or extravascular,
ECF volume, obtained by subtracting the plasma volume from the measured total ECF volume, accounts for approximately 15%
of body weight
The interstitial fluid is further complicated by having a rapidly equilibrating or functional component as well as several more
slowly equilibrating, or relatively nonfunctioning, components. The nonfunctioning components include connective tissue water
as well as transcellular water, which includes cerebrospinal and joint fluids. This nonfunctional component normally represents
only 10% of interstitial fluid volume (1 to 2% of body weight) and is not to be confused with the relatively nonfunctional ECF, often
called a third space, found in burns and soft tissue injuries
The normal constituents of ECF are with sodium the principal cation and chloride and bicarbonate the principal anions.
Electrolyte

Function

Distribution

Sodium (Na )

Essential role in fluid and electrolyte balance Represents about 90% of extracellular cations
accounts for half the osmolarity of ECF
Level in blood controlled by aldosterone, ANP and
Role in generation of action potentials
ADH

Potassium (K+)

Establishes resting membrane potential and Most abundant intracellular cation


essential in the repolarization phase of action Blood serum level controlled by aldosterone.
potentials in nervous and muscle tissue
Aids maintenance of fluid volume in cells
Helps regulate pH.

Calcium (Ca2+)

Roles in blood clotting, neurotransmitter release, Most abundant mineral in the body due to bone
maintenance of muscle tone, and excitability of content
nervous and muscle tissue
Principally extracellular
Blood level controlled chiefly by Parathyroid hormone
(PTH)

Chloride (Cl)

Helps balance anions in different fluid


compartments.

Most prevalent extracellular anion


Diffuses easily between interstitial space and ICF
Level controlled indirectly by aldosterone due to
relationship with sodium

Bicarbonate (HCO3) Major buffer of H+ in plasma


Second most prevalent anions in extracellular fluid
Helps maintain correct balance of anions and A small amount found in intracellular fluid
cations in ECF and ICF
Blood level controlled by kidneys which can both form
and excrete bicarbonate

Remember
If an isotonic salt solution is added to or lost from the body fluids, only the volume of the ECF is changed. The acute loss of an
isotonic extracellular solution, such as intestinal juice, is followed by a significant decrease in ECF volume and little, if any, change
in ICF volume. Fluid is not transferred from the intracellular space to refill the depleted extracellular space as long as the osmolality
remains the same in the two compartments.

Physiology

121

If water alone is added to or lost from the ECF, the concentration of osmotically active particles changes. Sodium ions account
for most of the osmotically active particles in ECF and generally reflect the tonicity of other body fluid compartments. If ECF is
depleted of sodium, water passes into the intracellular space until osmolality is again equal in the two compartments
The concentration of most other ions within the ECF compartment can be altered without significant change in the total number of
osmotically active particles, thus producing only a compositional change. For instance, a rise of the serum potassium concentration
from four to eight mEq per liter would have a significant effect on the myocardium, but it would not significantly change the effective
osmotic pressure of the ECF compartment. Normally functioning kidneys minimize these changes considerably, particularly if the
addition or loss of solute or water is gradual
An internal loss of ECF into a nonfunctional space, such as the sequestration of isotonic fluid in a burn, peritonitis, ascites, or
muscle trauma, is termed a distributional change. This transfer or functional loss of ECF internally maybe extracellular (e.g. as in
peritonitis) or intracellular (e.g. as in hemorrhagic shock). In any event, all distributional shifts or losses cause a contraction of the
functional ECF space.

Regulation of Fluid Transfer among Compartments


The transfer of fluid between vascular and interstitial compartments occurs at the capillary level and is governed by the
balance between hydrostatic pressure gradients and plasma oncotic pressure gradients
This relation is stated by the Starling equation:
Jv = Kf (DP Dp)
Where:
Jv is rate of fluid transfer between vascular and interstitial compartments, Kf is the water permeability of the capillary bed
DP is the hydrostatic pressure difference between capillary and interstitium, and
Dp is the oncotic pressure difference between capillary and interstitial fluids
Under normal circumstances, interstitial tissue pressure is low, and the DP term in the Starling equation represents the integrated
hydrostatic pressure gradient from arteriolar to venular ends of a capillary. Since interstitial fluid is protein poor, the Dp term in the
Starling equation represents the oncotic pressure of plasma proteins, principally albumin; five grams of albumin per deciliter of plasma
exerts an oncotic pressure of about 15 mm Hg.

Osmolal gap
It is the difference between measured serum osmolality and calculated serum osmolality. It is typically calculated as: OG = measured
serum osmolality (2 serum sodium + serum glucose + serum urea) Where: 2 serum sodium + serum glucose + serum urea = the
calculated serum osmolality and all measures are in mmol/L. OG = Osmolal gap. In US customary units the calculated osmolarity is:
(2 sodium) + glucose/18 + BUN/2.8
Causes of an Elevated Osmolal Gap are numerous
Ethanol intoxication
Methanol ingestion
Isopropanol ingestion
Ethylene glycol ingestion

Acidosis and Alkalosis: (USMLE Favorite)


Refer to the mechanism by which a given acid base disturbance is reached
Primary refers to the initiating process of acid base disturbance, while secondary refers to a compensatory process
Mixed acid base disturbances are combinations of two or more primary acid base disturbances
The pH of arterial blood and interstitial fluid normally ranges between 7.38 and 7.42 despite wide variations in dietary intake of acids
or alkali
The arterial pH range over which cardiac function, metabolic activity and CNS function can be maintained is narrow; the widest range
of pH values compatible with life is from 6.8 to 7.8, or an interval of one pH unit.

122

USMLE Step 1 Platinum Notes

The major buffer system in ECF is the bicarbonate-carbonic acid pair. The relation between pH, bicarbonate and carbonic acid
concentrations in ECF maybe expressed according to the familiar Henderson-Hasselbalch equation:
pH = pK + log HCO3/ H2CO3
Where pK is the carbonic acid dissociation constant, HCO3 is the plasma bicarbonate concentration and H2CO3 is the plasma carbonic
acid concentration. The H2CO3 concentration is given by a PaCO2, where is the CO2 solubility constant and has a value of 0.0301, and
PaCO2 is the arterial carbon dioxide tension. Therefore, the Henderson-Hasselbalch equation becomes
pH = 6.1 + log HCO3/0.03 PCO2
Primary changes in the numerator (blood bicarbonate concentration) refer to primary metabolic changes, while primary changes in
the denominator (blood carbon dioxide tension) refer to primary respiratory changes
Proton shifts: Between the ECF and ICF stabilize the plasma pH against acute fluctuations. But the ultimate maintenance of pH
balance requires that input of acid or base into the body be matched by output of acid or base so that the HCO3/H2CO3 ratio and the
total bicarbonate content in the ECF remain constant. The cardinal systems involved in these external processes are the kidneys for
bicarbonate balance, and the lungs for CO2 balance.

The Serum Anion Gap


Sodium is the principal cation in extracellular fluids. The sum of plasma chloride plus bicarbonate concentrations is less than the serum
sodium concentration; the remaining anions required for electroneutrality, generally not reported with routine serum electrolyte
measurements, are referred to as unmeasured anions, or as the serum anion gap. A convenient formula for calculating the serum
anion gap is the following:
Serum anion gap = Na+ (Cl + HCO3)
Where Na+, Cl and HCO3 are the serum sodium, chloride and bicarbonate concentrations, respectively
The anion serum gap includes primarily phosphates and sulfates derived from tissue metabolism, lactate and keto acids arising from
incomplete combustion of carbohydrates and fatty acids, and negatively charged protein molecules, principally albumin. The normal
value for unmeasured anions, or the serum anion gap, is 10 to 12 mEq per liter; albumin and other proteins normally account for about
half the anion gap
An increased serum anion gap generally indicates the presence of metabolic acidosis
A reduced serum anion gap provides an index to certain other disorders
The anion gap will be reduced if the sodium concentration falls while the chloride plus bicarbonate concentrations are unchanged
or, in other words, when the concentration of another cation in serum is increased while the serum osmolality remains normal. This
may occur in multiple myeloma of the immunoglobulin G (IgG) variety if the myeloma proteins are cationic at pH 7.4. Hyperviscosity
syndromes also may result in a reduced anion gap.

The Urinary Anion Gap


The urinary anion gap, defined as:
Urinary anion gap = (Na+ + K+) Cl
It is useful in evaluating patients with hyperchloremic acidosis. The test provides an approximate index to urinary NH4+ excretion, as
measured by a negative urinary anion gap, that is, urinary (Na+ + K+) is less than urinary Cl. Thus, in hyperchloremic metabolic acidosis,
a normal renal response would be a negative urinary anion gap, generally in the range of 30 to 50 mEq per liter. In such an instance,
the hyperchloremic acidosis is probably due to gastrointestinal losses rather than a renal lesion. In contrast, a positive urinary anion
gap implies a renal tubular disorder.

Remember
Water constitutes roughly 60% of body weight
Na, Cl, HCO3 are predominantly in ECF
K, P, Mg are predominantly in ICF

Measurement of Body Fluids


Total Body water
ICF
ECF

About 60% of body weight


40%
20%

Physiology
Total body water
ECF
Plasma volume

Tritrated water, Deuterium Oxide, Antipyrine


Inulin, Mannitol
Evans Blue, radiolabelled albumin

ECF is rich in: Na+


ICF is rich in: K+
Endolymph is rich in: K+

Anion Gap: (Repeat)

Anion gap = unmeasured ions in plasma


Normal cations in plasma: Na+, K+, Ca++, Mg++
Normal anions in plasma: Cl, HCO3, albumin, phosphate, lactate
Sum of positive and negative charges is equal
Anion gap = (Na+ + K+ ) (Cl + HCO3)
Normal AG = 1012 mmol/l

Terms Frequently Asked

Endocytosis: Substance transported into cell by infoldings of cell membrane around substance and internalizing it
Pinocytosis: Engulfing liquid substances by enfolding of cell membrane
Phagocytosis: Engulfing soild substances by enfolding of cell membrane
Exocytosis: Reverse of endocytosis
Emiocytosis: Excretion of specific hormones and granules by cell is emiocytosis
Requires calcium
Transcytosis: Vesicular transport within cell. (epithelial cells of intestine)

Proteins in Vesicular Transport


AP 1 clathirin: Involved in transportation from Golgi bodies to lysosomes
AP 2 clathirin: Involved in transportation to endosomes
CO PI: Coating proteins in vesicles for transportation between endoplasmic reticulum and Golgi apparatus
CO PII: Coating proteins in vesicles for transportation between endoplasmic reticulum and Golgi apparatus
Dynamin: Vesicle formation from Golgi complex and cell membrane
Docking protein: V snare protein and T snare proteins present on target cells

Cutaneous Vascular Responses


White reaction:
Appearance of pale stroke line when pointed object is drawn lightly over skin
Due to precapillary sphincter contraction
Triple response:
1. Red reaction: Red line appearing at site of injury
Due to dilatation of precapillary sphincter. (histamine and bradykinin)
2. Flare: Diffuse irregular outside red reaction due to dilatation of arteriole and precapillary sphincter
3. Wheal: Swelling or localized edema within area of flare
Due to increased capillary permeability
Dermatographia: Striking triple response on touching the skin

123

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USMLE Step 1 Platinum Notes

Muscle Contraction
The skeletal muscle fibers are cylindrical in shape.
The length varies from 1 mm to 15 cm. The width varies from 10 microns to 80 microns.
Each muscle fiber has a thick sarcolemma
The cytoplasm is acidophilic and granular and is composed of Actin, Myosin and Tropomyosin.
The Cytoplasm contains longitudinal Myo fibrils or Sarcostyles which are striated transversely.
Each Myofibril or Sarcostyles is formed of smaller filaments called as Myofilaments.
The Myofilaments are of two types:
Thin or Actin Filaments
Thick or Myosin Filaments
The Transverse striations are due to presence of dark and light bands
The Sarcomere is the unit of contraction
It is formed of Actin and Myosin
Actin is present in light band and Myosin is present in the dark band

Remember

A: Anisotropic; broad, dark; remains constant in width despite degree of contraction


I: Isotropic; broad, light; only thin filaments (no thick); narrows during contraction
Z: (Zwischenscheiben) bisects I band; drawn together during contraction
H: (Heller) light band bisects A band; only thick filaments (no thin); narrows during contraction
M: (Mittelscheibe) denser band bisects H band.

Heads of Myosin contain actin binding site and possess ATPase activity
Tropomyosin is a relaxing protein
Troponin I inhibits interaction of myosin with actin
Troponin T binds other troponins to tropomyosin
Troponin C has binding sites for calcium which initiates contraction
Tropomyosin covers the active sites of actin
RMP of skeletal and cardiac muscle is 90 mV
Repolarization is due to pottasium efflux
Depolarization is due to sodium influx
Treppe or stair case phenomenon is due to increased availability of Calcium for binding to troponin C
Rheobase is the minimum amount of current to cause excitation
Chronaxie is the shortest duration for a stimulation to excite tissue with a current strength twice the rheobase
Newborns have longer chronaxies
Skeletal muscles have shorter chronaxies
Cold lenthens chronaxie
Vagal stimulation shortens chronaxie
For smooth muscle contraction presence of cellular calcium is essential to cause contraction
Force of muscle contraction is independent of amplitude of action potential
Nerve fibers and anesthesia:
SUSCEPTIBILITY: Type C > Type B > Type A
Nerve fibers and pressure
SUSCEPTIBILITY: Type C < Type B < Type A

Physiology

125

Golgi Tendon Organ

It is an encapsulated sensory receptor


Detects muscle tension
Involved in inverse stretch reflex
325 muscle fibers on an average are attached to golgi tendon organ
Impulses are transmitted by type nerve fibers
It is inhibitory and protective
Golgi tendon reflex is bisynaptic.

Muscle Spindle
312 mm long structure containing intrafusal muscle fibers enclosed in capsule of connective tissue
It is a receptor for myotactic or stretch reflex
Central zone has no actin and myosin
Peripheral zone has actin and myosin
Are of two types:
Intrafusal
Extrafusal
Intrafusal are of two types:
Nuclear bag and
Nuclear chain fibers
Two types of sensory nerve endings are
Primary annulospiral endings
Secondary flower spray endings

Neurapraxia : No anatomic disruption


Axonometesis : Axon and myelin disruption
Neurontemesis : Complete division of nerve
Degeneration distal to cut end : Wallerian degeneration

The skeletal muscle fibers are two types: Red Fibers and white fibers
Red Fibers

White Fibers

Have irregular striations

Have regular striations

Have central nuclei

Have peripheral nuclei

Have rich vascular supply

Have poorer blood supply

Nonfatiguable

Are fatiguable

Are poor in mitochondria, Myoglobin, fats

Are rich in Myoglobin, fats

Example : Skeletal muscle


Examples: diaphragm, muscles of eye, mastication
They react quickly, with brief, forceful contractions, Their contraction in response to nervous stimulation is slow
but cannot sustain contraction for long periods
and steady, resulting in their designation as slow fibers
They are thus termed fast fibers

Red Blood Cell


Mature Red cell is 8 micrometer in diameter
Mature Red cell is anucleate

126

USMLE Step 1 Platinum Notes

Mature Red cell is discoid in shape


Mature Red cell is pliable
Average life of red cell is 100120 days
Hematopoiesis is the process by which formed elements of the blood are produced
In the BM (Bone Marrow) first morphologically recognizable precursor is the PRO normoblast Erythropoietin is produced by the
peritubular cells within the kidney
There is daily replacement of 0.81% of all circulating red cells
Hematopoiesis is the process by which formed elements of the blood are produced. Stem cells are capable of producing all classes
of cells
In the BM (Bone Marrow) first morphologically recognizable precursor is the PRO normoblast. This cell can undergo 45 cell divisions
that result in production of 1632 mature red cells
Erythropoietin (EPO) is produced by the peritubular cells within the kidney. These cells are specialized epithelial cells. A small
amount of EPO is also produced by Hepatocytes.

Cardiovascular Physiology
Artery/Arteriole Resistance Vessel
Capillary (Mx Surface area) Exchange Vessel
Vein Capacitance Vessel
BP = Cardiac output x Peripheral resistance
BP measured by sphygmomanometer is less than arterial BP actually
Small cuff = High BP
Thick walled vessels = High BP
Obesity = High BP
Pulse Pressure = Systolic pressure Diastolic Pressure
Mean Arterial Pressure = Diastolic Pressure +1/3 of Pulse Pressure
Ventricular End Diastolic Volume: Volume of blood in ventricular cavity at the end of atrial contraction (n) = 120 ml. Determines
Preload
Ventricular End Systolic Volume: Volume of blood in ventricular cavity at the end of ejection (n) = 40 ml
Stroke Volume: Volume of blood ejected with each heart beat. CO/HR (n) = 70 80 ml
Ejection Fraction: Ratio of stroke volume to End Diastolic Volume (SV/EDV) (n) = 50 70%
Cardiac Output: Volume of blood expelled from one side of heart per minute
Can be detected by:
Ficks principle
Echocardiography
Thermodilution
Cardiac index = CO/Body surface area
Normal cardiac index IS 3.2

FrankStarling Law
This principle illustrates the relationship between cardiac output and left ventricular end diastolic volume (or the relationship
between stroke volume and right atrial pressure.)

Physiology

127

Determinant of cardiac output


The Frank-Starling principle is based on the length-tension relationship within the ventricle. If ventricular end diastolic volume
(preload) is increased it follows that the ventricular fiber length is also increased, resulting in an increased tension of the muscle
In this way, cardiac output is directly related to venous return the most important determining factor of preload. When heart rate
is constant, cardiac output is directly related to preload (up to a certain point.)
An increase in preload will increase the cardiac output until very high end diastolic volumes are reached. At this point cardiac
output will not increase with any further increase in preload, and may even decrease after a certain preload is reached
Also, any increase or decrease in the contractility of the cardiac muscle for a given end diastolic volume will act to shift the curve
up or down, respectively.

Frank-starling curve

Regional Blood Flow


Blood flow is controlled mainly by arterioles
Velocity of blood is maximum in large veins

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USMLE Step 1 Platinum Notes

Blood flow of liver > kidney > brain > heart


Carbon dioxide produces vasodilation in brain
Exercise produces venoconstriction in splanchnic circulation
Exercise produces increase in coronary circulation
Hypoxia produces vasoconstriction in pulmonary circulation
PGE1, PGI2 produce renal vasodilation.

Myocardial Action Potential

Phases of myocardial action potential


Phase 0 rapid depolarization
Rapid sodium influx
These channels automatically deactivate after a few ms
Phase 1 early repolarization
Efflux of potassium
Phase 2 plateau
Slow influx of calcium
Phase 3 final repolarization
Efflux of potassium
Phase 4 restoration of ionic concentrations
Resting potential is restored by Na+/K+ ATPase
There is slow entry of Na+ into the cell decreasing the potential difference until the threshold potential is reached, triggering a
new action potential

Physiology

129

Ventricular Muscle

Phase 0
Phase 1
Phase 2
Phase 3

Membrane Depolarization
Rapid Repolarization
Slow Repolarization
Rapid Repolarization

permeability to Na
permeability to Na, permeability to K
permeability to Ca
Inactivation of Ca channels, permeability to K

Pacemaker Cells

Slow upstroke Action Potential


Smaller magnitude of Action Potential
No Fast Sodium channels
Spontaneous Depolarization

Inotropic State: (Myocardial Contractility)


A number of factors determine the level of ventricular performance at any given ventricular end-diastolic volume
Adrenergic Nerve Activity: The quantity of norepinephrine released by adrenergic nerve endings in the heart is determined by
the adrenergic nerve impulse traffic. This mechanism is the most important one that acutely modifies myocardial contractility
under physiologic conditions
Circulating Catecholamines: When stimulated by adrenergic nerve impulse, the adrenal medulla releases catecholamines, which,
when they reach the heart, augment both heart rate and myocardial contractility
The Force-Frequency Relation: The position of the myocardial force-velocity curve is also influenced by the rate and rhythm of
cardiac contraction; e.g. ventricular extrasystoles result in postextrasystolic potentiation, presumably by increasing the quantity
of Ca2+ that enters the cardiac cell. The contractility of the normal (but not of the failing) heart is augmented by an increase in
frequency of contraction
Exogenously Administered Inotropic Agents: Isoproterenol, dopamine, dobutamine, and other sympathomimetic agents,
cardiac glycosides, Ca2+, amrinone, milrinone, and other phosphodiesterase inhibitors all improve the myocardial forcevelocity relation and therefore maybe used to stimulate ventricular performance
Physiologic Depressants: Included among these are severe myocardial hypoxia, ischemia, and acidosis. Acting either singly
or in combination, these influences depress the myocardial force-velocity curve and left ventricular work at any given ventricular
end-diastolic volume
Pharmacologic Depressants: These include many antiarrhythmic drugs such as procainamide and disopyramide; calcium
antagonists such as verapamil; beta blockers; and large doses of barbiturates, alcohol, and general anesthetics as well as
many other drugs
Loss of Myocytes: When a sufficiently large portion of ventricular myocardium becomes nonfunctional or necrotic, as occurs
transiently during ischemia and permanently in myocardial infarction total ventricular performance at any given level of enddiastolic volume becomes depressed.

Exercise: Physiological Change


Blood pressure
Systolic increases, diastolic decreases
Leads to increased pulse pressure
In healthy young people the increase in MABP is only slight
Cardiac output
Increase in cardiac output maybe 35-fold
Results from venous constriction, vasodilation and increased myocardial contractibility, as well as from the maintenance of right
atrial pressure by an increase in venous return
Heart rate up to 3-fold increase
Stroke volume
Up to 1.5-fold increase

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USMLE Step 1 Platinum Notes

Central Venous Pressure


Normal Pressure: 2 cm H2O to 12 cm H2O
Causes of CVP: Noncardiogenic shock
Causes of CVP: Heart Failure, Expansion of Blood volume, PEEP

Isometric Contraction
Mitral and tricuspid valve close (c-c)
Aortic and pulmonary valve open

Isometric Relaxation
Mitral and tricuspid valve open
Aortic and pulmonary valve close

Normal coronary blood flow is 250 ml at rest


It is 5% of cardiac output
Blood flow to left ventricle is twice that of right ventricle
Atrial blood flow is half of ventricular flow
Most of coronary blood flow occurs in diastole

Chrontropic effect
Ionotropic effect
Dromotropic effect
Bathmotropic effect

Effect on heart rate


Effect on force of contraction
Effect on conduction of impulses through heart
Effect on excitability of heart

ECG and JVP

Physiology
SA node discharges most rapidly
SA node is located sub epicardially
Pacemaker cells are present in SA node
AP of SA and AV node are due to calcium
RMP of myocardial fibers is 90 mV
Depolarization is from endocardium to epicardium
Repolarization is also from endocardium to epicardium
Speed of conduction is fastest in Purkinje fibers
Speed of conduction is least in AV node

Waves of normal ECG

Normal ECG
Wave/Segment

Cause

Duration (Second)

P wave

FromTo

Atrial depolarization

0.1

QRS complex

Ventricular Depolarization

0.08 0.10

T wave

Ventricular Repolarization

0.2

P R interval

Onset of P wave to onset of Q wave

0.18 (0.12 to 0.2)

Q T interval

Onset of Q wave and end of T wave

0.4 0.42

Intervals in ECG

131

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USMLE Step 1 Platinum Notes

The 12 conventional ECG leads record the difference in potential between electrodes placed on the surface of the body
These leads are divided into two groups:
Six extremity (limb) leads and six chest (precordial) leads. The extremity leads record potentials transmitted onto the frontal plane
and the chest leads record potentials transmitted onto the horizontal plane
The six extremity leads are further subdivided into three bipolar leads (I, II and III) and three unipolar leads (aVR, aVL and aVF)
Each bipolar lead measures the difference in potential between electrodes at two extremities:
Lead I left arm-right arm voltages
Lead II left leg-right arm, and
Lead III left leg-left arm
The six chest leads are unipolar recordings obtained by electrodes in the following positions:
Lead V1, fourth intercostal space, just to the right of the sternum;
Lead V2, fourth intercostal space, just to the left of the sternum;
Lead V3, midway between V2 and V4;
Lead V4, midclavicular line, fifth intercostal space;
Lead V5, anterior axillary line, same level as V4; and
Lead V6, midaxillary line, same level as V4 and V5.

Remember
First-degree AV block, more properly termed prolonged AV conduction, is classically characterized by a PR interval > 0.20s
Second-degree heart block (intermittent AV block) is present when some atrial impulses fail to conduct to the ventricles
Mobitz type I second-degree AV block
(AV Wenckebach block)
It is characterized by progressive PR interval prolongation prior to block of an atrial impulse
This type of block is almost always localized to the AV node and associated with a normal QRS duration, although bundle
branch block may be present
In Mobitz type II second-degree AV block
Conduction fails suddenly and unexpectedly without a preceding change in PR intervals
It is generally due to disease of the His-Purkinje system and
It is most often associated with a prolonged QRS duration
Third-degree AV block
It is present when no atrial impulse propagates to the ventricles
If the QRS complex of the escape rhythm is of normal duration, occurs at a rate of 40 to 55 beats per minute, and increases with
atropine or exercise, AV nodal block is probable
Congenital complete AV block is usually localized to the AV node
Refractoriness is a property of cardiac cells that defines the period of recovery that cells require after being discharged before
they can be reexcited by a stimulus.
The absolute refractory period is defined by that portion of the actionpotential during which no stimulus, regardless of its
strength, can evoke another response.
The effective refractory period is that part of the action potential during which a stimulus can evoke only a local, nonpropagated
response.
The relative refractory period extends from the end of the effective refractory period to the time that the tissue is fully recovered.
During this time, a stimulus of greater than threshold strength is required to evoke a response, which is propagated more slowly
than normal.

Physiology

133

Heart Sounds
Heart sounds

Occurs during

Cause

Characteristics

First

Isometric contraction and ejection Closure of AV valves (Mitral Tricuspid)


period

Second

Protodiastole and part of isometric Closure of semilunar valves (Aortic, Short, sharp and high pitched.
relaxation
Pulmonary)
Resembles the word DUBB

Long, soft and low pitched. Resembles


the word LUBB

Third Heart Sound is due to Rapid Ventricular filling


Fourth Heart sound
It is due to ventricular distension caused by forceful atrial contraction
Heard during ventricular filling phase
Correlates with second filling phase

Waves in JVP

JVP waves

a wave First positive wave and its due to atrial systole


x wave Fall of pressure in atrium, coincides with atrial diastole
c wave It is due to rise in atrial pressure during isometric contraction during which the AV valves bulges into atrium
x1 wave Occurs during ejection period, when AV ring is pulled towards ventricles causing distension of atria
v wave Occurs during isometric relaxation period or during atrial diastole
y wave Due to opening of AV valve and emptying of blood into ventricle.

Pathological CVP Wave forms:


In atrial fibrillation, a waves will be absent, and in atrioventricular disassociation, a waves will be dramatically increased
(cannon waves) as the atrium contracts against a closed tricuspid valve
In tricuspid regurgitation, the c wave and x descent will be replaced by a large positive wave of regurgitation as the blood
flows back into the right atrium during ventricular contraction. This can elevate the mean central venous pressure, but it is not an
accurate measurement. A better way of estimating CVP in this case would be to look at the pressured between the regurgitation
waves for a more accurate mean
In cardiac tamponade, all pressure will be elevated, and the y descent will be nearly absent.

134

USMLE Step 1 Platinum Notes

Reflexes
The Bainbridge reflex, also called the atrial reflex
It is an increase in heart rate due to an increase in central venous pressure
Increased blood volume is detected by stretch receptors located in both atria at the venoatrial junctions
The Bainbridge reflex and the Baroreceptor reflex act antagonistically to control heart rate
The baroreceptor reflex acts to decrease heart rate when blood pressure rises
When blood volume is increased, the Bainbridge reflex is dominant
When blood volume is decreased, the Baroreceptor reflex is dominant
The oculocardiac reflex
Also known as Aschner phenomenon
It is a decrease in pulse rate associated with traction applied to extraocular muscles and/or compression of the eyeball
The reflex is mediated by nerve connections between the trigeminal cranial nerve and the vagus nerve of the parasympathetic
nervous system.

Respiratory Physiology
Number of alveoli in man: 300 million
Carbon dioxide is primarily transported in arterial blood as bicarbonate
Oxygen delivery to tissues depends on
Cardiac output
Hb
Affinity of Hb for oxygen
Normal value of PO2 is: 80 mm Hg
Arterial CO2 Level is: 40 mm Hg

Physiology of Respiration

During inspiration intrapleural pressure becomes more negative


Respiration stops in late expiration because of dynamic compression of airways
Total lung capacity depends on compliance
Nitrogen wash out method detects functional residual capacity
FRC is not estimated by spirometry
Slow and deep breathing are the most economical way of breathing.

The Respiratory neurons of the medulla are responsible for the main neural control of breathing. This control center is composed of
two groups of respiratory neurons:
The dorsal respiratory group (DRG) that consists primarily of inspiratory neurons that connect with phrenic motor neurons; and
The ventral respiratory group (VRG) that contains a mixture of both I neurons and expiratory (E) neurons.
Selective electrical stimulation of either I or E neurons in the ventral group will result in inspiration or expiration, respectively. The VRG,
however, is especially important in sending expiratory signals to the abdominal group of muscles to increase pulmonary ventilation
during times of increased respiratory drive. The basic medullary pattern of breathing can be modified by efferent activity arising in the
apneustic and pneumotaxic centers of the pons, as well as by motor impulses originating in the cerebral cortex
Transection of various brainstem structures and transection of the vagus nerves reveals information about the neural control
of breathing
Transection of the brainstem at the caudal end of the pons allows spontaneous respiration to continue, but the pattern of
breathing is irregular. This indicates that the rhythmic, automatic control of breathing originates at some point inferior to the pons
Transection of the brainstem below the medulla causes an immediate halt in breathing, reinforcing the concept of medullary
control as the primary stimulus for ventilation.

Physiology

135

Transection of the brainstem rostral to the pons results in normal breathing whereas transection at the caudal border of the
pons causes irregular breathing. This finding indicates that the pons exhibits a modifying influence on the medulla. In fact, if the
pontine pneumotaxic center (composed of the medial parabrachial and the Klliker-Fuse nuclei) is damaged, respiration becomes
slower and the tidal volume becomes greater. These nuclei contain both inspiratory and expiratory neurons that modify the
medulla. If both vagi are cut, the depth of inspiration is markedly increased. This occurs because stretching of the lungs during
inflation normally stimulates afferent pulmonary vagal fibers
These afferent impulses limit inspiratory impulses to slow inspiration. Without intact vagi, prolonged inspiration occurs.

Lung volumes

The All Important Respiratory Volumes


Measurement

Value (Male/Female)

Calculation

Description

Total lung capacity = 6.0/4.7 L


(TLC)

= IRV + Vt + ERV + RV

The volume of air contained in the lung at the end of


maximal inspiration
Depends on lung compliance

Vital capacity (VC)

= IRV + Vt + ERV

The amount of air that can be forced out of the lungs after
a maximal inspiration. (Rohtak 97)

= 4.8/3.6 L

Forced vital capacity = 4.8/3.7 L


(FVC)

The amount of air that can be maximally forced out of the


lungs after a maximal inspiration. Emphasis on speed.

Tidal volume (Vt)

= 500/390 mL IC-IRV

Residual volume (RV)

= 1.2/0.93 L

Expiratory reserve volume (ERV)

= 1.2/0.93 L

Inspiratory reserve volume (IRV)

= 3.3/2.3 L

Functional residual capacity (FRC) = 2.4/1.9 L


Inspiratory capacity (IC)
= 3.8/2.7 L

Measured IRV =
VC - (TV + ERV)
= ERV + RV
= TV + IRV

The amount of air breathed in or out during normal


respiration. The volume of air an individual is normally
breathing in and out.
The amount of air left in the lungs after a maximal
exhalation
The amount of air that is always in the lungs and can never
be expired (i.e. the amount of air that stays in the lungs after
maximum expiration).
The amount of additional air that can be pushed out after
the end expiratory level of normal breathing. (At the end of
a normal breath, the lungs contain the residual volume plus
the expiratory reserve volume, or around 2.4 liters. If one then
goes on and exhales as much as possible, only the residual
volume of 1.2 liters remains).
The additional air that can be inhaled after a normal tidal
breath in. The maximum volume of air that can be inspired in
addition to the tidal volume.
The amount of air left in the lungs after normal expiration.
The maximal volume that can be inspired following a
normal expiration.

136

USMLE Step 1 Platinum Notes

Anatomical dead space

= 150/120 mL

Physiologic dead volume

= 155/120 mL

The volume of the conducting airways. Measured with


Fowler method.
The anatomic dead space + alveolar dead space
Under normal conditions equal to anatomic dead space.

Lung volumes

Intra-alveolar Pressure during Inspiration and Expiration


As the external intercostals and diaphragm contract, the lungs expand. The expansion of the lungs causes the pressure in
the lungs (and alveoli) to become slightly negative relative to atmospheric pressure. As a result, air moves from an area of
higher pressure (the air) to an area of lower pressure (our lungs and alveoli). During expiration, the respiration muscles relax
and lung volume descreases. This causes pressure in the lungs (and alveoli) to become slight positive relative to atmospheric
pressure. As a result, air leaves the lungs.

Spirometry
Conventionally, a spirometer is a device used to measure timed expired and inspired volumes, and from these we can calculate how
effectively and how quickly the lungs can be emptied and filled. The measurements that are usually made are as follows:
VC (vital capacity) is the maximum volume of air which can be exhaled or inspired during either a forced (FVC) or a slow (VC)
maneuver
FEV1 (forced expired volume in one second) is the volume expired in the first second of maximal expiration after a maximal
inspiration and is a useful measure of how quickly full lungs can be emptied
FEV1/VC is the FEV1 expressed as a percentage of the VC or FVC (whichever volume is larger) and gives a clinically useful index of
airflow limitation
FEF 2575% is the average expired flow over the middle half of the FVC maneuver and is regarded as a more sensitive measure of
small airways narrowing than FEV1
PEF (Peak expiratory flow) is the maximal expiratory flow rate achieved and this occurs very early in the forced expiratory maneuver.
Ventilation Perfusion Ratio

Ideally Ventilation = Perfusion, i.e. V/Q = 1


Apex of Lung V > Q Wasted Ventilation
Base of Lung V < Q Wasted Perfusion
With exercise V/Q approaches zero

Pulmonary Circulation
It is a Low Resistance
High Compliance Bed
Hypoxia produces pulmonary vasoconstriction. (unique feature)

Physiology

137

Response to High Altitude

Ventilation (EARLIEST CHANGE)


Sensitivity of central receptors
Response of carotid bodies
Erythropoietin
2 3 DPG
Mitochondria
Renal excretion of Bicarbonate
Respiratory alkalosis
Pulmonary edema when occurs is due to increased pulmonary capillary pressure

A number of physiologic changes occur in a person living at high altitude. The diminished barometric pressure at high altitude
causes alveolar hypoxia and arterial hypoxia. Pulmonary vasoconstriction occurs in response to alveolar hypoxia; therefore,
the diameter of the pulmonary vessels would be greater in the brother living at sea level. Increased erythropoietin production
(choice B), caused by arterial hypoxia, leads to increases in hematocrit in people living at high altitude
Mitochondrial density increases in people chronically exposed to the hypoxemia caused by living at high altitude
At high altitudes, the ventilation rate increases, causing a respiratory alkalosis. The kidney then compensates by increasing
the excretion of HCO3
Increasing the rate of respiration is a very useful adaptation to the hypoxic conditions of high altitude. The primary
stimulus is the hypoxic stimulation of peripheral chemoreceptors.
Type I cells or type I pneumocytes
These are squamous epithelial cells that make-up 97% of the alveolar surfaces
They are specialized to serve as very thin (often only 25 nm in width) gas-permeable components of the blood-air barrier
Type II cells
Are also called type II alveolar cells, type II pneumocytes, great alveolar cells, and alveolar septal cells, cover the
remaining 3% of the alveolar surface
They are interspersed among the type I cells, to which they attach by desmosomes and occluding junctions
Type II cells are roughly cuboidal with round nuclei
Type II cells are secretory cells secreting pulmonary surfactant.
Alveolar macrophages
Known also as dust cells, these large monocyte-derived representatives of the mononuclear phagocyte system are found
both on the surface of alveolar septa and in the interstitium
They also phagocytose blood cells that enter the alveoli as a result of heart failure
These alveolar macrophages, which stain positively for iron pigment (hemosiderin), are thus designated heart failure cells
Clara cells
Are nonmucous and nonciliated secretory cells found in the primary bronchioles of the lungs
Main functions of Clara cells are to protect the bronchiolar epithelium by secreting a small variety of products, including
Clara cell secretory protein (CCSP) and a component of the lung surfactant
They are also responsible for detoxifying harmful substances inhaled into the lungs.
Surfactant

It is (Dipalmitoyl Lecithin)
It is secreted by Type II Pneumocyte
Synthesis begins at 1618 weeks of gestation
Maintains alveolar integrity
Breaks structure of water in alveoli
Deficiency causes Hyaline Membrane Disease

138

USMLE Step 1 Platinum Notes

Smoking surfactant production


Surfactant:
Surface Tension
Compliance
Prevents pulmonary edema
Glucocorticoids accelerate surfactant production
It is used therapeutically nowadays
Deficiency Causes
IRDS
HMD
Patchy atelectasis
Pulmonary alveolar proteinosis

Nernest Equation/Chloride shift


Bicarbonate diffuses intoplasma and same quantity of chloride diffuses into RBC in venous circulation
In place of bicarbonate chloride moves into RBC from plasma
Occurs in one second
Bohr Effect
Affinity of Oxygen for Hb decreases with fall in pH
Haldane effect
It is reverse of Bohr effect
Binding of Oxygen with hemoglobin displaces carbon dioxide from blood
Deoxygenated Hb binds more H+ than oxy hemoglobin
Hering-Bruer reflex: Overinflation of lung causes stretch receptors in bronchi and bronchioles to send inhibitory signals to
inspiratory center through vagus. (Distension of lung causes slowing of respiratory rate.)
Heads Reflex Inflation of lungs induces more inflation
Heads Reflex is due to irritant receptors in lungs
J receptor reflex: J receptors are present in close association with pulmonary capillaries
On stimulation of j receptors, apnea followed by hyperapnea, bradycardia and hypotension occurs. Bronchospasm also occurs.
Davenport diagram is used to determine type and severity of Acidosis/Alkalosis
Siggard-Anderson Nomogram is used for calculating abnormalities of acid base balance. (Plasma Bicarbonate)

Control of Respiration

Inspiratory center
Expiratory center
Pneumotaxic center
Apneustic center

Dorsal respiratory group of Neurons: Inspiration


Ventral respiratory group of Neurons: Expiration
Peripheral chemoreceptors are located in Carotid and Aortic bodies
Transection of brainstem produces irregular and gasping respiration. (Less smooth respiration)
Damage to pneumotaxic center causes slow and deep respiration
Damage to vagi nerves causes increase in depth of inspiration
Only hypercapnia not Hypocapnia stimulates receptors
Respiratory center is inhibited during swallowing and vomiting.

Dorsal Medulla
Ventral Medulla
Pons (DORSAL)
Pons

Physiology

Oxygen Hb Dissociation Curve

Oxygen Hb dissociation curve


Oxygen Hb dissociation curve is S shape or sigmoid shape

Factors influencing oxygen - Hb dissociation

139

140

USMLE Step 1 Platinum Notes

To left ()

To right ()

CO
HbF
PCO2
2, 3-DPG
Temp

[H+] , pH
Temp
PCO2
2, 3-DPG

Additional
Shift to left

Shift to right

Increase pH

Decrease pH

Decrease in temp

Increase in temp

Fetal blood
Oxygen affinity of Hb

Excess of 2, 3 DPG

Increase PCO2 (Bohr effect)


Sickle cell Hb
Shock
RDS
CHF

In anemia 2, 3 DPG concentration increases


2, 3 DPG unloads oxygen to tissues

In a healthy adult, 24 hour production of CO2 is about 330 liters


Diffusion capacity for carbon dioxide as compared to that of O2 is 20 times
Average area of the alveolar walls in contact with capillaries in both lungs is about 70 sq m
Diffusion capacity of lungs for CO2 is 10 30 ml/min/mm Hg
Normal composition of venous blood is PO2 40 mm Hg, PCO2 46 mm Hg and Hb saturation 75%
Peak expiratory flow rate is 400 500 L/mt
The presence of Hb increases the O2 carrying capacity of the blood by 70 fold
Intrapleural pressure (recoil pressure) required to prevent collapse of the lung 4 mm Hg in presence of surfactant
Intrapleural pressure at the end of deep inspiration is 4 mm Hg
Intrapleural pressure during expiration is 2 mm Hg
Hypoxia causes pulmonary vasoconstriction but cerebral vasodilation.
In lungs Angiotensin I is converted into Angiotensin II
Transport of CO2 is maximum in the form of bicarbonate.

Never to be Forgotten
Respiratory Acidosis
Respiratory Alkalosis
Metabolic Acidosis
Metabolic Alkalosis

CO2

No change
No change

pH

HCO3

PCO2 is the most important variable in regulation of ventilation


Central chemoreceptors respond to changes in [H+]
Peripheral chemoreceptors respond to changes in PO2, PCO2, H+ conc. of arterial blood

Physiology

141

Clinically Important
Cheyne-Stokes breathing is characterized by irregular pattern of respiratory dysfunction (apnea and hyper apnea) suggests
that central respiratory mechanism are no longer functioning adequately
Opium poisoning, uremia, CCF, Hypoxia.
Apneustic breathing is seen after head trauma and is characterized by inspiratory breath holding that lasts many seconds,
followed by brief exhalations.
Biots breathing is seen in some patients with CNS disease (e.g. meningitis). It consists of periods of normal breathing interrupted
suddenly by periods of apnea.
Hysterical breathing may produce hyperventilation, i.e. rapid, intense breathing that causes the PaCO2 to decrease
Kussmaul breathing occurs in diabetic coma and consists of continuous, rapid, deep breathing seen in Diabetic ketoacidosis,
uremia
Ondines curse loss of automatic respiratory control
Apnea: Cessation of respiration

Cyanosis

Reduced Hb > 4 gm/dl


Oxygen saturation < 85%
Methemoglobin > 1.5 gm/dl
Sulfhemoglobin > 0.5 gm/dl

Difference in Hb and myoglobin

Shift to right

Difference between Obstructive Lung Disease and Restrictive Lung Disease


Obstructive lung disease

Restrictive lung disease

TLC

TLC

RV

RV

TV

TV

VC

VC

FEV1

FEV1

FVC

FVC

FEV1/FVC

FEV1/FVC

PaCO2

PaCO2 (N )or

142

USMLE Step 1 Platinum Notes

Carbon Monoxide Poisoning Causes: (USMLE Favorite)


Carbon monoxide has approximately 240 times the affinity for hemoglobin than does oxygen. In a sense, the hemoglobinCO dissociation curve is shifted very far to the left compared to the hemoglobin-O2 dissociation curve. This means that the
binding of hemoglobin to carbon monoxide is virtually irreversible. (The carbon monoxide that cigarette smokers inhale
is cleared only when senescent red cells are phagocytized in the spleen and the hemoglobin is degraded.) In addition, the
carbon monoxide shifts the hemoglobin-O2 dissociation curve to the left, making the unloading of O2 to the tissues very
difficult. When too much hemoglobin is tied up with carbon monoxide, the person dies. The carbon monoxide-hemoglobin
complex has a bright red color; a distinctive feature of carbon monoxide poisoning that can be helpful either at autopsy or in
living patients is that this color makes the skin and organs also appear bright cherry red
Normal PO2
Oxygen saturation
Metabolic Acidosis
Cherry red skin discoloration
CO has 210 times more affinity for oxygen than hemoglobin
Form of Hypoxia produced is anemic hypoxia
Oxygen dissociation curve shifts to left

Hypoxia

Hypoxic Hypoxia: High altitude, Respiratory diseases Test by: PaO2


Anemic Hypoxia: Anemia, CO Poisoning: Test by Oxygen content (HB%)
Stagnant Hypoxia: Cardiogenic shock: Test by A-V difference of O2
Histotoxic Hypoxia: Cyanide poisoning: Test by A-V difference/ PO2 of venous blood

Low arterial PO2


Oxygen affinity also decreases
Response to oxygen is good
Hypoxic hypoxia is the mc type
Causes rise in pulmonary arterial pressure
Carbon dioxide is the most potent stimulus for respiration
Carbon dioxide affects respiratory center by influence on H+ concentration in CSF
CO2 causes:
CNS Depression
Ventilation
Sensory acuity
Confusion, coma, death

Oxygen Toxicity Causes


CNS Effects (Bert Effect)
Hyper irritability
Muscular twitching
Convulsions
Dizziness, Irritability, disorientation
Pulmonary effects (Smith Effect)
Tracheobronchial irritation
Pulmonary edema
Congestion and atelectasis

Physiology

143

Retinal effects:
Retrolental fibroplasia
Retinal damage
Burnt out Tissue
Due to metabolic rates and excess heat production with tissue damage

Mountain Sickness
Adverse effects of Hypoxia at High Altitude
Develops 824 hours after arrival and lasts 48 days
Low PO2 stimulation is the main cause leading to ventilation blowing of CO2 which inhibits respiratory center causing respiratory
distress
Expansion of gases in GIT occurs Nausea, Vomiting
Pulmonary edema (Permeability) Breathlessness
Cerebral edema (Cerebral vasodilation) Headache, Irritability, Insomnias, Weakness
Acclimatization is by:
Hyperventilation
Hb
Polycythemia
Mitochondria
Cardiac Output
2, 3 DPG
Diffusion capacity
Reticulocytosis
Erythropoietin

Renal Physiology
Role of Kidneys: Primarily regulation or homeostasis
Regulation of blood plasma and interstitial fluid composition (homeostasis), especially inorganic ions (e.g. Na+, K+, Cl, Ca2+)
and osmolality (osmotic activity of dissolved particles)
Regulation of body fluid volume fluid balance
Regulation of blood plasma and interstitial fluid pH
Excretion of (nonvolatile) metabolic end products (e.g. urea, uric acid, creatinine, NH4+) and foreign solutes (e.g. some
drugs)
Endocrine organ, secreting
a. Renin, for regulation of Na+, ECF (extracellular fluid) volume, vascular resistance
b. Erythropoietin, for regulation of erythrocyte production
c. Calcitriol, related to calcium regulation
Metabolic functions e.g. peptide degradation, synthesis of NH3 and H+

RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
Adrenal Cortex
Zona Glomerulosa (on outside) Mineralocorticoids mainly aldosterone
Zona Fasciculata (middle) Glucocorticoids mainly cortisol
Zona Reticularis (on inside) Androgens mainly dehydroepiandrosterone (DHEA)

144

USMLE Step 1 Platinum Notes

Kidneys
Each kidney contains about one million nephrons
Juxtra medullary nephrons constitute only 15% of nephrons
Filtration barrier of kidneys is formed by:
Podocytes
Endothelial cells
Basement membrane

Renin
It is released by JG cells in kidney in response to reduced renal perfusion, low Na+
Converts angiotensinogen to angiotensin I
Factors stimulating renin secretion
Low BP
Hyponatremiae
Sympathetic nerve stimulation
Catecholamines
Erect posture

Angiotensin

ACE in lung converts angiotensin I angiotensin II


Produced in liver
Vasoconstriction leads to raised BP
Stimulates thirst
Stimulates aldosterone and ADH release

Aldosterone

Released by zona glomerulosa


Causes retention of Na+ in exchange for K+/H+ in distal tubule
Aldosterone is produced in zona glomerulosa of adrenal glands
It binds to MR (Mineralocorticoid receptors) in renal tubular cells

It Causes

Increased Na reabsorption
Increased potassium excretion
Increased hydrogen secretion
Increased ammonia excretion
Increased magnesium excretion

Renin Aldosterone

Renovascular Hypertension
Fibromuscular Dysplasia
Diuretic use
Malignant Hypertension
Reninoma

Physiology
Sites of action of hormones

Aldosterone: Cortical ducts and distal tubules


Angiotensin II: Afferent arteriole constriction reduces GFR
ADH: Medullary collecting duct
ANP: Collecting duct

Commonly asked and Repeated Questions in Renal Physiology

Major part of glomerular filtrate is absorbed in PCT


Substances completely reabsorbed in PCT
Glucose
Proteins, amino acids, vitamins, acetoacetate
Bicarbonate
Water
In prescence of vasopressin mx reabsorption of water occurs in PCT
Substances partially absorbed in PCTNa, K, Cl (7/8 reabsorbed in PCT)
Maximum water absorption occurs at PCT
Glucose transport occurs with sodium
Substances secreted in PCT: H+, PAH (para amino hippurate). Creatinine
H+ are actively secreted in proximal tubules, distal tubules, collecting ducts
Hyperosmilality in the interstitum is the prerequisite for excretion of concentrated urine
Urea is reabsorbed from inner medullary collecting ducts only in presence of ADH
K+ is actively secreted in Late Distal tubules and Collecting ducts
Macula densa is the epithelial cells of the distal tubule that comes to contact with the arterioles
Tubuloglomerular feedback is mediated by sensing NaCl in macula densa
Juxtaglomerular cells produce renin
Are smooth muscle cells of afferent arteriole
Lies in relation to glomerulus
Consists of macula densa
Renin acts on angiotensinogen and convert it into angiotensin I.

Loop of henle does not handle urea


Urea has no T m value

Effect of angiotensin, aldosterone

145

146

USMLE Step 1 Platinum Notes

Site of Action of Diuretics


Thiazides
Chlorthiazide

Distal tubule

Hydrochlorthiazide

Distal tubule

Chlorthalidone

Distal tubule

Indapamide

Distal tubule

Metolazone

Proximal and distal tubules

Loop diuretics
Frusemide

Loop of Henle

Bumetanide

Loop of Henle

Ethacrynic acid

Loop of Henle

Carbonic anhydrase inhibitors


Acetazolamide

Proximal tubule

Potassium sparing diuretics


Spironolactone

Distal tubule and collecting duct

Triamterene

Distal tubule and collecting duct

Amiloride

Distal tubule and collecting duct

Remember
Filtration fraction = GFR/RPF = 20%
Clearance = Urine concentration x flow rate/Plasma Concentration
If Clearance < GFR, there is net tubular reabsorption
If Clearance > GFR, there is net tubular secretion
If Clearance = GFR, there is no net secretion/reabsorption
GFR = insulin clearance NOT Insulin = 125 ml/min
RPF = PAH Clearance = 500800
Normal creatinine levels: 0.61.2 mg%
Urea clearance: 88 ml/minute.
Excretion rate = Clearance Plasma concentration
or
Clearance [C] = Excretion excretion rate/Plasma concentration [P]
Excretion rate = Urine concentration[U] Volume[V] of urine formed per unit time
so
Cx = Ux V/Px
Cx = Clearance of substance x
Ux = Concentration of x in urine
Px = Concentration of x in blood plasma
V = Rate of urine formation
Determination of GFR (Glomerular filtration rate): If a substance is filtered but not reabsorbed or secreted (nor metabolized or
synthesized) by the kidney, then its clearance must equal GFR. Substances which are only filtered include insulin and (more-or-less)
creatinine
Determination of RPF (Renal plasma flow): If a substance is completely cleared from the renal blood (combination of filtration
and secretion) in one pass through the kidney, then its clearance is equal to RPF. A substance which fulfills this criteria is PAH (Para
Amino Hippuric acid), as long at TmPAH Is not exceeded.
Determination of tubular transport: If the clearance of a filtered substance is less than GFR, then that substance must be
reabsorbed. If the clearance of a substance is greater than GFR, then that substance must be secreted.

Physiology

147

Determination of fraction excreted: For substances filtered and reabsorbed, the fraction of the amount filtered (called the
filtered load) that is excreted is given by the ratio of CX/GFR.

Clearance

Demonstrating: Relationship between arterial pressure and renal blood flow

At low systemic arterial pressure, renal blood flow is reduced, compromising renal function and even kidney vitality.

Important Enzyme Deficiencies


21 Hydroxylase deficiency

Hypotension, Hyponatremia, Hyperkalemia

17 Hydroxylase deficiency

Hypertension, Ambigious genitalia

5 Reductase deficiency

Testosterone Feminization

GIT Physiology
Substance

Site of absorption

Duodeneum
Jejunum
Jejunum
Terminal ileum
Terminal ileum

Iron
Calcium
Folate
Vit B 12
Bile salts

148

USMLE Step 1 Platinum Notes

Oxyntic cells of gastric gland contain receptors for PGE2, M3, H2, Somatostatin
Chief cells/Zymogen cells secrete Pepsinogen
Oxyntic/Parietal Cells secrete Intrinsic Factor and HCl

Remember: Other Important cells of GIT, Hormones and their Function


Hormone

Source of Secretion

Actions

Gastrin

G cells of stomach; duodenum, jejunum, Stimulates the secretion of gastric juice


Ant Pituitary, Pancreas and Brain
Increase the gastric motility
Stimulates the release of pancreatic hormones.

Secretin

S cells of duodenum, jejunum and ileum

Stimulates secretion of watery, alkaline and pancreatic


secretions
Inhibits gastric secretion
Causes contraction of pyloric sphincter
Most potent stimulus is acidic chyme.

Cholecytokinin

I cells in duodenum, jejunum and ileum

Stimulates contraction of gallbladder


Activates secretin;
Inhibits gastric motility;
Increases secretion of enterokinase and intestinal
motility
Protein stimulates CCK section.

Gastric inhibitory peptide (GIP)

K cells in duodenum and jejunum

Inhibits secretion of gastric juice, gastric motility and


increase insulin secretion.

Ingestion causing release

Gastric Secretion
Stimulated by:
Stomach distension
Acetylcholine
Gastrin
Histamine
Decreased by:
H2 blockers
Secretin
Gastric emptying:
Stimulated by gastrin and distension of stomach
Decreased by cholecystokinin.

Physiology

149

Motilin
Motilin is a polypeptide secreted by enterochromaffin cells
It acts on G protein coupled receptors. Motilin is a 22 amino acid polypeptide hormone which in humans is encoded by the MLN
gene
Motilin secreted by endocrine M cells (these are not the same M cells that are in Peyers patches) that are numerous in crypts of the
small intestine, especially in the duodenum and jejunum
Based on amino acid sequence, motilin is unrelated to other hormones. Because of its ability to stimulate gastric activity, it was
named Motilin.
Its circulating level increases at approximately 100 minutes in interdigestive state and is the major regulator of MMCs that
control GIT motility in between meals
Erythromycin binds to these motilin receptors and is used for treating gastric hypomotility.
Pacemaker of small intestine is in second part of duodenum.
Cephalic phase of gastric secretion is mediated by: parasympathetics
Gastric phase of gastric secretions is mediated by hormones
Intestinal motility is stimulated by:
Distension
Ach Cholecystokinin
Gastrocolic reflex is a mass reflex
Enterogastric reflex: chyme entering intestines inhibits gastric motility
Stimulated by:
Duodenal distension
Acidity of duodenal chyme
Osmolarity of chyme
Protein/fat breakdown products

Sites of Absorption

Iron is actively absorbed in duodenum


Fat is maximally absorbed in jejunum
Vitamin B12 is absorbed in ileum
Calcium is maximally absorbed in ileum
Maximum absorption of bile is seen in ileum
Electrolytes are absorbed in colon

Dietary Fiber

Increases bulk of stools


metabolism of sugar in GIT
Decreases stool transit time
Prevent against colonic cancer
Examples:
Pectin
Cellulose
Hemicellulose

Fat
Fat is the largest reserve of energy in body
Fat is maximally absorbed in jejunum

150

USMLE Step 1 Platinum Notes

Short chain Fatty acids are maximally absorbed in Colon


Digestion of fats occurs by:
Gastric lipase
Collipase
Bile salts
Pancreatic lipase
Fat in stool > 6 gms/day is indicative of malabsorption
Bile absorption is maximum in ileum

Leptin
Associated with puberty
Secreted from adipose tissue
Decreased hunger

Physiology of Bile

Secreted by hepatocytes
Most potent stimulant for bile secretion is bile salts
Composed of water, Bile salts, Cholesterol
Bile salts are amphipathic
Primary Bile Acids: Cholic acid, Chenodeoxycholic acid
Secondary Bile Acids: Deoxycholic acid, Lithocholic acid
Cholagogues are substances causing gallbladder contraction
CCK
Fatty acids
Amino acids
Cholerectics are substances increasing secretion of bile
Secretin
Bile salts
Vagal stimulation

Insulin
Insulin acts through activation of receptor tyrosine kinase activity
Insulin receptor has two subunits:
1. Alpha subunit: which is extracellular and binds to insulin
2. Beta subunit: which is transmembranous and has tyrosine kinase activity functioning in signal transduction
Insulin Increases
Glucose uptake
Glycogen synthesis
Protein synthesis
Fat synthesis
Insulin Decreases
Gluconeogenesis
Glycogenolysis
Lipolysis

Physiology

151

Insulin is a polypeptide Hormone


Insulin is an anabolic hormone
It is a hypoglycemic hormone
Insulin is secreted by Beta cells of Pancreas
Secreted along with Cpeptide in 1: 1 ratio
In fetus secretion begins by 3 month
Insulin Secretion is stimulated by increased blood glucose
Insulin Secretion is inhibited by epinephrine
Insulin is prepared on a large scale by recombinant DNA technology from mRNA
Pork insulin differs from human insulin by one amino acid only
Insulin DOES NOT cross placenta

Alpha cell Glucagon


Beta cells Insulin
Delta cells Somatostatin
F or PP cells Pancreatic polypeptide

Hormones
Hormones can be divided into five major classes:
1. Amino acid derivatives such as:
Dopamine
Catecholamines, and
Thyroid hormone
2. Small neuropeptides such as:
Gonadotropin-releasing hormone (GnRH)
Thyrotropin-releasing hormone (TRH)
Somatostatin and
Vasopressin
3. Large proteins such as:
Insulin
Luteinizing hormone (LH), and
PTH produced by classic endocrine glands;
4. Steroid hormones such as:
Cortisol and
Estrogen that are synthesized from cholesterol-based precursors
5. Vitamin derivatives such as:
Retinoids (vitamin A) and
Vitamin D
A variety of peptide growth factors, most of which act locally, share actions with hormones
As a rule, amino acid derivatives and peptide hormone interact with cell-surface membrane receptors
Steroids, thyroid hormones, vitamin D and retinoids are lipid-soluble and interact with intracellular nuclear receptors.

Remember the Latest Source and Nature of Hormones


Hormone

Structure

Source

FGF-23 (phosphatonin)

Protein

Bone

Osteocalcin

Peptide

152

USMLE Step 1 Platinum Notes

Glucocorticoids (e.g. cortisol)

Steroids

Mineralocorticoids (e.g. aldosterone)

Steroids

Androgens (e.g. testosterone)

Steroids

Adrenaline (epinephrine)

Tyrosine derivative

Noradrenaline (norepinephrine)

Tyrosine derivative

Estrogens (e.g. estradiol)

Steroid

Ovarian follicle

Progesterone

Steroid

Corpus luteum and placenta

Human chorionic gonadotropin (HCG)

Protein

Trophoblast and placenta

Androgens (e.g. testosterone)

Steroid

Testes

Erythropoietin (EPO)

Protein

Kidney

Calcitriol

Steroid derivative

Calciferol (Vitamin D3)

Steroid derivative

Skin

Atrial-natriuretic peptide (ANP)

Peptides

Heart

Incretins

Peptides

Stomach and intestine

Somatostatin

Peptides

Neuropeptide Y

Peptide

Ghrelin

Peptide

PYY3-36

Peptide

Serotonin

Tryptophan derivative

Leptin

Protein

Retinol Binding Protein 4

Protein

Adiponectin

Protein

Secondary Messengers
cAMP
DAG

IP 3
Ca++
Protein kinase
NO acts as cellular signalling molecule

C AMP mediates action of


PTH
LH
FSH, HCG
ADH
Calcitonin
Glucagon
C GMP mediates action of
ANF
NO
Insulin acts through tyrosine kinase

Adrenal cortex

Adrenal medulla

Fat cells (adipocytes)

Physiology

153

Ca++, Phosphatidyl inophosphate mediates action of


Ach
Angiotensin II
Oxytocin

Thyroid hormones act on intracellular receptors


Retinoic acid, act on intracellular receptors
(Steroids) act on intracellular receptors
Androgens, estrogen, progesterone, glucocorticoids, mineralocorticoids act on intracellular receptors
Vitamin D3 and thyroid belong to steroid receptor family

Calcium Metabolism
Parathormone:
Stimulates osteoclastic activity, thereby increasing bone resorption by mobilizing calcium and phosphate;
Increases the reabsorption of calcium by the renal tubules, thus reducing the urinary excretion of calcium;
Augments the absorption of calcium from the gut;
Calcium reabsorption takes place from proximal small intestine
Reduces the renal tubular reabsorption of phosphate, thus promoting phosphaturia.
Calcitonin:
It is secreted by the Parafollicular cells of the Thyroid (thyrocalcitonin)
It lowers the serum calcium and affects calcium storage in bones; quite the opposite action of parathormone
Acts by decreasing bone absorption
That means inhibits osteoclastic activity.
Parathyroid hormone-related protein (PTH-rP):
It is a hypercalcemic factor with similar bioactivity to that of parathyroid hormone
Low calcium levels stimulate its secretion
Since its isolation from cancer cell lines and carcinoma of the breast, strong evidence has emerged that it is an important hormonal
mediator of cancer-associated hypercalcemia in patients with solid tumors.
PARATHYROID HORMONE MECHANISMS OF ACTION
PTH binds to a plasma membrane receptor; the PTH receptor then causes a rise of cyclic 3, 5-adenosine monophosphate (cAMP)
and other second messengers in the cytoplasm of its target cells. The consequence is rapid effects of PTH on the target cells in
bone and
kidney. A different peptide, termed parathyroid hormone-related peptide, with homology to PTH at the amino terminus, is secreted
by many cancers, causing hypercalcemia through its interactions with PTH receptors
PARATHYROID HORMONE ACTION IN BONE
PTH in bone stimulates osteoblasts and osteoclasts. The effects on osteoclasts are indirect because these cells lack receptors for PTH.
Very high PTH levels result in clear excess of bone resorption over bone formation. Controversy exists over whether mild PTH excess
might have a net anabolic effect selectively in trabecular bone
PARATHYROID HORMONE ACTION IN KIDNEY
PTH acts in the kidney to stimulate the synthesis of 1, 25 (OH) 2D by increasing the activity of 25OHD3 1a-hydroxylase in the proximal
tubules. PTH acts in the distal portions of the nephron to increase tubular reabsorption of calcium. In addition, PTH inhibits phosphate
reabsorption in the distal, and perhaps also the proximal, tubules. PTH also inhibits bicarbonate reabsorption
PARATHYROID HORMONE ACTION ON INTESTINE
PTH has no important direct action on the intestine. However, the direct renal effect of PTH to increase serum 1, 25 (OH) 2D causes
highly important secondary effects in the intestine

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USMLE Step 1 Platinum Notes

Calcium
Calcium is absorbed in proximal small intestine
Absorption is increased by acidic pH, proteins
Absorption is decreased by phosphates and oxalates
Ionized form is the active form of calcium
A decrease in the concentration of free calcium ions in plasma results in
Increased neuromuscular irritability and tetany
Peripheral and perioral paresthesia
Carpal spasm
Pedal spasm, anxiety, seizures
Bronchospasm, laryngospasm
Chvosteks sign
Trousseaus sign
Erbs sign
Lengthening of the QT interval of the electrocardiogram
Substance

Serum calcium

Serum phosphate

Vitamin D

PTH

Calcitonin

Pituitary Gland
The anterior pituitary is often referred to as the master gland
Called Hypophysis cerebri
Remember Epiphysis cerebri is Pineal Gland
The anterior pituitary gland produces six major hormones:
Prolactin (PRL)
Growth hormone (GH)
Adrenocorticotropin hormone (ACTH)
Luteinizing hormone (LH)
Follicle-stimulating hormone (FSH), and
Thyroid-stimulating hormone (TSH)
Pituitary hormones are secreted in a pulsatile manner
The pituitary gland weighs ~600 mg
It is located within the sella turcica ventral to the diaphragm sella
The hypothalamic-pituitary portal plexus provides the major blood source for the anterior pituitary
The posterior pituitary is supplied by the inferior hypophyseal arteries
The Posterior Lobe is directly innervated by hypothalamic neurons (supraopticohypophyseal and tuberohypophyseal nerve tracts)
via the pituitary stalk
Thus, posterior pituitary production of vasopressin (antidiuretic hormone; ADH) and oxytocin
It is particularly sensitive to neuronal damage by lesions that affect the pituitary stalk or hypothalamus
Vasopressin and oxytocin are typical Neural Hormones. They are secreted into the circulation by nerve cells
The term neurosecretion is classic for these two hormones
B oth are synthesized in Para ventricular and Supraoptic nuclei and transported via hypothalmoneurohypophyseal tracts to
posterior pituitary
Posterior lobe of pituitary is important in their formation and they are synthesized as a part of large precursor molecule

Physiology

155

Both vasopressin and oxytocin have a characteristic neurophysin attached with them. In the granules of the neurons that secrete
them
Neurophysin I in case of oxytocin and Neurophysin II in case of Vasopressin
These neurophysins were initially thought to be binding molecules but now they are thought to be parts of precursor molecule
The vasopressin and Neurophysin II after being secreted forms secretory granules called Herrings bodies.

Reproductive Physiology
Potency: Dihydrotestosterone > Testosterone > Androstenendione
Testosterone is converted to DHT by enzyme 5 reductase
Testosterone is converted into estrogen and estrodial by aromatase

FSH stimulates formation of Secondary follicle to Graffian Follicle


Estrogen is responsible for Proliferative phase
LH stimulates ovulation
LH maintains corpus luteum
FSH receptors are present on granulosa cells
Progesterone is responsible for Secretory phase

Male sex hormones are called the androgens (secreted by leydig cells); testosterone, dihydro testosterone and androstenedione
Mullerian ducts gives rise to female accessory sex organs such as vagina, uterus and fallopian tube
Wolffian duct gives rise to male accessory sex organs such as epididymis, vas deferens and seminal vesicles
Fetal testes begin to secrete the testosterone at about 2nd to 4th month of embryonic life
The secretion from seminal vesicles contains fructose, phosphorylcholine, fibrinogen, ascorbic acid, citric acid, pepsinogen, acid
phosphatase and prostaglandin
Fructose and citrate acts as fuel for the spermatozoa
Prostatic secretion is rich in enzymes, zinc and citrate
Androgen appears to be essential for spermatogenesis. Whereas FSH is required for spermatic maturation

Menopause Causes HAVOC


Hot flushes
Atrophy vagina
Osteoporosis
Coronary artery disease
Features
Estrogen
FSHLH
GnRH
Prolactin increases Dopamine Synthesis
Dopamine inhibits Prolactin Synthesis
Dopamine agonists (Bromocriptine) inhibit Prolactin synthesis

Important Points in Reproductive Physiology


Spermatogenesis occurs at lower temperatures at about 32 C
Spermatozoa acquire motility in epididymis

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USMLE Step 1 Platinum Notes

Capacitation (Fertilization capabilities) occurs in female genital tract


Sperms move at a speed of 13 mm/min
Semen contains high concentration of prostaglandins
Sperms reach uterine tubes in 3060 minutes after copulation
In female genital tract do not survive for more than 48 hours
Estrogen content of fluid in Rete Testis is high
Spermatozoa contain a special enzyme Germinal Angiotensin II Converting enzyme
Testosterone is produced from pregnanalone
Testosterone is produced by Leyding cells
CART WHEEL appearance of nucleus is seen in sertoli cells
Blood testis barrier is formed by sertoli cells
Receptors for FSH are present in sertoli cells
Inhibin is secreted by sertoli cells

Thyroid Hormones
The thyroid gland produces two related hormones, thyroxine (T4) and triiodothyronine (T3) Thyroid hormones act through
nuclear hormone receptors to modulate gene expression
TSH, secreted by the thyrotrope cells of the anterior pituitary serves as the most useful physiologic marker of thyroid
hormone action
Thyroid hormones feedback negatively to inhibit TRH and TSH production
Thyroid hormones are derived from a large iodinated glycoprotein
Iodide uptake is a critical first step in thyroid hormone synthesis
Iodide uptake is mediated by the Na+/I symporter (NIS), which is expressed at the basolateral membrane of thyroid follicular
cells, followed by Organification, Coupling, Storage, Release
TSH is the dominant hormonal regulator of thyroid gland growth and function
Excess iodide transiently inhibits thyroid iodide organification, a phenomenon known as the Wolff-Chaikoff effect
T4 is secreted from the thyroid gland in at least 20-fold excess over T3
Both hormones circulate bound to plasma proteins, including thyroxine-binding globulin (TBG), transthyretin (TTR, formerly
known as thyroxine-binding prealbumin, or TBPA) and albumin
Thyroid hormones act by binding to nuclear receptors, termed thyroid hormone receptors (TRs) a and b.

Effects
Brain Maturation
Bone Growth
BMR
Beta adrenergic effects
Wolf Chaikoff effect is Iodine itself inhibits organic binding.

Hypertrophy of Zona Glomerulosa Conns Syndrome


Hypertrophy of Zona Fasiculata Cushings Syndrome
Adrenal Cortical Atrophy Addisons Disease
Hypertrophic Adrenal Medulla Pheochromocytoma
Hypertrophic Adrenal Medulla Neuroblastoma

Physiology

157

Hormones in Stress
Adrenaline
Vasopressin
Cortisol
Glucagon
Epinephrine
Insulin is not increased

Melatonin
It is a pineal hormone
It is serotegenic
It is secreted predominantly at night in both day- and night-active species
Exogenous melatonin increases sleepiness and may potentiate sleep when administered to good sleepers attempting to sleep
during daylight hours at a time when endogenous melatonin levels are low
Increased serotonin N acetyl transferase activity occurs in darkness.

Sleep

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USMLE Step 1 Platinum Notes

EEG waves are called Berger rhythm


Normal EEG is bilaterally symmetrical
Alpha waves: 813 Hz seen in awake patient with eyes closed
Beta waves: 14 Hz seen in awake with eyes open
Theta waves: 47 Hz seen in hippocampus
Delta waves: 35 Hz seen in deep sleep
DTAB is order of increasing frequency. (Digest TAB)

Sleep stages
REM Sleep:
Light phase with difficult arrousal
Called paradoxical sleep
Disorders of REM sleep:
Nightmares (remembered)
Narcolepsy
Nocturnal penile trumescene

NREM Sleep
BP
HR
Disorders of NREM sleep:
Sleep walking
Sleep talking
Night terror
Bruxism
Nocturnal enuresis

Iron Metabolism

The major role of iron is to carry O2 as part of the heme


O2 also is bound by a heme protein in muscle, myoglobin
Iron also is a critical element in iron-containing enzymes, including the cytochrome system in mitochondria
Iron absorbed from the diet or released from stores circulates in the plasma bound to transferrin, the iron transport protein
In a normal individual, the average red cell life span is 120 days

The balance of iron metabolism in the organism is tightly controlled and designed to conserve iron for reutilization
There is no excretory pathway for iron, and the only mechanisms by which iron is lost from the body are blood loss (via
gastrointestinal bleeding, menses, or other forms of bleeding) and the loss of epidermal cells from the skin and gut
Iron absorption takes place largely in the proximal small intestine

Physiology

Factors influencing iron absorption

Hemoglobin

Hb A
Hb F
Hb A 2
Hb H
Hb S
Hb Barts

Alpha 2, Beta 2
Alpha 2, Gamma 2
Alpha 2, Delta 2
Beta 4
Beta 6 val- glu
Gamma 4

Blood Coagulation Factors

1, 2, 5, 7, 9, 10
2, 7, 8, 9, 10
2, 7, 9, 10
5, 8
5, 10

Produced in liver
Levels increased with oral contraceptives
Vitamin K required
Unstable in stored blood
Good for growth of hemophilus organisms

Physiology of Eye

Rods are responsible for dim light or night vision or scotopic vision. (Electric Rods are used at night)
Cones are responsible for color vision, sensitive to day light and acuity of vision
Rhodopsin is the photosensitive pigment of rods cells
Hemholtz Theory states that there are three kinds of cones in retina corresponding to three colors
Most sensitive in Green light and least sensitive in Red light
Photosensitive pigment in cones are:
Porpyropsin Red
Iodopsin Green
Cyanopsin Blue
Test for visual acuity Snells chart (distant vision) and Jaegers chart (near vision)
Test for color blindness Ishiharas color chart
Mapping of visual field Perimetry
Nearest point at which the object is seen clearly is about 7 to 40 cm
Farthest point is infinite
Protanomoly refers to defect in red cones
Deutranomoly refers to defect in green cones
Trianamoly refers to defect in blue cones

159

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USMLE Step 1 Platinum Notes

Cell Adhesion Molecules


Cells are attached to Basal Lamina and each other by cell adhesion molecules (CAMs)
They are:
Integrins
Adhesion molecules of IgG Superfamily
Cadherins
Selectins

Nitric Oxide
Nitric oxide is NO
It is also called as EDRF (Endothelial derived relaxing factor)
It is produced from arginine by enzyme NO synthetase
NO has a short t (4 seconds)
It acts via c GMP pathway
It relaxes smooth muscles specifically
It prevents platelet aggregation
It functions as a neurotransmitter
It mediates bactericidal actions of macrophages
Acts as:
Free radical
Vasodilator
Oxidizing agent
Catalyst
NO, ANP, BNP act through c GMP
Remember:
Calmodulin is Ca Dependent
Calmodulin acts through Protein Kinase

Inflammatory Mediators

Histamine is present in mast cells, basophils, enterochromaffin cells


Has three types of receptors H1, H2, H3
Formed by decarboxylation of histidine
Alter venular permeability
Mediates triple response

Natriuretic Peptides
Atrial distention and/or a sodium load cause release into the circulation of atrial natriuretic peptide (ANP), a polypeptide; a highmolecular-weight precursor of ANP is stored in secretory granules within atrial myocytes.
Release of ANP causes
Excretion of sodium and water by augmenting glomerular filtration rate
Inhibiting sodium reabsorption in the proximal tubule, and
Inhibiting release of renin and aldosterone; and
Arteriolar and venous dilatation by antagonizing the vasoconstrictors
Thus, ANP has the capacity to oppose sodium retention and arterial pressure elevation in hypervolemic states
The closely related brain natriuretic peptide (BNP) is stored primarily in cardiac ventricular myocardium and is released when ventricular
diastolic pressure rises.

Physiology

161

Its actions are similar to those of ANP


Circulating levels of ANP and BNP are elevated in congestive heart failure but not sufficient to prevent edema formation
In addition, in edematous states (particularly heart failure), there is abnormal resistance to the actions of natriuretic peptide
increase the concentrations of cyclic GMP in the kidney, adrenal glomerulose, vascular smooth muscle and platelets. Elevated circulating
concentrations of ANP and particularly BNP correlate with a poor prognosis in heart failure:
Natriuretric substance
Promotes sodium excretion
Decreases blood pressure
Acts by c GMP Pathway
The 'Encapsulated'mechanoreceptors include:
Pacinian corpuscles in skin and connective tissues that sense (rapidly adapting touch) pressure and vibration. They look like
onion bulbs
Meissners corpuscles in dermal papillae of non-hair bearing skin of hands, feet, genitalia, nipples and mouth that provide tactile
discrimination. They look like nutmegs
Ruffinis corpuscles in skin and joints that respond to stretch and pressure
Golgi tendon organs located where muscle inserts into tendon sense stretch for proprioception
Muscle spindles in skeletal muscles are composed of nerve endings in association with specialized intrafusal muscle fibers that
function to detect stretch for reflexes
The Nonencapsulated endings include:
Peritricial nerve endings around hair follicles that detect touch through movement of hair
Merkels disks on nonhair bearing skin such as the hands that perceive touch. It is present in epidermis.

Important Regions of CNS


The Locus Ceruleus is adense collection of neuromelanincontaining cells in the rostralpons. It appears blue-black in unstained
brain tissue. These cells contain norepinephrine
The Basal nucleus of Meynert is one of the structures that degenerates in Alzheimers disease
The Caudate nucleus degenerate in Huntingtons disease (GABAergeic) neurons
The Substantianigra contains the nigrostriatal neurons that are the source of striat aldopamine. This cell group degenerates in
Parkinsons disease
The Ventral Tegmentalarea is located in the midbrain and is an important source of dopamine for the limbic and cortical areas.
Over activity of this cell group is a popular theory of the etiology of Schizophrenia
Aphasia should be diagnosed only when there are deficits in the formal aspects of language such as naming, word choice,
comprehension, spelling and syntax
Dysarthria and mutism do not, by themselves, lead to a diagnosis of aphasia
In approximately 90% of right handers and 60% of left handers, aphasia occurs only after lesions of the left hemisphere
A language disturbance occurring after a right hemisphere lesion in a right hander is called crossed aphasia

Wernickes Aphasia
Damage: Comprehension is impaired for spoken and written language
Language output is fluent
The tendency for paraphasic errors maybe so pronounced that it leads to strings of neologisms, which form the basis of what is
known as jargon aphasia.

Brocas Aphasia
Brocas area is present in inferior frontal gyrus
Concerned with word formation

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USMLE Step 1 Platinum Notes

Damage: Speech is nonfluent, labored, interrupted by many word finding pauses and usually dysarthric
Brocas: Broken Speech

Global Aphasia
Speech output is nonfluent and comprehension of spoken language is severely impaired. Naming, repetition, reading and writing
are also impaired
This syndrome represents the combined dysfunction of Brocas and Wernickes areas and usually results from strokes that
involve the entire middle cerebral artery distribution in the left hemisphere.

Conduction Aphasia
Speech output is fluent but paraphasic, comprehension of spoken language is intact, and repetition is severely impaired. Naming
and writing are also impaired.

Anomic Aphasia
This form of aphasia maybe considered the minimal dysfunction syndrome of the language network. Articulation, comprehension,
and repetition are intact, but confrontation naming, word finding and spelling are impaired.

Main Hypothalamic Nuclei and Their Functions


Thirst and water balance

Supraoptic nucleus
Supraoptic nucleus controls ADH secretion

Hunger

Lateral nucleus

Satiety

Ventromedial nucleus

Regulation of Autonomic Nervous system

Anterior Hypothalamus

Circadian Rhythm

Suprachiasmatic nucleus

Heat production

Posterior hypothalamus

Cooling

Anterior hypothalamus

Sexual functions

Septate nucleus

Control of anterior pituitary

By releasing factors

Control of posterior pituitary

By hormones produced in hypothalamic nuclei

Functions of Hypothalamus
Food intake
Temperature control
Hypophyseal control
Nonshivering thermogenesis is because of noradrenaline
Nonshivering thermogens are secreted by heart, liver small intestine
Nonshivering thermogenesis is mediated by 3 receptors
Heat loss depends mostly on environmental temperature

Physiology

163

Ascending Tracts of Spinal Cord


Situation

Tract

Function

Anterior white funiculus

Anterior spinothalamic tract

Crude touch sensation

Lateral white funiculus

Lateral spinothalamic tract

Pain and temperature sensation

Ventral spino cerebellar tract

Subconscious kinesthetic sensations

Dorsal spino cerebellar tract

Subconscious kinesthetic sensations

Spinotectal tract

Concerned with spinovisual reflex

Fasiculus dorsolateralis

Pain and temperature sensations

Spinoreticular tract

Conciousness and awareness

Spinoolivary tract

Proprioception

Spinovestibular tract

Proprioception

Fasciculus gracilis
Fasciculus cuneatus

Posterior white funiculus

Tactile sensation
Tactile localization
Tactile discrimination
Vibratory sensation
Conscious kinesthetic sensation
Stereognosis

Descending Tracts of Spinal Cord


Situation

Tract

Function

Pyramidal tracts

Anterior corticospinal tract


Lateral corticospinal tract

Control voluntary, skilled movements


Forms upper motor neurons
Forms pyramids

Extra Pyramidal
tracts

Medial longitudinal fasciculus

Coordination of reflex ocular movement


Integration of movements of eyes and neck

Anterior vestibulospinal tract

Maintenance of muscle tone and posture


Maintenance of position of head and body during acceleration

Lateral vestibulospinal tract


Reticulospinal tract

Coordination of voluntary and reflex movements


Control of muscle tone
Control of respiration and blood vessels.

Tectospinal tract

Control of movement of head in response to visual and auditory impulses.

Rubrospinal tract

Facilitatory influence on flexor muscle tone

Olivospinal tract

Control of movements due to proprioception

Main excitatory neurotransmitter in CNS is: Glutamate


Main inhibitory neurotransmitter in CNS is GABA

Action of Sympathetic and Parasympathetic Divisions of ANS


Effector Organ
Eye

Sympathetic Division

Parasympathetic Division

Ciliary muscle

Relaxation

Contraction

Pupil

Dilatation

Constriction

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Effector Organ

Sympathetic Division

Parasympathetic Division

Lacrimal secretion

Decrease

Increase

Salivary secretion

Decrease in secretion and vasoconstriction

Increase in secretion and vasoconstriction

Motility

Inhibition

Acceleration

Secretion

Decrease

Increase

Sphincters

Constriction

Relaxation

Relaxation

Contraction

Detrusor muscle

Relaxation

Contraction

Internal sphincter

Constriction

Relaxation

Sweat glands

Increase in secretion

Heart rate and force

Increase

Decrease

Blood vessels

Constriction of all blood vessels except Dilatation


those in heart and skeletal muscle

Bronchioles

Dilatation

GIT

Gallbladder
Urinary bladder

Constriction

Flight or Fright response is seen in Sympathetic stimulation. Example of seeing a lion and subsequent body respone
BMR: To runaway
Vasodilation of vessels of heart and skeletal muscle
Dilatation of Pupils: To increase field of vision to escape not to frighten the lion
Urinary and fecal spincters need to close. No need of micturating/defecating at this stage
Increase heart rate
Increase blood pressure
Increase total peripheral resistance

Cerebellum
Purkinje cells are the largest neurons in the body
The axons of Purkinje cells are the only output from cerebellar cortex and these pass to deep nuclei
From the cerebellar nuclei they project to other parts (Thalamus, Brainstem)
Layers of Cerebellum
Molecular layer
Purkinje layer
Granular layer
Nuclei of Cerebellum
Dentate
Emboliform
Globoose
Fastigial
Types of Neurons in Cerebellum
Golgi cells
Basket cells
Granule cells
Stellate cells
Purkinje cells (end in cerebellar nuclei)

Physiology

165

Remember

The Cerebellum is not a Sensory Organ


Removal of cerebellum does not result in loss of any sensation
The Cerebellum Is not a motor Organ
Stimulation of cerebellum does not produce movement
The function of cerebellum is
It coordinates and smoothens the action of different muscle groups
It times their contraction properly
In this way it produces smooth and accurate movements

Diseases of the Cerebellum


Diseases of the cerebellum result in inability to do movements smoothly and accurately. This condition is called cerebellar ataxia
or cerebellar asynergia
Disturbance of Gait: Gait is similar to that of as drunken person; Lesion in one cerebellar hemisphere results in a tendency to
fall towards that side. {Right Side of Body is under control of Right Cerebellar hemisphere}. Lesions of cerebellar ataxia are not
corrected by vision
Decomposition of movements: A movement is broken into components i.e. the Shoulder, elbow and the wrists move separately
and not in a synchronized way
Dysmetria: Inability to stop a movement at a desired point, i.e. overshooting, past pointing, etc.
Dysadiadochokinesia: Inability to stop one movement and immediately to follow it up with other movement of opposite nature,
i.e. rapid pronation and supination
Scanning speech: Due to lack of synergy of muscles used in speaking, the spacing of sounds is irregular with pauses at wrong
places
Hypotonia
Decreased tendon reflexes
Intention tremor
Sometimes Nystagmus

Basal Nuclei or Basal Ganglia


Subcortical
Intracerebral
Grey matter masses
They are concerned with planning and programming of movements
They include:
Caudate nucleus + Lentiform nuclei (Corpus Straitum)
Amygdaloidal nucleus
Claustrum
Functions:
The basal ganglia are concerned with the control of skilled movements, coordinated movements as well as involuntary movements
and regulation of reflex and muscular activity
As a result disease processes effecting basal ganglia can lead to diseases which can be:
More Movements (Hyper kinetic), Less Movement (Hypo kinetic)
Movement Disorders and their nuclei:
Parkinsonism: Lesion of Globus Pallidus

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Chorea: Lesion of Caudate Nucleus


Athetosis: Lesion of Putamen
Hemiballismus: Lesion of Subthalamic nucleus

Parkinson's disease

Parkinsonism Patient
1. Acalculia: A selective impairment of mathematical ability
2. Achalasia: Condition in which food accumulates in the esophagus and the organ becomes highly diluted. It is due to increased
resting lower esophageal sphincter tension and incomplete relaxation of this sphincter on swallowing.
3. Ageusia: Absence of the sense of taste
4. Agnosia: Inability to recognize objects by a particular sensory modality even though the sensory modality itself is intact. Lesions
producing these defects are generally in the parietal lobe.
5. Akinesia: Difficulty in initiating movements and decreased spontaneous movement.
6. Ataxia: In coordination due to errors in the rate, range, force and direction of movement.

Superficial Reflexes- Mucus Membrane Reflexes


Reflex
Corneal reflex

Stimulus
Irritation of cornea

Response
Blinking of eye
(closure of eyelids)

Afferent Nerve
V Cranial nerve

Center
Pons

Efferent Nerve
VII Cranial nerve

Physiology

167

Conjunctival reflex

Irritation of
conjunctiva

Blinking of eye

V Cranial nerve

Pons

VII Cranial nerve

Nasal reflex
(sneezing reflex)

Irritation of nasal
mucus membrane

Sneezing

V Cranial nerve

Motor nucleus of
V Cranial nerve

X Cranial nerve and


upper cervical nerves

Pharyngeal reflex
mucus membrane

Irritation of
Retching or of
pharyngeal gagging mouth
opening

IX Cranial nerve
X Cranial

Nuclei of nerve

X Cranial nerve

IX Cranial nerve
X Cranial

Nuclei of nerve

X Cranial nerve

Uvular reflex (while Irritation of uvula


talking)

Raising of uvula

Superficial Reflexes- Cutaneous Reflexes


Reflexes

Stimulus

Response

Center-Segments of Spinal
Cord Involved

Scapular reflex

Irritation of skin at the interscapular Contraction of scapular muscles C5 to T1


space
and drawing in of scapula

Upper abdominal
reflex

Stroking the abdominal wall below Ipsilateral contraction of abdominal T6,7,8,9


the costal margin
muscle and movement of umbilicus
towards the site of stroke

Lower abdominal
reflex

Stroking the abdominal wall at Ipsilateral contraction of abdominal T10,11,12


umbilical and iliac level
muscle and movement of umbilicus
towards the site of stroke

Cremasteric reflex

Stroking the skin at upper and inner Elevation of testicles


aspect of thigh

L1,2

Gluteal reflex

Stroking the skin over glutei

Contraction of glutei

L4,5 S1,2

Bulbocavernous reflex

Stroking the dorsum of glans penis

Contraction of bulbocavernous

S3,4

Anal reflex

Stroking the perianal region

Contraction of anal sphincter

S4,5

Deep Reflexes
Reflex

Stimulus

Response

Center-Spinal
Segments Involved

Jaw Jerk

Tapping the middle of the chin Closure of mouth


with slightly opened mouth

Pons V Cranial
nerve

Biceps Jerk

Percussion of biceps tendon

Flexion of forearm

C 5, 6

Triceps Jerk

Percussion of triceps tendon

Extension of forearm

C 6, 7,8

Supinator Jerk or radial periosteal


reflex

Percussion of tendons over distal Supination


end (styloid process) of radius
forearm

and

flexion

of C7, 8

Wrist tendon or finger flexion reflex Percussion of wrist tendons

Flexion of corresponding finger

C 8, T1

Knee Jerk or patellar tendon reflex

Extension of leg

L2,3,4

Planter flexion of foot

L5 S1S2

Percussion of patellar ligament

Ankle Jerk or Achilles tendon reflex Percussion of Achilles tendon

Susceptibility of Nerve Fibers


Pressure

Type A

Hypoxia

Type B

Anesthesia

Type C

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USMLE Step 1 Platinum Notes

Type A have largest diameter, Highest conduction velocity, function in Proprioception


Type A and B are Myelinated
Type C has least diameter, least conduction velocity, unmyelinated
Nerve conduction velocity is more in upper limbs than in lower limbs

Neurotransmission

Chemical Classification of Neurotransmitters


Acetylcholine
Biogenic Amines
Catecholamines: Dopamine, norepinephrine (NE) and epinephrine
Indolamines
Serotonin and histamine (5-Hydroxytryptamine or 5-HT)
Amino Acids
GABAGamma (-aminobutyric acid)
Glycine
Aspartate
Glutamate
Neuropeptides
Substance P
Endorphins and Enkephalins
Somatostatin, gastrin, cholecystokinin, oxytocin, vasopressin, Leutinizing hormone releasing hormone (LHRH)
Purines
Adenosine
ATP

Physiology
Gases and Lipids
Nitric Oxide (NO)
Carbonmonooxide (CO)
Cannabinoids

Acetylcholine (Ach)
Acetylcholine (Ach) was the first neurotransmitter to be identified. It is the most abundant neurotransmitter in the brain
Released at neuromuscular junctions and some ANS neurons
Synthesized by enzyme choline acetyltransferase
Degraded by the enzyme acetylcholinesterase (AChE)

Catecholamines
Catecholamines-Dopamine, norepinephrine (NE), and epinephrine are synthesized from Tyrosine
It is involved in reward-pleasure and learning
Dopamine is the principle neurotransmitter involved in Addiction pathway

Serotonin
Broadly distributed in the brain, derived from Tryptophan
Involved in sleep, dreaming, hunger and arousal
Play roles in emotional behaviors and the biological clock
Depletion of serotonin in brain leads to depression

GABA
GABAGamma (-aminobutyric acid) is the major inhibitory neurotransmitter in CNS
Synthesized from decarboxylation of Glutamate
Involved in regulating anxiety
Maybe related to eating or sleep disorders

Endorphins, Enkephalins and Substance P


Substance P is the mediator of pain signals
Endorphins and Enkephalins act as natural opiates; reduce pain perception
They also depress physical functions like breathing and may produce physical dependence

Purines such as ATP


Purines such as ATP
Act in both the CNS and PNS
Produce fast or slow responses
Induce Ca2+ influx in astrocytes
Provoke pain sensation

169

170

USMLE Step 1 Platinum Notes

Nitric Oxide (NO)


Synthesized on demand
Activates the intracellular receptor guanylyl cyclase to cyclic GMP
Involved in learning and memory

Endocannabinoids
Lipid soluble; synthesized on demand from membrane lipids
Bind with G proteincoupled receptors in the brain
Involved in learning and memory

Blood Brain Barrier


It is formed by
Capillary Endothelium
Basement Membrane
Foot Processes of Astrocytes

Features
It is a selective barrier, only certain substances can pass across the barrier
The permeability of the barrier is inversely related to the size of the molecules
The permeability of the barrier is directly related to the lipid solubility of the substance
The barrier is more permeable to certain substances in the newborn than in the adults. It is because of the fact that it is under
developed in the newborn and especially in the preterm fetuses
The barrier undergoes breakdown in case of direct injury to brain or secondary to toxin/chemical induced damage
The Tight Junction between the endothelial cells is responsible for the Blood Brain Barrier
The Blood Brain Barrier is deficient at some regions in the CNS, e.g. in next table

Area Postrema
Organum Vasculosum of the lamina terminalis
Subfornical organ
The posterior pituitary

These areas are called Circum Ventricular Organs

Important Molecules

P53
bcl2
fas
c myc
ras
Caspaces

Tumor suppressor gene


Negative regulator of Apoptosis
Activator of apoptosis
Transcription factor which commits cells to mitosis
G protein. Most commonly mutated gene in Solid Tumors
Activates Apoptosis

Changes in Exercise
Oxygen uptake
Left shift of oxygen Hb Dissociation curve.

Physiology

171

ventilation
CO2 Excretion
PaO2
HR
CO
RR
BP
Blood flow To brain unaltered
Insulin Sensitivity
Causes Hyperkalemia
Endorphin levels (Relieves depression)

Changes in Aging

Vital capacity decreases


Glucose tolerance decreases
GFR decreases
Colonic motility decreases
Bone mass decreases
BP increases
Prostate size usually increases
Brain atrophies
Vaginal mucosa atrophies
Hematocrit remains same

Some Laws of Physiology: (Frequently Asked)


1. Laplaces Law
For a globular structure, P = 2T / r
Where P: transmural force
T: wall tension
r : Radius of the globular structure
2. Frank-Starlings Law: The force of contraction is directly proportional to the initial length of muscle fiber.
3. All or None Law: The action potential fails to occur if the stimulus is subthreshold in magnitude, and it occurs with constant amplitude
and from regardless of the strength of the stimulus, if the stimulus is at or above threshold intensity.
4. Bell- Magendie Law: In the spinal cord, the dorsal roots are sensory and the ventral roots are motor.
5. Landsteiners Law:
a. Where an agglutinogen is present on the membrane of RBC, the corresponding agglutinin must be absent in the plasma
of that person
b. Where, in an individual, the RBCs are devoid of an agglutinogen, plasma shall contain the corresponding agglutinin.
6. Ficks Law
This law states: Vg = A / T D (P1 P2)
Where Vg = volume of the gas diffusing through the membrane per min
A = total surface area of alveolo-capillary membrane of the two lungs taken together
T = thickness of alveolo-capillary membrane
D = diffusion constant of the gas
P1 P2 = pressure of the gas in the alveoli and within the capillary blood

172

USMLE Step 1 Platinum Notes

7. Dermatomal Rule: When pain is referred, it is usually to a structure that developed from the same embryonic segment or
dermatome as the structure in which the pain originates.
8. Monro- Kellie Doctrine: Brain tissue and spinal fluid are essentially incompressible; hence the volume of blood, spinal fluid and
brain in the cranium at anytime must be relatively constant.
9. Weber Fechner Law
It states that the magnitude of the sensation felt is proportionate to the log of the intensity of the stimulus
In other words: R = KSA
Where R = sensation felt
S = intensity of the stimulus and for any specific sensory modality
K and A = are constants
10. Law of Projection: No matter where a particular sensory pathway is stimulated along its course to the cortex, the conscious
sensation produced is referred to the location of the receptor. This principle is called Law of Projection
Involved in phantom limb sensation
11. Size principle: In general, slow muscle units are innervated by small, slowly conducting motor neurons and fast units by large,
rapidly conducting motor neurons

Sites of Important Receptors

Hearing
Rotational acceleration
Linear acceleration
Arterial BP
Arterial PO2 and PCO2

Hair cells of organ of Corti


Hair cells of semicircular canals
Hair cells of utricle and saccule
Stretch receptors in Carotid sinus/Aortic arch
Glomus cells of Aortic and Carotid Bodies

Carotid body

Important Substances and their Role: (USMLE Favorite)


Bradykinin: stimulation of visceral smooth muscle
Nitric oxide: vasodilator
Clathirin: receptor mediated endocytosis

Physiology

173

Natriuretic Peptides: (USMLE Favorite)


Atrial distention and/or a sodium load cause release into the circulation of atrial natriuretic peptide (ANP), a polypeptide; a highmolecular-weight precursor of ANP is stored in secretory granules within atrial myocytes
Release of ANP causes
Excretion of sodium and water by augmenting glomerular filtration rate
Inhibiting sodium reabsorption in the proximal tubule, and
Inhibiting release of renin and aldosterone; and
Arteriolar and venous dilatation by antagonizing the vasoconstrictors
Thus, ANP has the capacity to oppose sodium retention and arterial pressure elevation in hypervolemic states
The closely related brain natriuretic peptide (BNP) is stored primarily in cardiac ventricular myocardium and is released when
ventricular diastolic pressure rises
Its actions are similar to those of ANP
Circulating levels of ANP and BNP are elevated in congestive heart failure but not sufficient to prevent edema formation
In addition, in edematous states (particularly heart failure), there is abnormal resistance to the actions of natriuretic
peptide increase the concentrations of cyclic GMP in the kidney, adrenal glomerulose, vascular smooth muscle, and platelets.
Elevated circulating concentrations of ANP and particularly BNP correlate with a poor prognosis in heart failure
Natriuretric substance
Promotes sodium excretion
Decreases blood pressure
Acts by c GMP Pathway
Cell Adhesion Molecules
Cells are attached to Basal Lamina and each other by cell adhesion molecules (CAMs)
They are:
Integrins
Adhesion molecules of IgG Superfamily
Cadherins
Selectins

Nitric Oxide: (USMLE Favorite)


Nitric oxide is NO
It is also called as EDRF (Endothelial derived relaxing factor)
It is produced from arginine by enzyme NO synthetase
NO has a short t (4 seconds)
It acts via c GMP pathway
It relaxes smooth muscles specifically
It prevents platelet aggregation
It functions as a neurotransmitter
It mediates bactericidal actions of macrophages
Acts as:
Free radical
Vasodilator
Oxidizing agent
Catalyst
NO, ANP, BNP act through cGMP

174

USMLE Step 1 Platinum Notes

REMEMBER
Somatomedins: (USMLE Favorite)
Are polypeptide growth factors secreted by liver, and other tissues, which mediate the growth-promoting effects of GH
Somatomedins exhibit sequence homology with insulin and proinsulin, they belong to the insulin family
Because of their resemblance to insulin, they can bind to insulin receptors and elicit insulin-like effects
At least four somatomedins have isolated, but by far the most important of these is somatomedin C (also called IGF-I)
The somatomedins, have characteristics:
Regulation of their concentration in serum by growth hormone
Stimulation of sulfate incorporation into the cartilage proteoglycan chondroitin sulfate
Insulin- like effects on both adipose and muscle tissue, and
Mitogenicity for fibroblasts

Effects of IGF-I

Ubiquitin

Ubiquitin is itself a protein that degrades other proteins i.e. unfriendly, for proteins
It is a highly conserved protein
Degradation by Ubiquitin occurs in Proteosomes by a process which is ATP dependent
Before degradation proteins are bound to binding proteins
Ubiquitin tags proteins for degradation.

Physiology

175

USMLE Case Scenario


A matrix glycoprotein inhibits the cell adhesion effect of fibronectin and permits cells to detach from the matrix and migrate.
The appearance of this glycoprotein in the wound matrix correlates with the initiation of epithelial and mesenchymal cell
migration. The matrix glycoprotein is:
1. Tenascin
2. Laminin
3. Brabykinin
4. Heparin
5. Incertin
6. Fibronectin
Ans. 1. Tenascin

USMLE Case Scenario


Maximum absorption of the water occurs at:
1. Proximal convoluted tubule
2. Distal convoluted tubule
3. Collecting duct
4. Loop of henle
Ans. 1. Proximal convoluted tubule

USMLE Case Scenario


Ghrelin is secreted from:
1. Endocrinal cells of the pancreas
2. Epithelium of the fundus
3. Epithelium of the antrum
4. Epithelial cells of the jejunum
Ans. 2. Epithelium of the fundus

USMLE Case Scenario


During embryological development, hematopoiesis occurs in different organs at different times. Which of the following are
the correct organs, in the correct sequence, at which hematopoiesis occurs embryologically?
1. Amnion, yolk sac, placenta, bone marrow
2. Placenta, liver and spleen, yolk sac, bone marrow
3. Placenta, spleen and lymphatic organs, bone marrow
4. Yolk sac, bone marrow, liver and spleen
5. Yolk sac, liver, spleen and lymphatic organs, bone marrow
Ans. 5. Yolk sac, liver, spleen and lymphatic organs, bone marrow
By the third week of development, hematopoiesis begins in the blood islands of the yolk sac. Beginning at 1 month of age
and continuing until 7 months of age, blood elements are also formed in the liver. Hematopoiesis occurs in the spleen and
lymphatic organs between 2 and 4 months, and in the bone marrow after 4 months.

USMLE Case Scenario


Calcitonin is secreted by:
1. Thyroid gland
2. Parathyroid gland
3. Adrenal glands
4. Ovaries
Ans. 1. Thyroid gland

176

USMLE Step 1 Platinum Notes

USMLE Case Scenario


QRS complex is due to:
1. Ventricular repolarization
2. Ventricular depolarization
3. Atrial repolarization
4. Atrial depolarization
Ans. 2. Ventricular depolarization

USMLE Case Scenario


GABA is produced from:
1. Alanine
2. Glycine
3. Glutamate
4. Glutamine
Ans. 3. Glutamate

USMLE Case Scenario


Brocas area is concerned with:
1. Word formation
2. Comprehension
3. Repetition
4. Reading
Ans. 1. Word formation

USMLE Case Scenario


Agranular endoplasmic reticulum is involved in the synthesis of:
1. Protein
2. Lipid
3. Carbohydrate
4. Vitamin D
Ans. 2. Lipid

USMLE Case Scenario


CO2 is primarily transported in the arterial blood as:
1. Dissolved CO2
2. Carbonic Acid
3. Carbamino-hemoglobin
4. Bicarbonate
Ans. 4. Bicarbonate

USMLE Case Scenario


The enzyme associated with the conversion of androgen to estrogen in the growing ovarian follicle is:
1. Desmolase
2. Isomerase

Physiology

177

3. Aromatase
4. Hydroxylase
Ans. 3. Aromatase

USMLE Case Scenario


Respiratory acidosis is compensated by:
1. Renal excretion of bicarbonate and excretion of base
2. Renal excretion of bicarbonate and excretion of acid
3. Renal retention of bicarbonate and excretion of acid
4. Renal retention of bicarbonate and excretion of base
Ans. 3. Renal retention of bicarbonate and excretion of acid

USMLE Case Scenario


Cortisol is secreted by:
1. Zona glomerulosa
2. Zona fasciculata
3. Zona reticularis
4. Zona medulla
Ans. 2. Zona fasciculata

USMLE Case Scenario


Brocas area situated in:
1. Superior temporal gyrus
2. Inferior temporal gyrus
3. Superior frontal gyrus
4. Inferior frontal gyrus
Ans. 4. Inferior frontal gyrus

USMLE Case Scenario


The extracellular matrix is the complex, cross-linked structure of proteins and polysaccharides that surrounds cells and
organizes the geometry of tissues. Collagen is the principal component of the extracellular matrix. The rate-limiting enzyme
in collagen synthesis is:
1. Lysyl hydroxylase
2. Prolyl hydroxylase
3. Lysyl oxidase
4. Prolyl oxidase
Ans. 2. Prolyl hydroxylase

USMLE Case Scenario


A 50-year-old drug addict man was brought to the emergency room in a stuporous state. Blood pressure is
100/50 mm Hg, heart rate 110 beats/min, respiratory rate 34/min, and his temperature is 103F. Below are his lab results:
Sodium 152 mEq/L (135145)
Potassium 2.4 mEq/L (3.55.0)
Chloride 108 mEq/L (95105)
Bicarbonate 11 mEq/L (2426)

178

USMLE Step 1 Platinum Notes

pH 7.2 (7.357.45)
PCO2 25 mm Hg (3545)
It implies an acid base status suggestive of:
1. Metabolic acidosis and metabolic alkalosis
2. Metabolic acidosis with partial respiratory compensation
3. Respiratory acidosis and partial metabolic compensation
4. Respiratory acidosis
Ans. 2. Metabolic acidosis with partial respiratory compensation

USMLE Case Scenario


A 55-year-old man is brought to the emergency room by his son in a stuporous and obtunded condition. Physical examination
reveals BP 120/70 and pulse 90 (supine); and BP 90/50 and pulse 120 (standing).
Serum chemistries are:
Na+ = 141 mEq/L
Cl = 87 mEq/L
K+ = 2.9 mEq/L
HCO3 = 42 mEq/L
Arterial pH = 7.53
PCO2 = 50 mm Hg
The disease process that best accounts for this problem:
1. Ethylene glycol poisoning
2. Chronic obstructive pulmonary disease
3. Congestive heart failure
4. Lactic acidosis
5. Vomiting
6. Chronic renal failure
Ans. 5. Vomiting

USMLE Case Scenario


Capacitance of sperm is attained in:
1. Epididymis
2. Genital tract
3. Vagina
4. Fallopian tube
Ans. 4. Fallopian tube

USMLE Case Scenario


Neuroendocrine responses contributes to meeting the enhanced energy demands during exercise is:
1. Glucagon stimulation of hepatic glycogen synthesis
2. Epinephrine stimulation of hepatic glycogenolysis
3. Epinephrine inhibition of hepatic glycogenolysis
4. Norepinephrine-induced stimulation of insulin release
5. Cortisol inhibition of gluconeogenesis
Ans. 2. Epinephrine stimulation of hepatic glycogenolysis

USMLE Case Scenario


Elevated fasting plasma glucose levels in pregnant women with no history of diabetes maybe related to:
1. Increased estrogen production
2. Decreased progesterone clearance

Physiology

179

3. Increased h PL/GH production


4. Increased insulin degradation
5. Decreased prolactin levels
Ans. 3. Increased hPL/GH production

USMLE Case Scenario


Testosterone production is mainly contributed by:
1. Leydig cells
2. Sertolie cells
3. Seminiferous tubules
4. Epididymis
Ans. 1. Leydig cells

USMLE Case Scenario


The processing of short-term memory to long-term memory is done in:
1. Prefrontal cortex
2. Hippocampus
3. Neocortex
4. Amygdala
Ans. 2. Hippocampus

USMLE Case Scenario


Basal ganglia is involved primarily in:
1. Planning and programming of voluntary movements
2. Processing of cognitive functions
3. Sensory-motor integration
4. Language function
Ans. 1. Planning and programming of voluntary movements

USMLE Case Scenario


Which of the following can be present in hyperosmolar coma in a diabetic patient?
1. Low plasma glucose
2. Low plasma potassium
3. High plasma pH
4. High plasma ketones
Ans. 4. High plasma ketones

USMLE Case Scenario


A 88-year-old woman from Mexico is admitted to the hospital following about of severe vomiting and generalized weakness.
Initial laboratory values reveal elevated Ca2 levels. The referring physician tells you that she has breast cancer and her bone
scan indicates metastasis to bone. The most likely cause of hypercalcemia is:
1. Increased PTH production
2. Increased responsiveness of the PTH receptor 1
3. Increased PTHrP production
4. Decreased responsiveness to calcitonin
Ans. 3. Increased PTHrP productions

180

USMLE Step 1 Platinum Notes

USMLE Case Scenario


FIGLU excretion in the urine, is an index of the deficiency of:
1. Thiamine
2. Niacin
3. Pyridoxine
4. Folate
Ans. 4. Folate

USMLE Case Scenario


In a 55-year-old anion gap needs to be calculated. The anion gap is calculated as:
1. [K+] + [HCO3 + Cl]
2. [Na+] + [Cl + HCO3]
3. [Na+] [HCO3 + Cl]
4. [Mg] + [HCO3 + Cl]
5. [Mg] + [HCO3 + Cl]
Ans. 3. [Na+] [HCO3 Cl]

USMLE Case Scenario


Intrinsic Factor of Castle is secreted by which of the following cells in gastric glands:
1. Chief cells
2. Parietal cells
3. Enterochromaffin cells
4. cells
Ans. 2. Parietal cells

USMLE Case Scenario


A 25-year-old man from New Jersy after a fight incurs blunt trauma to his upper outer arm. On physical examination, there is
a 2 3 cm contusion. He bleeds but the initial soft tissue bleeding stops in a few minutes and the size of the bruise does not
increase. Which of the following chemical mediators is most important in this episode of hemostasis?
1. Leukotriene
2. Neurokinin
3. Bradykinin
4. Prostaglandin
5. Prostacyclin
6. Plasminogen
7. Thromboxane
Ans. 7. Thromboxane
It is released by platelets to promote formation of a stable secondary plug to achieve hemostasis

USMLE Case Scenario


A 55-year-old man has severe chest pain for the past 6 hours. Laboratory studies show an elevated serum troponin I. A
coronary angiogram is performed emergently and reveals >85 % occlusion of the left anterior descending artery (LAD). An
irreversible injury to myocardial fibers will have occurred when?
1. Cellukar swelling
2. Fat stores are depleted+
3. Glycogen stores are depleted

Physiology

181

4. Cytoplasmic sodium increases


5. Karyorrhexis
6. Intracellular pH
7. Blebs form on cell membranes
Ans. 1. Cellukar swelling

USMLE Case Scenario


Ovulation is primarily caused by preovulatory surge of:
1. Estradiol
2. Luteinizing hormone
3. Progesterone
4. Follicle stimulating hormone
Ans. 2. Luteinizing hormone

USMLE Case Scenario


The parvocellular pathway, from the lateral geniculate nucleus to the visual cortex, carries signals for the detection of:
1. Movement, depth and flicker
2. Color vision, shape and fine details
3. Temporal frequency
4. Luminance contrast
Ans. 2. Color vision, shape and fine details

USMLE Case Scenario


A single-breath carbon monoxide diffusion capacity (DLCO) is done in a 33-year-old patient. In this test, the patient is required
to inhale low, nontoxic concentrations of carbon monoxide, hold the breath for 10 seconds, and then exhale. This test is rapid,
simple, safe and painless. DLCO is an estimate of:
1. Pulmonary capillary surface area
2. Respiratory reserve
3. Elastic recoil
4. Airway resistance
Ans. 1. Pulmonary capillary surface area

USMLE Case Scenario


The supraoptic nucleus of the hypothalamus is believed to control secretion of which of the following hormones?
1. Serotonin
2. Oxytocin
3. Growth hormone
4. Adrenocorticotropic hormone
Ans. 2. Oxytocin

USMLE Case Scenario


Central Chemoreceptors are most sensitive to following changes in blood:
1. PCO2
2. PCO2
3. H+
4. PO2
Ans. 1. PCO2

182

USMLE Step 1 Platinum Notes

USMLE Case Scenario


The Hyperkinetic features of the Huntingtons disease are due to the loss of:
1. Nigrostriatal dopaminergic system
2. Intrastriatal cholinergic system
3. GABA-ergic and cholinergic system
4. Intrastriatal GABA-ergic and cholinergic system
Ans. 3. GABA-ergic and cholinergic system

USMLE Case Scenario


The Myelin sheath is formed around the nerve fibers in the central nervous system by:
1. Astrocytes
2. Microglia
3. Oligodendrocytes
4. Protoplasmic astrocytes
Ans. 3. Oligodendrocytes

BIOCHEMISTRY

Biochemistry

DNA: (HIGH YIELD POINTS FOR USMLE)


Deoxyribonucleic acid (DNA) is the hereditary material of the cell
Important points about Structure of DNA
DNA consists of two strands of nucleotides wrapped around each other to form a complex double helix
The building blocks of each strand are deoxyribonucleotides, which consist of one of four basesadenine (A), guanine (G),
cytosine (C), and thymine (T)a sugar-deoxyribose, and a covalently joined phosphate group
The deoxyribose molecules are linked by phosphates to form the backbone of DNA
The double helix is held together by the hydrogen bonds that form between the bases on the two complementary strands
oriented in antiparallel directions
RNA is similar to DNA except that the deoxyribose sugar of DNA is replaced by a ribose moiety in RNA, and instead of Thymine T,
RNA uracil (U)
Transcription results in the production of a precursor messenger RNA (pre-mRNA) that contains both intron and exon
sequences
The introns are excised
Exons are ligated together in a two-stage splicing process that results in a mature mRNA that can be exported from the nucleus and
translated to produce the desired protein
While still in the nucleus, the spliced mRNA undergoes further processing
The 5 end of the RNA is capped by a guanosine derivative
A string of adenylic acid residues (polyA) is added to its 3end to stabilize the transcript for transit within the cellular environment
Watson and Crick theory pertains to DNA
Human genome contains 3 x 109 base pairs
Histones are proteins present in DNA
New DNA synthesis occurs in interphase

High Yield Points


Most DNA occurs as Right Handed Double Helical called B DNA.
Rare Left Handed Double Helical called Z DNA
Negative super coiling occurs if DNA is wound loosely
Positive super coiling occurs if DNA is wound Tightly
Topoisomerases are enzymes that change amount of supercoiling in DNA molecules
DNA Topoisomerase II can induce negative supercoiling or Remove Positive super coils
DNA Topoisomerase I can relax supercoiling
Heterochromatin

Euchromatin

Highly condensed
Inactive

Loosely condensed
Active

186

USMLE Step 1 Platinum Notes

Prokaryotes have single origin of Replication


Eukaryotes have multiple origin of Replication

Remember
New synthesized strand is made in 5 3 direction
Template is scanned in 3 5direction
New synthesized strand is complimentary and antiparallel
Daunorubicin and Doxorubicin exert their effect by intercalating between bases of DNA and thereby interfering with activity of
Topoisomerase II
Cisplatin on the other hand binds tightly to DNA causing structural Distortion

Important Points about DNA and RNA (Repeated in USMLE Frequently)


DNA repair: Single
strand

DNA/RNA/ protein
synthesis direction
Types of RNA

Polymerases: RNA

Start and Stop


codons

Promoter
Enhancer

Single strand, excision-repair-specific glycosylase recognizes and removes damaged base


Endonuclease makes a break several bases to the 5 side
Exonuclease removes short stretch of nucleotides. DNA polymerase fills gap
DNA ligase seals
DNA and RNA are both synthesized in 53 direction
Protein synthesis also proceeds in the 5 3 direction
mRNA is largest type of RNA
rRNA is the most abundant type of RNA
tRNA is the smallest type of RNA
Eukaryotes:
RNA polymerase I make rRNA
RNA polymerase II makes mRNA
RNA polymerase III makes t RNA
No proofreading function. RNA polymerase II opens DNA at promoter site (A-T-rich upstream sequenceTATA and CAAT)
-amanitin inhibits RNA polymerase II
Prokaryotes:
RNA polymerase makes all three kinds of RNA
AUG (or rarely GUG) is the initiation codon
AUG codes for methionine, which may be removed before translation is completed. In prokaryotes the initial
AUG codes for a formyl-methionine (f-met)
Stop codons: UGA, UAA, UAG
Site where RNA polymerase and multiple other transcription factors bind to DNA upstream from gene locus
Stretch of DNA that alters gene expression by binding transcription factors. May be close to, far from, or even
within (in an intron) the gene whose expression it regulates

Transcription and translation

Biochemistry

187

Functions of Different Types of DNA Polymerases


In Eukaryotes
DNA Polymerase synthesizes leading strand
DNA Polymerase synthesizes lagging strand
DNA Polymerase replicates mitochondrial DNA
DNA Polymerase , DNA polymerase participate in DNA Repair

Functions of Different Enzymes (Remember Thoroughly)


Site

Prokaryotic

Eukaryotic

Recognition of origin of replication

DNA A Protein

Unwinding of DNA Helix

Helicase

Helicase

Stabilization of unwound Template strand

Single stranded binding protein (SSB)

Single stranded binding protein (SSB)

Synthesis of RNA Primers

Primase

Primase

Synthesis of DNA
Leading strand+ Proof reading
Lagging strand

DNA Polymerase III

DNA Polymerase

DNA Polymerase III

DNA Polymerase

Removal of RNA Primers

DNA Polymerase I

Joining of Okazaki Fragments

DNA ligase

DNA ligase

Removal of Positive super coils

DNA Topoisomerase II
(DNA gyrase)

DNA Topoisomerase II

RNA Polymerase
In bacteria RNA polymerase synthesizes almost all of the RNA
RNA polymerase is a multi subunit enzyme
One component of RNA polymerase is the sigma subunit which enables RNA Polymerase to recognize promoter regions on the
DNA
Other component is the rho factor or termination factor which enables RNA Polymerase to recognize termination regions on
the DNA

Mitochondrial DNA: (Cases asked in USMLE)


Thirteen out of 100 polypeptides required for oxidative phosphorylation are coded by mitochondrial DNA
Defects in oxidative phosphorylation are most likely as a result of alterations in mitochondrial DNA as it has a mutation rate
about ten times greater than nuclear DNA
This is because there are no introns and a mutation invaribly strikes a coding sequence (axon)
Tissues with greatest ATP requirement (CNS, Skeletal muscle, Heart muscle, Kidney, Liver) are most affected
Mitochondrial DNA is maternally inherited because mitochondria from sperms do not enter the fertilized egg
Mitochondrial DNA is closed and circular and 16.5 kb in length
MELAS (Mitochondrial Encephalopathy, Lactic Acidosis and Stroke like episodes) are attributed to mitochondrial mutations. Other
diseases associated with mitochondrial DNA are:
Lebers Hereditary Optic Neuropathy
MELAS (Mitochondrial encephalopathy with lactic acidosis and stroke like episodes)
Myopathy

188

USMLE Step 1 Platinum Notes

MERRF Syndrome: (Myoclonic epilepsy and ragged red fibers.)


Cardiomyopathy
Strokes
Lactic acidosis
External Ophthalmoplegia
Optic atrophy
NARP (Neuropathy, ataxia and retinitis pigmentosa)
Pearsons syndrome
Sensorineural deafness
Diabetes mellitus

Hereditary DNA Repair Disorders


Xeroderma pigmentosum:
Hypersensitivity to sunlight/UV, resulting in increased skin cancer
Incidence and premature aging
Cockayne syndrome:
Hypersensitivity to UV and chemical agents
Trichothiodystrophy:
Sensitive skin, brittle hair and nails
Werners syndrome:
Premature aging and retarded growth
Blooms syndrome:
Sunlight hypersensitivity, high incidence of malignancies
(Especially leukemias)
Ataxia telangiectasia:
Sensitivity to ionizing radiation and some chemical agents
All of the above diseases are often called segmental progerias (accelerated aging diseases) because their victims appear elderly
and suffer from aging-related diseases at an abnormally young age
Other diseases associated with reduced DNA repair function include
Fanconis anemia
Hereditary breast cancer and
Hereditary colon cancer

Xeroderma pigmentosa: (Repeated in USMLE)

Extreme UV sensitivity
Exposure of cell to UV light can result in the covalent joining of two adjacent pyrimidines (Usually Thymines) producing a dimer
These Thymine dimmers prevent DNA polymerase from replicating the DNA strands
Pyrimidine dimmers can be formed in the skin cells of humans exposed to unfiltered sunlight
In Xeroderma Pigmentosa, the cells cannot repair the damaged DNA, resulting in accumulation of mutations and skin cancers
The most common form is produced by absence of enzyme UV specific Exonuclease/Endonuclease
Excessive freckling
Multiple skin cancers
Corneal ulcers

Biochemistry

189

Transposons
Are pieces of DNA that move readily from the one site to another either within or between the DNAs of bacteria, plasmids and
bacteriophages
They are also known as Jumping Genes
They can code for drug resistance, enzyme, toxin or a variety of metabolic enzymes
They can either cause mutation in the gene into which they insert or alter the expression of nearby genes
In contrast to plasmids or bacterial viruses, transposons are not capable of independent replication
They replicate as a part of recipient DNA

Prions
Prions are proteins which are normally found in the body. Prions become infectious or pathogenic due to misfolding of the proteins
Prions are normally present in human. The prion protein, endogenous to the human is PrP (which is a glycoprotein rich in b sheets)
PrPsc is the infectious form of the Prion. (It is formed due to mutation in PrP)
The key to become infectious lies in changes in three dimensional conformation of PrP, i.e. there is abnormality in protein folding
(the a helical secondary structure of PrP changes to b sheets in PrPsc)
So, PrPsc is a misfolded PrP and this conformational difference cause PrPsc to resist proteolytic degradation
Misfolded proteins are quite dangerous for the body because they possess a remarkable property that they can cause other
normally folded prions to distort into the same misfolded state. Thus, misfolded proteins, i.e. prions are able to replicate and
spread throughout tissue without using either DNA or RNA
The infective agent is thus an altered version of a normal protein which acts as a template for converting more normal protein
to the pathogenic conformation

Enzymology

Enzymes do not alter Energy of Reaction


Enzymes lower Energy of Activation
Vmax = Maximum velocity with specified amount of enzyme
Km = Concentration of substrate required to produce half V max

Competitive Inhibition
It is reversible
Substrate and inhibitor resemble each other
V max is same, Km is increased
Substrate affinity to enzyme is lowered

Noncompetitive Inhibition

It is reversible or irreversible
Substrate and inhibitor do not resemble each other
V max is decreased, Km is unaltered
Substrate affinity to enzyme is not lowered

Allosteric Inhibition
Here inhibitor binds to enzyme at a site different than active site

190

USMLE Step 1 Platinum Notes

Does not follow Michaelis Menten Kinetics


Follows sigmoid kinetics
Km is raised but V max is unchanged in some allosteric inhibition reactions
Substances that reduce the activity of an enzyme are called inhibitors
Reversible inhibitors bind to an enzyme but rapidly dissociate from it in contrast to irreversible inhibitors which bind tightly and
dissociate very slowly from the enzyme
There are several types of reversible inhibitors:
Competitive inhibitors usually resemble the substrate and compete with it for binding at the active site

Thus, increasing the concentration of substrate will decrease the percent inhibition of the enzyme. The Vmax is unchanged, but the
Km is increased

A noncompetitive inhibitor binds with equal affinity to both enzyme and enzyme-substrate complex

This binding leads to a distortion of the substrate binding site, so new substrate cannot bind and/or the product cannot be
released. In this kind of inhibition, the Vmax is decreased but the Km is not altered

An uncompetitive inhibitor does not bind to free enzyme, but binds to the enzyme-substrate complex at a site other than
the catalytic site. Once bound by the inhibitor, the enzyme is trapped in the enzyme-substrate complex state until the inhibitor
dissociates. In this kind of inhibition, the slope of the reaction (which is the ratio Km/Vmax) remains the same, but both Vmax and
Km are reduced.

Remember
Michaelis Menten (Km) reflects the affinity of enzymes to that substrate
It is equal to the substrate concentration at which reaction velocity is half of V max
Low Km reflects high affinity of enzyme
High Km reflects low affinity of enzyme

Metabolic Processes and their Sites


Processes occurring in cytosol:
Glycolysis
Glycogenolysis
Glycogenesis
HMP Shunt (Pentose phosphate synthesis)
Fatty acid synthesis
Bile acid synthesis
Cholesterol synthesis
Processes occurring in Mitochondria:
Fatty acid oxidation(Beta)
Electron transport chain
Krebs/TCA Cycle
Oxidative phosphorylation
Processes occurring in both mitochondria and cytosol:
Urea synthesis
Gluconeogenesis

Biochemistry

191

Sites of metabolic processes

Sites of
Protein synthesis: RER
Steroid synthesis: Smooth ER
Sorting of Proteins: Golgi bodies (Dictyosome)

Medically Important Enzymes Frequently asked


Reverse Transcriptase:
It is an RNA dependent DNA polymerase that requires an RNA Template to direct the synthesis of new DNA
AZT, ddC, ddI (Antiretrovirals) act on reverse transcriptase
Restriction Endonucleases:
Are Bacterial enzymes that cleave double stranded DNA into smaller fragments
Each enzyme cleaves DNA at a specific 46 base long nucleotide sequence producing DNA segments called restriction fragments
These enzymes form either sticky ends or blunt ends on the DNA
The DNA sequence recognized by a restriction enzyme is called a restriction site
Telomerase
Is an enzyme that completes replication of Telomers
Telomeres are repetitive sequences at ends of DNA

192

USMLE Step 1 Platinum Notes

Telomerase is present in embryonic cells, stem cells and cancer cells


DNA polymerase is unable to replicate the end of a DNA chain completely, resulting in loss of DNA with each replication. This
problem has been solved by a mechanism that replicates tandem repeats of a six-nucleotide sequence (GGGTTA) to the ends
of each chromosome. These repeated sequences are called telomeres and are replicated through an RNA-dependent DNA
polymerase called telomerase
Normal somatic cells do not express telomerase, and the replicative lifetime of such cells is limited to approximately 30 cell
divisions due to the progressive loss of telomere repeats; the limit imposed on somatic cell division is called the Hayflick limit, at
which time replicative senescence occurs
Germ cells express telomerase and have a long (possibly unlimited) replicative lifetime
Cancer cells express telomerase and in cancer cells is thought to be a component of the neoplastic process, assuring that the cell
will be able to undergo many divisions without inducing senescence or genetic catastrophe. Inhibition of telomerase activity in
cancer cells could have antitumor effects
Human pluripotential stem cells express high levels of telomerase, an enzyme that is essential for allowing repeated replication
of the ends of eukaryotic chromosomes
The capacity to divide indefinitely is provided by activation of telomerase, which allows continued replication of chromosomes
by addressing the unique need of chromosome ends to be continually renewed to a proper length to allow normal mitosis
The capacity to invade and metastasize is conveyed by elaboration of matrix metalloproteases and plasminogen activators
and the capacity to recruit host stromal cells at the site of invasion through tumor-induced angiogenesis.

Classification of Enzymes
Class 1

Oxidoreductases: Transfer of hydrogen or addition of oxygen; e.g. Lactate dehydrogenase (NAD);


Glucose-6-phosphate dehydrogenase (NADP); Succinate dehydrogenase (FAD); di-oxygenases

Class 2

Transferases: Transfer of groups other than hydrogen


Example, Aminotransferase. (Subclass: Kinase, transfer of phosphoryl group from ATP, e.g. Hexokinase)

Class 3

Hydrolases: Cleave bond and add water, e.g. Acetyl choline esterase; Trypsin

Class 4

Lyases: Cleave without adding water, e.g. Aldolase; HMG CoA lyase; ATP Citrate lyase. (Subclass:
Hydratase; add water to a double bond)

Class 5

Isomerases: Intramolecular transfers. They include racemases and epimerases. Examples, Triose
phosphate isomerase

Class 6

Ligases: ATP dependent condensation of two molecules, e.g. Acetyl CoA carboxylase; Glutamine
synthetase; PRPP synthetase

USMLE Case Scenario


The lack of chromosomal shortening allows the malignant cells to undergo many more divisions than the normal cells. Which
of the following enzymes is most likely to have this effect?
1. Reverse transcriptase
2. DNA polymerase
3. Isomerase
4. Phosphodiesterase
5. Telomerase
6. Protein kinase
7. Topoisomerase
Ans. 5. Telomerase

Mutations
Transistion: A point mutation that replaces purine-pyrimidine base pair with different purine-pyrimidine base pair
Transversion: A point mutation that replaces purine-pyrimidine base pair with different pyrimidine-purine base pair

Biochemistry
Mutation

193

Effect on Protein

Silent

New codon specifies same amino acid

None

Missense

New codon specifies new amino acid

Decrease in function

Non sense

New codon is Stop codon

Usually non functional

Frameshift

Deletion/addition of base

Usually non functional

USMLE Case Scenario


A 2-month-old, breastfed baby that was normal at birth begins to develop GI problems and cirrhosis of the liver. Molecular
analysis indicates a normal amount of galactose-1-phosphate uridyl transferase (GALT) mRNA, but no observable enzyme
activity. Which of the following would be the best possible explanation for this?
1. Gene deletion
2. Nonsense mutation
3. Premature transcription termination sequence in the DNA
4. Promoter mutation
5. RNA splicing mutation
Ans. 2. Nonsense mutation
It is a mutation in the DNA that leads to a premature stop codon when the mRNA is being translated into protein. The mRNA would
be transcribed correctly, but when the protein was being translated, it would be stopped prematurely, leading to a truncated protein.

Collagen

Collagen formation begins with transcription of mRNA from appropriate


DNA genes in the nucleus. While still within the nucleus, the mRNA is spliced
It is then transported through the cytoplasm to the ribosomes on the rough endoplasmic reticulum
Individual chains are translated on the ribosomes, with the ends feeding into the endoplasmic reticulum lumen. Within the lumen,
glycosylation of the individual chains occurs
The material then moves toward the Golgi bodies (whose lumens are connected to the endoplasmic reticulum) where the triple
helices of procollagen form
The procollagen is then secreted into the extracellular space, where cleavage of pro-peptides and cross- linking of different
triplehelices occurs, maturing the collagen
The extracellular space is the site of procollagen cleavage and cross- linking
The nucleus is the site of mRNA transcription and splicing
The rough endoplasmic reticulum is the site of chain translation and glycosylation

Disorders of Collagen Synthesis


Scurvy

Deficient hydroxylation secondary to Ascorbate deficiency

Osteogenesis imperfecta

Mutations in collagen genes

Ehler Danhlos syndrome

Mutations in collagen genes, Lysine and Hydroxylase genes

Menkes disease

Deficent cross linking secondary to Cu deficiency

Scurvy [USMLE CASE]


A 72-year-old retired engineer alcoholic male who lives alone is admitted to the hospital for evaluation of wounds on limbs that
are not healing well
On physical examination, multiple ecchymoses are noted on the posterior aspect of his thighs and front of arm. Careful
examination of his skin reveals minute hemorrhages around hair follicles and splinter hemorrhages in the nail beds.
Laboratory examination is remarkable for hemoglobin of 9 (normal 1418 g/dL); no other hematologic abnormalities are
noted. He is most probably suffering from Scurvy.

194

USMLE Step 1 Platinum Notes

USMLE High Yield Points


Vitamin C deficiency causes scurvy
Seen primarily among poor and elderly people and alcoholics who consume <10 mg/d of vitamin C. Symptoms of scurvy primarily
reflect impaired formation of mature connective tissue and include bleeding into skin (petechiae, ecchymoses, perifollicular
hemorrhages);
Absence of vitamin C leads to impaired hydroxylation of proline residues in the nascent procollagen chains, leading to weakness
of blood vessel walls
Clinical Features:
It is characterized by perifollicular hemorrhages, fragmentation of hairs, purpura, ecchymoses
Splinter hemorrhages, and hemorrhages into muscle. In patients with normal dentition, gum changes
(Swelling, bleeding, loosening of teeth) are also noted
Without supplementation with vitamin C
Death may eventually occur
Other generalized symptoms include weakness, fatigue, and depression
In children, vitamin C deficiency may cause impaired bone growth
Laboratory diagnosis of vitamin C deficiency is made on the basis of low plasma or leukocyte levels
Administration of vitamin C (200 mg/d) results in marked improvement in the symptoms of scurvy in a matter of several days

Osteogenesis Imperfecta (OI): (USMLE Case Scenario)


A 5-month-old infant has fracture clavicle, fracture left radius, fracture right clavicle. Fractures are in different stages of healing. X-ray
reveals thin bones with thin cortices. There is no evidence of child abuse
The child has most likely: Osteogenesis imperfect.

USMLE High Yield Points

OI is also called as Brittle bone disease or Lobstein syndrome


Basic defect is in Collagen Type 1
It is transmitted either as AD or AR Inheritance
Type 1 OI is THE MOST COMMON TYPE
OI is inherited as autosomal dominant trait mostly
Blue sclera is present in several types of OI But not all
Grey sclera is a feature as well. Other ocular features of OI are:
-

Saturn ring, Arcus juvenilis, Hypermetropia and Retinal Detachment are seen

The sclera is normal in some types of OI

Feature of OI is generalized osteopenia with recurrent fractures and skeletal deformity. Fracture healing however is normal.
Fracture in utero may be seen. Laxity of joint ligaments leads to hypermobility
Some people have associated dentogenesis imperfecta: small fragile and discolored teeth
Dermis may be abnormally thin and skin is susceptible to easy bruising
Hearing loss due to involvement of inner and middle ear bones may produce deafness
Wormian bones are a feature
Pop corn calcification and whorls of radiodensities are a radiographic feature
Treatment is largely supportive

Biochemistry

195

Ehler Danlos Syndrome


Defect in normal synthesis and processing of collagen
Thin skin with easy bruising
Arterial intestinal or uterine rupture can occur

Menkes Disease: USMLE HighYield Points


Menkes disease also known as kinky hair disease, is an X-linked neurodegenerative disease of impaired copper transport
Named after noting the similarity of kinky hair to the brittle wool of Australian sheep raised in areas with copper-deficient soil,
he demonstrated abnormal levels of copper and ceruloplasmin in these patients
In Menkes disease, transport of dietary copper from intestinal cells is impaired, leading to the low serum copper levels. Abnormal
copper transport in other cells leads to paradoxical copper accumulation in duodenal cells, kidney, pancreas, skeletal muscle, and
placenta.
Hair changes: Abnormal kinky hair, eyebrows, and eyelashes. Often lightly or abnormally pigmented; can be white, silver, or gray
Associated are abnormal facies, Progressive cerebral degeneration and connective-tissue abnormalities. Loose skin at the
nape of the neck and over the trunk
Joint hyper mobility, Polypoid masses, which can be multiple, in the gastrointestinal tract, umbilical and inguinal hernias,
which can be bilateral, Bladder diverticula, Dilated ureters, Emphysema, Arterial rupture Brachial, lumbar, and iliac artery
aneurysms, Internal jugular vein aneurysms.
Menkes Kinky hair syndrome is associated with the defecive functioning of several copper-dependent enzymes due to impaired
copper absorption, transport, or metabolism. Lysyl oxidase is a copper-requiring enzyme that catalyzes the oxidative deamination
of lysyl residues linking two adjacent chains of tropoelastin polypeptides into an insoluble network.
Decreased lysyl oxidase (LO) activity accounts for the connective-tissue fragility and vascular abnormalities in Menkes disease

Vitamins
Important Vitamin Deficiencies: (Repeated in USMLE)
Vitamin

Enzyme

Deficiency State

Thiamine (B1)

Pyruvate dehydrogenase
Ketoglutarate dehydrogenase
Transketolase

Wernicke Korsakoff Syndrome


Wet Beriberi
Dry Beriberi

Biotin

Pyruvate carboxylase
Acetyl CoA carboxylase
Propionyl CoA carboxylase

Consumption of eggs containing avidin


Alopecia, Muscle pains

Pyridoxine

Aminotransferases

Riboflavin

Dehydrogenases

Corneal neovascularization
Chielosis/stomatitis
Magenta tongue

Niacin

Dehydrogenases

Pellagra
Diarrhea, Dementia, Dermatitis, Death

Pantothenic

Fatty acid Synthase


Fatty acyl CoA synthase

Rare
Burning foot syndrome

Isoniazid therapy
Sidderoblastic anemia
Chielosis/stomatitis
Convulsions

196

USMLE Step 1 Platinum Notes

Folic Acid

Thymidylate synthase

Alcholics and pregnancy


Homocystenemia
Macrocytic anemia
Neural tube defects

Vitamin B12
Extrinsic factor of castle

Homocysteine methyltransferase
Methyl malonyl CoA mutase

Pernicious anemia
Megaloblastic anemia
Neuropathy
SACD
Methyl malonic aciduria

Vitamin C
post translation modifier

Propyl and Lysyl hydroxylase


Dopamine hydroxylase

Diet deficient in citrus


Scurvy

Fat Soluble Vitamins


Vitamin A (acts as hormone)

Night blindness
Xerophthalmia
Follicular Hyperkeratosis

Vitamin D

Rickets
Osteomalacia

Vitamin E
Prevents lipid peroxidation

Hemolysis
Retinitis pigmentosa
Neurological problems

Vitamin K
(Gamma carboxylation)
Post translation modifier

Bleeding tendency with PT normal BT


Deficiency of vitamin K produces a clotting disorder characterized by an elevated prothrombin
time and easy bleeding, particularly in neonates (hemorrhagic disease of the newborn).
The biochemical basis for this hemorrhagic tendency is that glutamate residues on Factors II
(Thrombin), VII, IX, and X must be converted to gamma-carboxyglutamate residues (in a vitamin
K-requiring reaction) for optimal activity.

Synthesis of vitamin D

Vitamin K Deficiency
The symptoms of vitamin K deficiency are due to hemorrhage, and newborns are particularly susceptible because of low fat stores,
low breast milk levels of vitamin K, sterility of the infantile intestinal tract, liver immaturity, and poor placental transport. Intracranial
bleeding, as well as gastrointestinal and skin bleeding, can occur in vitamin Kdeficient infants 17 days after birth. Thus, vitamin K
(1 mg IM) is given prophylactically at the time of delivery.

Biochemistry

197

USMLE Clinical Scenario


A child has cystic fibrosis. His parents report a history of recurrent respiratory tract infections and bulky, foul-smelling stools. After
assessment of his respiratory tract illness, the practitioner should also look for signs of which vitamin deficiency.
Fat soluble vitamin deficiency (A, D, E, K)

Remember: Conversions: Vitamins are required for

The conversion of homocysteine to methionine requires vitamin B12


Conversion of methylmalonyl CoA to succinyl CoA requires vitamin B12
Degradation of cystathionine requires vitamin B6
Hydroxylation of proline requires vitamin C

Vitamin A is necessary for formation of retinal pigments (deficiency can cause night blindness) and for appropriate differentiation
of epithelial tissues (including hair follicles, mucous membranes, skin, bone, and adrenal cortex)
Vitamin C is necessary for collagen synthesis
Vitamin D is important in calcium absorption and metabolism
Vitamin E is important in the stabilization of cell membranes
Vitamin K is necessary for normal blood coagulation

Hypervitaminosis (A): USMLE Favorite


Acute toxicity
It is manifest by increased intracranial pressure, vertigo, diplopia, bulging fontanels in children, seizures, and exfoliative dermatitis; it
may result in death
Chronic vitamin A intoxication has
Manifestations Include:
Dry skin, cheilosis, glossitis, vomiting, alopecia, bone pain, hypercalcemia, lymph node enlargement, hyperlipidemia, amenorrhea,
and features of:
Pseudotumor cerebri with increased intracranial pressure and papilledema
Congenital malformations, spontaneous abortions, craniofacial abnormalities, and valvular heart disease

USMLE Clinical Scenario


A chronic alcoholic develops severe memory loss with marked confabulation. Deficiency of which of the vitamins would be
most likely to contribute to the neurologic damage?
Wernicke-Korsakoff syndrome refers to the constellation of neurologic symptoms caused by thiamine deficiency
A severe memory deficit, which the patient may attempt to cover by making up bizarre explanations (confabulation), is prominent
Anatomical damage to the mamillary bodies and periventricular structures has been postulated as the cause
In the US severe thiamine deficiency is seen most commonly in chronic alcoholics
Thiamine deficiency can also damage peripheral nerves (dry beriberi) and the heart (wet beriberi).

High Yield Facts

Folic acid deficiency produces megaloblastic anemia without neurologic symptoms


Niacin deficiency produces pellagra, characterized by depigmenting, dermatitis, chronic diarrhea, and death
Riboflavin deficiency produces ariboflavinosis, characterized by glossitis, corneal opacities, dermatitis, and erythroid hyperplasia
Vitamin B12 deficiency produces megaloblastic anemia accompanied by degeneration of the posterolateral spinal cord

198

USMLE Step 1 Platinum Notes

Substance Accumulation in Different Diseases


Accumulation of galactocerebrocide occurs in Krabbe disease, which is due to galactocerebrocide deficiency
Accumulation of glucocerebroside occurs in Gaucher disease, which is due to defects in -glucocerebrosidase. The
reticuloendothelial cells and CNS are affected
Accumulation of GM2 ganglioside occurs in Tay
Sachs disease because of hexosaminidase deficiency. The swollen ganglion cells of the retina contribute to a classic sign of TaySachsthe macular cherry-red spot
Accumulation of sphingomyelin in a variety of organs occurs in Niemann-Pick disease, which is due to a defect in sphingomyelinase
Accumulation of sulfatide occurs in Metachromatic leukodystrophy, caused by aryl sulfatase A deficiency

USMLE Case Scenario


A 3-year-old retarded child is seen by a specialist. The childs history is significant for failure to thrive and progressive
neurologic deterioration, including deafness and blindness. Physical examination is remarkable for hepatosplenomegaly, as
well as a cherry-red spot on funduscopic examination. These symptoms are consistent with a diagnosis of:
Tay-sachs Disease

Lysosomal Storage Disease


Fabrys
Disease

Lysosomal
Storage Disease

X-Linked Recessive
Angiokeratomas (skin lesions) over lower
Alpha-Galactosidase A deficiencybuild up of trunk, fever, severe burning pain in extremities,
cardiovascular and cerebrovascular involvement.
ceramide trihexoside in body tissues

Hunters
Syndrome

Lysosomal
Storage Disease

X-Linked Recessive. L-iduronosulfate sulfatase Similar to but less severe than Hurler Syndeficiencybuild up of mucopolysaccharides drome. No corneal clouding. Hepatospleno(heparan sulfate and dermatan sulfate)
megaly, micrognathia, retinal degeneration, joint
stiffness, mild retardation, cardiac lesions

Hurlers
Syndrome

Lysosomal
Storage Disease

Autosomal Recessive. -L-iduronidase deficiency - Gargoyle-like facies, progressive mental


accumulation of mucopolysaccharides (heparan deterioration, stubby fingers, death by age 10.
sulfate, dermatan sulfate) in heart, brain, liver, Similar to Hunters Syndrome
other organs

MPS IV (Morquio Syndrome)


Characterized by severe skeletal diseases that resemble the spondyloepiphyseal dysplasias
There is extreme shortening of the trunk due to multiple vertebral collapses
The long bones are relatively spared
Joint laxity can lead to osteoarthritis-like destruction of the joints
Upper cervical spinal cord compression due to atlanto axial instability predisposes to subluxation and paralysis
Many patients have mitral valve insufficiency that can be functionally significant

I Cell Disease

USMLE Case Scenario


A Child with large tongue, coarse facial features and club foot is seen by a pediatrician. You hear the doctor talking to his
colleague that the child has a problem with Phosphorylation of their mannose residues. The most likely possibility is a disease
called I-cell disease.

Biochemistry

199

It is an inborn error that led to the discovery of how enzymes are imprinted to reside in lysosomes. Patients with I-cell disease
have inherited defects in the recognition markers required to direct enzymes to the endocytic receptor of plasma membrane
and to its capture in the acidic milieu of the lysosome. Patients lack all cellular lysosomal enzymes. Instead cells are filled with
inclusion bodies (hence I-cell). The misdirected lysosomal enzymes are secreted and are present in excess in plasma but are
missing from cells. These extracellular enzymes were found to lack mannose 6-phosphate residues and lead to importance
of the post-translational mechanisms by which enzymes are directed to the lysosome by adding phosphorylated mannose.
Individuals with I-cell disease lack this phosphotransferase activity.
Lysosomal enzymes are glycosylated and modified
In the Golgi complex specific mannose residues are phosphorylated
This phosphorylation directs them towards lysosomes. In absence of Phosphorylation of their mannose residues, these enzymes
are (not directed to lysosomes) but to extracellular space and inclusions accumulate in cell
Specifically, the Golgi apparatus incells of these patients has an abnormal N-acetyl-glucosaminotransferase (N-acetylglucosamine1-phosphotransferase), and is not able to add the necessary recognition marker mannose phosphate to enzymes usually destined
to enter lysosomes. A complete deficiency of this enzyme (type I form of I cell disease) causes death early in life; partial deficiencies
(Type III form) produce milder disease (pseudo-Hurler syndrome) with survival to adulthood
Features:
Coarse facial features
Macroglossia, Gingival hyperplasia
Club foot, club hand
Cardiorespiratory failure

USMLE Case Scenario


A child with coarse facies, corneal clouding, joint stiffness and mental retardation is found to have a partial defect in
N-acetylglucosaminotransferase. Damage to this enzyme directly affects which of the following biochemical functions?
Targeting of enzymes for lysosomes: N-acetylglucosamine-1-phosphotransferase to add the recognition marker mannose
phosphate to enzymes destined to enter lysosomes. Consequently, there is a generalized defect in lysosome function.

Glycolysis
Glycolysis is conversion of glucose to pyruvate under aerobic condition
Glycolysis is conversion of glucose to lactate under anerobic condition
Mature RBC do not contain enzymes of TCA cycle
Glycolysis occurs in cytosol
Cancer cells derive energy by glycolysis
Sodium fluoride is used as an anticoagulant for estimating blood glucose to prevent glycolysis
Flouride inhibits enolase
Glycolysis is regulated at three steps involving irreversible reactions catalysed by enzymes namely
Hexokinase
Phosphofructokinase
Pyruvate kinase

Citric Acid Cycle


Also called Krebs cycle
First substrate is pyruvate

200

USMLE Step 1 Platinum Notes

ATP is produced in steps catalyzed by:


Isocitrate dehydrogenase
Succinate dehydrogenase
Succinate thiokinase
Malate dehydrogenase
Pyruvate dehydrogenase contains:
Decarboxylase
Transacetylase
Dehydrogenase
Substrate level phosphorylation occurs in reaction catalyzed by: Succinyl Co A thiokinase

Glycogen Synthesis
Insulin is produced in the beta cells of the pancreatic islets
It is initially synthesized as a single-chain 86-amino-acid precursor polypeptide, preproinsulin.
The mature insulin molecule and C peptide are stored together and cosecreted from secretory granules in the beta cells
Human insulin is now produced by recombinant DNA technology
Glucose is the key regulator of insulin secretion by the pancreatic beta cell, although amino acids, ketones, various nutrients,
gastrointestinal peptides, and neurotransmitters also influence insulin secretion
Glucose stimulates insulin secretion through a series of regulatory steps that begin with transport into the beta cell by the GLUT2
glucose transporter
Glucose phosphorylation by glucokinase is the rate-limiting step that controls glucose-regulated insulin secretion
Insulin binding to the receptor stimulates intrinsic tyrosine kinase activity, leading to receptor autophosphorylation
In the fasting state, low insulin levels promote hepatic gluconeogenesis and glycogenolysis to prevent hypoglycemia
Low insulin levels decrease glycogen synthesis, reduce glucose uptake in insulin-sensitive tissues, and promote mobilization of
stored precursors
Reduced insulin levels are also permissive in allowing glucagon to stimulate glycogenolysis and gluconeogenesis by the liver and
renal medulla
These processes are of critical importance to ensure an adequate glucose supply for the brain

REGULATION
Glycogen Synthesis
(Glycogen synthetase)
Activated by

Insulin
Glucose

Inhibited by

Glucagon
Epinephrine

Glycogen Breakdown
(Glycogen Phosphorylase)
Activated by

Glucagon
Epinephrine

Inhibited by

Insulin
Glucose

Biochemistry

201

Gluconeogenesis

Occurs from glycerol, alanine, lactate


Major contributor is alanine
Gluconeogenic capability is determined by fructose 1, 6 biphosphate
Enzyme common to gluconeogenesis and glycolysis is phosphofructokinase

Enzymes Controlling

Fructose 1,6 Biphosphate


Pyruvate carboxylase
Phosphoenol pyruvate carboxykinase
Glucose 6 phosphatase

Well Fed State


Ingestion of glucose.blood glucoseinsulin releasephosphatase activityfructose 2,6 biphosphatase

Fasting State
Ingestion of glucose.blood glucoseglucagon releasecAMPProtein kinase fructose 2,6 biphosphatase

Remember: High Yield Points about Important Enzymes


The Three irreversible steps of glycolysis are catalyzed by hexokinase,phosphofructokinase-1 and pyruvate kinase
Fructose-1,6-bisphosphatase is the enzyme that splits fructose-1,6-bisphosphate into fructose-6-phosphate and inorganic
phosphate. It is required for gluconeogenesis
Glucose-6-phosphatase is a liver enzyme that hydrolyzes glucose-6-phosphate to glucose. A deficiency of this enzyme leads to
von Gierke disease, also known as glycogen storage
Pyruvate dehydrogenase is a mitochondrial enzyme that converts pyruvate to acetyl CoA. This enzyme requires thiamine
pyrophosphate, lipoamide, and FAD as cofactors
Glucokinase is a liver enzyme that converts glucose to glucose-6-phosphate. Unlike hexokinase, it is specific for glucose and is
unresponsive to the level of glucose-6-phosphate. Its function is to store excess glucose so it has a very high Km (i.e. a low affinity)
for glucose, becoming active only when the concentration of glucose is very high.

202

USMLE Step 1 Platinum Notes

Pyruvate kinase catalyzes the conversion of phosphoenol pyruvate to pyruvate in the glycolytic pathway. It is activated by
fructose-1, 6-biphosphate, the product of the committed step of glycolysis, and is allosterically inhibited by ATP, alanine, and
acetyl CoA
Glycogen synthase is involved in the synthesis of glycogen. Glucagon (and epinephrine) stimulates the phosphorylation and
inactivation of glycogen synthase
Pyruvate kinase catalyzes the last reaction of glycolysis. It is inhibited by glucagon (thus decreasing the amount of glucose
consumption). Glucagon promotes the phosphorylation of pyruvate kinase, which renders it inactive.

Glucose 6 Phosphate Dehydrogenase Deficiency


A child who develops hemoglobinuria following a meal of beans

It is X linked Recessive
Most common enzyme deficiency
Causes episodic hemolytic anemia because of decreased ability of RBCS to withstand oxidative stress
G6PD is the first and rate limiting step of HMP shunt responsible for NADPH production
NADPH is the cofactor for production for glutathione reductase forming reduced glutathione which is a potent antioxidant
In its absence H2O2 accumulates in RBC causing cell membrane damage leading to hemolysis.
Pallor, Hemoglobinuria, Jaundice, Heinz bodies, Bite Cells are seen.
Oxidized hemoglobin denatures and precipitates in the form of Heinz bodies.

Pyruvate Kinase Deficiency


Pyruvate kinase is a glycolytic enzyme; pyruvate kinase deficiency is an autosomal recessive disorder, affecting males and females
approximately equally.
If this enzyme is deficient, red cells have trouble producing enough ATP to maintain the Na+/K+ pump on the plasma membrane,
secondarily causing swelling and lysis.

HMP Shunt
Present in cytoplasm and also known as Pentose phosphate pathway
No ATP is directly produced or consumed in this cycle
Particularly important in liver and mammary glands

Biochemistry

203

Generates
NADPH
Ribose 5 P for Nucleotide synthesis
Xylulose 5 phosphate
6 Phosphogluconolactone
Glyceraldehydes 3 phosphate
Seodoheptulose 7 phosphate

NADPH is used for

Fatty acid synthesis


Steroid synthesis
Drug metabolism
Glutathione reduction
Generation of superoxide in phagocytes by NADPH oxidase
Uronic acid pathway

ATP Yield

Anaerobic glycolysis: 2 ATP per glucose molecule


Aerobic glycolysis: 8 ATP per glucose molecule
Krebbs cycle: 12 ATP per acetyl co A
HMP Shunt: O
Palitic acid oxidation:129ATP
Stearic acid oxidation: 146 ATP

Remember
Brain, liver, muscles uses glucose as primary fuel
Heart uses fatty acids as primary fuel
In starvation brain and heart use ketone bodies as fuel

Glycogen Storage Diseases


1. von Gierkes
Disease

Glucose-6-phosphatase Protruding abdomen because of marked hepatomegaly, hypotrophic


deficiency
muscles, truncal obesity, a rounded doll face
Severe symptomatic hypoglycemia is frequent, often occurring during the
night or after even short periods of reduced caloric intake
Even minor delays or reduction of carbohydrate intake may provoke
hypoglycemic attacks that are accompanied by lactic acidosis

2. Pompe Disease

Lysosomal alpha-1,
Profound muscle hypotonia, weakness, hyporeflexia, glossomegaly,
4-glucosidase
massive cardiomyopathy without murmurs but no hepatomegaly except
deficiency
with cardiac failure
Acid maltase deficiency The ECG shows a huge QRS complex, left or biventricular hypertrophy and
(AMD),
shortened PR interval

3. Cori Disease

Debranching enzyme

4. Andersons Disease Branching enzyme

Mild Hypoglycemia, Hepatomegaly


Infantile Hypotonia, cirrhosis

204

USMLE Step 1 Platinum Notes

5. Mc Ardle Disease

Muscle Phosphorylase

Increasing intolerance for strenuous exercise


Strenuous muscle activity is accompanied by severe cramps and may be
followed by myoglobinuria, which can precipitate anuria and renal failure

6. Hers Disease

Liver phosphorylase

Pronounced hepatomegaly, without splenomegaly


Protuberant abdomen due to muscle hypotonia are the most striking
features

7. Tauris Disease

Phosphofructokinase
Deficency

USMLE Case Scenario


A 3-month-old boy is evaluated for failure to thrive, seizure. Examination Shows truncal obesity, hepatomegaly. Serum
chemistries demonstrate severe hypoglycemia, hyperlipidemia, lactic acidosis, and ketosis. Which of the following diseases
best accounts for this presentation?
Von Gierkes Disease

USMLE Case Scenario


A 23-year-old engineer to a physician with complaints of severe muscle cramps and weakness with even mild exercise. Muscle
biopsy demonstrates glycogen accumulation, but hepatic biopsy is unremarkable. Which of the following is the most likely
diagnosis?
Mc Ardles Disease

Galactosemia
Galactosemia occurs in two very different clinical forms
Deficiency of galactokinase produces very mild disease with the only significant complication being cataract formation. In contrast,
homozygous deficiency of galactose-1-phosphate uridyltransferase produces severe disease culminating in death in infancy.
In addition to galactosemia and galactosuria, these patients have impaired renal tubular resorption leading to aminoaciduria,
gastrointestinal symptoms, hepatosplenomegaly, cataracts, bleeding diathesis, hypoglycemia, and mental retardation
Pathologically, the CNS shows neuronal loss and gliosis and the liver shows fatty change progressing to cirrhosis.
Three enzyme deficiencies implicated
GPUT Deficiency( Galactose 1 Po4 uridyl transferase) most common
UDP galactose 4 epimerase deficiency
Galactokinase deficiency
AR condition
Newborn presents with failure to thrive, vomiting, diarrhea and Jaundice
Hepatomegaly, Cataract (oil drop cataract), Mental retardation, E.coli sepsis
Cataract because of accumulation of galactilol
Reducing sugar seen in urine
Rapid diagnosis and rapid removal of galactose from diet

Essential Fructosuria

Fructokinase deficiency
AR Condition
Benign, asymptomatic
Fructose accumulates in urine

Biochemistry
Hereditary Fructose Intolerance:
Aldolase B deficiency
Sever hypoglycemia, vomiting, hepatomegaly and hyperuricemia
Hepatic failure and death if not treated

Electron Transport Chain


Electron transport chain is located in inner mitochondrial membrane
Internal respiration is exorgenic and catabolic
Mitochondrial membrane protein contain transporter of NADH, NADPH and ATP
In electron transport chain FADH gives 2 ATP
In electron transport chain NADH gives 3 ATP
Cyanide inhibits cytochrome oxidase
Cyanide inhibits Complex IV
Carbon monoxide, cyanide and azide inhibit cytochrome oxidase
Dinitrophenol is uncoupler of oxidation and phosphorylation
Uncouplers of oxidative phosphorylation are:
Snake venom, Serum bilirubin, T 4, Free fatty acids
Electron Transport Inhibitors
Rotenone, amobarbital, chlorpromazine (complex I)
Antimycin A, BAL, phenformin (complex II)
Cyanide, azide, CO, H2S (complex III)
ATP ase Inhibitors
Oligomycin, atractyloside, bongregate
Uncoupling agents
2, 4 Dinitrophenol

Fatty Acids
Saturated fatty acids:
Butyric acid
Palmitic acid
Stearic acid
Monounsaturated fatty acids:
Oleic acid
Elaidic acid
Polyunsaturated fatty acids PUFA:
Linoleic Acid
Linolenic Acid
Arachdonic Acid

Essential Fatty Acids are

Linoleic acid
Linolenic acid
Ecosopantanoic acid
Docosa Hexanoic acid
Arachidonic acid

205

206

USMLE Step 1 Platinum Notes

Fatty Acid Synthesis


Occurs in cytoplasm
Most fatty acids are synthesized in the liver.
Fatty acids to a lesser extent are also synthesized in Lactating breast, adipose tissue and kidney
Fatty acids are synthesized in cytosol.
Carbon atoms needed for fatty acid synthesis are provided by acetyl COA
Energy for fatty acid synthesis is provided by ATP
Reducing equivalents for fatty acid synthesis are provided by NADPH
The regulated step in fatty acid synthesis is catalyzed by acetyl COA carboxylase which requires Biotin
Citrate is the allosteric activator of enzyme acetyl CO A carboxylase and long chain fatty acyl COA is the inhibitor
Insulin also activates the enzyme
Epinephrine and glucagon inactivate the enzyme
Acetyl co A carboxylase containing Biotin is the rate limiting step
It is activated by insulin (Promotes fatty acid synthesis)
Fatty acid synthetase is a large multi enzyme complex containing Acyl carrier protein, Pantothenic acid.
Ketosis results from a marked increase in free fatty acid release from adipocytes, with a resulting shift toward ketone body synthesis
in the liver. Reduced insulin levels, in combination with elevations in catecholamines and growth hormone, lead to an increase in
lipolysis and release of free fatty acids
In Diabetic Keto Acidiosis, the ketone body, b-hydroxybutyrate, is synthesized at a threefold greater rate than acetoacetate
Ketone body formation occurs in Liver
Ketone bodies are by products of fatty metabolism
Ketone bodies are normally produced from Acetyl CoA
Normal excretion of ketone bodies daily is 1 mg
Ketone bodies are utilized by conversion of acetoactetate to acetoacetyl COA
Ketone body formation without glycosuria is a feature of starvation

Bile
Major components of bile by weight include water (82%), bile acids (12%), lecithin and other phospholipids (4%), and unesterified
cholesterol (0.7)
The primary bile acids, cholic acid and chenodeoxycholic acid (CDCA), are synthesized from cholesterol in the liver
Are conjugated with glycine or taurine
Are excreted into the bile
Secondary bile acids, including deoxycholate and lithocholate, are formed in the colon as bacterial metabolites of the primary
bile acids
In normal bile, the ratio of glycine to taurine conjugates is about 3:1
Bile acids are detergents that in aqueous solutions and above a critical concentration of about 2 mM form molecular aggregates
called micelles
Cholesterol alone is poorly soluble in aqueous environments, and its solubility in bile depends on both the total lipid concentration
and the relative molar percentages of bile acids and lecithin
Normal ratios of these constituents favor the formation of solubilizing mixed micelles, while abnormal ratios promote the
precipitation of cholesterol crystals in bile
Lipoproteins and their clinical significance
Lipoproteins are spherical particles made-up of lipid and protein molecules
The major lipids of the lipoproteins are cholesterol, triglycerides, and phospholipids

Biochemistry

207

Triglycerides and the esterified form of cholesterol (cholesteryl esters) are nonpolar lipids that are insoluble in aqueous
environments (hydrophobic) and comprise the core of the lipoproteins.
Phospholipids and a small quantity of free (unesterified) cholesterol, which are soluble in both lipid and aqueous environments
(amphipathic), cover the surface of the particles, where they act as the interface between the plasma and core components.
Apolipoproteins also occupies the surface of the lipoproteins; the apolipoproteins play crucial roles in the regulation of lipid
transport and lipoprotein metabolism.
Lipoproteins have been classified on the basis of their densities into five major classes:
Chylomicrons
Very low density lipoproteins (VLDL)
Intermediate-density lipoproteins (IDL)
LDL
High-density lipoproteins (HDL)
Chylomicrons

Transports dietary cholesterol/ TG from intestine to tissues(Apo B)

Apo B 48
Apo C II
Apo E

VLDL

Transports TG from Liver to Tissues

Apo B 100
Apo C II
Apo E

LDL

Delivers cholesterol to cells

Apo B 100

IDL
HDL

Apo E
Picks up cholesterol from blood vessels

Apo A1

APOLIPOPROTEINS The apolipoproteins (apos) provide structural stability to the lipoproteins and determine the metabolic fate of
the particles upon which they reside

Important Points to be remembered


LDL has only one apoprotein B100

LDL has the highest Cholesterol content and is most atherogenic


Chylomicrons have highest triglyceride content
Chylomicrons contain Apo A, Apo B, Apo C, Apo E
LDL delivers cholesterol to extrahepatic tissues (Cells)
LDL has scavenging action

LDL receptors are widely present on cell membranes, liver and extrahepatic tissues
After binding with receptors LDL is taken in by endocytosis
A rise of intracellular cholesterol inhibits the synthesis of new LDL receptors
HDL is good as it scavenges body cholesterol and transports cholesterol from liver to tissues. (reverse cholesterol transport)

Secondary Hyperlipidemias
Disease
Diabetes
Nephritic syndrome
Hypothyroidism
Biliary obstruction

Serum cholesterol
Increased
Increased
Increased
Increased

Serum triglyceride
Increased
Increased
Increased
Normal
Contd...

208

USMLE Step 1 Platinum Notes

Contd...

Disease
Pregnancy
Alcoholism
Oral contraceptives

Serum cholesterol
Normal
Normal
Normal

Serum triglyceride
Increased
Increased
Increased

Familial Hypercholesterolemia

FH is due to mutations in the gene for the LDL receptor and is genetically heterogeneous
Plasma levels of LDL cholesterol are elevated at birth and remain so throughout life
In untreated adults, total cholesterol levels range from (275 to 500 mg/dL)
Plasma triglyceride levels are typically normal, and
HDL cholesterol levels are normal or reduced

As would be expected of a disorder with decreased numbers of LDL receptors, the fractional clearance of LDL apo B is reduced
LDL production is increased because the liver secretes more VLDL and IDL and more IDL particles are converted to LDL rather
than taken up by the hepatic LDL receptors
FH heterozygotes usually develop severe atherosclerosis in early or middle age
Tendon xanthomas, which are due to both intracellular and extracellular deposits of cholesterol, most commonly involve the
Achilles tendons and the extensor tendons of the knuckles
Tuberous xanthomas, which are softer, painless nodules on the elbows and buttocks,
Xanthelasmas, which are barely elevated deposits of cholesterol on the eyelids, are common
Successful therapy should be aimed at increasing Apo B 100 receptor gene products in hepatocyte cell membranes
Type II Familial Hyper cholestrolemia is due to defective LDL receptors with high LDL and cholesterol levels
Type I Familial Hyperlipoproteinemia is due to deficiency of lipoprotein lipase or Apo C II with increased chylomicrons and
triglycerides
Familial hypercholesterolemia, which is due to defective function of the LDL receptor
More than 200 mutations in the gene for the LDL receptor have been identified. The gene has 5 general domains and 18 exons.
Defects near exons 7 to 14 are in the region of homology with epidermal growth factor receptor precursor. This region of the molecule
is needed for dissociation of LDL from the receptor in the endosome. Receptors with a defect in this area (sometimes called class II
mutations) also have trouble being initially transported to the Golgi complex (transport-deficiency alleles) and become trapped in
endoplasmic reticulum.

Familial Lipoprotein Lipase Deficiency


Autosomal recessive disorder:
It is due to the severe impairment or absence of LPL, leading to massive accumulation of chylomicrons in plasma
Manifestations begin in infancy and include pancreatitis, eruptive xanthomas, hepatomegaly, splenomegaly, foam cell
infiltration of the bone marrow and when the level of triglycerides is (1000 mg/dL), lipemia retinalis. Atherosclerosis is not
accelerated
The diagnosis is suspected by finding a creamy layer (chylomicrons) at the top of plasma that has incubated overnight;

Abetalipoproteinemia

It is AR disease
Defective synthesis or secretion of Apo B with
Low levels of chylomicrons, VLDL and LDL
Low levels of Cholesterol and Triglycerides

Biochemistry

209

Clinical features include:


Fat Malabsorption
Failure to thrive
Neuropathy
Spinocerebellar degeneration
Retinitis pigmentosa
Acantholysis
Treatment is with low fat, High calorie diet
Chylomicrons are Lipoproteins lowest in density
Chylomicrons are Lipoproteins largest in size
Chylomicrons are Lipoproteins with highest percentage of lipid
Chylomicrons are Lipoproteins lowest percentage of protein
Lipid Metabolism Disease

Deficiency

Fabrys

Alpha galactoside- A (Ceramide trihexoside accumulates)

Niemann- Picks

Sphingomyelinase (RBC appear as foam cells)

Tay- Sachs

Hexosaminidase A

Sandhoff disease

Hexosaminidase A and B

Krabbe Leukodystrophy

Galacto Cerebrosidase

Metachromatic Leukodystrophy

Arylsulfatase A

Gaucher disease

Gluco Cerebrosidase

Tangier Disease

Lipid Metabolism Disturbed (Low Alpha lipoprotein)

Gauchers Cells
Glucocerebrosides accumulate in massive amounts within phagocytic cells throughout the body in all forms of Gaucher disease. The
distended phagocytic cells, known as Gaucher cells, are found in the spleen, liver, bone marrow, lymph nodes, tonsils, thymus, and
Peyer patches. Similar cells may be found in both the alveolar septa and the air spaces in the lung.

Tangiers Disease

lpha lipoprotein (HDL)deficiency


HDL,
LDL,
Apo A because of high catabolic rates; abnormal cholesterol uptake into and/or efflux from macrophages; increased apo AI
clearance
Large orange tonsils
Corneal opacities
Relapsing polyneuropathy
No premature atherosclerosis
It is a rare familial disorder characterized by alpha-lipoprotein deficiency, which leads to very low high-density lipoprotein
(HDL), recurrent polyneuropathy, lymphadenopathy, and hepatosplenomegaly due to storage of cholesterol esters in
reticuloendothelial cells. The association of orange-yellow tonsillar hyperplasia (due to the cholesterol ester deposition there as
well) with Tangier disease is a sufficiently distinctive clue in physical diagnosis to be worth remembering.

210

USMLE Step 1 Platinum Notes

Lecithin: cholesterol acyltransferase (LCAT) deficiency (Fish-eye disease)


Decreased LCAT activity in plasma leads to accumulation of excess unesterified cholesterol in plasma and body tissues
Total plasma cholesterol level variable with
Decrease in esterified cholesterol and
Increase in unesterified cholesterol
Elevated VLDL level; structure of all lipoproteins is abnormal
Corneal opacities, hemolytic anemia, renal insufficiency, premature atherosclerosis

Wolmans Disease
AR disorder
Lipid storage disease
Lysosomal acid lipase deficiency causes accumulation of triglycerides,cholestrylesters and other fats within the cells of affected
individuals
Lipids accumulate in various organs
Calcification of adrenals
Hepatospleenomegaly, poor weight gain, anemia, jaundice, and features of severe malnutrition occur
Lipid Mobilization:
Adipose Tissue breakdown yields Fatty acids plus Glycerol
Hormone sensitive lipase is responsible
Hormone sensitive lipase is activated by:
Epinephrine
Insulin
Cortisol
Sphingolipids
Sphingomyelin: Phosphorylcholine
Cerebrosides: Galactose or glucose
Gangliosides: N acetyl neuraminic acid
Disease

Enzyme deficiency

Substance Accumulated

Symptoms

Tay sachs

Hexosaminidase

Ganglioside

Cherry red spot in macula


Psychomotor retardation

Gauchers

Glucocerebrosidase

Glucocerebroside

Erosion of bones
Hepatosplenomegaly
Crumpled paper inclusions in macrophages

Niemann Picks

Sphingomyelinase

Sphingomyelin

Cherry red spot in macula


Mental
Retardation
Zebra body inclusions
Foamy Macrophages

Tay-Sachs Disease
An autosomal recessive disorder caused by the deficiency of hexosaminidase A, which leads to the accumulation of
ganglioside GM2 in neurons, producing a degenerative neurologic disease. Children appear normal at birth, but then begin to
suffer from diminished responsiveness, deafness, blindness, loss of neurologic function, and seizures. A cherry-red spot on the

Biochemistry

211

macula may be seen by ophthalmoscopic examination. The incidence is higher among Jews of Eastern European descent. Since
the parents must be heterozygotes for the mutant hexosaminidase. A allele, they would be expected to have diminished levels of
the enzyme.

Ketoacidosis
Occurs In type I IDDM
Urinary Acetoacetate, Hydroxy butyrate
Urinary Nitroprusside test Positive
The hyperglycemia of DKA results from increased hepatic glucose production (gluconeogenesis and glycogenolysis) and
impaired peripheral glucose utilization
The decreased ratio of insulin to glucagon promotes gluconeogenesis, glycogenolysis, and ketone body formation in the
liver, as well as increasing substrate delivery from fat and muscle (free fatty acids, amino acids) to the liver
Insulin deficiency also reduces levels of the GLUT4 glucose transporter, which impairs glucose uptake into skeletal muscle
and fat and reduces intracellular glucose metabolism

Amino Acid Metabolic Defects


Phenylketonuria:

Phenylalanine Hydroxylase

Mental retardation, seizures, hyperactivity


Tremor

Mousy odor of urine

Microcephaly, Hypopigmentation
Failure to grow are features
Musty urine
Alkaptonuria:

Homogentisate oxidase

Urine darkens on standing


Pigmentation of the sclerae and ears
Generalized darkening of the concha, anthelix and
helix of the ear are typical
Arthritis
Pigmentation of heart valves, larynx, tympanic
membranes, and skin
Arthritis

Maple syrup urine disease (MSUD)

Branched chain Ketoacid Valine, Leucine, Isoleucine defect


dehydrogenase
Maple syrup urine
Lethargic baby, Loses weight, Ketosis, Coma

Homocystinuria

Cystathionine synthetase

Mental retardation, MI, Osteoporosis


Dislocation of lens

(Abnormal methionine metabolism)

It is inherited as AR triat
Patients can be responsive to Vitamin B6
(Pyridoxine)
Albinism

Tyrosinase

White hair
Photosensitivity
Strabismus
Nystagmus
Photophobia

212

USMLE Step 1 Platinum Notes

USMLE Case Scenario


A 10-year-old girl is seen by a doctor for removal of multiple squamous cell carcinomas of the skin. The patient has nearly
white hair, pink irises, very pale skin, and a history of burning easily when exposed to the sun. This patients condition is
albinism
The most common form of albinism is caused by a deficiency of copper-dependent tyrosinase (tyrosine hydroxylase), blocking the
production of melanin
From the aromatic amino acid tyrosine. Affected individuals lack melanin pigment in skin, hair, and eyes, and are prone to develop
sun-induced skin cancers, including both squamous cell carcinomas and melanomas
This question is simple if you know that tyrosinase is an enzyme in the
Biosynthetic pathway for melanin formation from tyrosine. A lack of tyrosinase causes one form of albinism; a second form is
caused by defective tyrosine uptake
Patients with albinism are:
Vulnerable to developing cancers of the skin of all types, including basal cell carcinoma, squamous cell carcinoma, and
melanoma. The melanomas are unusual in that they are non-pigmented (amelanotic) rather than black, since the patients
cannot form melanin.

Albinism
It is an example of an inborn error in which the pathophysiologic mechanism is directly related to the lack of an end
product. Tyrosine is converted by the action of a cytosolic tyrosinase first to dopa and then dopamine.
Dopamine can then be converted either to the red-yellow pigment phenomelanin or to the black-brown pigment
eumelanin. These reactions occur in the melanosomes produced in the melanocytes and exported to the keratinocytes.
Color of skin is an inherited factor that depends on several genes and is a function of the intensity of the pigment in
the skin and not the number of melanocytes, which is constant for all humans. Although skin color is a polygenic trait,
single genes can have a profound effect on this color, as evidenced by the albino phenotype. In humans, oculocutaneous
albinism (OCA) is inherited as an autosomal recessive trait.
An X-linked and autosomal recessive form of ocular albinism also exists. Individuals with OCA are classified as either
tyrosinase-negative or positive for tyrosine activity in hair bulbs. Tyrosinase-negative individuals form no pigment, and
prenatal monitoring for tyrosinase activity in cultured amniocytes is possible.
A tyrosinase-positive OCA has been associated with an autosomal recessive gene located on chromosome 15q11-13 (the
P gene). A wide variation in phenotypic expression of OCA is reported from very severe neurologic deficiency with ocular
and sarcomatous skin cancers to mild cosmetic problems.

Amino Acid Transport Defects


Cystinuria
Defective transport of Basic amino acids (COAL: Cystine, Ornithine, Arginine, Lysine)
Cystine calculi and cystine crystals in urine
Cyanide Nitrosoprusside Test positive

Hartnups Disease
Defective renal and intestinal transport of Tryptophan
Malabsorption, Ataxia, Pellagrous rash

USMLE Case Scenario


A 10-year-old child is suspected of having pellagra because of chronic symptoms including diarrhea, a red scaly rash, and mild
cerebellar ataxia. However, his diet is not deficient in protein and he appears to be ingesting adequate amounts of niacin.
A sister has a similar problem. Chemical analysis of his urine demonstrates large amounts of free amino acids. Which of the
following is the most likely diagnosis?

Biochemistry

213

1. Alkaptonuria
2. Carcinoid syndrome
3. Ehlers-Danlos syndrome
4. Hartnups disease
5. Scurvy
Ans. 4. Hartnups disease
The child has Hartnups disease. This condition clinically resembles pellagra (diarrhea, dementia, and dermatitis), and may
be misdiagnosed as this nutritional (niacin) deficiency. In fact, niacin therapy may actually be helpful in controlling the
symptoms. The underlying problem is a defect in the epithelial transport of neutral amino acids, including tryptophan, which
can act as a precursor of niacin. The defective amino acid transport leads to poor absorption of dietary amino acids as well as
excess amino acid secretion in the urine.

Fanconis Syndrome
Generalized Tubular damage
Aminoaciduria, Glycosuria, Phosphaturia (AGP)
Renal Tubular disorders, Progressive Renal Failure
Exopeptidases:
Carboxypeptidases
Aminopeptidase
Prolidase
Endopeptidases:
Elastase
Trypsin
Chymotrypsin
Collagenase

Urea Cycle

Takes place in liver and brain


1st two reactions occur in mitochondria
1st two reactions are rate controlling reactions
Combination of Hyperammonemia+ Blood Glutamine+Blood urea suggests defect in Urea Cycle. Lethargy, vomiting, coma
are associated

Genetic Defects in Urea Synthesis


Carbomyl Phosphate Synthetase
Ammonia +Blood Glutamine+Blood urea

Ornithine Transcarbomylase
Ammonia +Blood Glutamine+Blood urea

No increase in Uracil or orotic acid

Increase in Uracil or orotic acid

Urea Cycle Disorders


Diseases
Hyperammonemia
type 1
Hyperammonemia
type 2

Enzyme deficit
CPS-I
(OTC) Ornithine
transcarbamoylase

Features
Very high NH3 level levels in blood. Autosomal recessive
Mental retardation
Ammonia level high in blood
Increased glutamine in blood, CSF and urine
Orotic aciduria due to the channelling of carbamoyl phosphate into Pyrimidine
synthesis
Xlinked
Contd...

214

USMLE Step 1 Platinum Notes

Contd...

Diseases
Hyperornithinemia

Enzyme deficit
Defective ornithine
transporter protein

Features
Failure to import ornithine from cytoplasm to mitochondria
Defect in ORNT1 gene
Hyperornithinemia, hyperammonemia and homocitrullinuria is seen (HHH
syndrome)
Decreased urea in blood
Autosomal recessive condition.

Citrullinemia

Argininosuccinate
synthetase

Autosomal recessive inheritance. High blood levels of ammonia amd citrulline.


Citrullinuria (12 g/day).

Argininosuccinic
aciduria

Argininosuccinate
lyase

Argininosuccinate in blood and urine. Friable brittle tufted hair (Trichorrhexis


nodosa).

Hyperargininemia

Arginase

Arginine increased in blood and CSF. Instead of arginine, cysteine and lysine
are lost in urine.

Ammonia is Generated

From amino acids: by Aminotransferase and Glutamate dehydrogenase


From urea by urease
From amines by amine oxidase
From glutamine by glutaminase

Defects of Purine and Pyrimidine Metabolism


Orotic Aciduria

Orotic acid
phosphoribosyltransferase/
OMP decarboxylase

Autosomal recessive
A newborne with Megaloblastic anemia
Lack of pyrimidine synthesis with orotic acid crystals in urine
needed for hematopoesis

Lesch Nyhan
Syndrome

Deficiency of HGPRT

X linked recessive

A child with cerebral palsy,repeated self


biting and needle shaped crystals in urine
with hyperuricemia

Autosomal recessive

A boy with severe immunodeficiency with


B and T cells

Severe combined
Adenosine deaminase
immunodeficiency deficency
SCID

USMLE Case Scenario


A baby that was apparently normal at birth begins to show a delay in motor development by 6 months of age. At three year
of age, the child begins to develop spasticity and writhing movements. At age four, compulsive biting of fingers and lips
and head-banging appear. At puberty, the child develops arthritis, and death from renal failure occurs at age 21
The patient has a classical case of Lesch-Nyhan syndrome, an X-linked disorder due to severe deficiency of the purine
salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). This defect is associated with excessive de
novo purine synthesis, hyperuricemia, and the clinical signs and symptoms described. The biochemical basis of the often
striking self-mutilatory behavior. Treatment with allopurinol inhibits xanthine oxidase and reduces gouty arthritis, urate
stone formation, and urate nephropathy
A Partial deficiency of HPRT, the Kelley-Seegmiller syndrome, is associated with hyperuricemia but no central nervous system
manifestations

Allopurinol
Allopurinol and its metabolite, oxipurinol (alloxanthine), decrease the production of uric acid by inhibiting the action of xanthine
oxidase, the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid.

Biochemistry

215

Allopurinol thereby decreases uric acid concentrations in both serum and urine
Also, allopurinol increases reutilization of hypoxanthine and xanthine for nucleotide and nucleic acid synthesis via an action
involving the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase)
The resultant increase in nucleotide concentration leads to feedback inhibition of de novo purine synthesis.

Hyperuricemia

Increased Purine synthesis: Lesch Nyhan Syndrome,Type I glycogen storage disease


Increased Purine Turnover: High purine diet, Myeloproliferative disorders, Exfoliative diseases (Psoriasis)
Decresed uric acid excretion: Primary gout, Renal failure, alcohol, starvation
Drugs:
Thiazides
Loop diuretics
Pyrimidine
Ethambutol
Salicylates
Cytotoxic agents

USMLE Case Scenario


A 47-year-old male patient presents with painful arthritis in the right big toe and uric acid renal stones. He has been
taking allopurinol for his condition. He is suffering from Gout
This patient has gout, characterized by painful joints due to the precipitation of uric acid crystals caused by excessive
production of uric acid (a minority of cases are associated with underexcretion of uric acid)
Kidney disease is also seen due to accumulation of uric acid in the tubules. The disease mostly affects males, and is
frequently treated with allopurinol, an inhibitor of xanthine oxidase. Xanthine oxidase catalyzes the sequential oxidation
of hypoxanthine to xanthine to uric acid.

Important Molecules/Substances Frequently asked In Examinations


Glycoproteins
Glycoproteins are also called mucoproteins
Glycoproteins are proteins that have oligosaccharide side chains covalently attached to their polypeptide back bones
Most of the plasma proteins in humans except albumin are glycoproteins
Certain hormones (HCG, TSH) are also glycoproteins
Glycoproteins contain N terminal signal sequences which direct the growing polypeptide chain to ER (Endoplasmic Reticulum
and Golgi Complex) where Carbohydrates are added and Proteins are sorted to their proper destination.
Functions of glycoproteins:
Cell surface recognition
Cell surface antigenicity
Components of extracellular matrix
Composition of globular proteins in plasma

Glycosaminoglycans
(GAG) Glycosaminoglycans are large complexes of negatively charged, unbranched heteropolysaccharide chains usually
composed of repeating disaccharide units
They produce gel like matrix and hold large quantities of water
They are also called as mucopolysaccharides

216

USMLE Step 1 Platinum Notes

They are synthesized in Golgi bodies


They are degraded by lysosomal hydrolases
Deficency of lysosomal hydrolases results in accumulation of GAG causing mucopolysaccharidoss. Examples are:
Chondritin 4 sulfate
Chondritin 6 sulfate
Heparin
Heparin sulfate
Keratin sulfate
Dermatin sulfate
Hyaluronic acid

Glutathione
Glutathione is a tripeptide (Glutamyl-cysteinyl-glycine) present in most cells. It serves as an important reducing agent along
with ascorbate, vitamin E and beta carotene
It detoxifies hydrogen peroxide. This reaction catalyzed by selenium requiring glutathione peroxidase forms oxidized glutathione
After this cells regenerate the essential glutathione in a reaction catalyzed by glutathione reductase
Glutathione also helps in transport of certain amino acids into the cell
It has electron donating properties and functions as an intracellular reducing agent (antioxidant effects).
Reduced glutathione detoxifies hydrogen peroxide
It acts as a carrier of amino acids in kidney
It helps in conjugation reactions and detoxification of xenobiotics
Following an acute ingestion of Acetaminophen, sulfate and glucuronide pathways become saturated, resulting in an increased
fraction and amount of acetaminophen metabolized to NAPQI and eventual glutathione depletion when this occurs, free NAPQI
binds covalently to hepatocytes and causes their lysis (centrilobular necrosis). Less often, hepatotoxicity develops following the chronic
ingestion of therapeutic or slightly greater amounts in conditions associated with decreased glutathione reserves (e.g. alcoholism,
childhood, acute starvation, chronic malnutrition).

Other Antioxidants

Vitamin A
Vitamin E
Vitamin C
Catalase
Superoxide dismutase
NADPH

PAF
PAF is a potent Glycerophospholipid and a phospholipid activator and mediator of leucocyte functions such as inflammation,
platelet aggregation, anaphylaxis
Neutrophils, basophils, platelets and endothelial cells produce PAF
PAF Mediates bronchoconstriction
PAF Causes platelet aggregation

Prostaglandins
LTA4:
Produced in leucocytes, platelets, mast cells, vascular tissue

Biochemistry

217

LTC4, LTD4, LTE4:


Contraction of smooth muscle
Bronchoconstriction
Vasoconstriction
vascular permeability
Components of SRSA
LTB4:
Chemotaxis
Adhesion of WBC
Release of lysosomal enzymes
Thromboxanes:
Produced mainly in platelets
Promotes platelet aggregation
Vasoconstriction
Smooth muscle contraction
Prostacyclins:
Produced by endothelium of vessels
Vasodilation
Inhibits platelet aggregation
Cortisol inhibits Phospholipase A2
Aspirin, Indomethacin, Phenylbutazone inhibit Both COX 1 and COX 2
Coxibs are selective COX 2 inhibitors (Celecoxib)

Ionophores
Ionophores are organic molecules synthesized by microbes to facilitate movement of ions across membranes
Their properties are because of lipophilic nature and penetrate lipid membranes
They have hydrophilic core and hydrophobic periphery
Valinomycin is an ionophore
Representative ionophores (with the ion(s) they act upon)
1. 2, 4 - Dinitrophenol (H+)
2. Beauvericin (Ca2+, Ba2+)
3. Gramicidin A (H+, Na+, K+)
4. Ionomycin (Ca2+)
5. Monensin (Na+, H+)
6. Nigericin (K+, H+, Pb2+)
7. Salinomycin (K+)
8. Valinomycin (K+)

Zellwegers Syndrome
Peroxisomes are single membrane organalles that are responsible for oxidation of fatty chains. Deficiency of Peroxisomes causes
Zellwegers syndrome with accumulation of long chain fatty acids.

Rate Limiting Steps

Cholesterol synthesis
Ketone body synthesis
Fatty acid synthesis
Bile acid synthesis

HMG CoA reductase


HMG CoA Synthetase
Acteyl Co A Carboxylase
7 hydroxylase

218

USMLE Step 1 Platinum Notes

Important Inhibitors of Medically Important Enzymes

Xanthine oxidase:
Folate reductase:
Lactate Dehyrogenase:
Dihydrofolate reductase:
Vitamin K synthesis:

Allopurinol
Methotrexate
Oxamates
Amethroptin
Dicumarol

Diagnostic Techniques
Blot Type

Material Analyzed

Southern blot
ASO titer

DNA
DNA

Northern blot
Microarray

RNA
RNA or c DNA

Western blot
ELISA
Proteomics

Protein
Protein/antibodies
Proteins

Dot Blot

DNA, RNA or Protein

Proteomics: Study of all proteins expressed in a genome, including their abundance, distribution, post translational modification,
function and interaction with other molecules.
DNA library: Collection of cloned restriction fragments of DNA of an organism
Genomic library: It is a collection of fragments of double stranded DNA obtained by digestion of total DNA of an organism with
restriction endonucleases and subsequent ligation to appropriate vector.
Probe: It is a single stranded piece of DNA usually labeled with radio isotope that has nucleotide sequence complimentary to DNA
molecule of interest
Nucleotide sequence of a probe is complimentary to DNA of interest called Target DNA
Vector is a molecule of DNA to which fragment of DNA to be joined is attached.

Polymerase Chain Reaction


The polymerase chain reaction (PCR) is now the most frequently used technique in molecular biology.
Used to study a specific area of DNA using short complementary sequences of DNA (oligonucleotides) from both the 3 and the 5
ends of the DNA to be studied.
These oligonucleotides build copies of the DNA (amplifies) using a heat stable polymerase (Taq 1).
It is then possible to heat the mixture and the DNA strands will separate.
On cooling, the DNA can once more be duplicated and the process repeated again and again leading to an exponential increase
in the copies of the two fragments.
The main advantages of this technique are that it is very quick, highly sensitive and very robust and it can be used to study
mRNA as well as DNA.
It can also be used to study very small amounts of almost any tissue, e.g. the blood spots on a Guthrie card or the cells found in a
mouth wash sample.
The technique is widely used in molecular diagnosis of genetic disease. It is also being used in infectious disease to confirm the
presence of infectious agents and in immunology to identify the human leukocyte antigen (HLA) haplotype.

Biochemistry

219

Ion-exchange Chromatography
Process in which exchange of ions in solution form with that on to surface form occurs in is Ion exchange:
Ion-exchange chromatography is a process that allows the separation of ions and polar molecules based on their charge.
It can be used for almost any kind of charged molecule including large proteins, small nucleotides and amino acids. The solution
to be injected is usually called a sample, and the individually separated components are called analytes.
It is often used in protein purification, water analysis, and quality control. Ion exchange chromatography retains analyte molecules
on the column based on coulombic (ionic) interactions.
The stationary phase surface displays ionic functional groups (R-X) that interact with analyte ions of opposite charge. This type of
chromatography is further subdivided into cation exchange chromatography and anion exchange chromatography.
The ionic compound consisting of the cationic species M+ and the anionic species B-can is retained by the stationary phase.
Cation exchange chromatography retains positively charged cations because the stationary phase displays a negatively charged
functional group.

Salting out

Proteins are purified using differences in protein solubility in varying salt concentrations
The solubility of proteins varies according to the ionic strength of the solution and hence according to the salt concentration
Two distinct effects are observed
At low salt concentrations, the solubility of the protein increases with increasing salt concentration (increasing ionic strength),
and effect termed salting in
As the salt concentration (ionic strength) is increased further, the solubility of the protein begins to decrease
At high ionic strength, the protein will be almost completely precipitated from the solution (salting out)
Since proteins differ markedly in their solubilities at high ionic strength, salting-out is a very useful procedure to assist in the
purification of a given protein. The commonly used salt is Ammonium sulfate, as it is very water soluble
The ammonium sulfate concentration is increased stepwise, and the precipitated protein is recovered at each stage
The precipitated protein is then removed by centrifugation and then the ammonium sulfate concentration is increased to a value
that will precipitate most of the protein of interest whilst leaving the maximum amount of protein contaminants still in solution
This technique is useful to quickly remove large amounts of contaminant proteins, as a first step in many purification schemes. It is
also often employed during the later stages of purification to concentrate protein from dilute solution following procedures such
as gel filtration.

Restriction Fragment Length Polymorphism (RFLP)


It is a difference in homologous DNA sequences that can be detected by the presence of fragments of different lengths after
digestion of the DNA samples in question with specific restriction endonucleases
It is a DNA Variation sequence
RELP, as a molecular marker, is specific to a single clone/restriction enzyme combination
An RFLP probe is a labeled DNA sequence that hybridizes with one or more fragments of the digested DNA sample after
they were separated by gel electrophoresis, thus revealing a unique blotting pattern characteristic to a specific genotype at a
specific locus. Short, single-or-low-copy genomic DNA or cDNA clones are typically used as RFLP probes
RFLPs are visualized by digesting DNA from different individuals with restriction enzyme, followed by gel electrophoresis
to separate fragments according to size, then blotting and hybridization to a labeled probe that identifies the locus under
investigation. An RFLP is demonstrated when ever the Southern blot pattern obtained with one individual is different from the one
obtained with another individual
RFLP is an important tool in
Genome mapping
Localization of genes from genetic disorders
Determination of risk for diseases, and paternity testing
Test which uses oligomer with single base pair substitution: RFLP

220

USMLE Step 1 Platinum Notes

Paper Chromatography
Technique for identification and determination of amino acids
The Principle: A small amount of solvent is put at the bottom of a jar. A strip of absorptive paper, with a concentrated spot of the
mixed amino acids near the bottom, is suspended in the jar so that its end dips into the solvent. The solvent moves slowly up the
strip of paper, carrying the amino acids with it. As the amino acids travel at different speeds, they separate from one another. The
paper is then treated with a reagent which strains the amino acids so they can be detected and identified. The location reagent
used for amino acids is ninhydrin
Chromatography paper contains about 1520% water, held to the paper fibers. This water acts as the stationary phase in paper
chromatography. Amino acids are separated according to their solubility in the water and in an organic solvent (the mobile
phase) moving up the paper. The most non-polar amino acids migrate the furthest, due to their greater solubility in the organic
solvent
Paper also acts as an adsorbent, having an affinity for polar groups.

Amino Acids
Phenylalanine and Tyrosine are precursors of Cathecolamines.
Tryptophan is precursor for Serotonin, Niacin.
Valine and isoleucine are branched chain amino acids whose metabolism is abnormal in MSUD. (Maple Syrup Urine Disease).
Proline has an imino group.
Essential AA: Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine.
Histidine is a buffer at normal pH. It can protonate or deprotonate.
Glycine is the smallest and simplest AA.
Glycine is responsible for flexibility of proteins.
Hydrophilic AA are present on outer surface of membrane.
Hydrophobic AA are present in transmembrane region
Most of the amino acids do not absorb visible light and hence are colorless
Aromatic amino acids are the only amino acids that absorb light. They are:
Tryptophan (contains indole ring)
Tyrosine
Phenylalanine
Histidine
Tryptophan is the major amino acid contributing to ability to absorb light in the range of 250290 nm.

Biochemistry

221

Glucogenic amino acids are:


Alanine, Arginine, Asparagine, Aspartate
Cysteine
Glutamate, Glutamine, Glycine
Methionine, Theronine, Valine
Ketogenic Amino acids are:
Leucine, Lysine

Mechanism Pathway of Important Enzymes


Pathway

G protein

Protein Kinase

Examples

c AMP

Adenyl cyclase

Protein Kinase A

Glucagon
Epinephrine

PIP2

Phospholipase

Protein Kinase B

Vasopressin

C GMP

Guanyl cyclase

Protein Kinase C

ANF
NO

Proteins
1o Structure specific order of Amino Acids in peptide chain
2o Structure spatial relationship of neighboring Amino Acid residues, e.g. Helix
3o Structure spatial relationship of distant Amino Acid residues by arrangement of secondary structure
4o Structure spatial relationship between individual Polypeptide chains

Alpha Helix, Beta Sheet and Beta Bends are Secondary Structures
Alpha helix can be composed of more than one polypeptide chains. It is a spiral structure with polypeptide backbone and side
chains of amino acids
It is stabilized by hydrogen bonds
Each turn of the helix has 3.6 amino acids
Proline disrupts alpha helix because of geometric incompatibility of imino group of proline
Beta sheets are secondary structures in which all peptide bonds are involved in hydrogen bonding
Beat sheets are both parallel and anti parallel
Beta bends are also called reverse turns
Beta bends often contain glycine
Proline can also be present
Motifs are super secondary structures
Domains are a type of tertiary structure

222

USMLE Step 1 Platinum Notes

Levels of protein structure


Hydroxylation of proline in fibroblasts generates the modified amino acid hydroxyproline. This is an example of post-translational
modification.
Hydroxyproline is involved in stabilizing the three-dimensional triple helix structure of collagen.
Cysteine is unique in its ability to form a covalent disulfide bond with another cysteine residue elsewhere in the protein molecule,
thereby forming a cystine residue.
Such strong disulfide bonds stabilize the three-dimensional structure of the protein.
Glycine is abundant in fibroblasts since it constitutes every third amino acid in the primary sequence of collagen. However, glycine
is not hydroxylated.
Serine tyrosine and threonine can all be phosphorylated post-translationally to form phosphoserine, phosphotyrosine, and
phosphothreonine, respectively. These phosphorylated amino acids are believed to play a role in signal transduction.
Primary structure: Peptide bonds
Secondary structure: hydrogen bonds
Tertiary structure: disulfide bonds

Important Elements

Magnesium: Kinases, Phosphatases, Ribonuclease, Adenyl cyclase, Transketolase


Copper: Cytochrome Oxidase, Tyrosinase, Superoxide dismutase
Zinc: Carboxy peptidase
Molybedenum: Xanthine Oxidase
Manganese: Pyruvate Carboxylase

Effects of Mineral Deficiencies


Arsenic (Impaired growth, infertility)
Boron (Impaired energy metabolism, Impaired brain function)
Nickel (Impaired-growth and reproduction)
Silicon (Impaired growth) and
Vanadium (Impaired skeletal formation)

Biochemistry
Zn is a cofactor in many enzymes. Some of the important ones are:
Carbonic anhydrase
Lactate/Alcohol Dehyrogenase
DNA polymerase
RNA polymerase
Alkaline phosphatase

Globulins
Alpha 1 globulins: AFP, 1 AT, Trypsin
Alpha 2 globulins: Cerruloplasmin, Haptoglobin
Beta globulin: Transferrin, CRP, Hemopexin

Important Tests in Biochemistry


Zwengers test: Cholesterol
Fouchets test bile pigments
Hays sulfur test bile salts
Xanthoproteic test: Proteins
Selivanoffs test: Fructose in urine
Rotheras test: Ketone bodies
Gerhardts test: Ketosis
Molishs test: Color test for sugar
Guthries test: Phenylketonuria
Exton Rose test: Glucose Tolerance test
Cyanide nitroprusside test: Phenyl ketonuria
Benedicts test: Glucose in urine
Sulkowitz test: Urinary calcium
Biurate test: protein

Heme Protein
1. Cytochrome
2. Hemoglobin
3. Myoglobin
4. Catalase
Heme proteins are specialized proteins containing Heme as a prosthetic group
Heme itself is a complex of Protoporphyrin IX and Ferrous iron
Hemoglobin binds four molecules of oxygen
Hemoglobin exists in two forms Deoxygenated form or (T) Taut form and
Oxygenated form or (R) relaxed form
Oxygen dissociation curve of Hb is sigmoidal

223

224

USMLE Step 1 Platinum Notes

Myoglobin binds one molecule of oxygen


Oxygen dissociation curve of Myoglobin is Hyperbolic

Gems about Hemoglobin


Earliest Hemoglobin

Hb Gowers
Hb Fetal
Hb Adult
Hb A2

22
22
22
22

Configuration of Hemoglobins

Most common Hb is: HbA


Adult Hb is HbA is: 22
Fetal Hb is Hb F is: 22
Minor Adult Hb is HbA2 is: 22

Clinically Important Points About


Methemoglobin

Form of oxidized HB
(Fe2+ replaced by Fe3+)
Oxygen carrying capacity
Phenacetin, Primaquine, Sulfonamides, Nitrites, Nitrates cause Methemoglobinemia.

Carboxy Hemoglobin
Hb combines with CO (Carbon Monoxide NOT Dioxide) to form Carboxy Hemoglobin
Affinity of Hb for CO is 200 times more than that of O2, hence CO displaces O2

Glycosylated Hemoglobin

Adult Hb binds with glucose during 120 day life cycle of RBC
It is an irreversible reaction
Normally up to 9% of adult Hb is Glycosylated
In diabetes >9 % Hb is glycosylated
It is useful for providing picture of long-term state of diabetic control

Important Inhibitors of Medically Important Enzymes

Xanthine oxidase
Folate reductase
Lactate Dehyrogenase
Dihydrofolate reductase
Vitamin K synthesis

Allopurinol
Methotrexate
Oxamates
Amethroptin
Dicumarol

Biochemistry

Aconitase
Citrate
ketoglutarate dehydrogenase arsenate
Succinate dehydrogenase
Enolase
Glyceraldehydes 3 phosphate

Flouroacetate
Flouroacetate
Malonate
Fluoride
Iodoacetate

Metabolic Functions of Subcellular Organelles


Organelle
Nucleus
Endoplasmic
Reticulum

Golgi body
Lysosome
Mitochondria

Cytosol

Function
DNA replication, transcription
Biosynthesis of proteins, glycoproteins, lipoproteins
Drug metabolism
Ethanol oxidation
Synthesis of cholesterol (partial)
Maturation of synthesized protein
Degradation of proteins, carbohydrates, lipids and nucleotides
Electron transport chain
ATP generation
TCA cycle
Beta oxidation of fatty acids
Ketone body production
Urea synthesis (part)
Heme synthesis (part)
Gluconeogenesis (part)
Pyrimidine synthesis (part)
Protein synthesis
Glycolysis
Glycogen metabolism
HMP shunt pathway, transaminations, fatty acid synthesis
Cholesterol synthesis, heme synthesis (part), urea synthesis (part)
Pyrimidine synthesis (part), purine synthesis

Enzymes used for Diagnostic Purpose


Enzyme
Urease
Uricase
Glucose oxidase
Peroxidase
Hexokinase
Cholesterol oxidase
Lipase
Horse radish peroxidase
Alkaline phosphatase
Restriction endonuclease
Reverse transcriptase

Used for Testing


Urea
Uric acid
Glucose
Glucose; Cholesterol
Glucose
Cholesterol
Triglycerides
ELISA
ELISA
Southern blot; RFLP
Polymerase chain reaction (RT = PCR)

225

226

USMLE Step 1 Platinum Notes

Nonfunctional Plasma Enzymes used in Clinical Diagnosis


Serum Enzymes

Diagnostic use

Amylase and lipase

Acute pancreatitis

Aminotransferases

Myocardial infarction

Aspartate aminotransferase (AST or SGOT)


Alanine aminotransferase (ALT or SGPT)

Viral hepatitis

Acid Phosphatase

Prostate cancer

Alkaline phosphatase

Obstructive liver diseases, bone diseases and hyperparathyroidism

Creatine kinase

Muscle disorders and Myocardial infarction

Ceruloplasmin

Wilsons disease

Gamma-glutamyl transpeptidase

Liver diseases

Lactate dehydrogenase

Myocardial infarction

Sub cellular Organelle

Marker enzyme

Inner membrane:
ATP Synthase
Cathepsin
Galactosyl transferase
Glucose-6-phosphatase
Lactate dehydrogenase

Mitochondria
Lysosome
Golgi complex
Microsomes
Cytoplasm

Key Enzymes under Well Fed Conditions, Fasting and Starvation


Enzyme
Glucokinase
Phosphofructokinase 1
Fructose 1,6 biphosphatase
Pyruvate carboxylase
PEPCK
Glycogen phosphorylase
Glycogen synthase
Carnitine acyl transferase
Acetyl CoA carboxylase
Hormone sensitive lipase

Fed
Increase
Increase
Decrease
Decrease
Decrease
Decrease
Increase
Increase
Decrease

Fasting
Decrease
Decrease
Increase
Increase
Increase
Increase
Decrease
Increase
Decrease
Increase

Starvation
Decrease
Decrease
Increase
Increase
Increase
Decrease
Increase
Decrease
Increase

PEPCK = phospho enol pyruvate carboxy kinase; F-6-P = fructose-6-phosphate; F-2, 6-bisP=fructose-2,
6-biphosphate; G-6-P = glucose-6-phosphate.

Enzyme Deficiencies in Porphyrias

Erythropoetic porphyria
Heridetary Porphyria
Vaiegate Porphyria
Acute Intermittent porphyria
Porphyria cutanea Tarda
Congenital Erythropoetic porphyria

Ferrochelatase
Coproporphynogen Oxidase
Protoporphyrinogen Oxidase
Porphobilinogen Deaminase
URO Decarboxylase
URO III cosynthetase

Biochemistry

Important Biochemical Tests


Barfoeds test

Differentiates monosaccharides disaccharides

Mucic acid test

Detects galactose

Biuret test

Detects proteins

Xanthopretic test

Detects phenylalanine, tyrosine, tryptophan

Millions test

Detects tyrosine

Sullivan reaction

Detects cysteine

Acrolein test

Detects triglycerides

Leiberman Burchard reaction


Salkowskys reaction

Detects cholesterol

Rothera test
Legals test
Gerhardts test

Detects ketone bodies

Biochemically useful Competitive Inhibitors


Drug

Enzyme Inhibited

Allopurinol

Xanthine oxidase

6-mercapto-purine

Adenylosuccinate synthetase

5-fluorouracil

Thymidylate synthase

Azaserine

Phosphoribosyl-amidotransferase

Cytosine arabinoside

DNA polymerase

Acyclovir

DNAP of virus

Neostigmine

ACh-esterase

Alpha-methyl dopa

Dopa-decarboxylase

Lovastatin

HMGCoA-lowering

Oseltamiver

Neuraminidase

Dicoumarol

Vit.K-epoxide-reductase

Penicillin

Transpeptidase

Sulphonamide

Pteroid synthetase

Trimethoprim

FH2-reductase

Pyrimethamine

FH2-reductase

Methotrexate

FH2-reductase

227

228

USMLE Step 1 Platinum Notes

USMLE Case Scenario


Tangier disease is a rare familial disorder characterized by deficiency of an enzyme, which leads to very low high density
lipoprotein (HDL), recurrent polyneuropathy, lymphadenopathy, and hepatosplenomegaly due to storage of cholesterol
esters in reticuloendothelial cells. The enzyme deficency is:
1. G6 Phosphatase
2. Pyruvate kinase
3. alpha-lipoprotein deficiency
4. Urea cycle enzyme deficiency
5. Multiple carboxylase deficiency
Ans. 3. Alpha-lipoprotein deficiency

USMLE Case Scenario


A baby presents with refusal to feed, skin lesions, seizures, ketosis organic acids in urine with normal ammonia; likely
diagnosis is:
1. Proprionic aciduria
2. Multiple carboxylase deficiency
3. Maple syrup urine disease
4. Urea cycle enzyme deficiency
Ans. 2. Multiple carboxylase deficiency

USMLE Case Scenario


The primary role of chaperones is to help in:
1. Protein synthesis
2. Protein degradation
3. Protein denaturation
4. Protein folding
Ans. 4. Protein Folding

USMLE Case Scenario


A young man finds that everytime he eats dairy products he feels very uncomfortable. His stomach becomes distended. He
develops gas and diarrhea frequently. These symptoms do not appear when he eats foods other than dairy products. Which of
the following is the most likely enzyme in which this young man is deficient?
1. a-amylase
2. b-galactosidase
3. a-glucosidase
4. Sucrase
Ans. 4. Sucrase

USMLE Case Scenario


A child with large tongue, coarse facial features and club foot is seen by a pediatrician. You hear the doctor talking to his colleague
that the child has a problem with Phosphorylation of their mannose residues. The most likely possibility is a disease called:
1. Fabrys disease
2. Gauchers disease
3. Mc Ardles disease
4. Forbes disease
5. I-cell disease
Ans. 5. I-cell disease

Biochemistry

229

USMLE Case Scenario


Proteins targeted for destruction in eukaryotes are covalently linked to:
1. Clathrin
2. Pepsin
3. Laminin
4. Ubiquitin
Ans. 4. Ubiquitin

USMLE Case Scenario


The defect in sickle cell anemia is amino acid substitution/s but the globin chain is still made. The gene may less commonly
be present in some Mediterranean and eastern Arabian populations. There is enough fetal hemoglobin at birth to prevent
sickling with sickle cell disease. Sickle cell disease represents:
1. Missense mutations involve a change in many amino acids
2. Missense mutations involve a change in a single amino acid (valine for glutamic acid)
3. Missense mutations involve a change in a single amino acid (glutamic acid for valine)
4. Nonsense mutations involve a change in a single amino acid (valine for glutamic acid)
5. Nonsense mutations involve a change in a single amino acid (glutamic acid for valine)
Ans. 2. Missense mutations involve a change in a single amino acid (valine for glutamic acid)

USMLE Case Scenario


Northern blot test is used for:
1. DNA analysis
2. RNA analysis
3. Analysis of proteins
4. Enzyme analysis
Ans. 2. RNA analysis

USMLE Case Scenario


Which Apoprotein helps in the transport of chylomicrons from intestine to liver?
1. Apoprotein B
2. Apoprotein A
3. Apoprotein C
4. Apoprotein E
Ans. 1. Apoprotein B

USMLE Case Scenario


True about G protein coupled receptors is:
1. G proteins bind to hormones on the cell surface
2. All the three subunits alpha, beta and gamma should bind to each other for G protein to act
3. G proteins act as inhibitory and excitatory because of difference in alpha subunit
4. G protein is bound to GTP in resting state
Ans. 3. G proteins act as inhibitory and excitatory because of difference in alpha subunit

230

USMLE Step 1 Platinum Notes

USMLE Case Scenario


Collagen of which type is found in hyaline cartilage:
1. Type I
2. Type II
3. Type III
4. Type IV
Ans. 2. Type II

USMLE Case Scenario


A 34-year-old male patient presents with pain in the right big toe and uric acid renal stones. He has been taking allopurinol
for his condition. What biochemical defect would likely be found in this patient?
1. A defect in fatty acid synthesis
2. An abnormality of the purine degradation pathway
3. An inability to synthesize essential amino acids
4. Defective topoisomerases
5. Increased levels of leukotrienes
Ans. 2. An abnormality of the purine degradation pathway
This patient has gout, characterized by painful joints due to the precipitation of uric acid crystals caused by excessive
production of uric acid (a minority of cases are associated with underexcretion of uric acid). Kidney disease is also seen due
to accumulation of uric acid in the tubules. The disease mostly affects males, and is frequently treated with allopurinol, an
inhibitor of xanthine oxidase. Xanthine oxidase catalyzes the sequential oxidation of hypoxanthine to xanthine to uric acid.

USMLE Case Scenario


Vitamin K is required for:
1. Hydroxylation
2. Chelation
3. Transamination
4. Carboxylation
Ans. 4. Carboxylation

USMLE Case Scenario


NO is synthesized from:
1. Uracil
2. Aspartate
3. Guanosine
4. Arginine
5. Alanine
Ans. 4. Arginine

USMLE Case Scenario


A one and a half year-old retarded childs history is significant for failure to thrive and progressive neurologic deterioration,
including deafness and blindness. Physical examination is remarkable for hepatosplenomegaly, as well as a cherry-red spot
on funduscopic examination. The most likely diagnosis is:
1. Fabrys Disease
2. Mcardles Disease

Biochemistry

231

3. Hunter syndrome
4. Niemann-Pick disease
5. Pompes disease
6. Tyrosinosis
7. Cystinosis
8. Von Gierkes disease
Ans. 4. Niemann-Pick disease
It is due to a deficiency of sphingomyelinase, leading to an accumulation of sphingomyelin. The cherry-red spot is also a
characteristic of Tay-Sachs disease, but hepatosplenomegaly suggests Niemann-Pick disease rather than Tay-Sachs.

USMLE Case Scenario


Vitamin A intoxication causes injury to:
1. Lysosomes
2. Mitochondria
3. Endoplasmic reticulum
4. Microtubules
Ans. 1. Lysosomes

USMLE Case Scenario


A 23-year-old engineer to a physician with complaints of severe muscle cramps and weakness with even mild exercise. Muscle
biopsy demonstrates glycogen accumulation, but hepatic biopsy is unremarkable. Which of the following is the most likely
diagnosis?
1. Fabrys Disease
2. Hunter syndrome
3. Niemann-Pick disease
4. Pompes disease
5. Tyrosinosis
6. Cystinosis
7. Von Gierkes disease
8. Mcardles Disease
Ans. 8. Mcardles Disease

USMLE Case Scenario


Lead inhibits incorporation of iron into heme. The diminished heme synthesis leads to a hypochromic, microcytic anemia, and
there may be mild hemolysis. Basophilic stippling can be an indicator of toxic injury to RBCs. Lead poisoning is characterized by:
1. Elevated zinc protoporphyrin and decreased free erythrocyte protoporphyrin
2. Decreased zinc protoporphyrin and elevated free erythrocyte protoporphyrin
3. Decreased zinc protoporphyrin and decreased free erythrocyte protoporphyrin
4. Elevated zinc protoporphyrin and elevated free erythrocyte protoporphyrin
Ans. 4. Elevated zinc protoporphyrin and elevated free erythrocyte protoporphyrin

USMLE Case Scenario


The Similarity between Vit C and Vit K is:
1. Both help in conversion of proline to hydroxy-proline
2. Both help in post-translational modification
3. Both have anti infective activity
4. Both are involved in coagulation cascade
Ans. 2. Both help in post-translational modification

232

USMLE Step 1 Platinum Notes

USMLE Case Scenario


A patient was diagnosed with isolated increase in LDL. His father and brother had the same disease with increased cholesterol.
The likely diagnosis is:
1. Familial type III hyperlipoproteinemia
2. Abetalipoproteinemia
3. Familial lipoprotein lipase deficiency (type I)
4. LDL receptor mutation
Ans. 4. LDL Receptor Mutation

USMLE Case Scenario


The gaps between segments of DNA on the lagging strand produced by restriction enzymes are rejoined/sealed by:
1. DNA Ligases
2. DNA Helicase
3. DNA topoisomerase
4. DNA phosphorylase
Ans. 1. DNA Ligases

USMLE Case Scenario


Intron is not found in:
1. Nuclear DNA
2. Mitochondrial DNA
3. B DNA
4. Z DNA
Ans. 2. Mitochondrial DNA

USMLE Case Scenario


Agranular cytoplasmic reticulum is involved in the synthesis of:
1. Protein
2. Lipid
3. Vitamin
4. Carbohydrate
Ans. 2. Lipid

USMLE Case Scenario


A 45-year-old obese female from Mexico presents to her dermatologist. She noticed that her hair is falling out. On questioning,
she reports having followed a strict fat-free diet. Her alopecia is probably related to a deficiency of which of the following
vitamins?
1. Vitamin A
2. Vitamin C
3. Vitamin D
4. Vitamin E
5. Vitamin K
Ans. 1. Vitamin A
Vitamin A is necessary for formation of retinal pigments (deficiency can cause night blindness) and for appropriate
differentiation of epithelial tissues (including hair follicles, mucous membranes, skin, bone and adrenal cortex).

Biochemistry

233

USMLE Case Scenario


Coenzyme responsible for carboxylation reaction is:
1. Biotin
2. FAD
3. NADH
4. Thiamine pyrophosphate
Ans. 1. Biotin

USMLE Case Scenario


Xeroderma pigmentation is caused due to a group of closely related abnormalities in:
1. Mismatch repair
2. Base excision repair
3. Nucleotide excision repair
4. Phagosomes
Ans. 3. Nucleotide excision repair

USMLE Case Scenario


If cellular proteins do not fold into a specific conformation, their functions are affected. Certain disorders arise, if specific
proteins are misfolded. Which of the following disorders arises due to conformational isomerization?
1. Familial fatal insomnia
2. Hepatitis delta
3. Pernicious anemia
4. Lesch-Nyhan syndrome
Ans. 1. Familial fatal insomnia

USMLE Case Scenario


Fluoride, used in the collection of blood samples for glucose estimation, inhibits the enzyme:
1. Glucokinase
2. Hexokinase
3. Enolase
4. Glucose-6-phosphatase
Ans. 3. Enolase

USMLE Case Scenario


During replication of DNA, which one of the following enzymes polymerizes the Okazaki fragments?
1. DNA Polymerase I
2. DNA Polymerase II
3. DNA Polymerase III
4. RNA Polymerase I
Ans. 3. DNA Polymerase III

USMLE Case Scenario


In an experiment, biologic characteristics of neoplastic and non-neoplastic cells are analyzed in culture. The biochemical
experts report that it is observed that cell division in cells derived from malignant neoplasms, but not in normal cells, is aided
by the presence of an enzyme which repairs progressive chromosomal shortening. The lack of chromosomal shortening
allows the malignant cells to undergo many more divisions than the normal cells. Which of the following enzymes is most
likely to have this effect?
1. Reverse transcriptase
2. DNA polymerase

234

USMLE Step 1 Platinum Notes

3. Isomerase
4. Phosphodiesterase
5. Telomerase
6. Protein kinase
7. Topoisomerase
Ans. 5. Telomerase

USMLE Case Scenario


Refsums disease is due to deficiency of:
1. Malonate dehydrogenase
2. Thiophorase
3. Succinate thiokinase
4. Phytanic alpha oxidase
5. HGPRT
6. Telomerase
7. Galactokinase
Ans. 4. Phytanic alpha oxidase

USMLE Case Scenario


A 10-year-old girl is seen by a doctor for removal of multiple squamous cell carcinomas of the skin. The patient has nearly
white hair, pink irises, very pale skin, and a history of burning easily when exposed to the sun. This patients condition is due
to deficency of:
1. Malonate dehydrogenase
2. Thiophorase
3. Succinate thiokinase
4. Phytanic alpha oxidase
5. HGPRT
6. Tyrosine hydoxylase
7. Galactokinase
Ans. 6. Tyrosine hydoxylase
The disease is albinism. The most common form of albinism is caused by a deficiency of copper-dependent tyrosinase (tyrosine
hydroxylase), blocking the production of melanin from the aromatic amino acid tyrosine. Affected individuals lack melanin
pigment in skin, hair, and eyes, and are prone to develop sun-induced skin cancers, including both squamous cell carcinomas
and melanomas.

USMLE Case Scenario


The molecule, which is the intiator of cataract formation in the eye lens is:
1. Sorbitol
2. Mannitol
3. Inositol
4. Galacticol
Ans. 4. Galacticol

USMLE Case Scenario


A newborn infant refuses breast milk since the 2nd day of birth, vomits on force-feeding but accepts glucose-water, develops
diarrhea on the third day, by 5th day she is jaundiced with liver enlargement and eyes show signs of cataract. Urinary
reducing sugar was positive but blood glucose estimated by glucose oxidation method was found low. The most likely cause
is deficiency of:
1. Galactose-1-phosphate uridyl transferase

Biochemistry

235

2. Beta galactosidase
3. Glucose-6-phosphatase
4. Galactokinase
Ans. 1. Galactose-1-phosphate uridyl transferase

USMLE Case Scenario


Excessive ultraviolet radiation is harmful to life. The damage caused to the biological systems by ultraviolet radiation is by:
1. Inhibition of DNA synthesis
2. Formation of thymidine dimmers
3. Ionization
4. DNA fragmentation
Ans. 2. Formation of thymidine dimmers

USMLE Case Scenario


Euchromatin is the region of DNA that is relatively:
1. Uncondensed
2. Condensed
3. Overcondensed
4. Partially condensed
Ans. 1. Uncondensed

USMLE Case Scenario


Proteins are linear polymers of amino acids. They fold into compact structures. Sometimes, these folded structures associate
to form homo-or hetero-dimers. Which one of the following refers to this associated form?
1. Denatured state
2. Molecular aggregation
3. Precipitation
4. Quaternary structure
Ans. 4. Quaternary structure

USMLE Case Scenario


Basement membrane degeneration is mediated by:
1. Metalloproteinases
2. Oxidases
3. Elastases
4. Hydroxylases
Ans. 1. Metalloproteinases

USMLE Case Scenario


A ten year old child with aggressive behavior and poor concentration is brought with presenting complaints of joint pain and
reduced urinary output. Mother gives history of self mutilitative behavior stating that he tends to mutilate his fingers. Which
of the following enzymes is likely to be deficient in this child?
1. HGPRT
2. Adenosine Deaminase
3. Galactokinase
4. Acid Maltase
5. Hydroxylase
Ans. 1. HGPRT

236

USMLE Step 1 Platinum Notes

USMLE Case Scenario


A child presents with massive hepatomegaly and hypoglycemia. There is no improvement in blood glucose on administration
of Glucagon. The probable diagnosis is:
1. von Gierke disease
2. McArdle disease
3. Coris disease
4. Forbes disease
Ans. 1. von Gierke Disease

USMLE Case Scenario


A 2-month-old, breastfed baby that was normal at birth begins to develop GI problems and cirrhosis of the liver. Molecular
analysis indicates a normal amount of galactose-1-phosphate uridyl transferase (GALT) mRNA, but no observable enzyme
activity. Which of the following would be the best possible explanation for this?
1. Gene deletion
2. Nonsense mutation
3. Premature transcription termination sequence in the DNA
4. Promoter mutation
5. RNA splicing mutation
Ans. 2. Nonsense Mutation
A nonsense mutation is a mutation in the DNA that leads to a premature stop codon when the mRNA is being translated
into protein. The mRNA would be transcribed correctly, but when the protein was being translated, it would be stopped
prematurely, leading to a truncated protein.

USMLE Case Scenario


A child has cystic fibrosis. His parents report a history of recurrent respiratory tract infections and bulky, foul-smelling stools.
After assessment of his respiratory tract illness, the practitioner should also look for signs of which vitamin deficiency.
1. Vitamin C
2. Vitamin A
3. Vitamin B1
4. Vitamin B6
Ans. 2. Vitamin A

USMLE Case Scenario


A 10-year-old child is suspected of having pellagra because of chronic symptoms including diarrhea, a red scaly rash, and mild
cerebellar ataxia. However, his diet is not deficient in protein and he appears to be ingesting adequate amounts of niacin.
A sister has a similar problem. Chemical analysis of his urine demonstrates large amounts of free amino acids. Which of the
following is the most likely diagnosis?
1. Alkaptonuria
2. Carcinoid syndrome
3. Ehlers-Danlos syndrome
4. Hartnups disease
5. Scurvy
Ans. 4. Hartnups Disease

MICROBIOLOGY

Microbiology

HIGH YIELD USMLE POINTS


Prokaryotes

Absence of nuclear membrane


Absence of nucleolus
Absence of DNA
Absence of cytoplasmic organalles
Absence of sterols/muramic acid
Bacteria are prokaryotes

Eukaryotes

Presence of nuclear membrane


Presence of nucleolus
Presence of DNA
Presence of cytoplasmic organalles
Presence of sterols/ muramic acid

USMLE Case Scenario


After a skin infection in the nail, A Pathologist is talking about a nonmotile organism is found to be eukaryotic, with both RNA
and DNA present. Ribosomes are 80 S and reproduction occurs by budding. Most likely the organism is:
1. Virus
2. Bacteria
3. Fungus
4. Viroid
Ans. 3. Fungus

Characteristics of Different Organisms


Characteristics

Viruses

Bacteria

Fungi

Nucleic acid

Either DNA/RNA

Both Present

Both Present

Nucleus

Absent

Prokaryotic

Eukaryotic

Ribosomes

Absent

70 S

80 S

Mitochondria

Absent

Absent

Present

Motility

Nil

Present

Nil

Binary fission

Budding

Reproduction

240

USMLE Step 1 Platinum Notes

USMLE Case Scenario


Lipopolysaccharide is an important component of:
1. Gram-positive cells
2. Gram-negative cells
3. Neither gram-positive nor gram-negative cells
4. Both gram-positive and gram-negative cells
Ans. 2. Gram-negative cells

Difference between Gram-Positive and Gram-Negative Cells


Component

Gram-Positive Cells

Gram-Negative Cells

Peptidoglycan

Thick

Thin

Teichoic acid

Present

Absent

Periplasmic space

Absent

Present

Lipopolysaccharide

Absent

Present

USMLE Case Scenario


Which of the following structures is found only in gram-negative microorganisms:
1. Cell envelope
2. Exotoxin
3. Peptidoglycan
4. Periplasmic space
Ans. 4. Periplasmic space

FUNCTIONS OF DIFFERENT COMPONENTS OF CELL ENVELOPE


(USMLE High Yield Points)
Capsule: Antiphagocytic and immunogenic
Capsulated organisms:
Pneumococus
Anthrax bacillus
Bordetella
Meningococci

Klebsiella
Cryptococcus, H. influenza
Bacteroids
V. parahemolyticus

Teichoic acid: Attachment to epithelial surfaces and immunogenic


Cell wall: Rigid support, protection from osmotic damage
Cytoplasmic membrane: Membranous matrix for respiratory pathways and cell wall synthesis
Porin proteins: Passive transport of aqeous materials
Perplasmic space: Extracellular enzymes, osmotic pressure
Inner membrane: Matrix for enzymes of respiratory pathways and cell wall synthesis

Detection Techniques

Flagella are detected by Dark ground microscopy


Fimbriae are detected by Hemagglutination
Spores are detected by Acid fast (ZN staining)
Capsules are detected by India ink/Quelling reaction

Microbiology

241

Phases of Bacterial Growth Cycle


Lag Phase

Nutrients incorporated

Log Phase

Rapid cell division

Stationary Phase

Cell Death = Cell formation

Death Phase

Cell death > Cell formation

Phases of bacterial growth

USMLE Case Scenario


An antibiotic, such as penicillin, which modifies cell wall synthesis, tends to be most effective during which phase of bacterial
growth in a closed system?
Ans. Log phase

BACTERIAL CONJUGATION: (USMLE FAVORITE)


Bacterial conjugation is the transfer of genetic material between bacteria through direct cell-to-cell contact.
Discovered in 1946 by Joshua Lederberg and Edward Tatum.
Conjugation is a mechanism of horizontal gene transfer
The prototype for conjugative plasmids is the F-plasmid, also called the F-factor.The F-plasmid is an episome (a plasmid that can integrate
itself into the bacterial chromosome by genetic recombination) of about 100 kb length.The host bacterium is called F-positive or F-plus(d
enoted F+). Strains that lack F plasmids are called F-negative or F-minus (F-).
Bacterial conjugation is often incorrectly regarded as the bacterial equivalent of sexual reproduction or mating.
It is merely the transfer of genetic information from a donor cell to a recipient.

Transduction
Transduction is the process by which DNA is transferred from one bacterium to another by a virus
It also refers to the process whereby foreign DNA is introduced into another cell via a viral vector
This is a common tool used by molecular biologists to stably introduce a foreign gene into a host cells genome.
When bacteriophages (viruses that infect bacteria) infect a bacterial cell, their normal mode of reproduction is to harness the
replicational, transcriptional, and translation machinery of the host bacterial cell to make numerous virions, or complete viral particles,
including the viral DNA or RNA and the protein coat.

242

USMLE Step 1 Platinum Notes

Bacterial Transformation
Bacteria transformation maybe referred to as a stable genetic change brought about by taking up naked DNA (DNA without
associated cells or proteins), and competence refers to the state of being able to take up exogenous DNA from the environment.
Procedure

Process

DNA Transferrred

Conjugation

Bacterium to Bacterium

Chromosomal/Plasmid

Transduction

By Virus

Any Gene

Transformation

DNA taken Directly

Any DNA

Plasmids: (USMLE Favorite)


Extrachromosomal genetic material
Generally have covalently, closed, circular DNA (ccc)
One class of plasmids, Episomes maybe integrated into bacterial DNA
Plasmids carry genetic material for variety of genes, (Fertility genes, antibiotic resistance, exotoxins)
Involved in multi drug resistance transfer.

Bacteriophage
Viral DNA maybe inserted into bacterial chromosome as prophage by a temperate virus which directs the synthesis of a virulence
factor making bacterium more pathogenic.

Transposons

Mobile genetic elements that can move themselves from one DNA to other
Jumping genes
Create additional mutations
Have sequences of indirect repeats of bases at each end

According to Shape Bacteria are Classified into

Cocci: Spherical shaped bacteria


Bacilli: Rod shaped cell
Vibrio: Comma shaped cells
Spirilla: Rigid spiral forms
Spirochetes: Flexuous spiral forms
Actinimycetes: Branching filamentous form
Mycoplasma: Lacks cell wall, hence do not possess stable morphology

USMLE Case Scenario


An intravenous drug abuser is found to have infective endocarditis. Most common organism in Acute Endocarditis: Staph
aureus. The organism is:
1. A Gram-positive coccocus
2. A Gram-negative rod
3. A Gram-positive coccus
4. A Gram-positive rod
Ans. 3. A Gram-positive coccus

Microbiology

243

USMLE Case Scenario


Among the following which is an obligate intracellular organism:
1. Nocardia
2. Chlamydia
3. Bacillus
4. Legionella
Ans. 2. Chlamydia

USMLE Case Scenario


A 26-year-old male complains of a severe headache and weakness. His condition rapidly deteriorates over a period of hours. A
lumbar puncture is performed and a Grams stain of spinal fluid reveals Neisseria meningococcus. The organism is:
1. Gram-negative diplococci
2. Gram-positive cocci
3. Gram-positive bacillus
4. Obligate intracellular organism
Ans. 1. Gram-Negative Diplococci

CLASSIFICATION: FREQUENTLY ASKED IN USMLE


Gram-Positive Cocci:
Streptococcus
Staphylococcus
Gram-Positive Spore forming Bacilli:
Bacillus Anthraxus (Aerobic)
Clostridium (Anaerobic)
Gram-Positive Nonspore forming Bacilli:
Corynebacterium diphtheriae
Listeria
Actinomyces
Nocardia
Gram-Negative Cocci:
Neisseria gonococcus, meningococcus
Gram-negative Rods:
Hemophilus
Bordetella
Legionella
E coli
Serratia
Klebsiella
Salmonella
Shigella
Vibrio
Pseudomonas

244

USMLE Step 1 Platinum Notes

Obligate intracellular parasites:


Rickettsia
Chlamydia
Thin walled spirochetes:
Treponema
Borrelia
Leptospira
Wall less:
Mycoplasma

USMLE Case Scenario


A 33-year-old Indian reported in New York and is found to have chronic weight loss, pyrexia and easy fatiguibility. A chest
X-ray reveals miliary form of tuberculosis. The feature of the organism causing the disease is:
1. Aerobe
2. Obligate aerobe
3. Anaerobe
4. Obligate anaerobe
Ans. 2. Obligate aerobe

USMLE Case Scenario


Gastric ulcers are associated with malignancy, and therefore biopsy should be performed when they are discovered. This
association with malignancy is not found with duodenal ulcers. The increased risk for malignancy with gastric ulcers is a good
reason to test patients for H pylori and initiate treatment if it is found. H pylori is a:
1. Aerobe
2. Anaerobe
3. Obligate aerobe
4. Microaerophilic
Ans. 4. Microaerophilic
Obligate aerobes
Use oxygen dependent mechanisms to generate ATP
Examples
Pseudomonas aeruginosa
Mycobacterium tuberculosis
Nocardia
Obligate anaerobes
Lack catalase and superoxide dismutase
Examples (ABC)
Actinomyces
Bacteroids
Clostridium

Microaerophilic
Campylobacter
H pylori

Microbiology

245

USMLE Case Scenario


An organism causing otitis media in children and pneumonia in adults. With a peculiar growth requirement, requiring factor
X (hematin) and factor V (NAD). The most likely organism is:
1. H. influenza
2. B. pertusis
3. M. tuberculosis
4. Klebsiella
Ans. 1. H. Influenza

Remember Bacterial Cultures: (High Yield for USMLE)


Smith noguchi medium: Spirochetes
Selenite F Broth: Salmonella, shigella
Dorset egg medium: Mycobacterium
Noguchi medium : Borellia
BYCE medium: Legionella
Lofflers serum slope: Corynebacterium diphtheria
Tellurite media: Corynebacterium diphtheria
Thayer martin media: N.gonorrhea
Korthof media: Leptospira
Staurts media: Leptospira
Fletcher media: Leptospira
Chocolate agar: H.influenza
Bordet gengou: B.pertusis
Lownstein Johnson: M.tuberculosis
Sabourdars media: Fungi
Skirrows media: Campylobacter Jejuni

USMLE Favorite
EXOTOXIN

ENDOTOXIN

Mostly Gram-positive bacteria

Gram-negative bacteria

Polypeptides

Lipopolysaccharides

Highly toxic

Low toxicity

Highly antigenic

Poorly antigenic

Toxoids used as vaccines

No toxoids, no vaccines

Heat sensitive

Heat stable

Secreted from cell

Not secreted from cell

Antiphagocytic Structures (CAMP)

Capsule
Pilli of Neisseria Gonorrhea
M protein of streptococcus pyogenes
A protein of staph aureus

246

USMLE Step 1 Platinum Notes

Pathogenesis of shock

Capsulated Organisms

Streptococcus Pneumoniae
Klebsiella Pneumoniae
Hemophilus influenza
Pseudomonas Aeruginosa
Neisseria meningitidis
Cryptococcus neoformans

USMLE Case Scenario


Cryptococcus is nondimorphic yeast, meaning that it exists only in the yeast form and it reproduces by budding. It is found
worldwide in bird droppings (think pigeons). It can also cause transient pulmonary illness in otherwise healthy individuals.
The feature of Cryptococcus is that:
1. It is capsulated so takes India ink stain
2. It is noncapsulated so takes India ink stain
3. It is capsulated so does not take India ink stain
4. It is noncapsulated so does not take India ink stain
Ans. 1. It is capsulated so takes India ink stain

Understanding Toxins Commonly asked in USMLE Examination


Pseudomonas alpha toxin, which is responsible for the tissue damage, inhibits Protein synthesis by acting on EF-2 with a
primary target cell in the liver
The diphtheria toxin has a similar action, although its target cells are heart and nerve
Anthrax toxin is an Adenylate cyclase that causes fluid loss from cells
Botulinum toxin is a neurotoxin that decreases acetylcholine synthesis
Cholera toxin acts to increase adenylate cyclase activity by ribosylation of GTP-binding protein
Clostridium perfringens alpha toxin is a lecithinase
Escherichia coli labile toxin works in a fashion similar to the cholera toxin
Pertussis toxin causes fluid loss by ribosylating Gi
Shiga toxin decreases protein synthesis by inhibiting the 60S ribosomal subunit
Streptococcal erythrogenic toxins act similarly to the diphtheria toxin, but do so by increasing cytokine production
Tetanus toxin is a neurotoxin that inhibits the inhibitory neurotransmitters glycine and GABA
TSST-1 is a superantigen that acts by increasing cytokine production and decreasing liver clearance. A superantigen, such as
TSST- 1 or staphylococcal enterotoxin, cross-links the variable domain of the TCR b chain to the MHC class II molecule and
specifically induces massive T cell activation.

Microbiology

247

REMEMBER
Clostridial Associations in USMLE

USMLE Case Scenario


Among the following organisms would most likely cause infection after a sterilization procedure that killed vegetative cells
but did not kill spores?
1. Chlamydia
2. Clostridium
3. Pseudomonas
4. Streptococcus
Ans. 2. Clostridium
Clostridium botulinum spores (found in honey) in the babys gastrointestinal tract. Patients improve when honey is removed
from the diet. This disorder is most common in children under the age of six months; older children and adults do not appear to be
vulnerable to this form of botulism, but are susceptible to botulism caused by ingestion of preformed toxin
Clostridium difficile causes pseudomembranous colitis, especially after antibiotic therapy
Clostridium perfringens causes gas gangrene and gastroenteritis, and it is not associated with ingestion of honey
Clostridium tetani causes tetanus, and does not cause a foodborne illness in infants.

Important Bacterial Toxins: (USMLE Favorite)


Corynebacterium Diphtheria

Diphtheria

Inactivates EF2: shuts down protein synthesis

Clostridium tetani

Tetanus

Blocks release of Glycine

Clostridium boutilinium

Boutilism

Blocks release of Acetyl choline

Clostridium difficile

Pseudomembranous colitis

Exotoxin BCytotoxin disaggregates actin filaments

Clostridium perfringens

Gas gangrene

Alpha toxin acting as lecithinase

Bacillus anthraxus

Anthrax

Edema factor, Lethal factor

Staph aureus

TSS

Superantigen binding directly to MHC II

Stret pyogenes

Scarlet fever

Superantigen

E coli

Watery diarrhea

Stimulates adenylate cyclase (Gs)

Vibrio cholera

Cholera

Stimulates adenylate cyclase (Gs)

Bordetella Pertussis

Whooping cough

Stimulates adenylate cyclase (Gi)

Main toxins

USMLE Case Scenario


Pseudomembranous colitis occurs as a result of treatment with clindamycin or ampicillin. You would confirm your suspicion
by sending a stool culture to be tested for the presence of the:
1. Toxin
2. Flagella

248

USMLE Step 1 Platinum Notes

3. Bacteria
4. Virus
Ans. 1. Toxin

USMLE Case Scenario


An injection of a substance from gram-negative bacteria into the vascular system will rapidly produce myocardial dysfunction,
hypotension, disseminated intravascular coagulation and coma resembling septic shock. The substance is most likely:
1. Lipopolysaccharide
2. Protein only
3. Saccharide
4. Hapten
Ans. 1. Lipopolysaccharide

USMLE Case Scenario


A 18-year-old, ill-appearing woman comes OPD with a fever. She notes the recent development of nausea, diarrhea, and a
rash. Her last menstrual period began 3 days ago. Physical examination is remarkable for blood pressure of 90/40 mm Hg and
heart rate of 120 beats per minute. A diffuse erythematous rash with desquamation over feet is noted. Infection with which of
the following toxin is the most likely cause of these signs and symptoms?
1. Clostridium perfringens toxin
2. Shigella dysenteriae toxin
3. Staphylococcus aureus toxin
4. Staphylococcus epidermidis toxin
Ans. 3. Staphylococcus aureus toxin

Toxins c AMP levels (PACE)

Pertusis toxin
Anthrax toxin
Cholera toxin
E coli toxin (labile)

Site

Important organism

Skin

Staph Epidermidis

Nose

Staph Aureus

Mouth

Strept Viridians

Dental plaque

Strept Mutans

Vagina

Lactobacillus, E coli, Group B Strept

Colon

Bacteroids, E coli

Throat

Strept Viridians

USMLE Case Scenario


Bacillus anthracis is found in many animal species, and humans can acquire the organism either through contact with the
animals or from locally contaminated soiL Feature of colonies of Anthrax bacillus is:
1. Swimming Growth
2. Swarm of Gnats or Fish in Stream
3. Stalactite Growth
4. Medusa Head
Ans. 4. Medusa Head

Microbiology

249

Colony Appearances
Colony Appearance in culture

Organism

1. Draughtsman (Concentric Rings)

Pneumococci

Medusa Head
Frosted Glass
Inverted Fir Tree in Stab Culture
String of pearls

B Anthracis

2. Swimming Growth (Fishy or Seminal Smell)

Proteus

3. Swarm of Gnats or Fish in Stream

V Cholerae

4. Stalactite growth

Yersinia Pestis

5. Thumb print appearance, Bisected pearls or mercury drops, B Pertussis


Aluminium Paint appearance
6. Cigar bundle (globi) appearance

M Leprae

7. Fried egg

Mycoplasma

8. Bread crumb

Actinomyces israelii

9. Oil Paint

Staphylococci

10. School of Red fish

H ducreyi

11. Stately Motility

Clostrida

Gram-Positive Bacilli
Corynebacterium Diphtheriae

Aerobic
Catalase +
Nonhemolytic
Toxin production

Diphtheria

Listeria monocytogenes

Aerobic
Hemolytic

Meningoencephalitis in neonates, immunocompromised

Bacillus anthracis
Bacillus cereus
Bacillus anthracis

Aerobic spore
forming

Anthrax
Food poisoning (reheated rice)
Most common form: cutaneous (hide porters disease)
Most fatal form: pulmonary (wool sorters disease)

Anaerobic, spore
forming

Food poisoning, gas gangrene


Gas gangrene
Tetanus
Botulism
Pseudomembranous colitis

Aerobic, rod shaped

Tuberculosis

Clostridium welchii
Clostridium septicum
Clostridium tetani
Clostridium botulinium
Clostridium difficile

Mycobacterium tuberculosis
M aviumintercellulare
M leprae

Cervical LAP
Cannot be
cultured
Acid fast rods
Cooler parts of
body
Do not follow
kochs postulates

Leprosy

250

USMLE Step 1 Platinum Notes

USMLE Case Scenario


A gram-positive spore-forming rod that is associated with food poisoning outbreaks following the ingestion of fried rice. The
organism survives the boiling of the rice because it is a spore-former. It germinates as the rice cools, grows, and elaborates an
enterotoxin that is responsible for the nausea and vomiting characteristic of the disease. The most likely organism is:
1. Bacillus anthracis
2. Bacillus cereus
3. Staph aureus
4. Salmonella
Ans. 2. Bacillus cereus

USMLE Case Scenario


A 33-year-old cave digger who has been excavating acave develops a pustule on his hand. The pustule then ruptures to form
a black eschar surrounded by expanding brawny edema. Which of the following gram-positive organisms is the most likely
cause of this condition:
1. Clostridium welchii
2. Clostridium tetani
3. Bacillus anthracis
4. Clostridium botulinium
Ans. 3. Bacillus anthracis

USMLE Case Scenario


A 58-year-old has developed thick, erythematous nodules on her ears and nose with significant associated sensory loss. The
nodules have grown slowly over the course of many years. Biopsy of the lesions shows dermal granulomas with giant cells
but no acid-fast bacteria. Culture on blood agar and Lowenstein-Jensen medium shows no growth. The disease is identified
as leprosy. The organism is:
1. Gram-positive, acid fast rod
2. Gram-positive, nonacid fast rod
3. Gram-negative, acid fast rod
4. Gram-negative, nonacid fast rod
Ans. 1. Gram-positive, acid fast rod
Hansens disease: A key feature in the description is the fact that the organism is acid-fast. Both of the mycobacteria,
M avium-intracellulare and M leprae are strongly acid-fast, that is they retain the carbol fuchsin dye in the face of acidalcohol decolorization. M leprae has a predilection for the skin and cutaneous nerves, thereby producing the symptoms of
depigmentation and anesthetic cutaneous lesions. This loss of peripheral nerve function leads to many of the disfiguring
features of the disease; because the patients do not have normal pain sensation, they sustain repeated injuries. In addition,
the organism attacks cartilage and causes granuloma formation in the skin, leading to some of the facial disfigurement.

Gram-Negative Bacilli: (High Yield for USMLE)


Hemophilus influenza
Hemophilus parainfluenza
Hemophilus aegyptius
Hemophilus ducreyi

Needs factor X and V, satellite


phenomenon

Koch weeks bacillus

Acute epiglottitis, meningitis in children, otitis


media
COPD Exacerbations
Conjunctivitis
Genital ulcers, chancroid

Bordetella pertusis

Cocco bacillus
Bordet Gengou media

Whooping cough

Yersenia pestis
Yersenia enterocolitica

Aerobic, bipolar staining

Bubonic plague, pneumonic plague


Gastroenteritis, Pseudoappendicitis

Microbiology

251

Pasturella multicoida

Aerobic

Wound sepsis following dog bites

Vibrio cholera
Vibrio para hemolyticus

Aerobic curved motile rod

Cholera
Food poisoning (sea food) shellfish

Campylobacter

Microaerophilic

Acute diarrhea (bloody)


Gullian barre syndrome
Reactive arthritis

E coli

Aerobic, lactose fermenter, enterotoxin UTI, Peritonitis, cholecystitis, neonatal meningitis, travelers diarrhea
HUS, TTP, hemorrhagic colitis
Verocytotoxin, shiga like toxin

E coli 0157: H7

Nonsorbitol fermenting
Klebsriella pneumoniae

Aerobic, lactose fermenter

Proteus mirabilis

Shigella

Nonlactose fermenters
Nonmotile

Bacillary dysentery

Bacteroids

Anaerobic, nonsporing

Abscesses, septicemia

Fusobacterium

Anaerobic, nonsporing

Vincents angina, gingivitis

Acinetobacter

Anaerobes

Hospital acquired infections

Borrelia vincenti
Borrelia recurrentis
Borrelia duttoni
Borrelia burgdorfei

Helicobacter pylori

Swarming growth on agar


Aerobic nonlactose fermenter
Peritrichous flagella
Urease positive

Aerobic
Anaerobic
Anaerobic
Anaerobic

Pneumonia (currant jelly)

Spiral, flagellate
Microaerophilic
Urease positive
Invasive
Campys medium, Skirrows agar

UTI

Vincents angina
Relapsing fever (r-r)
Relapsing fever
Lyme disease

Peptic ulcer, gastric cancer, gastric lymphoma


Extra gastric diseases

Treponema pallidum
Treponema pertenue
Treponema carateum

Anaerobic, spiral, motile


Anaerobic
Anaerobic

Syphilis
Yaws
Pinta

Leptospira icterohemorrhagica
Leptospira canicola

Anaerobic
Anaerobic

Weils disease
Canicola fever

Obligate intracellular bacteria

Obligate intracellular bacteria


smallest free living bacteria
no cell wall
sterols in membrane

Primary atypical pneumonia


Urethritis, PID

Rickettsia prowazekii
Ricketssia mooseri
Ricketssia burnetti
Ehrlichia chaffeensis

Mycoplasma pneumonia
(Eaton agent)

Ureaplasma urealyticum
M hominis

Epidemic typhus
Endemic typhus
Q fever
Ehrlichiosis

Pyelonephritis
PID

252

USMLE Step 1 Platinum Notes

USMLE Case Scenario


An organism is causing urinary tract infections. It has ability to breakdown urea is thought to contribute to the development of
struvite kidney stones due to the elevation of urine pH by production of ammonia. The said organism is also having swarming
motility. The organism is identified as proteus species. It is a:
1. Aerobic nonlactose fermenter
2. Anaerobic nonlactose fermenter
3. Aerobic lactose fermenter
4. Anaerobic lactose fermenter
Ans. 1. Aerobic nonlactose fermenter

USMLE Case Scenario


A 33-year-old patient presents with a red macule or papule at the site of the tick bite. This lesion, called erythema chronicum
migrans, slowly expands to form a large annular lesion with a red border and central clearing. The patient also has severe
headache, stiff neck, chills, arthralgias and profound malaise and fatigue. The causative organism is:
1. Borrelia vincentii
2. Borrelia recurrentis
3. Borrelia duttonii
4. Borrelia burgdorferi
Ans. 4. Borrelia burgdorferi

USMLE Case Scenario


A child presents with chronic enteritis, failure to thrive, hypoalbuminemia, and hypokalemia. Other findings include acute
right lower quadrant abdominal pain, tenderness, nausea and vomiting. The infection mimics appendicitis or Crohns disease.
Most likely organism is:
1. Yersinia enterocolitica
2. Hemophilus aegyptius
3. Borrelia duttonii
4. Hemophilus ducreyi
Ans. 1. Yersinia enterocolitica

USMLE Case Scenario


A 66-year-old man is brought to a rural hospital. He has severe bronchopneumonia after sudden onset of chills, fever, and
headache several days ago. One day later, he coughed up blood-tinged sputum. Chest X-ray reveals patchy infiltrates and
segmental consolidation. Which organism with bipolar staining pattern is the most likely cause of this mans pneumonia?
1. Yersinia Pestis
2. Streptococcus pneumonia
3. Staph aureus
4. Leptosporia
Ans. 1. Yersinia Pestis

USMLE Case Scenario


A curved, gram-negative rod which is microaerophilic is causing enterocolitis with diarrhea and less commonly, chronic
gastritis. Most likely the organism is:
1. Vibrio cholera
2. H pylori
3. E coli
4. Campylobacter jejuni
Ans. 4. Campylobacter jejuni

Microbiology

253

USMLE Case Scenario


A 8-year-old girl is bitten in the leg by a dog. She presents the next day with fever and bone pain localized to her right calf.
X-ray reveals a lytic lesion of the left femur. Results of the boneculture are pending. Infecting organism is most likely to be:
1. Pasteurella
2. Bartonella
3. Yersinia
4. Bordetella
Ans. 1. Pasteurella

USMLE Case Scenario


An infection is characterized by rapidly evolving cellulitis starting at the site of the bite. A gram-negative rod was found to be
spread via dog bites. Most likely organism is:
1. Pasteurella
2. Bartonella
3. Yersinia
4. Bordetella
Ans. 1. Pasteurella
Actinomyces israelli

Anaerobic, branching filaments, non acid fast, sulfur Actinomycosis, lumpy jaw
granules

Nocardial asteroids

Anaerobic, branching filaments, partially acid fast

Staph Aureus: USMLE High Yield


Gram-positive
Cluster-forming coccus, nonmotile, nonspore forming facultative anaerobe
Fermentation of glucose produces mainly lactic acid.+
Ferments mannitol (distinguishes from S epidermis)+
Catalase positive+
Coagulase positive +
Coagulase is responsible for pathogenecity
Golden yellow colony on agar
Normal flora of humans found on nasal passages, skin and mucous membranes
Food poisoning is due to preformed endotoxin
Occurs within 6 hours of food intake
Panton valentine leucocidin is seen in staph infections
Especially diary products involved in poisoning
CAUSES:
Acute osteomyelitis
Acute mastitis
Botromycosis
SSSS
Furunculosis, carbuncle
Acute endocarditis
Sycosis barbae
Tropical polymyositis

Nocardiosis

254

USMLE Step 1 Platinum Notes

Methicillin Resistant Staphylococcus Aureus (MRSA)


MRSA is a major nosocomial pathogen
Causes severe morbidity and mortality worldwide
40% of nosocomial Staph aureus infections are methicillin resistant
Hospital personnel maybe carriers
Spread by hand, usually of health care workers
Microbiology
Methicillin resistance is mediated by the mecA gene
Encodes a single additional penicillin binding protein PBP2a
Expression of mecA can be either constitutive or inducible
Risk factors for MRSA coloniation (USMLE Favorite)
Advanced age
Male gender
Previous hospitalization
Length of hospitalization
Stay in ICU
Chronic medical illness
Prior and prolonged antibiotic therapy
Presence and size of a wound
Exposure to colonized or infected patient
Presence of invasive indwelling device
Clinical presentations
Pneumonia
Surgical site infections
Line sepsis
Intra-abdominal infections
Osteomyelitis
Toxic shock syndrome
Infection control
Screening of patients and staff
Handwashing
Use of gowns and gloves
Topical antimicrobials
Isolation of patients
Environmental cleaning
Management
Vancomycin is used
Teicoplanin maybe used if the isolate is resistant to vancomycin
Linezolid is new class of antimicrobial agent, active against MRSA and VRE
Quinupristin/Dalfopristin are newer alternative

USMLE Case Scenario


Microbiologic studies on a gram-positive coccus isolated from a skin abscess demonstrate a positive catalase test and a
positive coagulase test. This is most consistent with which of the following organism:
1. Staph aureus
2. Streptococcus
3. Neisseria gonorrhea
4. Neisseria meningococcus
Ans. 1. Staph Aureus

Microbiology

255

USMLE Case Scenario


A 22 -year-old, ill-appearing woman comes to the emergency room with a fever. She notes the recent development of nausea,
diarrhea, and a rash. Her last menstrual period began 2 days ago. Physical examination is remarkable for blood pressure of
88/40 mm Hg. A diffuse erythematous rash with areas of desquamation over the hands and feet is noted. Infection with which
of the following agents is the most likely cause of these signs and symptoms?
1. Streptococcus
2. Neisseria gonorrhea
3. Neisseria meningococcus
4. Staph aureus
Ans. 4. Staph Aureus

USMLE Case Scenario


A 4-year-old girl with a history of hydrocephalus is brought to the neurologist by her parents with a severe headache and
fever. The girl underwent a surgery for a ventricular-peritoneal shunt 2 months ago and the neurologist suspects that an
infection has occurred. Organisms would most likely be isolated from the shunt tubing is:
1. Staph aureus
2. Streptococcus
3. Staphylococcus epidermidis
4. Meningococcus
Ans. 3. Staphylococcus epidermidis

USMLE Case Scenario


A 56-year-old has developed acute osteomyelitis in his left tibia. The most common organism a pathologist would be thinking
about is:
1. Streptococcus
2. Staphylococcus epidermidis
3. Meningococcus
4. Staph aureus
Ans. 4. Staph aureus

Streptococci: USMLE High Yield


C carbohydrate is used for Lancfield classification
M protein is mainly responsible for pathogenecity
MC organism causing cellulitis: streptococcus pyogenes
Causes:
Erysipelas
Scarlet fever
Purpureal sepsis
Non suppurative infections: rheumatic fever, glomerulonephritis
Are usually initially speciated by their hemolytic capacity on sheep blood agar. Beta-hemolytic streptococci include groups A, B, and
D S agalactiae is the classic group B streptococcus. The non beta-hemolytic streptococci consist principally of the pneumococci and
the viridans group.

High Yield Points Repeated Often: (USMLE Favorite)


Str. agalactiae

Neonatal meningitis, neonatal sepsis

Str. Bovis

Endocarditis

Str. Pneumonia

Pneumoniae, Otitis media

256

USMLE Step 1 Platinum Notes

Str. Mutans

Dental caries

anaerobic streptococci

Purpureal sepsis

Str. Pyogenes

Erysipelas, Cellulitis
Impetigo, scarlet fever, Rheumatic fever, Acute Glomerulonephritis

Str. Viridians

Endocarditis

USMLE Case Scenario


A 1-week-old female infant with symptoms of vomiting and anorexia has a temperature of 102 F. A bulging fontanel is noted
on physical examination. The most likely coccusis:
1. Streptococcus agalactiae
2. Streptococcus pneumonia
3. Streptococcus viridians
4. Streptococcus pyogenes
Ans. 1. Streptococcus agalactiae

USMLE Case Scenario


A 55-year-old man presents with an episode of shaking chills the previous night. He has now developed right-sided pleuritic
chest pain, fever, sweats, malaise, purulent sputum, and mild hemoptysis. On examination, the patient is diaphoretic but
alert, with right basilar rales. Chest X-ray films show a right lower lobe infiltrate with blunting of the right costophrenic angle.
The causative organism implicated is:
1. Streptococcus agalactiae
2. Streptococcus pneumonia
3. Streptococcus viridians
4. Streptococcus pyogenes
Ans. 2. Streptococcus pneumonia
Streptococcus agalactiae

Group b Streptococci. Gram-positive


Beta hemolytic
Bacitracin Resistant
Hydrolyses hippurate
C AMP test positive

Acute Meningitis: Commonest Bacterial Organisms


Neonates: Group B streptococci, E coli
Adolescents and young adults: N meningitidis
Elderly: Strept Pnemoniae, Listeria Monocytogenes
Beta hemolysis is shown by:
Strep pyogenes
Strept agalataciae
Staph aureus
Listeria monocytogenes
Bacillus subtilis
Alpha hemolysis is shown by:
Strep pneumonia
Strep viridians

Microbiology

257

Sterpt mutans
Strep sanguis
Enterococcus

USMLE High Yield


The catalase test is used to differentiate Staphylococci from Streptococci. Staphylococci are catalase positive, Streptococci are
catalase negative
The coagulase test is used to differentiate Staph aureus from the other Staph spp. Staph aureus is coagulase positive; the others
are negative
Sensitivity to novobiocin is used to differentiate Staph saprophyticus (resistant) from Staph epidermidis (sensitive)
Sensitivity to optochin is used to differentiate Strep pneumoniae (sensitive) from viridans Strep (resistant).
Catalase + ve
Coagulase + ve

Staph aureus

Catalase ve
Coagulase ve

Streptococcus

Catalase + ve
Coagulase ve

Novibocin sensitive st epidermidis


Novibocin resistant st saprophyticus

Distinguishing strept and staph

Streptococcus Bovis

The main nonenterococcal group D streptococcal species that causes human infections is S bovis
S bovis endocarditis is often associated with neoplasms of the gastrointestinal tract
3/4 Most frequently a colon carcinoma or polyp 3/4 but is also reported in association with other bowel lesions
S bovis are reliably killed by penicillin as a single agent, and penicillin is the treatment of choice for S bovis infections.

USMLE Case Scenario


A 88-year-old patient from North America with colorectal cancer develops severe septicemia complicated by bacterial type of
endocarditis among the below mentioned choices. You would expect the blood cultures to grow.
1. Streptococcus agalactiae
2. Streptococcus bovis
3. Streptococcus pneumonia
4. Streptococcus pyogenes
Ans. 2. Streptococcus bovis

Catalase Positive Organisms are


Staph aureus
Pseudomonas
Aspergillus
Candida
Citrobacter
Enterobacter
E coli
Klebsiella
Shigella
Yersinia

258

USMLE Step 1 Platinum Notes

Gems about Pneumococcus


Gram-positive
Capsulated
Most virulent: Type C
Draughtsman colonies
Quelling reaction seen
Vaccine is made from capsule
Lanceolate, flame shaped diplococcus
Bile soluble
Optochonin sensitive
Virulence is due to capsule

USMLE Case Scenario


A Eight year-old boy from California presents to the pediatrician because his mother noticed a smoky color to his urine.
The child suffered a sore throat several weeks ago that was left untreated. Physical examination reveals hypertension and
mild generalized edema. Urinalysis is significant for red blood cell casts. Which of the following accurately describes the
microorganism responsible for this childs illness?
1. Streptococcus
2. Staphylococcus
3. Gonococcus
4. Camplyobacter
Ans. 1. Streptococcus

USMLE Case Scenario


Which of the following organisms is the most common cause of community-acquired pneumonia?
1. Chlamydia pneumoniae
2. Mycoplasma pneumoniae
3. Staphylococcus aureus
4. Streptococcus pneumonia
Ans. 4. Streptococcus pneumonia

Neisseria Gonococcus USMLE High Yield

Means flow of seeds


Intracytoplasmic Gram-negative
Noncapsulated
Do not ferment maltose. Ferments glucose
Kidney shaped
Causes:
Urethritis
Cervicitis
Salpingitis
Vaginitis
Conjunctivitis
Meningitis, arthritis, endocarditis

Microbiology

259

USMLE Case Scenario


A sexually active 22-year-old manfrom Kansas develop sacute epididymitis and orchitis. Needle biopsy demonstrates a
prominent leukocytic infiltrate with numerous neutrophils. Which of the following organisms is the most likely cause of this
mans infection?
1. Escherichia coli
2. Mycobacterium tuberculosis
3. Neisseria gonorrheae
4. Staphylococcus
Ans. 3. Neisseria gonorrheae

Neisseria Meningococcus

Gram-negative diplococcic
Capsulated
Carriers are a source of infection
Cause Waterhouse-Friderichsen syndrome, Meningitis
Neisseria meningitides: Capsule + Maltose Fermentation+
Neisseria gonococcus: Capsule-Maltose Fermentation

Corynebacterium Diphtheriae: USMLE High Yield

Gram-positive, nonmotile, nonsporing, noncapsulated


Babes ernest/volutin granules seen/Metachromatic granules seen
Loefflers serum slope, Tellurite media used
Eleks gel precipitation test used
Incubation period 26 days
Faucial (tonsillar) not facial diphtheria is the commonest type of diphtheria
Pseudomembrane formation is a feature
Bulls neck (cervical lymphadenopathy) occurs in diphtheria
Diphtheria toxin inhibits protein synthesis
Toxin is phage mediated
Corynebacterium parvum is used as immunomodulator
Corynebacterium pseudotuberculosis is Nocards bacillus
Corynebacterium minnusitum causes Erythrassma.

Diphtheria
Daisy head colony (C Diphtheriae) gravis
Frogs egg colony (C Diphtheriae) intermedius
Poached egg colony (C Diphtheriae) mitis

260

USMLE Step 1 Platinum Notes

Corynebacterium Minutissimum
It is a part of normal skin flora
It is lipophilic, Gram-positive, aerobic, catalase positive but nonspore forming diphtheroid
It ferments glucose, dextrose, sucrose, maltose and mannitol
Erythrassma is a chronic superficial infection of intertriginous areas
Organism causing erythrassma is Corynebacterium Minutissimum
Erythrassma produces coral red fluorescene under wood light secondary to production of porphyrins

Anthrax

USMLE Case Scenario

An organism produces cutaneous disease (malignant pustule or eschar) at the site of inoculation in handlers of animal skins.
Most likely organism is:
1. Bacilus anthracus
2. Pseudomonas Aeruginosa
3. Neisseria meningitides
4. Cryptococcus neoformans
Ans. 1. Bacilus anthracus

USMLE Case Scenario


A disease is found to produce severe hemorrhagic pneumonia in a person handling carcasses or skins. The organism causing
the disease is a gram-positive rod. Most likely organism is:
1. Yersinia
2. Francisella
3. Spirillum
4. Anthrax
Ans. 4. Anthrax

Anthrax: USMLE High Yield

It is a Zoonosis
Gram-positive, nonmotile, capsulated, sporing
Cutaneous anthrax commonest
Painless malignant pustule. (CHARBON)
Hide porters disease is cutaneous anthrax
Wool sorters disease is pulmonary anthrax
Colony woes for a student
Colony characteristics for the organism
Medusa head
Inverted fir tree appearance
Frosted glass appearance
String of pearl appearance
Mc Faydens reaction positive
PLET medium used

Gems about Clostridia


Clostridium Tetani:
Gram-positive
Anaerobic spore forming bacilli
Motile with swarming tendency
Strict anaerobe

Microbiology

261

Spherical and terminal spores: (drum stick) CL tetani


Oval and terminal spores: (tennis racket) CL difficile
Central or sub terminal: (spindle) other species
Tetanospasmin is the toxin. Blocks release of inhibitory neurotransmitters glycine/GABA.
Generalized tetanus is the mc form
Most effective way of preventing tetanus is tetanus toxoid.

Clostridial Myonecrosis (Gas Gangrene)


80% of cases are caused by C perfringens
Alpha toxin is the most important toxin responsible
C novyi, C septicum, and C histolyticum cause the other cases
Typically, gasgangrene begins with the sudden onset of pain in the region of the wound, which helps to differentiate it from
spreading cellulitis
Once established, the pain increases steadily in severity but remains localized to the infected area and spreads only if the infection
spreads.

Clostridium Botulinium

The CNS is not affected by the toxin of CL botulinium


Blocks release of Ach at synapses and NM junction
Infant botulism is caused by ingestion of spores food borne botulism is due to ingestion of preformed toxin
Symmetric descending paralysis is a feature of botulinism

Clostridium Gifficile

Causes pseudomembranous colitis


It is a normal gut commensal
Almost all antibiotics even the ones used in treatment of pseudomembranous colitis can cause the disease
Metronidazole is the DOC
Vancomycin is also effective in treatment
Cytotoxin assay in stools is the best test

USMLE Case Scenario


A 6-month-old infant presents with failure to thrive, progressive muscular weakness, and poor head control Mother typically
feeds the baby food sweetened with honey. Which of the following organisms is most likely to be responsible for the childs
presentation?
1. Clostridium botulinum
2. Clostridium difficile
3. Clostridium perfringens
4. Clostridium tetani
Ans. 1. Clostridium botulinum

USMLE Case Scenario


A 10-month-old baby presents to the pediatric emergency room with a 1-day history of poor feeding and generalized
weakness. The mother states that she often feeds the baby honey to pacify her. The most likely organism is:
1. Clostridium botulinum
2. Clostridium difficile
3. Clostridium perfringens
4. Clostridium tetani
Ans. 1. Clostridium botulinum

262

USMLE Step 1 Platinum Notes

USMLE Case Scenario


A 66-year-old alcoholic man with brain and pulmonary abscess and is treated with antibiotics for last two weeks. He develops
nausea, vomiting, abdominal pain and voluminous green diarrhea. Which of the following organisms can be most likely
responsible for this patients symptoms?
1. Clostridium botulinum
2. Clostridium difficile
3. Clostridium perfringens
4. Clostridium tetani
Ans. 2. Clostridium difficile

USMLE Case Scenario


An obligate anaerobic, spore-forming, gram-positive bacillus. Which is an important cause of infection following trauma and
surgery and can cause gas gangrene and food poisoning is:
1. Clostridium botulinum
2. Clostridium difficile
3. Clostridium perfringens
4. Clostridium tetani
Ans. 3. Clostridium perfringens

USMLE Case Scenario


A 7-month-old baby presents to pediatrician with a 1-day history of poor feeding and generalized weakness. The mother states
that she often feeds the baby honey. The toxin responsible for this presentation works by which of the following mechanisms?
1. It blocks the release of acetylcholine from the nerve terminal
2. It blocks the release of inhibitory neurotransmitters such as glycine and GABA
3. It has a subunit that inactivates an elongation factor by ADP-ribosylation
4. It stimulates guanylate cyclase
Ans. 1. It blocks the release of acetylcholine from the nerve terminal

Gems about Enterobacteriaceae


E coli, Klebsiella, enterobacter: Ferments lactose
Salmonella, shigella, proteus, pseudomonas: Do not Ferment lactose
Capsular
Antigen
Flagellar antigen
Ferment glucose: E coli, Proteus, Klebsiella
Includes:
Escherichia
Klebsiella
Proteus
Enterobacter
Serratia
Citrobacter
Morganella
Providencia, and
Edwardsiella as well as the genus Actinetobacter from the family Neisseriaceae
Six distinct pathotypes of intestinal pathogenic E coli exist: (1) enterotoxigenic E coli (ETEC); (2) Shiga toxin-producing E coli (STEC)/
enterohemorrhagic E coli (EHEC); (3) enteropathogenic E coli (EPEC); (4) enteroinvasive E coli (EIEC); (5) enteroaggregative E coli
(EAEC); and (6) diffusely adherent E coli (DAEC). Organisms of these pathotypes are acquired via the fecal-oral rout.

Microbiology

263

ETEC is the most common cause of travelers diarrhea


EHEC estimated 50% of all cases of HUS are caused by EHEC infection
EPEC is an important cause of infant diarrhea
EIEC shares many features with Shigella infection; however, unlike Shigella, EIEC causes disease only at a high inoculum (108 to
1010 CFU). Penetrate Hela cells in tissue culture
Sereny test in diagnosis used. Nonmotile and Noniactose fermenting
EAEC: These pathotypes have been described primarily in developing countries and mostly affect young children. These strains
may also cause some cases of travelers diarrhea. A high inoculum is required for infection. In vitro, the organisms exhibit a diffuse
or stacked-brick adherence pattern.

USMLE Case Scenario


An organism is found to be a major cause of travelers diarrhea with watery stools and is a very important pathogen in
neonates, who become infected during passage through the birth canaL The most likely organism is:
1. E coli
2. Rota virus
3. Norwalk virus
4. Campylobacter
Ans. 1. E coli

USMLE Case Scenario


A 42-year-old man from New Jersy presents to surgery department with a tender prostate gland. An acute bacterial infection
of prostate is suspected. Which of the following organisms is the most common pathogen in this setting?
1. Enterobacter
2. Escherichi
3. Klebsiella
4. Proteus
Ans. 2. Escherichi

USMLE Case Scenario


Acute pyelonephritis is an infectious disease involving the kidney parenchyma and the renal pelvis. The most common
organism causing acute pyelonephritis in an adult is:
1. E coli
2. Proteus
3. Klebsiella
4. Pseudomonas
Ans. 1. E coli

Gems about Proteus


Causes only 1 to 2% of cases of UTI in healthy women, and Proteus species cause only 5% of cases of hospital-acquired UTI
Swarming motality
Fishy/seminal odor
Urease positive
Dienes phenomenon shown
Proteus is responsible for 10 to 15% of cases of complicated UTI, primarily those associated with catheterization; in the setting of longterm catheterization. This high prevalence is due to the ability of Proteus to produce high levels of urease, which hydrolyzes urea to
ammonia and results in alkalization of the urine
This situation, in turn, leads to precipitation of organic and inorganic compounds, with the

264

USMLE Step 1 Platinum Notes

Formation of struvite and carbonate-apatite crystals


Biofilm formation on catheters, and/or the
Development of calculi
Proteus becomes associated with the stones and usually can be eradicated only by complete stone removal overtime, staghorn
calculi may form and lead to obstruction and renal failure.

USMLE Case Scenario


A 33-year-old male presents with UTI. An organism isolated is found to have swarming growth on solid media and production
of urease and hydrogen sulfide), associated with urinary tract infections and development of struvite kidney stones. The most
likely organism is:
1. E coli
2. Proteus
3. Klebsiella
4. Pseudomonas
Ans. 2. Proteus

Gems about Klebsiella


Causes only a small proportion of cases of community-acquired pneumonia
Friedlanders bacillus
This infection occurs primarily in hosts with underlying disease, such as alcoholics, diabetics, and individuals with chronic lung
disease
Presentation with earlier, less extensive infection is more common than that with the classic lobar infiltrate with a bulging fissure
Currant jelly sputum is a feature in lung infections

USMLE Case Scenario


An highly encapsulated organism is found to cause a bronchopneumonia with patchy infiltrates involving one or more lobes
with red sputum in a debilitated alcoholic. Most likely organism is:
1. E coli
2. Proteus
3. Klebsiella
4. Pseudomonas
Ans. 3. Klebsiella

Shigella: USMLE High Yield

Gram-negative
Noncapsulated
Nonmotile
Lactose nonfermenters
Ferment mannitol except S dysentrae
Subdivided on basis of Mannitol fermentation
Most virulent type is S dysentiae
Stool culture is the best test

USMLE Case Scenario


A Gram-negative, noncapsulated nonlactose fermenting organism is causing dysentery (multiple, small-volume stools with
blood, mucus and pus associated with abdominal cramps and tenesmusin a 33-year-old male. Most likely organism is:
1. Proteus
2. E coli

Microbiology

265

3. Pseudomonas
4. Shigella, dysentrae
Ans. 4. Shigella dysentrae

Salmonella: USMLE High Yield

Gram-negative
Peritrichate flagella
Need tryptophan as growth factor
Selenite F is used as growth medium
Affects Payers patches in intestines
H antigen is the most immunogenic
VI agglutination detects carriers
VI antigen is not seen in normal population
Blood culture is the gold standard for diagnosis
Diazo reaction is also used for diagnosis

USMLE Case Scenario


A 26-year-old woman with a history of sickle cell disease presents with fever and severe bone pain localized to her left tibia.
X-ray reveals a lytic lesion and blood cultures reveal infection. A bone culture grows gram-negative rods. The organism
responsible is:
1. Salmonella
2. Klebsiella
3. E coli
4. Francisella
Ans. 1. Salmonella

USMLE Case Scenario


A 4-year-old boy presents with a 1-day history of loose stools, fever, abdominal cramping, headache and myalgia. He has no
blood in the stool. The incubation period is 36 hours after ingestion of contaminated food or water. Which of the following is
most likely the causative agent of his diarrhea?
1. Vibrio
2. Bacillus cereus
3. Francisella
4. Salmonella
Ans. 4. Salmonella

Vibrio Cholera: USMLE High yield

Isolated by Koch
Most cases are subclinical
Gram-negative bacilli, aerobic
Noncapsulated, comma shaped
Motile with polar flagellum
Ferments glucose, transported in alkaline medium
Toxin action is CAMP mediated
Darting motility
Cary Blair medium used

266

USMLE Step 1 Platinum Notes

Venkata Raman medium used


Humans are the reservoir
Survives boiling for 30 seconds
Survives in cold temperature (ice for 46 weeks)
Causes rice water stools/ Pea soup diarrhea
Nonhalophilic

USMLE Case Scenario


A comma-shaped organism is found to be sensitive to acidic pH, is a gram-negative rod and causes severe enterotoxin-induced
diarrhea, with rice-water stools and dehydration. Most likely organism is:
1. Proteus
2. Vibrio cholera
3. Klebsiella
4. Francisella
Ans. 2. Vibrio cholera

Pseudmonas: USMLE High Yield


Pseudomonas aerugenosais a gram-negative, aerobic, motile bacillus
Cetrimide agar is the selective media for Pseudomona saerugenosa
EXOTOXIN A inhibits protein synthesis
Pseudomonas aerugenosa produces pigments
Pyocyanin
Pyoverdin
Pyorubin and
Fluorescein
Produces blue green pus
Virulence factors are:
Pilli, Elastase, Exotoxin, Endotoxin, Alkaline protease, Hemolysin Alginate
Grape like odor
Slime layer formation
Pseudomonas aerugenosagrows at 3742 C
Pseudomonas aerugenosa hydrolyses arginine to citrulline and ammonia
Pseudomonas aerugenosa oxidises indophenols
Pseudomonas aerugenosa does not ferment lactose
Piperacillin is an antipseudomonal pencillin. (p-p)

USMLE Case Scenario


A 5-year-old child with cystic fibrosis presents with chronic productive cough. On physical exam, he is febrile and lung exam
reveals intercostal retractions, wheezing, rhonchi, and rales. Chest X-ray demonstrates patchy infiltrates and atelectasis and
Grams stain of the sputum reveals slightly curved, motile gram-negative rods that grow aerobically. The microorganism
responsible for this childs pneumonia is also the most common cause of which of the following diseases?
1. Pseudomonas
2. E coli
3. Proteus
4. Klebsiella
Ans. 1. Pseudomonas

Microbiology

267

USMLE Case Scenario


A 85-year-old man with a history of diabetes presents with left ear pain and drainage of pus from the ear canal. He has swelling
and tenderness over the left mastoid bone. Most likely organism is:
1. E coli
2. Proteus
3. Klebsiella
4. Pseudomonas
Ans. 4. Pseudomonas

USMLE Case Scenario


A 23-year-old engineer was involved in a serious accident and received second- and third-degree burns over his body. He was
placed in the burn unit and, on his twelfth day of his admission, developed a wound infection with a bluish-green exudate.
A gram-negative, motile organism was isolated that was oxidase-positive, did not ferment lactose, sucrose, or glucose, but
grew on MacConkeys agar and produced a fruity aroma on that medium. Which of the following organisms was most likely
isolated?
1. Pseudomonas
2. E coli
3. Proteus
4. Klebsiella
Ans. 1. Pseudomonas

USMLE Case Scenario


A 70-year-old diabetic patient presents with an unresolved skin lesion on his foot. The lesion began several weeks ago as a
blister and has since become a painful, erosive, expanding sore 6 cm in diameter, with a black necrotic center and raised red
edges. Most likely diagnosis is Ecthyma Gangrenosum. Disease is caused by:
1. E coli
2. Proteus
3. Klebsiella
4. Pseudomonas
Ans. 4. Pseudomonas

USMLE Case Scenario


A 2-year-old boy with an indwelling urinary catheter in place develops a urinary tract infection. Urine culture grows out a
lactose-negative, oxidase-positive, gram-negative rod. Which of the following agents is the most likely cause of this boys
urinary tract infection?
1. Escherichia coli
2. Klebsiella pneumonia
3. E Proteus mirabilis
4. Pseudomonas aeruginosa
Ans. 4. Pseudomonas aeruginosa
Pseudomonas aerugenosa causes:
Serious infections in burn patients
Shock with bullous lesions
Ecthyma gangrenosum
Shanghai fever
Hot tub folliculitis
Multi drug resistance is due to biofilm production in cornea

268

USMLE Step 1 Platinum Notes

Pseudomonas pseudomallei
Causes Meliodosis
Also called Whitmores bacillus
Great imitator disease
Pseudomonas Mallei
Causes glanders

Gems about Yersinia

Plague is an acute, febrile, zoonotic disease caused by infection with Yersinia pestis
Y pestis is a gram-negative coccobacillus in the family Enterobacteriaceae
It is microaerophilic, nonmotile, nonsporulating, oxidase and urease negative and biochemically unreactive
Bipolar staining
Safety pin appearance
Waysons staining done for identification
Stalactite growth
The organism is nonfastidious and infective for laboratory rodents. It grows well, if slowly, on routinely used microbiologic
media (e.g. sheep blood agar, brain-heart infusion broth and MacConkey agar)
The colonies are gray-white with irregular surfaces, described as having a hammered-metal appearance when viewed
microscopically
When stained with a polychromatic stain (e.g. Wayson or Giemsa), Y. pestis isolated from clinical specimens exhibits a characteristic
bipolar appearance, often resembling closed safety pins
Bubonic plague, the most common form
It is almost always caused by the bite of an infected flea but occasionally results from direct inoculation of infectious fluids
Septicemic and pneumonic plague can be either primary or secondary to metastatic spread
Because fleas often bite the legs, femoral and inguinal nodes are most commonly involved; axillary and cervical nodes are next
most commonly affected. The enlarging bubo becomes progressively painful and tender
The bubo of plague is distinguishable from lymphadenitis of most other causes, however, by its rapid onset, its extreme
tenderness, the accompanying signs of toxemia, and the absence of cellulitis or obvious ascending lymphangitis
Pneumonic plague is most infectious. pneumonic plague develops most rapidly and is most frequently fatal
Streptomycin is the drug of choice
Tetracycline is the doc for prophylaxis

Erysipelothrix rhusiopathiae is a pleomorphic, gram-negative rod that causes a localized skin infection. It is an occupational disease of
fishermen, fish handlers, butchers, meat-processing workers, poultry workers, farmers, veterinarians, abattoir workers, and housewives.

USMLE Case Scenario


A 44-year-old man from rural America is brought to a rural hospital with severe bronchopneumonia. He suffered sudden
onset of chills, fever and headache several days ago. Two-day later, he complained of chest pain and difficulty breathing and
coughed up blood-tinged sputum. Chest X-ray reveals patchy infiltrates and segmental consolidation. Which of the following
organisms is the most likely cause of this mans pneumonia?
1. Clostridium perfringens
2. Francisella tularensis
3. Listeria monocytogenes
4. Yersinia pestis
Ans. 4. Yersinia pestis

Gems about Hemophilus


Gram-negative cocco bacillus
Grows on chocolate agar
Capsulated

Microbiology

269

Requires factor X and V


Satellitism is seen Chancroid is caused by H ducreyi
Shows school of fish appearance

USMLE Case Scenario


A 3-year-old boy from rural America is brought to the ENT emergency room in extreme respiratory distress, with a temperature
of 104 degrees Fahrenheit. He is drooling and has great difficulty swallowing, and on physical examination, an inspiratory
stridor is noted. An immediate lateral X-ray done shows swelling of the epiglottis. He has had no previous vaccinations. Which
of the following agents is the most likely cause of these symptoms?
1. Klebsiella pneumoniae
2. Hemophilus influenzae
3. Legionella pneumophila
4. Streptococcus
Ans. 2. Hemophilus influenzae

Gems about Bordetella

Gram-negative cocco bacillus


Capsulated
Bordet gengou media used
Causes whooping cough
Incubation period 12 weeks
Thumb printing appearance in culture films
Erythromycin prevents spread of disease in children

USMLE Case Scenario


A seven-week-old infant is brought to the emergency room with a 10-day history of coughing and choking spells. The white
blood cell count is elevated with 85% lymphocytes. The child is gasping for breath, experiencing paroxysms of coughing, and
vomits twice in the examination room. Encapsulated, gram-negative rods grow out on Bordet-Gengou media. Which of the
following microorganisms is the likely cause of these symptoms?
1. Hemophilus influenzae type b
2. Bordetella pertussis
3. Klebsiella pneumonia
4. Legionella pneumophila
Ans. 2. Bordetella pertussis

Gems about Brucellosis

It is a zoonosis
Malta fever/undulant fever/meditarrean fever
Gram-negative
Noncapsulated
Nonmotile
Nonsporing
No personperson transmission

Causative Organisms

B militensis from goat, sheep, cattle (most common)


B abortus from cattle
B suis from hogs
B canis from dogs

270

USMLE Step 1 Platinum Notes

USMLE Case Scenario


A 55-year-old veterinarian presents with a 2-month history of malaise, chills, sweats, fatigue, and weakness. He has anorexia
and has lost 5 kgs. He has intermittent fevers. A physical examination reveals mild lymphadenopathy, petechiae. What is the
most likely gram-negative etiologic agent?
1. Pseudomonas
2. Brucella
3. Vibrio
4. Klebsiella
Ans. 2. Brucella
Brucella survive in unpasteurized milk for up to 8 weeks
Brucella is transmitted most commonly through UN pasteurized milk/milk products, raw meat and bone marrow
It can also be contracted through inhalation in farm houses, slaughter houses, labs. Other routes are skin abrasion, inoculation,
conjunctival splashing
The common symptoms are fever, chills, diaphoresis, headache, myalgias, fatigue
Patient can look deceptively well with just fever
In severe cases Hepatosplenomegaly, Lymphadenopathy, arthritis, meningitis or pneumonia can occur
Rose Bengal Card test used
Milk Ring test used
Diagnosis is by culture, Phage typing, DNA Characteristics, Metabolic profiling (BACTEC)
Treatment is by combination therapy of aminoglycoside plus doxycycline for 4 weeks followed by doxycycline plus rifampin
for 4-8 weeks
In pregnancy TMP-SMZ plus rifampin for 812 weeks is given.

Gems about Mycobacterium Tuberculosis


Mycobacterium tuberculosis complex (consisting of M. tuberculosis, M. bovis, and M. africanum)

USMLE Case Scenario


Achronic meningoencephalitis, with a prolonged clinical course. Characterized pathologically by a dense granulomatous
infiltrate of the base of the brain with increased lymphocytes and slightly decreased glucose is usually caused by:
1. Mycobacterium tuberculosis
2. Neisseria meningococcus
3. Listeria
4. Bordetella
Ans. 1. Mycobacterium tuberculosis

USMLE Case Scenario


Which of the following microorganisms is an obligate aerobe?
1. Bacteroides fragilis
2. Clostridium perfringens
3. Escherichia coli
4. Mycobacterium tuberculosis
Ans. 4. Mycobacterium tuberculosis

Discovered by Robert Koch


Obligate aerobe
Acid fast
Acid fastness is due to mycolic acid and cell wall
Slightly curved rod

Microbiology

LJ Medium (Lowenstein Jonson Medium) used


Usually affects apical and posterior segments of upper lobes
Lung is the mc organ involved
Tubercular lymphadenitis is the mc extra pulmonary TB
Rapid diagnosis is by Auramine Rhodamine stain
Production of niacin is an important feature
Cord factor promotes virulence
Mycobacteium Para tuberculosis is Johnes bacillus

Caseation necrosis

Atypical Mycobacteria
Photochromogen: M kanasi
Scotochromogen: M scofulaceum
Nonchromogen: MAI
Rapid grower: M smegmatis
Buruli ulcer is caused by: M ulcerans
Swimming pool granuloma/Fish tank granuloma is caused by M marinum

Gems about M. Leprae

Gram-positive
Generation time 12 days
Acid fast bacilli. Less acid fast than M tuberculosis
Globi and cigar bundle appearance are a feature
Cultivated in Armadillo
Can be grown in foot pad of mice
Spreads by skinskin contact
Lepra cells are histiocytes

Treponema Pallidium

Causes syphilis
Gram-negative spirochete with polar flagellum
Has hylauronidase
Incubation period 9-90 days

271

272

USMLE Step 1 Platinum Notes

Primary lesion is a chancre. Painless ulcer with nontender inguinal lymphadenopathy


Condyloma lata is seen in secondary syphilis
Dark ground microscopy is used for diagnosis.104 organisms/ml are needed to be detected
Leviditti stain is used for staining
FTAABS is a specific test
VDRL is a slide flocculation test
VDRL is positive in secondary syphilis

USMLE Case Scenario


A 44-year old from New Orleans is referred to a neurologist because of ataxia. Neurological examination reveals a loss of
Proprioception and a wide-based, slapping gate. MRI reveals degeneration of the dorsal columns and dorsal roots of the
spinal cord. Organism implicated is most likely:
1. Mycobacterium leprae
2. Mycobacterium tuberculosis
3. Treponema pallidium
4. Klebsiella
Ans. 3. Treponema pallidium

USMLE Case Scenario


Aspirochete is causing a (a painless, indurated ulcer) at the site of inoculation. Most likely organism is:
1. Chlamydia
2. Mycoplasma
3. Mycobacteria
4. Treponema Pallidium
Ans. 4. Treponema Pallidium

USMLE Case scenario


An organism identified on dark ground microscopy caused testicular involvement with gumma formation, endarteritis, and/
or a prominent plasma cell infiltrate. Most likely organism is:
1. Chlamydia
2. Mycoplasma
3. Mycobacteria
4. Treponema Pallidium
Ans. 4. Treponema Pallidium

Borellia
Borrelia burgdorferi Causes Lymes disease. (erythema migrans)
Borrelia recurrentis causes relapsing fever
Kellys medium used
Lymes Disease:
Causative agent: B. burgdorferi
Vector: Ixodes tick
Features:
STAGE I: Localized disease, IP: 332 days, Erythema migrans at local site
STAGE II: Disseminated disease, Secondary skin lesions, meningitis, carditis
STAGE III: Oligoarticular arthritis, Encephalopathy, Polyneuropathy. Acrodermatitis atrophicans

Microbiology

273

USMLE Case Scenario


A 44-year-old woman vacationing in US is bitten by a tick. She does not seek medical treatment and eventually develops
chronic arthritis of the knee and hip joints and paralysis of the left facial muscles. Most likely disease is:
1. Erythema migrans caused by Borrelia burgdorferi
2. Erythema migrans caused by Borrelia recurrentis
3. Erythema nodosum caused by virus
4. Erythema abigne
Ans. 1. Erythema migrans caused by Borrelia burgdorferi
Erythema chronicum migrans is usually the first sign of the illness. This is a large red patch on the buttocks or chest that slowly
expands as the center blanches. Generally, patients also have constitutional symptoms, such as fever and chills + Stiff neck
may develop, along with other signs of meningeal irritation, because of an aseptic meningitis. +Bells palsy due to involvement
of branches of the facial nerve. + Arthritis + Cardiac abnormalities in Lyme disease include pericarditis and heart block.

Leptospirosis

Spirochetal infection
Rats, rice and rain associations
Transmitted by rat urine
Seen in sewage workers
Acute renal failure and jaundice is a feature
Leptospira icterohemorrhagica causes Weils disease
Weils syndrome, the most severe form of leptospirosis, is characterized by jaundice, renal dysfunction, hemorrhagic diathesis,
and high mortality. This syndrome is frequently but not exclusively associated with infection due to icterohemorrhagiae/
copenhageni.

USMLE Case Scenario


A 39-year-old American farmer develops fever with chills, myalgias, headache, skin rash, and vomiting. He is quite ill and
is hospitalized. Blood cultures demonstrate tightly coiled, thin, flexible spirochetes. The spirochetes are easily cultured in
serum-enriched nutrient agar. Which of the following organisms should be suspected:
1. Brucella
2. Treponema
3. Leptospira
4. Pseudomonas mallei
Ans. 3. Leptospira

USMLE Case Scenario


An Spirochetal infection is caused by contact with urine from infected animals such as rats. The disease is characterized
by abrupt-onset headache (98%), fever, chills, conjunctivitis, severe muscle aches, gastrointestinal symptoms, changes in
sensorium, rash, and hypotension. This phase lasts from 3 to 7 days. Meningeal symptoms hepatic dysfunction and renal
failure develops is later.
1. Brucella
2. Treponema
3. Leptospira
4. Pseudomonas mallei
Ans. 3. Leptospira

Gems about Mycoplasma


Eaton agent
The smallest free-living organisms known
Are prokaryotes that are bounded only by a plasma membrane

274

USMLE Step 1 Platinum Notes

Their lack of a cell wall is associated with cellular pleomorphism and resistance to cell wall-active antimicrobial agents, such as
penicillins and cephalosporins
Fried egg colonies
L forms seen. (Concept has changed now)
Mycoplasma pneumoniae causes primary atypical pneumonia, upper and lower respiratory tract infections
M genitalium and Ureaplasma urealyticum are established causes of urethritis and have been implicated in other genital
conditions
M hominis and U. urealyticum are part of the complex microbial flora of bacterial vaginosis
Mycoplasma Pneumoniae
M pneumoniae causes upper and lower respiratory tract symptoms
The infection is acquired by inhalation of aerosols

USMLE Case Scenario


A 22-year-old college student from Ohiopresents to the chest clinic complaining of weakness, malaise, and a chronic cough.
He has a fever of 100 degrees F and a dry cough; no sputum can be obtained for laboratory analysis, so a bronchial lavage
is performed and the washings are submitted to the laboratory. The laboratory reports that the organism is slow-growing.
Serodiagnosis reveal sagglutinins in the patients serum. Which of the following organisms is the most likely cause of this
students illness?
1. Mycoplasma pneumonia
2. Mycobacterium tuberculosis
3. Treponema pallidium
4. Chlamydia
Ans. 1. Mycoplasma pneumonia

USMLE Case Scenario


Certain organisms are found by a pasthologist in Main Hospital New York to be susceptible to the macrolide family of antibiotics
(erythromycin). These organisms lack a cell wall, hence they are indifferent to antibiotics that interfere with peptidoglycan
synthesis, such as penicillin. The organisms are most likely:
1. Mycobacteria
2. Mycoplasma
3. Treponema
4. Leptospira
Ans. 2. Mycoplasma

Actinomyces

Gram-positive
Nonmotile
Nonsporing
Nonacid fast
Noncapsulated
Mc form cervico facial
Lumpy jaw is a feature

Growth of actinomycetes usually results in the formation of clumps called grains or sulfur granules
Oral-Cervicofacial Disease
Actinomycosis occurs most frequently at an oral, cervical, or facial site, usually as a soft tissue swelling, abscess, or mass lesion that
is often mistaken for a neoplasm
The angle of the jaw is generally involved.

Microbiology

275

USMLE Case Scenario


Pathologist in New Orleans Pathology clinic finds Organisms to be normal inhabitants of the gastrointestinal tract that grow
under anaerobic and microaerophilic conditions. They are gram-positive rods; they grow as branching filaments and have
been confused with fungi. The yellow colonies are found in abscesses. Most Likely organism is:
1. Actinomyce
2. Anthrax
3. Aspergillus
4. Blastomyce
Ans. 1. Actinomyce

Nocardia

Strict aerobe
Acid fast
Causes Nocardiosis
Paraffin bait is used for isolation
Soil is natural habitat
Pneumonia is the mc manifestation

Listeria Monocytogenes
It is a gram-positive cocobacillus in short chains
That can be isolated from soil, vegetation and many animal reservoirs
Shows tumbling motility
Survives and multiplies in phagocytes
Human disease due to L monocytogenes generally occurs in the setting of pregnancy or of immunosuppression caused by illness
or medication
Antons test used

L monocytogenes grows well in cold temperatures


L monocytogenes causes meningitis and sepsis in neonates
L monocytogenes causes meningitis and sepsis in immunocompromised patients
L monocytogenes during pregnancy can cause abortion, premature delivery or sepsis during postpartum period.

Campylobacter: (USMLE Favorite)


Are motile
Nonspore-forming, curved gram-negative rods
Microaerophilic
The principal diarrheal pathogen is c. jejuni, which accounts for 80 to 90% of all cases of recognized illness due to campylobacters
Skirrows medium is culture medium
Butzlers medium is culture medium

H pylori: (USMLE Favorite)

It is a gram-negative, spiral, flagellate bacillus


It is noninvasive, living in gastric mucus; a small proportion of the bacterial cells are adherent to the mucosa
Its spiral shape and flagellae render H pylori motile in the mucous environment
Its efficient urease protects it against acid by catalyzing urea hydrolysis to produce buffering ammonia
In vitro, H pylori is microaerophilic and slow-growing and requires complex growth media

276

USMLE Step 1 Platinum Notes

Complete genomic sequence has been studied


Causes duodenal ulcers (stronger relation)
Causes gastric ulcers
Prevalence increases with age
Transmitted from man-man, fecal orally and orogastric route

Urease Positive Organisms

S aureus
Proteus
H pylori
Klebsiella
Cryptococcus
Nocardia
Diphtheroids
Yersinia pseudotuberculosis
Yersinia enterocolitica

USMLE Case Scenario


A 32-year-old pregnant woman develops a severe flu-like illness with fever, headache, myalgia, and backpain. As a
complication she has a spontaneous abortion. Examination of the abortus demonstrates severe amnionitis. Which of the
following organisms with tumbling motility would most likely be isolated from the placental membranes?
1. Borrelia burgdorferi
2. Leptospira interrogans
3. Listeria monocytogenes
4. Group B streptococcus
Ans. 3. Listeria monocytogenes

USMLE Case Scenario


An actinomycete causes a chronic lobar pneumonia that may metastasize to the brain. It is more common in the
immunocompromised. It is found in soil and aquatic environments. Organism is:
1. H pylori
2. Nocardia
3. Leptospira
4. Blastomyce
Ans. 2. Nocardia

USMLE Case Scenario


A Gram-positive coco bacillus is causing Infection during pregnancy that may result in sepsis, abortion or premature delivery.
Infection in the neonate may produce meningitis. In immunocompromised adults, either meningitis or sepsis may occur. The
organism is:
1. H pylori
2. Legionella
3. Leptospira
4. Listeria
Ans. 4. Listeria

USMLE Case Scenario


An organism is foud to be gram-negative, spiral, flagellate bacillus with microaerophilic character. Among the choices
mentioned below the most likely organism is:
1. H pylori
2. Legionella

Microbiology

277

3. Leptospira
4. Listeria
Ans. 1. H pylori

Legionellosis

Weakly gram-negative bacillus


Motile, nonencapsulated
Pleomorhic rods requiring Cysteine and Iron
Aerosols from natural reservoirs are the most common source of infection
No man to man transmission occurs
No animal reservoir occurs
Disease is limited to humans
Lungs are primarily effected
Legionellosis is an infectious disease caused by bacteria belonging to the genus Legionella
Over 90% of legionellosis cases are caused by Legionella pneumophila, a ubiquitous aquatic organism that thrives in warm
environments (25 to 45C F)

Legionellosis Takes Two Distinct Forms


Legionnaires disease, also known as Legion Fever (archaic), is the more severe form of the infection and produces pneumonia
Pontiac fever is caused by the same bacterium, but produces a milder respiratory illness without pneumonia which resembles
acute influenza
The time between the patients exposure to the bacterium and the onset of illness for Legionnaires disease is 2 to 10 days;
For Pontiac fever, it is shorter, generally a few hours to 2 days
Grown on BYCE medium (Bufferred Charcoal Yeast Extract)

USMLE Case Scenario


A pathologist reports mild walking pneumonia-like condition. The organism is motile, encapsulated and can be cultured
on a charcoal yeast extract medium, but identification is usually accomplished by immunofluorescent examination of the
pulmonary specimen. Most likely cause is:
1. Legionella
2. Leptospira
3. Listeria
4. Chlamydia
Ans. 1. Legionella

Remember: (USMLE Favorite)


Meleneys gangrene: Anaerobic bacterial synergistic gangrene is characterized by exquisite pain, redness, and swelling
followed by induration. These infections usually involve a combination of Peptostreptococcus spp. and S. aureus; the usual site
of infection is an abdominal surgical wound or the area surrounding an ulcer on an extremity
Necrotizing fasciitis, a rapidly spreading destructive disease of the fascia, is usually attributed to group A streptococci but
can also be caused by anaerobic bacteria, including Peptostreptococcus and Bacteroides spp. Gas maybe found in the tissues
Fourniers gangrene consists of cellulitis involving the scrotum, perineum, and anterior abdominal wall, with mixed anaerobic
organisms spreading along deep external fascial planes and causing extensive loss of skin.
Neutropenic enterocolitis (typhlitis) has been associated with anaerobic infection of the cecum but in the setting of
neutropenia may involve the entire bowel. The primary pathogen is thought by some authorities to be C. septicum, but other
clostridia and mixed anaerobic infections have also been implicated
Brain abscesses are frequently associated with anaerobic bacteria If optimal bacteriologic techniques are employed, as many as
85% of brain abscesses yield anaerobic bacteria most often anaerobic gram-positive cocci (especially peptostreptococci),
which are followed in frequency by Fusobacterium and Bacteroides spp.

278

USMLE Step 1 Platinum Notes

Enterococci: (USMLE High Yield Facts)


Lancefield group D includes the enterococci
Enterococci are distinguished from nonenterococcal group D streptococci by their ability to grow in the presence of 6.5%
sodium chloride
Significant pathogens for humans are E faecalis and E faecium
These organisms tend to produce infection in patients who are elderly or debilitated or in whom mucosal or epithelial barriers have
been disrupted or the balance of the normal flora altered by antibiotic treatment
Urinary tract infections due to enterococci are quite common, particularly among patients who have received antibiotic
treatment or undergone instrumentation of the urinary tract
Enterococci are a frequent cause of nosocomial bacteremia in patients with intravascular catheters
These organisms account for 10 to 20% of cases of bacterial endocarditis on both native and prosthetic valves
Enterococci are frequently cultured from bile and are involved in infectious complications of biliary surgery and in liver abscesses
Moreover, enterococci are often isolated from polymicrobial infections arising from the bowel flora (e.g. intraabdominal
abscesses), from abdominal surgical wounds, and from diabetic foot ulcers.

Anaerobic Infections
Nonsporing anaerobic bacteria are:
Bacteroids fragilis
Fusobacterium
Peptostreptococcus
Actinomyces israelli

USMLE Case Scenario


A 36-year-old female in New Jersy is diagnosed with subacute bacterial endocarditis after urologic instrumentation. Organisms
causing the same are gamma-hemolytic, gram-positive cocci that grow on bile-esculin agar. Most likely organisms are:
1. Streptococci
2. Staphylococci
3. Enterococci
4. Meningococci
Ans. 3. Enterococci

Rickettsial Diseases

Rickettesia are obligate intracellular parasites


Rickettesia divide by binary fission
Rickettesial diseases are transmitted by bites of arthropods
Typical lesion is vasculitis and these organisms effect endothelial lining of vessel walls
Lab diagnosis is based on serology rather than isolation of organisms.

Rocky mountain spotted fever: The most severe of the rickettsial diseases, is caused by Rickettsia rickettsii
Mediterranean spotted fever (boutonneuse fever) and other spotted fevers: The etiologic agent of mediterranean spotted
fever, R conorii
Rickettsial pox: caused by R akari
Endemic murine typhus (flea-borne) caused by R typhi
Epidemic typhus (louse-borne): Due to infection with R prowazekii is transmitted by the human body louse (pediculus humanus
corporis), which lives on clothes and is found in poor hygienic conditions (especially in jails, where the disease it causes is called
jail fever) and usually in cold areas
Brill-zinsser disease is a recrudescent, mild form of epidemic typhus occurring years after the acute disease, probably as a result
of immunosuppression or old age.

Microbiology

279

Scrub typhus caused by R tsutsugamushi


Ehrlichioses: Ehrlichiae are small, obligately intracellular bacteria with a gram-negative-type cell wall that grow in cytoplasmic
vacuoles to form clusters called morulae
Two distinct ehrlichia species cause human infections that can be severe and frequent
E chaffeensis, the agent of Human monocytotropic ehrlichiosis infects predominantly mononuclear phagocytic cells in tissues
and blood monocytes
A member of the E. phagocytophila group that infects cells of myeloid lineage is the agent of Human granulocytotropic
Ehrlichiosis
Q fever: Results from infection with C burnetii.

USMLE Case Scenario


A Disease is found to be due to reactivation of epidemic typhus infection caused by Rickettsia prowazekii. It can occur many
years after an infection that was not treated with antibiotics. The most likely disease is:
1. Human granulocytotropic Ehrlichiosis
2. Epidemic typhus
3. Brill-Zinsser disease
4. Endemic typhus
Ans. 3. Brill-Zinsser disease

USMLE Case Scenario


Organism most likely to be implicated as a cause of urethritis that persists after antibiotic therapy for gonorrhea:
1. Chlamydia
2. Rickettsia
3. Mycoplasma
4. Mycobacteria
Ans. 1. Chlamydia

USMLE Case Scenario


An obligate intracellular parasite that induces endocytosis and resides in the phagosome of infected epithelial cell is:
1. Rickettsia
2. Mycoplasma
3. Mycobacteria
4. Chlamydia
Ans. 4. Chlamydia

Chlamydia

Are obligate intracellular bacteria


Gram-negative
They possess both DNA and RNA
Have a cell wall and ribosomes
Mc Coy and HeLa cells used for detection
Multiply by binary fission

Elementary body is metabolically inert. (Extracellular)


Reticulate body is active. (Intracellular)
IDENTIFIED BY Nucleic acid amplification test NAAT
Inclusion body in conjunctivitis: HP (Halberstaedter prowazek bodies)
Inclusion bodies in LGV: Miyagawa bodies
Inclusion bodies in Psittacosis: Levinthal Colles Lille bodies

280

USMLE Step 1 Platinum Notes

Pecularities

Meta chromatic staining: Corynebacterium


Lancet shaped diplococcic: Pneumococci
Bean shaped diplococcic: Neisseria
Bipolar staining: Yersenia
Gulls wing: Campylobacter

Clinical scenarios: Most Likely Organism: (USMLE Favorite)


MC cause of lobar pneumoniae in elderly

Streptococcus pneumonia

lobar pneumonia with deep red (Currant jelly) sputum

Klebsiella pneumonia

Meningitis in neonate (Gram-positive organism)

Strep Agalactiae

Meningitis in neonate (Gram-negative organism)

E coli

Meningitis in neonate (Gram-positive Rod)

Listeria monocytogenes

Joint pains, skin petechiae, fever, in young female

Gonococcal arthritis

Patient on clindamycin complaining of diarrhea

Clostridium difficile

Abdominal pain, bloody diarrhea and flask shaped ulcers

Entameba histolitica

Important Culture Media


Thayer Martinmedia

Neisseria Gonorrhea

Chocolate agar with Factor X and V

H. influenza

Bordet Gengou

Bordetella Pertussis

Lownstein Johnson

Mycobacterium Tuberculosis

Charcoal Yeast Agar

Legionella

USMLE Case Scenario


A 4-week-old infant is brought with a 6-day history of coughing and choking spells. The white blood cell count is elevated with
92 % lymphocytes. The child is gasping for breath, experiencing paroxysms of coughing. Encapsulated; gram-negative rods
grow out on Bordet-Gengou media. Which microorganism is the likely cause of these symptoms?
1. Borellia
2. Legionella
3. Bordetella pertussis
4. Listeria
Ans. 3. Bordetella pertusis

Eponyms: USMLE
Eponyms
Whitmoores bacillus

Pseudomonas pseudomallei

Eaton agent

Mycoplasma

Johnes bacillus

Mycobacterium paratuberculosis

Batteys bacillus

Mycobacterium intercellulare

Freidlanders bacillus

Klebsiella Pneumoniae

Koch weeks bacillus

Hemophilus aegipticus

Nocard bacillus

Cornyebacterium Pseudotuberculosis

Microbiology

Tests for Organisms


Ascolis thermoprecipitation test

Anthrax, Plague

Xeno Diagnosis

Rickettsia

Naeglers reaction (is due to Lecithinase)

Clostrida

Green fluorescent on media with neutral red

CL Tetani

Cholera Red reaction indole formation and


Nitrates to Nitrites

Cholera

Strauss reaction

Pseudomonas Mallei

Neil Mooser reaction (Tunica reaction)

Rickettsia Mooseri

Satellitism

H Influenza
Diphtheria
Diphtheria
Diphtheria

a. Chinese letter pattern


b. Eleks test
c. Schick test
Dick test

Streptococci/pneumococci

Schultz- charlton reaction

Streptococci

MFadyeans reaction

B Anthrax

Stormy reaction in Culture

Cl Welchii

Milk Ring test (Rose Bengal Card test)

Brucellosis

Von- Pirquet test

Tuberculosis

Kochs phenomenon

Tuberculosis

Francis test (Dick test)

Pneumococci/streptococci

String Test

V Cholerae

Typical Appearances: (USMLE Favorite)


School of fish

Hemophilus ducreyi

Satellitism

Hemophilus influenza

Fried egg colony

Mycoplasma

Draughtsman colony

Pneumococcus

Swarming growth

Proteus

Oil paint appearance

Staph

Different Motilities: (USMLE Favorite)


Darting motility

Cholera

Swarming motility

Proteus

Spinning motility

Fusobacterium

Tumbling motility

Listeria

Diagnosis of Urethritis and Causative Organism

Gram-negative diplococcic in PMNs in urethral Exudate:


Culture negative specimen with inclusion bodies:
Organisms without cell wall and urease positive:
Flagellate protozoa with motility:

Neisseria gonorrhea
Chlamydiae trachomatis
Ureaplasma Urealyticum
Trichomonas vaginalis

281

282

USMLE Step 1 Platinum Notes

Vaginal Discharge
Yellow, pH>5, clue cells, amine odor
Cottage cheese discharge, pruritis, Vulvovaginitis
Frothy, Foamy discharge and motile trophozites seen

Vaginosis
Candida
Trichomonas vaginalis

USMLE Case Scenario


A Pap smear from a 33-year-old woman demonstrates protozoal parasites. These organisms are likely to be:
1. Treponema
2. Trichomonas vaginalis
3. Vaginosis
4. Candida
Ans. 2. Trichomonas vaginalis

USMLE Case Scenario


A 33-year-old female has Sexually transmitted disease. Pear-shaped flagellated protozoal infection characterized by a
malodorous, cheesy exudate and erythema of the external genitalia is caused by:
1. Treponema
2. Trichomonas vaginalis
3. Bacterial vaginosis
4. Candida
Ans. 2. Trichomonas vaginalis

USMLE Case Scenario


Chagas disease is an important cause of cardiac failure in some Latin American countries, and Brazilian cases can be associated
with megaesophagus and megacolon. The disease is Chagas disease, which is caused by:
1. Bacteria
2. Mycoplasma
3. protozoa
4. Virus
Ans. 3. Protozoa

Virology

Viruses: Smallest infectious agent containing only one kind of nucleic acid as their genome
Virion: Extracellular infectious particle
Largest virus: Poxvirus (300 nm)
Smallest Virus: Foot and Mouth Disease Virus (20 nm)
Capsid is a protein coat surrounding nucleic acids
Capsid+nucleic acid is Nucleocapsid

Features of Virus: (USMLE Favorite)

Ribosomes absent
Mitochondria absent
Motility absent
Nucleus absent But Nucleic acid Either DNA or RNA Present. That is why some viruses are DNA Viruses and others are RNA Viruses.
(Common Sense)

Microbiology

283

Virusoids are nucleic acids that depend on helper viruses to package the nucleic acids into virus-like particles
Viroids are simply molecules of naked, cyclical, mostly double-stranded, small RNAs and appear to be restricted to plants, in
which they spread from cell to cell and are replicated by cellular RNA polymerase II
Prions are protein molecules that can spread from cell to cell and effect changes in the structure of their normal counterparts
(cellular proteins). Prions have been implicated in neurodegenerative conditions such as Creutzfeldt-Jakob disease, Kuru, and
Gerstmann-Straussler disease. Prions have also been implicated in neurodegeneration associated with human infection with
bovine spongiform encephalopathy (mad cow disease).

Classification of Viruses
Nucleic Acid

DNA

Nucleic Acid

RNA

Capsid Symmetry

Enveloped/Naked

Family

Type of Strand

Icosahedral
Icosahedral
Icosahedral
Icosahedral
Complex

Naked
Naked
Naked
Enveloped
Complex
Coat

Parvoviridae
Papovaviridae
Adenoviridae
Herpes viridae
Pox
Hepadna

Positive strand

Capsid Symmetry

Enveloped/Naked

Family

Type of Strand

Icosahedral
Icosahedral
Icosahedral
Icosahedral

Naked
Naked
Naked
Enveloped

Picorna
Calci
Reo
Toga

Positive strand

Unknown or Complex
Unknown or Complex
Unknown or Complex
Unknown or Complex

Enveloped
Enveloped
Enveloped
Enveloped

Flavi
Areana
Corona
Retro

Positive strand

Helical

Enveloped
Enveloped
Enveloped
Enveloped

Buny
Orthomyxo
Negative strand
Paramyxo
Rhabdo

Virus with smallest genome: Parvo virus


Virus with genome having double stranded nucleic acid: Poxvirus, Reo virus
Virus with Segmented RNA: Influenza virus
Virus with split genome: Rota virus

Human Slow Virus Infections: (USMLE Favorite)


Virus/agent

Disease

Measles

Subacute sclerosing panencephalitis

Papovavarus (JC Virus)

Progressive multifocal leucoencephalopathy


HIV encephalopathy

Rubella

Progressive rubella panencephalitis

Retrovirus

Acquired Immuno Defeciency Syndrome

Prion disease

Kuru
Creutzfeldt-Jakob disease

284

USMLE Step 1 Platinum Notes

Poxviruses Causing Human Disease


Smallpox
Molluscumcontagiosum
Vaccina
Cow pox
Monkey pox
Buffalo pox
Orf

Herpesvirus Group Includes

HSV 1
HSV 2
Varicella zoster virus
EBV
CMV
RK Virus

Herpes Simplex Virus


Double stranded DNA virus
Orofacial infection mc caused by HSV 1
Genital infection mc caused by HSV 2
Causes:
Gingivostomatitis
Herpetic whitlow
Corneal infection
Esophagitis
Genital herpes
Herpetic gladiatorum
Meningitis/encephalitis (HSV 1). MC cause of sporiadiac viral encephalitis
Herpes virus 1 causes Herpes labialis
Herpes virus 2 causes Genital herpes.

Varicella Zoster Infection

Caused by VZV
Reactivates and can involve eye
Remains dormant in trigeminal ganglion
Causes herpes zoster
Post herpetic neuralgia
Infectivity lasts 6 days after onset of rash

EBV
Belongs to herpes group
Binds through CD 21receptor
Diseases caused by EBV:
Oral hairy leukoplakia
Chronic fatigue syndrome
Burkitts lymphoma

Microbiology

285

Anaplastic nasopharyngeal carcinoma


Tonsillar carcinoma
Angioimmunoblastic lymphadenopathy
Angiocentric nasal NK/T cell immuneproliferative lesions
T cell lymphoma
Thymoma
Gastric carcinoma, and
CNS lymphoma from patients with no underlying immunodeficiency
Paul bunnel test is done in infectious mononucleosis

USMLE Case Scenario


A 22-year-old college student from New York complains of a sore throat and fever. He describes feeling tired for the past few
days and reports a loss of appetite. On examination; he has pharyngitis with cervical lymphadenopathy. Blood tests reveal
lymphocytosis and the presence of heterophil antibodies. The virus responsible is:
1. EBV
2. HSV
3. CMV
4. Pox
Ans. 1. EBV

USMLE Case Scenario


An African child develops massive unilateral enlargement of his lower face in the vicinity of the mandible. Biopsy demonstrates
sheets of medium-sized blast cells with admixed larger macrophages. This type of tumor has been associated with viral
infection:
1. EBV
2. HSV
3. CMV
4. Pox
Ans. 1. EBV

USMLE Case Scenario


Encephalitis typically affects the inferomedial temporal lobes and orbitofrontal gyri. Most likely Double stranded DNA virus
implicated is:
1. EBV
2. HSV
3. CMV
4. Pox
Ans. 2. HSV

USMLE Case Scenario


A viral organism was isolated from a painful blister on the lip of a girl. The agent was found to double-stranded, linear DNA
and was enveloped. Most likely causative organism is:
1. EBV
2. HSV
3. CMV
4. Pox
Ans. 2. HSV

286

USMLE Step 1 Platinum Notes

CMV

MC congenital infections
Petechiae, hepatospleenomegaly, jaundice are the mc presenting features of congenital CMV infection
Cause of heterophile negative mononucleosis. (Kindly remember). Different from infectious mononucleosis
Fifty percent of renal transplant patients with fever 14 months after transplant have CMV infection.

USMLE Case scenario


Cytomegalovirus produces neonatal infections and infections in immunocompromised patients such as AIDS patients. CD4 counts are
usually <100 cells/mm3. The most common clinical presentation is chorioretinitis producing floaters, +visual field deficits+painless loss
of vision. CMV also produces encephalitis and may produce calcifying lesions in the CNS.

USMLE Case scenario


A 29-year-old was given a renal graft after a month of hemodialysis for end-stage renal failure. Later given immunosuppressive
therapy and presented one month after with general malaise, muscle aches and IgM anti-CMV antibodies were detected
in a current serum sample accompanied by a positive PCR signal for CMV antigen. These findings indicated primary CMV
infection in the recipient due to transplantation of a CMV-positive kidney into a CMV-negative recipient. He made a complete
recovery following prompt treatment with a combination of ganciclovir (a CMV-specific drug) and CMV-specific immune
globulin.

USMLE Case Scenario


Intranuclear owls eye inclusion bodies causing, a common STD in the United States manifested by mononucleosis-likes
symptoms. Most likely organism is:
1. EBV
2. HSV
3. CMV
4. Pox
Ans. 3. CMV

Adenovirus
Nonenveloped DNA virus
Mc manifestation is URTI in children
Mc manifestation is RDS in adults
Causes:
Diarrhea
Hemorrhagic cystitis
Epidemic keratoconjunctivitis

Picarnovirus

Poliovirus
Coxsackie A
Coxsackie B
Echovirus
Enterovirus
Hepatitis A virus
Rhinovirus

Microbiology

287

Enterovirus 70 causes: Acute hemorrhagic conjunctivitis


Enterovirus 70 causes: Acute epidemic keratoconjunctivitis
Adenovirus causes: Epidemic keratoconjunctivitis
Herpesvirus causes: Acute keratoconjunctivitis

Coxsackievirus
Herpangina
It is most commonly seen in infants and children, though can occur in adults
The incubation period lies between 3 and 5 days and fecal infectivity may last for several weeks
Local examination of the mouth will usually reveal hyperemia of the pharynx and characteristic papulovesicular lesions,
approximately 12 mm in diameter and surrounded by an erythematous ring
Most commonly the lesions are present over the tonsillar pillars, soft palate and uvula though on occasion the tongue maybe
involved
Aseptic Meningitis
It is the most common clinical manifestation and may result from infection by several different Coxsackie A virus strains
Coxsackievirus A7 is the most frequently implicated but other strains such as A9 have also been involved
Severe and fatal encephalitis has been described in only a small number of cases of Coxsackie A virus infection
Hand, foot and mouth disease (HFM)
Examination of the mouth often shows some mild ulceration over the tongue and further examination indicates the pearly
white vesicles, sometimes surrounded by a red halo, on the extremities
The lesions are mainly found over the ventral surface of the fingers and toes and have a characteristic distribution along the sides
of the feet. Some cases also show a maculopapular rash over the buttocks
Coxsackie A causes herpangina and hand-foot-and-mouth disease
Coxsackie B is seen in patients with pleurodynia, myocarditis, and pericarditis

Poliovirus
Poliovirus belongs to picarnoviradiae family and has icosahedral symmetry
Poliovirus is ether resistant
Poliovirus is a single stranded, positive sense, RNA Virus
Most common type is Type 1 Polio virus
Mc cause of epidemics: Type 1
Most difficult to eradicate: Type 1
Mc associated with paralysis: Type 1
Mc cause of vaccine induced paralysis: Type III
Most antigenic strain is Type 2
Most common manifestation is subclinical infection. (90%)
Descending assymetrical paralysis is the predominant sign
Proximal muscles are more involved than distal
No sensory loss
No autonomic disturbance
Inapparent infections mc feature transmitted by feco oral route
Spreads by both hematogeneous and neural route
Death in polio is mostly due to respiratory paralysis

Influenza Virus
Belongs to orthomyxovirus group
Enveloped RNA virus
Type A: Causes all pandemics and most epidemics

288

USMLE Step 1 Platinum Notes

Type C: Causes endemics


Type B: Causes Reyes syndrome. (mc)
Hemaglutinin and Neuraminidase is strain specific
Antigenic variation seen as:
Antigenic drift (minor change) seen. Small mutations in H and N
Antigenic shift (major change) seen

The Bird Flu Virus: (USMLE Favorite)

H5N1 IS THE AVIAN FLUE INFLUENZA VIRUS ALSO CALLED AS THE BIRD FLU VIRUS.
H5N1 was previously believed to cause outbreak in birds only. (enzootic)
H5N1 is a highly pathogenic virus
Risk factor is handling of infected poultry
H stands for Hemaglutinin and N in H5N1 Stands for Neuraminidase
Virus can pass vertically from mother to fetus

Swine Flu

Occurred in Mexico in may 2009 with threat of a pandemic spreading as far as Newzeland, Australia, Asia, UK, etc
Caused by swine influenza virus (SIV)
SIV usually infects pigs
Undercooked pork is a common cause
When infection spreads to humans, it is called zoonotic flu
Clinical features: chills, fever, sore throat, headache, coughing weakness
SIV subtype: H1N1CAUSED 2009 OUTBREAK
This strain has human to human transmission
The US Centers for Disease Control and Prevention recommends the use of Tamiflu (oseltamivir) or (zanamivir) for the
treatment and/or prevention of infection with swine influenza viruses
However, the majority of people infected with the virus make a full recovery without requiring antiviral drugs
The virus isolates in the 2009 outbreak have been found resistant to amantadine and rimantadine

Measles
Paramyxovirus
Causes rubeola (measles)
Infective period 4 days before and 5 days after appearance of rash

Kopiloks spots+maculopapular rash a feature


Otitis media is the MC complication
Hechts pneumonia/primary giant cell pneumonia is seen in measles
SSPE is a late complication. (RARE)

Mumps

Paramyxovirus
Bilateral parotid enlargement seen
Orchitis is the MC complication in post pubertal males
Meningoencephalitis can precede parotitis
One attack gives life long immunity
Incubation period varies from 23 weeks
Pain and swelling of parotids (earache) is a feature

Microbiology

289

Orchitis, ovaritis, pancreatitis, meningoencephalitis, throditis, neuritis, hepatitis and myocarditis are a feature
Mumps is leading cause of parotitis in children
Control of mumps is difficult because disease is infectious before a diagnosis is made.

Rubella
Toga virus
No carrier state
Cervical lymphadenopathy
Rubella can cause a congenital infection characterized by ocular problems (cataracts, retinopathy, microphthalmos, glaucoma),
cardiovascular problems, deafness, thrombocytopenic purpura, hepatosplenomegaly, CNS problems, and bony lesions
Congenital rubella causes: cataract+deafness+heat diseases.

Arboviruses: (USMLE Favorite)


Chikungunya

Japanese encephalitis
West nile
Yellow fever
Dengue
Kyanasaur forest disease
Sandfly fever
Rift valley fever
Hanta virus

alphavirus

flavivirus
flavivirus
flavivirus
flavivirus
flavivirus
bunyavirus
bunyavirus
bunyaviridae

Hantavirus

It is a RNA virus
Belongs to arbovirus
Causes hemorrhagic fever with nephritis
Causes hantavirus pulmonary syndrome

Rabies Virus
Rabies virus has negative polarity
Rhabdoviridae
Bullet shaped, neurotropic
Enveloped virus with ss RNA
It is Lyssavirus serotype 1
Inactivated by Phenol, UV radiation, Beta propiono lactone
Negri bodies are present inside nerve cells. Most characteristic finding in CNS is the formation of cytoplasmic inclusion bodies
called Negri Bodies (composed of fibrillary matrix and rabies virus particles) within neurons of ammons horn, Cerebral cortex,
Brainstem, Hypothalamus, Cerebellum and Dorsal spinal ganglia
Since first described by Negri in 1903, the Negri body has been regarded as a pathognomonic
Finding signifying the presence of rabies encephalitis. Negri bodies (light microscope) were found in the brain of a patient with
conclusive evidence in favor of the presence of rabies encephalitis
Brainstem encephalitis is a feature
Fluorescent stains are used for antemortem diagnosis.

290

USMLE Step 1 Platinum Notes

Hepatitis A virus

It is a nonenveloped 27-nm, heat-, acid- and


Ether-resistant RNA virus
In the hepatovirus genus of the picornavirus family
Previously called enterovirus 72
No chronic course
Inactivated by boiling, formalin, uv radiation

Hepatitis B Virus: (USMLE Favorite)


It is a DNA virus
Hepadnavirus Contains DNA dependent DNA polymerase and RNA dependent reverse transcriptase
Reverse transcriptase is coded by P gene
Dane particle is HBV
HBV strain in India is Ayw, Adr
HBV has maximum perinatal transmission risk
Oncogenicity present in Hepatitis B especially after neonatal infection
Carrier state present in Hepatitis B
Hepatitis B virus may present in blood and other body fluids and excretions such as saliva, breast milk, semen, vaginal
secretions, urine, bile, etc.
Feces not known to be infectious
HBs Ag is the first viral marker to appear in blood after infection; it remains in circulation throughout icteric course of
disease. In a typical case it disappears within roughly 2 months but may last for 6 months
HBs Ag is not demonstrable in circulation but antibody, anti H-Be appear in serum a week or two after appearance of Hbs Ag
Anti-Hbe Ag is the antibody marker to be seen in blood
Serological marker of acute hep B is: HBs Ag + core antibody
Epidemological marker of Hep B is: core antibody
HBe Ag (HB envelop antigen) appears in blood concurrently with HBs Ag
Hbe Ag is an indicator of intrahepatic viral replication and its presence in blood
Indicates high infectivity
For diagnosis of HBV infection, simultaneous presence of IgM, HBC indicates recent infection
Presence of IgG; anti H-Be indicates remote infection
Hep B vaccine is cell fraction derived.

Other Hepatitis Viruses


Hepatitis C virus
Which, before its identification was labeled non-A, non-B hepatitis,
It is a linear, single-stranded, positive-sense, RNA virus; (Enveloped)
HCV belongs to family Flaviviridae
Mc cause of post transfusion hepatitis
Causes chronic hepatitis
Hepatitis D
The delta hepatitis agent, or HDV, is a defective RNA virus
Coinfects with and requires the helper function of HBV (or other hepadnaviruses) for its replication and expression
Resembles plant viruses
Hepatitis E
Previously labeled epidemic or enterically transmitted non-A, non-B hepatitis,
HEV is an enterically transmitted virus
It is a Calci virus
Mortality in pregnancy is a feature of Hep E virus

Microbiology

291

Hepatic encephalopathy in pregnancy is seen


Fulminant hepatic failure can occur with Hep C in pregnancy
Hepatitis G
Also called GB virus
RNA virus
Blood borne virus
Resembles Hep C virus
Lamuvudine responsive
Spreads by fecal oral route -Hepatitis A and E
Spreads by percutaneous route -Hepatitis B, C and D
HTLV I cause adult T cell Leukemia/Lymphoma and Tropical spastic paraplegia. Other putative HTLV-I-related diseases In
areas where HTLV-I is endemic, diverse inflammatory and autoimmune diseases have been attributed to the virus, including
uveitis, dermatitis, pneumonitis, rheumatoid arthritis and polymyositis
HTLV II causes Hairy cell leukemia
HTLV III causes AIDS

USMLE Case Scenario


HTLV-1, or human T-cell lymphotrophic virus 1 can lead to T-cell leukemia 2030 years after the infection. The virus is:
1. A nonenveloped, single-stranded, RNA retrovirus
2. An enveloped, double-stranded, RNA retrovirus
3. An enveloped, single-stranded, DNA retrovirus
4. An enveloped, single-stranded, RNA retrovirus
Ans. 4. An enveloped, single-stranded, RNA retrovirus

USMLE FAVORITE
HIV virus

Positive sense, single stranded, RNA virus


Retro virus
Diploid
Attacks T helper cells and macrophages
Non segmented
Found in semen, saliva and blood

Contains two copies of ss (+) RNA, RNA dependent DNA Polymerase (Reverse Transcriptase), integrase and protease
Subtype A is most prevalent worldwide
Subtype C is most prevalent in India
Seroconversion takes 4 weeks

Heterosexual mode is the mc mode of transmission of HIV


Malefemale transmission >female-male
Accidential needle prick for health worker is 1%
RNA-DNA-RNA is the retroviral sequence in host celL
p 24 is used for early diagnosis
p 24 antigen disappears 68 weeks after HIV infection
CD 4 cells are attacked
CD 4: CD 8 ratio is reversed
Macrophages serve as reservoir of infection
Window period of AIDS: infection to appearance of antibodies in serum
Both ELISA and western blot are negative in window period.

292

USMLE Step 1 Platinum Notes

Cryptosporiodosis is the mc cause of diarrhea in AIDS


Oral ulcer in AIDS is commonly due to candida
MC cause of acute meningitis in AIDS: Cryptococcus
MC cause of tuberculosis in AIDS in tropical countries: Myc. Tuberculosis
Mc Cause of seizures in AIDS: Toxoplasmosis
Multifocal tumor of vascular origin in AIDS is: Kaposis sarcoma
MC opportunistic infection in AIDS in India is: Tuberculosis.

USMLE Case Scenario


Toxoplasmosis is a protozoan infection acquired by eating undercooked meat or by exposure to cat feces
Primary toxoplasmosis is usually asymptomatic. In patients with normal immunity, the organism can cause a heterophile-negative,
mononucleosis-like syndrome. In patients with AIDS, it causes ring-enhanced focal brain lesions and pneumonia.

STRUCTURAL GENES OF HIV VIRUS

HIV virus
Antigens
p 24
p 7p
p17

Proteins
Capsid protein
Core nucleocapsid protein
Matrix protein

Gag

Pol

Reverse transcriptase
Integrase
Protease

Produces ds DNA pro virus


Produces ds DNA integration into host DNA
Cleaves poly protein

Envelop

gp 120
gp 41

Surface protein that binds to CD4 on host cell


Transmembrane protein for cell fusion

Regulatory genes of HIV Virus


Tat: Transactivator protein: Activator of transcription
Rev: Regulator Protein: Regulator of transport of RNA to cytoplasm
Nef: Negative factor: Decrease MHC on infected T cells

Microbiology

293

Negative sense RNA Viruses


Parainfluenza virus

Croup, common cold, bronchitis

Mumps

Parotitis, pancreatitis, orchitis, memingoencephalitis

Measles

RSV

Bronchiolitis and pneumonia in infants

Rabies virus

Bites of rabid dogs


Negri Bodies
Bullet shaped from Rhabdo viridae

Marburg virus

Acute Hemmorrhagic fever

Ebolavirus

Acute Hemorrhagic fever

Influenza virus

Lassa Fever virus

Hemorrhagic fever in Africa

Rubeola
Cough, coryza, conjunctivitis, kopliks spots
Warthin Finkeldey cells
SSPE

Segmented
Enveloped nucleocapsid
Shows minor variation: antigenic drift
Major variation: antigenic shift
Shows Von Magnus phenomenon (on serial passing progeny with high
hemagluttination titer but low infectivity
Guillain barre and Ryes Syndrome associations

USMLE Case Scenario


A 3-year-old child develops voluminous watery diarrhea and vomiting. She is brought to the pediatrician by her parents and
evaluated. Which of the following viruses is the most likely cause of the childs diarrhea?
1. Norwalk virus
2. Rotavirus
3. Influenza virus
4. Parainfluenza virus
Ans. 2. Rota virus

USMLE Case Scenario


An enveloped Rhabdovirus produces encephalitis inpersons who have recently traveled outside of the US after a bite of dog.
The organism is most likely:
1. Togavirus
2. EB
3. Rabies virus
4. Influenza virus
Ans. 3. Rabies virus

USMLE Case Scenario


The Picornaviruses are positive single-stranded RNA viruses with a naked icosahedral nucleocapsid. This family does not
include:
1. Polioviruses
2. Pappiloma viruses
3. Echoviruses
4. Coxsackieviruses
Ans. 2. Pappiloma viruses

294

USMLE Step 1 Platinum Notes

USMLE Case Scenario


Progressive multifocal leukoencephalopathy is a rapidly progressive demyelinating disorder in which the JC virus infects
oligodendroglial cells in the brain. The Eosinophilic inclusions represent accumulations of JC virus which is a:
1. Papovavirus
2. Herpes virus
3. Retrovirus3
4. Arena virus
Ans. 1. Papova virus

USMLE Case Scenario


A 44-year-old mother brings her 4-year-old boy into the emergency room of ENT Department because he has developed a
harsh, barking cough with hoarseness. The virus responsible for this childs illness belongs to which of the following families?
1. Papovavirus
2. Paramyxovirus
3. Parvovirus
4. Picornavirus
Ans. 2. Paramyxovirus (para influenza)

USMLE Case Scenario


A paralytic disease affecting the ventral horn of the spinal cord and motor cortex, caused by RNA enterovirus is:
1. EBV
2. Poliovirus
3. Rabies virus
4. Influenza virus
Ans. 2. Polio virus

USMLE Case Scenario


A 66-year-old patient from wales presents to a physician because of pain during defecation accompanied by blood in the stool.
Physical examination demonstrates a large perianal mass. Pathologic examination of the rectal mass following resection
demonstrates a condyloma in which transformation to frank carcinoma has occurred. Which of the following viruses would
most likely be associated with these lesions?
1. EBV
2. CMV
3. HSV
4. HPV
Ans. 4. HPV
The tumor is anal carcinoma arising in a condyloma. Both condyloma and anal carcinoma are related to human papilloma
virus (HPV), which is also associated with cervical and penile condylomas and carcinomas.

USMLE Case Scenario


A Bullet shaped virus spreading along peripheral nerves to the central nervous system causing hydrophobia and copious
salivation. Most likely virus is:
1. Togavirus
2. EBV
3. Rabies virus
4. Influenza virus
Ans. 3. Rabies virus

Microbiology

295

USMLE Case Scenario


A 48-year-old female presents with malaise, loss of appetite, nausea, moderate fever, and jaundice. Laboratory tests indicate
a marked increase in serum transaminases. Serology for hepatitis viruses is performed and indicates positive results for the
presence of HBsAg, HBc IgM antibody, and HCV antibody. Antibody tests for HBsAb and HAV are negative. The results indicate:
1. Hepatitis A virus infection
2. Hepatitis B virus infection
3. Hepatitis C virus infection
4. Hepatitis D virus infections
Ans. 2. Hepatitis B virus infection

USMLE Case Scenario


Dysplasia of the cervix and later carcinomas of the cervix is found to be caused by a virusin a 30-year-old woman with a history
of multiple sexual partners. Most likely virus is:
1. EBV
2. CMV
3. HSV
4. HPV
Ans. 4. HPV

USMLE Case Scenario


A 3-month-old infant presents with a 3-day history of fever, cough, and poor feeding. On examination, the baby appears ill
and has a temperature of 102 F and a respiratory rate of 32. A chest X-ray film shows bilateral patchy infiltrates in the lungs.
Which of the following is the most likely etiologic agent?
1. Influenza virus
2. Parainfluenza virus
3. EBV
4. Respiratory syncytial virus
Ans. 4. Respiratory syncytial virus

USMLE Case Scenario


Pathologist describes a pandemic caused by the ability of the virus of Reoviridae family to undergo dramatic genetic changes
of type by reassortment of its segmented RNA genome - a trait called genetic shift. Virus implicated is:
1. Rotavirus
2. Ebola virus
3. Parainfluenza virus
4. EBV
Ans. 1. Rota virus

USMLE Case Scenario


A naked, icosahedral double-stranded circular DNA virus presents with anogenital warts. Most likely virus is:
1. EBV
2. CMV
3. HSV
4. HPV
Ans. 4. HPV

296

USMLE Step 1 Platinum Notes

USMLE Case Scenario


A 14-year-old student presents to the hospital complaining of a sore throat and fever. On examination, he has pharyngitis
with cervical lymphadenopathy. Blood tests reveal lymphocytosis and the presence of heterophil antibodies. Which of the
following virus is responsible for his illness?
1. Double-stranded, enveloped DNA virus
2. Double-stranded, nonenveloped DNA virus
3. Single-stranded, enveloped RNA virus
4. Single-stranded, nonenveloped DNA virus
Ans. 1. Double stranded enveloped DNA virus

USMLE Case Scenario


Among the choices mentioned below is a member of family Herpesviridae. It is an enveloped virus with an icosahedral
nucleocapsid that contains a double-stranded linear DNA genome.
1. CMV
2. Polio
3. HPV
4. Influenza
Ans. 1. CMV

USMLE Case Scenario


A single-stranded +RNA virus, is naked (i.e. nonenveloped) and hence will not be inactivated by lipid solvents such as ether.
The live virus vaccine had colonized the intestinal tract of the infant and was still being shed 2 weeks after the earlier oral
dose. The virus is:
1. HDV
2. Polio
3. EBV
4. CMV
Ans. 2. Polio

USMLE Case Scenario


A Virus produces neonatal infections and infections in immunocompromised patients such as AIDS patients and most common
clinical presentation is producing floaters, visual field deficits, and painless loss of vision. It also produces encephalitis and
may produce calcifying lesions in the CNS. Virus most likely is:
1. CMV
2. EBV
3. HSV
4. HHV
Ans. 1. CMV

USMLE Case Scenario


Kaposi Sarcoma is caused by:
1. HHV6
2. HHV7
3. HHV8
4. HHV9
Ans. 3. HHV 8

Double Stranded RNA Viruses


Reovirus
Rotavirus

URTI
Mc cause of infantile diarrhea
Noncultiviable virus
Detected by antigen in stools

Microbiology

297

Rota Virus

Reoviridae family
Double stranded RNA virus
Group A mc causative agent
Does not grow in cell cultures (noncultiviable)
Mc cause of diarrhea in infants
Causes destruction of mature enterocytes
Detected by antigen in stools

Diarrheas are a Feature of

Rotavirus
Adenovirus
Calcivirus
Enterovirus

Hemorrhagic Fever
African hemorrhagic fever:
Hemorrhagic fever with renal syndrome:
Dengue hemorrhagic fever:

Marburg/ebola virus
Hantavirus
Flavivirus

ONCOGENIC VIRUSES: (USMLE FAVORITE)


Virus

Disease

Pox disease

Molluscum contagiosum

Hepatitis B and C

Liver Cancer

EBV

Burkitts lymphoma (in malaria infested parts of Africa), and


Other lymphomas in immunosuppression;
Nasopharyngeal carcinomas

Human papilloma virus

Warts, genital warts, cervical, vulval, penile, anal and perianal carcinoma

HTLV-1

Adult T-cell Leukemia (RNA virus)

HHV 8

Kaposis sarcoma

Adenovirus, SV40

Malignant neoplasms in mice

Polyomavirus hominis 1 and 2

Are found in the urine of some transplant recipients

Human Pappiloma Virus


Deep plantar/palmar warts: HPV 1
Common warts/Verruca Vulgaris: HPV 2
Plane warts: HPV 3
Laryngeal Papillomas: HPV 6,11, 30
Anogenital warts (Condyloma accuminata): HPV 6,11
Butchers warts: HPV 7
Koilocytes are a feature of HPV infections
High oncogenic potential is with: HPV16, 18, 31, 33
Low oncogenic potential is with: HPV6,11, 42, 43

298

USMLE Step 1 Platinum Notes

Viruses and CNS: (USMLE Favorite)


Acute viral meningitis is most commonly due to enterovirus.
Fungal meningitis is mostly due to Candida, Aspergillus, Mucor and Cryptococcus.
Viral Encephalitis shows:
Perivascular cuffs
Microglial nodules
Neuronophagia
HSV1 particularly effects Temporal lobes, causes hemmorhagic necrosis of temporal lobes
Aspergillus and Mucor causes vasculitis with hemorrhage
Cryptococcus invades brain via Virchow Robins spaces with soap bubble lesions
Toxoplasmosis presents with ring enhancing lesions

Kaposis sarcoma

Kaposis sarcoma is common in homosexuals


KS arises from cells linning lymph vessels or blood vessels
KS is associated with HIV, immunosuppression, organ transplants
On skin Kaposis lesions are red/purple blotches which are asymptomatic or tender
GIT, liver, lung lesions can prove dangerous
Treatment of HIV with HAART reduces KS as well
Associated with HHV 8 virus
Common sites: Skin, GIT, Lymph nodes, Lungs
Classic KS as originally described was a relatively indolent disease affecting elderly men from the Mediterranean region, or of
Eastern European descent
Endemic KS was described later in young African people, mainly from sub-Saharan Africa, as a more aggressive disease which
infiltrated the skin extensively, especially on the lower limbs. This, it should be noted, is unrelated to HIV infection
Transplant Related KS had been described, but only rarely until the advent of calcineurin inhibitors (such as ciclosporin,
which are inhibitors of T-cell function) for transplant patients.

Erythema Infectiosum: (Fifth disease, Slapped cheek disease)


Erythema infectiosum is caused by parvovirus B19 (human parvovirus), a small, single-stranded DNA virus
In children the first sign of infection is usually marked erythema of the cheeks or slapped cheek appearance often with
relative circumoral pallor
Then 14 days after the slapped cheeks an itchy, erythematous, maculopapular rash develops on the trunk and limbs
As the rash on the limbs clears it leaves a lacy, reticular pattern. The rash may fluctuate over the next 13 weeks and a hot bath,
for example, may lead to recrudescence of an evanescent rash
Complications
Arthritis or arthralgia is more common in adults, but certainly can occur in children. It usually appears 16 days after the rash
but there maybe no history of rash at all
Arthritis is characteristically transient and asymmetrical, affecting wrists, knees, ankles, elbows and fingers, though it may
persist for weeks or even months
Children with sickle cell anemia, thalassemia major, hereditary spherocytosis or other hemolytic anemias, may have severe
aplastic crises with hemoglobin levels falling as low as 12 g/dl and no reticulocytes
Infection during pregnancy can result in hydrops fetalis due to fetal anemia, which maybe fatal, but no congenital syndrome
has been described in babies of infected mothers who delivered at term
The diagnosis can be made serologically by demonstrating parvovirus B19-specific IgM on an acute serum sample Treatment
Arthritis may require salicylates or nonsteroidal antiinflammatory agents
Children with aplastic crises may require blood transfusion until the red cell aplasia resolves spontaneously after 12 weeks.

Microbiology

299

Parvoviruses
Are small single-stranded DNA viruses, of which only serotype B19 is pathogenic for humans. This virus causes three distinct syndromes:
A childhood febrile rash known as erythema infectiosum (Fifth disease);
Aplastic crisis in individuals with chronic hemolytic diseases (sickle cell anemia, thalassemia, etc.); and congenital infections that
can present as stillbirth,
Hydrops fetalis (analogous to severe Rh incompatibility), or severe anemia.
Herpesvirus 6 (HHV-6) is the main causative agent for Roseola infantum
A common disease of infancy, characterized by fever and the appearance of an erythematous maculopapular rash as the fever
defervesces. It is generally benign.

Viral Hemorrhagic Fever

Lassa fever
Rift valley fever
Hf with renal syndrome
Hantavirus pulmonary syndrome
Yellow fever
Dengue hemorrhagic fever/dengue shock syndrome

Slow Viruses Diseases: (USMLE Favorite)


Group A
MaedI
Visna
Group B
Prion diseases
Caused By prion Protein
Prions are proteins
They are infectious
Most common infectious prion disease in humans
CJD
Kuru
Gerstmann Straussler disease
Fatal familial insomnia
Group C
SSPE
PML
SSPE
Subacute sclerosing panencephalitis (SSPE), a rare degenerative central nervous system (CNS) disease characterized by behavioral
and intellectual deterioration and convulsions, is a result of a persistent measles virus infection that develops years after the original
infection
PML
JC virus, a human papilloma virus the etiologic agent of progressive multifocal leukoencephalopathy (PML), is an important
opportunistic pathogen in patients with AIDS

Remember: (USMLE Favorite)


Nagleria

Primary amebic meningoencephalitis

Acanthamoeba

Keratitis
Granulomatous amebic encephalitis

300

USMLE Step 1 Platinum Notes

Entamoeba histolytica

Amebiasis with flask shaped ulcers

Giardia lamblia

Giardiasis (malabsorption)
Habitat: duodenum, jejunum
Falling leaf motility
Tennis racket shape
Trophozites and cysts seen in man
Associated with common variable immunodeficiency
May cause travelers diarrhea

Cryptosporidium

Diarrhea in immunocompromised

Trichomonas vaginalis

Trichomoniasis (frothy vaginal discharge)

Balantidium coli

Dysentery

Malaria
Plasmodium vivax

Benign tertian malariae

Plasmodium ovale

Benign tertian malariae

Plasmodium malaria

Quartan malaria

Plasmodium falciparum

Malignant malaria

Malarial Parasites
Species Identification
Mauriers clefts: P falciparium
Schuffners dots: P vivax
Zeimmans dots: P malariae
James dots: P ovale
Urban Malaria is caused by Anopheles Culcifacies
Type of malaria not seen in India is ovale
Size of RBC is increased in vivaxmalaria
The infective agent of malaria is sporozoite
Gametocytes are seen in PBF of falciparum malaria
Shizont is not seen in PBF
Relapse of malaria is seen in P ovale and P malariae

Important Features of P Falciparum


Splenic rupture is commonest with P falciparum
Parasitemia is highest with P falciparum
Most virulent form P falciparum
Exoerythrocytic stage is absent in P falciparum
Multiple infection of RBCS is seen in P falciparum
Most Virulent plasmodium species is P falciparum

Microbiology

301

KALA-AZAR: (USMLE FAVORITE)

L donovani
L tropica
L major
L braziliens

Visceral Leishmaniasis
Cutaneous Leishmaniasis
Cutaneous Leishmaniasis
Mucocutaneous Leishmaniasis

Splenomegaly is a feature
NNN (Novy, mc Neal, Nicolle) medium used
Aldehyde test + in 12 weeks
KALA-AZAR (Visceral Leishmaniasis; Dumdum Fever)
Kala-azar occurs in India, China, southern USSR, Africa, the Mediterranean basin, and several South and Central American
countries.
Children and young adults are particularly susceptible.
The protozoa (L donovani) invade the bloodstream and localize in the reticuloendothelial system, causing fever, pronounced
hepatosplenomegaly, emaciation, and pancytopenia.
The fever is seldom sustained and recurs irregularly.
Hypergammaglobulinemia is present.
The parasite maybe found in needle biopsy of the liver, spleen, bone marrow, skin lesions, or lymph nodes or in cultures from these
tissues or from blood.
Pentavalent antimony compounds and pentamidine are the drugs of choice.
Sodium stibogluconate (sodium antimony gluconate) is given once daily, slowly IV or IM in distilled water.
Trypanosoma cruzi

Chagas disease (American Trypanosomiasis)


Vector: reduvid bug
Romana sign +(Swelling around eyelids)
Megacolon, Megaesophagus, Cardiomyopathy are complications
Nifurtimox used in treatment

Trypanosoma brucei

Sleeping sickness (African Trypanosomiasis)


Tse tse fly transmits it
Posterior cervical lymphadenopathy (Winter Bottom sign seen)
Suramin and Melarsoprol used in treatment

Babesia microti

Babeiosis
Seen in immunocompromised/splenectomized patients
Resides in RBC

Toxoplasma gondii

Toxoplasmosis
Cat: definitive host
Oocyst found in cat
Intracerebral calcifications, chorioretinitis, microcephaly
Sabin Feld man test +
Pyremethamine + sulfadiazine used in treatment
Frenkels test+

USMLE Case Scenario


Chagas disease is characterized by facial edema and nodules, fever, lymphadenopathy, and hepatosplenomegaly. It affects
cardiac muscle most severely. It is most prevalent in Central and South America; with rare cases in the southern US. The
causative organism is:
1. Trypanosoma cruzi
2. Trypanosoma brucei

302

USMLE Step 1 Platinum Notes

3. Toxoplasma gondii
4. Babesia microti
Ans. 1. Trypanosoma cruzi
Onchocerca volvolus

River blindness

Wucheria bancrofti

Lymphadenitis
Elephantiasis

Genus

Disease produced

Tenia solium

Cysticercosis and enteritis

Tenia saginata

Enteritis

Entrobius Vermicularis

Pruritis ani

Ascaris lumbricoides

Enteritis, cholangitis

Ent. histolytica

Amebiasis

Naegleria and Acanthameba

Meningitis

Cryptosporidium Parvum

Cryptosporidiosis

Giardia lamblia

Giardiasis

Toxoplasma gondi

Intrauterine infection

USMLE Case Scenario


An organism inhibits the large intestine migrates at night into the perianal region to lay eggs, and can be identified by placing
cellophane tape on the perianal skin and then looking at the tape with a microscope. The most likely cause is:
Ans. Entrobius vermicularis

USMLE Case Scenario


A newborn has developed the classic triad of chorioretinitis (at birth), hydrocephalus, and cerebral calcifications. It is found
that Humans become infected with it by ingesting cysts in contaminated food or through contact with cat feces Most likely
organism is:
Ans. Toxoplasma gondii

USMLE Case Scenario


An organism occurs in the immunocompromised population and may cause severe diarrhea. The organism presents as minute
(25 mm) intracellular spheres or arc-shaped merozoites under normal mucosa, Most likely organism is:
Ans. Cryptosporum parvum

Common Names
Fish Tapeworm: Diphyllobotherium latum
Beef Tapeworm: Tenia saginata
Pork Tapeworm: Tenia solium
Dwarf Tapeworm: H. nana
Rat Tapeworm: H. diminuta
Dog Tapeworm: Echinococcus granulosus

Microbiology
Clonorchis sinesis

Chinese liver fluke

Fasciola hepatica

Sheep liver fluke

Fasciola buski

Giant intestinal fluke

Paragonimus westermanii

Lung fluke

Echinococcus granulosus

Hydatid cyst disease

Echinococcus multilocularis

Alveolar hydatid

303

USMLE Case Scenario


A fluke is producing obstruction of the biliary tract or pancreatic duct and are associated with an increased risk of
cholangiocarcinoma. Most likely organism is:
Clonorchis sinesis

Parasites Causing Autoinfection

Tenia solium
Strongyloides stercolis
Hymenolepsis nana
Enterobius vermicularis
Cryptosporidium parvum
Capillaria philippinesis

Loa Loa causes Calabar swellings


Wucheria bancrofti causes Lymphatic Filariasis
Strongyloides stercolis Larva currens
Toxocaria canis causes Visceral Larva migrans
Strongyloides stercolis causes cutaneous larva migrans

Filariasis

Wucheria bancrofti causes Filariasis


Habitat is lymph vessels and lymph nodes
Man is the definitive host
Innoculation is through bite of mosquito

Infective form is third stage larvae


Notice the difference in classic Filariasis and occult Filariasis
Classic Filariasis

Occult Filariasis (Meyer Kouwenaar Syndrome)

Caused by adult worms

Caused by microfilariae

Epitheloid granuloma is basic lesion

Eosinophilic granuloma is basic lesion

Lymphatic system involved

Lymphatic system
Liver
Lungs involved

Microfilaria present in blood

Microfilaria in tissues

Complement Fixation test insensitive

CFT Sensitive

304

USMLE Step 1 Platinum Notes

Tenia Solium
Cysticercosis in muscles
Cysticerci can develop in any voluntary muscle in humans. Invasion of muscle by cysticerci can cause myositis, with fever, eosinophilia,
and muscular pseudohypertrophy, which initiate with muscle swelling and later progress to atrophy and fibrosis. In most cases, it
is asymptomatic since the cysticerci die and become calcified.
Neurocysticercosis
Neurocysticercosis presents in many forms, depending on the localization of the cysts and disease activity. Sixty percent of the patients
with cysticerci are found to have them in the brain. These cysts increase and slowly leak their antigen into the subarachnoid CSF
producing meningitis and can further develop into arachnoiditis, which may lead to obstructive hydrocephalus, cranial nerve
involvement, intracranial hypertension, arterial thrombosis and stroke. In intraventricular cysticercosis, the cysts occur in the
lateral, third or fourth ventricles which maybe asymptomatic or if they block the flow of CSF, they may cause increased intracranial
pressure.
Ophthalmic Cysticercosis
In some cases, cysticerci maybe found in the globe, subconjunctiva, and extraocular muscles. Depending on the location, they may
cause visual difficulties that fluctuate with eye position, retinal edema, hemorrhage, a decreased vision or even a visual loss.
Subcutaneous Cysticercosis
Subcutaneous cysts are in the form of firm, mobile nodules, occurring mainly on the trunk and extremities. Subcutaneous nodules are
sometimes painful

Echinococcosis
It is also known as hydatid disease. (Echinococcus granulosus)
Hydatid cyst is a parasitic infection of humans by the tapeworm of genus echinococcus
It is a zoonosis
Echinococcus granulosus causes Cystic Echinococcuosis
Echinococcus multilocularis causing Alveolar Echinococcuosis
Echinococcus vogeli causes Polycystic disease
Echinococcus granulosus:
The liver is the most common organ effected followed by lungs, muscles, bones and kidneys.
Passage of hydatid membrane in emesis is called hydatid emesia.
Passage of hydatid membrane in stools is called hydatid enterica.
Echinococcosis is caused by larval stages of parasite
Man is an accidential intermediate host. Other intermediate hosts are sheep and cattle
The dog is the definitive host. (D-D)
Serological assay (Weinberg reaction) is specific example of Complement fixation test used in detection
ELISA is also sensitive
ARA C 5 is used in diagnosis.

Entamoeba Histolytica
Amebiasis is an infection with the intestinal protozoan Entamoeba histolytica
About 90% of infections are asymptomatic, and the remaining 10% produce a spectrum of clinical syndromes ranging from
dysentery to abscesses of the liver or other organs
E histolytica is acquired by ingestion of viable cysts from fecally contaminated water, food, or hands
Both trophozoites and cysts are found in the intestinal lumen, but only trophozoites of E histolytica invade tissue
Cyst has glycogen mass, chromidial bars, eccentric nucleus
Liver abscesses are always preceded by intestinal colonization, which maybe asymptomatic
The most common type of amebic infection is asymptomatic cyst passage
Amebic Liver Abscess Extraintestinal infection by E histolytica most often involves the liver
Pleuropulmonary involvement, which is reported in 20 to 30% of patients, is the most frequent complication of amebic liver
abscess.

Microbiology

Microscopic feature

305

Sites of abscess

USMLE Case Scenario


Patients typically present with diarrhea (often bloody) + right lower quadrant abdominal pain+fever. Amebic abscesses in the
liver are a complication due to invasion of the portal venous system by the ameba.
Primary amebic encephalitis: Naegleria fowleria
Fulminant amebic meningoencephalitis: Naegleria fowleria
Granulomatous amebic encephalitis: Balamuthia mandrillaris

Paracapillaria Philippinensis
It has long been known that the nematode Capillaria hepatica can cause a visceral larva migrans-like syndrome in people
who have eaten meat (e.g. infected liver) or sand containing the eggs of the worm
These children exhibit such symptoms as fever, eosinophilia, abdominal pain and hepatomegaly, with large numbers of typical
eggs being found in the liver on histological examination.
P philippinensis is a parasite of the small intestine and it is believed to be a zoonotic infection involving birds and freshwater
fish. Humans become infected by ingestion of eggs or infected raw fish, the usual intermediate host, and loads within the host
may increase as a result of autoinfection
Diagnosis of capillariasis is based upon histology or finding eggs and larvae in feces
These eggs are like those of Trichuris, but the polar plugs are inset and the shells are striated or pitted
Treatment for capillariasis is tiabendazole 25 mg/kg per day for 30 days or longer. Side effects and relapses are, however, common.
Mebendazole and albendazole are also reported to be effective for the treatment of capillariasis.

Gems Never to be forgotten


Pneumoniae after exposure to parrots

Chlamydiae psittaci

Pregnant women with cats

Toxoplasmosis gondii

Muscle pain and eosinophilia

Trichinosis (Trichinella spiralis)

Slaughter house worker with fever

Brucellosis

Gardener stuck with a thorn

Sporothrix schenckii

Aplastic anemia in Sickle cell Disease

Parvo virus B 19

Fungus Ball

Aspergillus

306

USMLE Step 1 Platinum Notes

USMLE Case Scenario


A patient (pigeon handler) presents with interstitial pneumonitis accompanied by headache, backache, and a dry, hacking
cough. A pale, macular rash is also found on the trunk (Horders spots). Likely organism is:
1. Histoplasma
2. Chlamydiae
3. Mycoplasma
4. Aspergillus
Ans. 2. Chlamydiae

USMLE Case Scenario


A nematode infection is caused by taking undercooked Pork with symptoms of diarrhea, periorbital edema, myositis, fever
and eosinophilia. Most likely organism is:
1. Tenia solium
2. Tenia saginata
3. Trichinella
4. Fasciola
Ans. 3. Trichinella

USMLE Case Scenario


An organism is found to be a pleomorphic, gram-negative rod that causes a localized skin infection and seems to be a cause
of an occupational disease of fishermen, fish handlers, and butchers. Most likely organism is:
1. Erysipelothrix
2. Brucella
3. Salmonella
4. Leptospira
Ans. 1. Erysipelothrix

NEVER TO BE FORGOTTEN: (USMLE FAVORITE)


Swollen jaw with sulfur granules

Actinomyces israelii

Necrotizing fasciitis

Sterptococcus pyogenes

Diaper rash with hyphae and yeast on microscopy

Candida

Burnt tissue with blue greenpus, grape like odor

Pseudomonas aeruginosa

Denuded superficial area of large skin area: SSS

Staph aureus

Pink umblicate warts with central debris

Molluscum contagiosum

Virus latent in sensory ganglia with unilateral reactivation

Varicella zoster virus

Virus latent in trigeminal ganglia

Herpes simplex virus 1, VZV

Virus latent in S2, S3

Herpes simplex virus 2

Conjunctivitis on first day of life

Chemical conjunctivitis

Purulent Conjunctivitis on day 1-4

Gonococcal conjunctivitis

Conjunctivitis on 3-10 days with inclusion bodies

Chlamydiae trachomatis

Follicular conjunctivitis with inturned eye lashes, Corneal scarring

Chlamydiae trachomatis

Chorioretinitis in immunocompromised

Toxoplasma gondii

Microbiology

Gram-positive cocci in clusters


Pear shaped trophozoites
Budding yeasts forming germ tubes
Yeast within macrophages
BLOODY E coli
Scotch tape test positive organism

Cholera toxin: Stimulates Gs


E coli heat labile toxin: stimulates Gs
Pertussis toxin: inhibits Gi
Diphtheria Toxin: acts on EF: Shuts down protein synthesis
Pseudomonas aeruginosa: acts on EF: Shuts down protein synthesis

307

Staph aureus
Giardia lamblia
Candida albicans
Histoplasma capsulatum
E coli 0157: H7
Entrobius vermicularis

CAUSATIVE ORGANISMS OF COMMONLY ASKED DISEASES: (USMLE FAVORITE)


Progressive postoperative Bacterial synergistic gangrene
Malignant Otitis externa

Microaerophillic, nonhemolytic Streptococci plus


staphylococci
Pseudomonas

Scleroma

Klebsiella rhinoscleromatosis

Sudoku

Spirillum minus

Botryomycosis

Staph aureus

Chicleros ulcer

Leishmania Mexicana

Espundia

L Braziliensis

Favus

Tricophyton Schonleneii

Erysipeloid

Erysipelothrix rhusiopathia

Important Causative Agents: (USMLE Favorite)

Necrotizing fasciitis: Group A streptococci


Purpureal sepsis: Group B streptococci
Sweaty tennis shoe syndrome: Pseudomonas
Fish handlers disease: Erysipelothrix rhusiopathiae
Granuloma infantisepticum: Listeria
Gay bowel syndrome: Shigella flexiniri
Human monocytic ehrilichiosis: E chaffeensis
Human granulocytic ehrilichiosis: E equi
Rat bite fever: Spirillum minus
Medittarenean spotted fever: Ricketssia conorii
Cat scratch disease: Bartonella hensla
Typhilitis: Pseudomonas aeruginosa
Red leg disease: Aeromonas

USMLE Case Scenario


A gram-negative rod that is a zoonotic agent causingan undulating febrile disease with malaise, lymphadenopathy and
hepatosplenomegaly. The normal route of exposure is via ingestion of the organism. Most likely organism is:
1. Borrelia
2. Brucella
3. Legionella3
4. Leptospira
Ans. 2. Brucella

308

USMLE Step 1 Platinum Notes

USMLE Case Scenario


A5-year-old child is bitten by a rat. Three days later, the child develops a rash characterized by discrete erythematous 24 mm
macules on the lower extremities and face, most obvious on the palms and soles. Most likely organism is:
1. Yersinia Pestis
2. Streptobacillus moniliformis
3. Pasturella
4. Yersinia enterocolitica
Ans. 2. Streptobacillus moniliformis

USMLE Case Scenario


Infection in AIDS Patient from New York is characterized by firm a nodule that often becomes umbilicated. Cause is found to
be viral most likely organism is:
1. HSV
2. HPV
3. Poxvirus
4. EBV
Ans. 3. Poxvirus

USMLE Case Scenario


A small, pleomorphic, gram-negative rod that a cause (rabbit fever) with bacteremia, splenomegaly, rash, pneumonia is most
likely caused by:
1. Francisella
2. Listeria
3. Leptospira
4. Brucella
Ans. 1. Francisella

USMLE Case Scenario


A gram-negative bacterium causing a local, chronic lymphadenitis, proliferation of blood and lymphatic vessels causing a
characteristic mulberry lesion in the skin and subcutaneous tissues of the afflicted individual and bacillary angiomatosis is:
1. Brucella
2. Bartonella
3. Legionella
4. Leptospira
Ans. 2. Bartonella

USMLE Case Scenario


A gram-positive spore-forming anaerobic rod causing (a spastic paralysis caused by toxin which blocks the release of the
inhibitory neurotransmitters glycine and gamma-aminobutyric acid [GABA]) is most likely:
1. Clostridium tetani
2. Clostridium difficile
3. Clostridium welchi
4. Bacillus anthracus
Ans. 1. Clostridium tetani

Generalizations asked in USMLE


First disease: Rubeola, (measles, kopliks spots)
Second disease: Scarlet fever, (circumoral pallor, pastias lines, strawberry tongue)
Third disease: Rubella, (Forschmiers spots, posterior cervical lymphadenopathy)

Microbiology
Fourth disease: SSSS, (Nikolskys sign)
Fifth disease: Erythema infectiosum (parvovirus b 19, slapped cheek appearance)
Sixth disease: Exanthem subitum, Roseola infantum
Ankylostoma duodenale:
Babesia:
Diphyllobithirum latum:

Iron deficiency anemia


Hemolytic anemia
Megaloblastic anemia

Microbiology of Sexually Transmitted/Genital Diseases


Syphilis: painless ulcer with painless Lymphadenopathy
Chancroid: (soft chancre) painful ulcer with painful lymphadenopathy.
LGV: un noticed painless papule with suppurative lymphadenopathy. Groove sign
Donovaniosis (Granuloma inguinale): painless subcutaneous nodules without lymphadenopathy with pseudobuboes.
Herpes genitalis: painful papule, with inguinal Lymphadenopathy
The chancre of CHANCROID IS PAINFUL IN CONTRAST TO SYPHILIS WHICH IS PAINLESS. Ducreyi makes you cry
Never forget the lines about Features of Chancroid:
Lesions are multiple in number in the form of ulcers which are painful with undermined and ragged edges
Accompanied by Tender and suppurative lymphadenopathy in the form of inguinal buboes.

Important Microbiological Tests


Dick Test

Scarlet Fever

Freis Test

Lymphogranuloma venereum

Kahns Test

Syphilis

Kveims Test

Sarcoidosis

Mono spot/ Paul Bunnel Test

Infectious Mononucleosis

Rose waaler Test

Rheumatoid Arthritis

Sweat Test

Cystic Fibrosis

Weil Felix Test

Rickettsial infection

Rumpel leed test (Capillary Fragility Test)

Scurvy

USMLE Clinical Case Scenarios


Frequent Repititions
Vomiting 16 hours after eating fried rice: Bacillus Cereus
Vomiting and Diarrhea 16 hours after eating contaminated food (Creams): Staph aureus
Diarrhea after ingestion of raw shell fish: Vibrio parahemolyticus
Watery Diarrhea with or without vomiting after travel in developing countries: ETEC
Diarrhea with rapid Fluid loss and Dehydration: V. cholera
Acute endocarditis: Staph aureus
Endocarditis in IV Drug abusers: Staph aureus
Megaloblastic Anemia with history of fish ingestion: Diphyllobothrium latum

309

310

USMLE Step 1 Platinum Notes

Vibrio vulnificus is an extremely invasive organism, producing a septicemia in patients after eating raw shellfish, or causing
wound infections, cellulitis, fasciitis, and myositis after exposure to seawater or after cleaning shellfish. Patients at high-risk
for septicemia include those with liver disease, congestive heart failure, diabetes mellitus, renal failure, hemochromatosis,
and immunosuppression.

Vibrio diarrhea

USMLE Repeated Favorites


Sporothrix schenckii. This organism is responsible for rose gardeners disease, known technically as sporotrichosis. The organism
enters through skin breaks in the fingers or hands, causing a chancre, papule, or subcutaneous nodule with erythema and
fluctuance. Ulcerating lesions appear along lymphatic channels, but the lymph nodes are not commonly infected. Potassium iodide
is the treatment for the subcutaneous manifestations.
Tularemia, which maybe spread by handling rabbits or rabbit skins, or by bites from ticks that feed on the blood of wild rabbits. The
causative organism is Francisella tularensis, a gram-negative coccobacillus. The disease begins as a rupturing pustule followed
by an ulcer, with involvement of regional lymph nodes. More serious cases can be complicated by bacteremia, splenomegaly, rash,
pneumonia, or endotoxemic shock.
Borrelia spp. causes relapsing fever (transmitted by ticks and lice) and Lyme disease (transmitted by ticks).
Brucella causes brucellosis after ingestion of contaminated milk or contact with Infected livestock.
Leptospira causes leptospirosis and Weils disease; the organism is acquired by ingestion of water contaminated with animal
urine.
Listeria causes listeriosis after contact with contaminated milk, vegetables, or with transplacental transmission.

Fungi: (USMLE Favorite)


Characteristics

Fungi

Nucleic Acid

Both

Nucleus

Eukaryotic

Ribosomes

80S

Mitochondria

Present

Motality

Nil

Reproduction

Budding

Microbiology

311

Dimorphic (having two forms) because they are spherical in tissue but grow like molds when cultured at room temperature
Histoplasmosis
Blastomycosis
Sporotrichosis
Coccidioidomycosis
Paracoccidioidomycosis
Penicillin marfenii

Fungi are Eukaryotic organisms


Fungal cell wall contains Chitin.(Chitin is a polysaccharide of long chains of N acetyl glucosamine.)
Fungal Cell membrane contains Ergosterol in contrast to human cell membrane which contains cholesteroL
STAINED by PAS
Most fungi reproduce asexually by forming asexual spores conidia
Fungi without sexual stage: fungi imperfectii
Fungi are culture in Saboubards medium
NON Culturable fungus: Rhinosporodium
Candida species other than Candida glabrata appear in tissue as both budding yeasts and tubular elements called pseudohyphae
Pneumocystis carinii is closer to fungi than to parasites by ribosomal sequences

Monomorphic, Hyphal fungi with dichotomus branching hyphae at acute angles: Aspergillus fumigates
Yeasts with pseudohyphae and true hyphae: Candida albicans
Monomorphic yeast with polysaccharide capsule: Cryptococcus
Non septate filamentous fungi: Mucor, Rhizopus, Absidia
Yeast with broadbased bud and double retractile cell wall: Blastomyces Dermatitidis
Fungus with Endospores and spherules: Coccidomyces immitis
Filamentous fungi with Tuberculate Macronidia: Histoplasma capsulatum

USMLE Case Scenario


A disease is seen mainly in the desert parts of the Southwest US. In the lungs, spherules containing endospores are seen. Most
likely disease is:
1. Coccidioidomycosis
2. Sporotrichosis
3. Paracoccidioidomycosis
4. Blastomycosis
Ans. 1. Coccidioidomycosis

USMLE Case Scenario


A Disease producing a localized cutaneous infection, following inoculation occurring in association with minor skin trauma
during gardening is:
1. Coccidioidomycosis
2. Sporotrichosis
3. Paracoccidioidomycosis
4. Blastomycosis
Ans. 2. Sporotrichosis

312

USMLE Step 1 Platinum Notes

USMLE Case Scenario


A disease is endemic in Latin America, especially in Brazil. The infected cells show a typical pilots wheel appearance due to
multiple yeasts sprouting out of a single parent cell. Most likely the disease is:
1. Coccidioidomycosis
2. Sporotrichosis
3. Blastomycosis
4. Paracoccidioidomycosis
Ans. 4. Paracoccidioidomycosis
Mycotoxicosis: Ingestion of fungal toxins produced in foodmost notably aflatoxin in pea nuts
Mycetismus: Illness from toxic ingestion of toxic mushrooms
Fungemia: Sever disseminated fungal infections in immunocompromised patients
Sick building syndrome: Inhalation of volatile fungal toxins which aggreviates allergies

Candida
Candidiasis, commonly called yeast infection or thrush, also known as Candidosis, Moniliasis, and Oidiomycosis is a fungal
infection (mycosis) of any of the Candida species, of which Candida albicans is the most common
It is an endogeneous infection
In immunocompetent persons, candidiasis is usually a very localized infection of the skin or mucosal membranes, including the
oral cavity (thrush), the pharynx or esophagus, the gastrointestinal tract, the urinary bladder, or the genitalia (vagina, penis)
MC fungal infection in neutropenic patients
Candidiasis is a very common cause of vaginal irritation, or vaginitis, and can also occur on the male genitals
In immunocompromised patients, Candida infections can affect the esophagus with the potential of becoming systemic, causing
a much more serious condition, a fungemia called candidemia
Shows Reynolds Braude phenomenon- ability to form germ tubes within 2 hours of incubation.
Candida shows Reynolds Braude Phenomenon (ability to form germ tubes within two hours when incubated in human serum
at 37oC).
Hepatosplenic candidiasis manifests as Bulls Eye Lesion.

USMLE Case Scenario


A 44-year-old woman in Mexicopresents to her gynecologist because of vaginal itchiness and discharge. Pelvic examination
demonstrates abundant white, curdy material in the vagina. Microscopic examination of the material demonstrates fungal
hyphae and yeast forms. Fungal Organism is:
1. Aspergillus
2. Trichomonas
3. Tinea
4. Candida
Ans. 4. Candida

USMLE Case Scenario


A lesion appears as creamy, white patches of exudate that can be scraped off an inflamed tongue or buccal mucosa of an AIDS
patient from Suburban America. Organisms appear as very large, gram-positive, spherical-to-ovoid organisms with budding
daughter cells in Gram-stained preparations. Most likely organism is:
1. EBV
2. HSV
3. Candida
4. CMV
Ans. 3. Candida

Microbiology

313

USMLE Case Scenario


A 33-year-old HIV-positive male from New York complains of pain on swallowing. Physical examination is remarkable for white
plaque-like material on his tongue and buccal mucosa, which is scraped and sent to the laboratory. The man is diagnosed with
acquired immunodeficiency syndrome (AIDS). With which of the following agents is the man most likely infected?
1. EBV
2. HSV
3. Candida
4. CMV
Ans. 3. Candida
Types of Dermatophyte Infections
Dermatophytes infect: skin, nails, hair
Athletes foot or tinea pedis T rubrum, T mentagrophytes, E floculossum
Jock itch or tinea cruris T rubrum, T mentagrophytes, E floculossum
Ringworm of the body or tinea corpora
Facial ringworm or tinea faciei
Blackdot ringworm or tinea capitis
MC agent: T tonsurans
Favus is other manifestation. Caused by T schoneilenni
Kerion is caused by T mentagrophytes and T verrucosum
Ringworm of the hands or tinea manuum
In most cases of tinea manuum, only one hand is involved. Frequently both feet are involved concurrently,
Thus the saying one hand, two feet
Ringworm of the nail, Onychomycosis, or tinea unguium

Mycetoma

Chronic granulomatous involvement of subcutaneous and deep tissues


Commonly effecting foot
Usually presents with ulcer on leg, indurated margins and discharging sinuses
Destruction of bone occurs
Actinomycetoma is caused by bacteria: nocardia, actinomadura, streptomyces, actinomyces
Eumycetoma is caused by fungus: madurella, pseudallescheria boydii, philphora

Cryptococcus

Cryptococcus is MonomorphicYeast
Has a Polysaccharide capsule
The environmental source is soil enriched with pigeon droppings
Prediliction for brain

Acute pulmonary infections are common in pigeon breeders


Cryptococcal meningitis is dominant in AIDS patients and patients with cancers
Latex particle agglutination test for capsular polysaccharide in CSF is rapid and sensitive
It is urease positive yeast
Microscopy on India ink wet mount is also used for diagnosis

Late infections (> 6 months after kidney transplantation) include CMV retinitis and a variety of CNS complications. Patients
(particularly those whose immunosuppression has been increased) are at risk for subacute meningitis due to Cryptococcus
neoformans. Cryptococcal disease may present in an insidious manner (sometimes as a skin infection before the development of
clear CNS findings).

314

USMLE Step 1 Platinum Notes

Cryptococcal Meningitis is the mc cause of acute meningitis in AIDS


Cryptococcal infections of the lung can be seen in patients with AIDS. Patients with pulmonary cryptococcal disease present with
fever, cough, dyspnea, and in some cases, hemoptysis. A focal or diffuse interstitial infiltrate is seen on chest X-ray in >90% of
patients. In addition, one may see lobar disease, cavitary disease, pleural effusions, and hilar or mediastinal adenopathy.
Indium In 111-labeled leukocyte scans have become useful as an adjunct to other diagnostic procedures in the detection of
gastrointestinal and central nervous system (CNS) infections, such as focal encephalitis, cryptococcal meningitis, and cytomegalovirus
encephalitis, in acquired immunodeficiency syndrome (AIDS) patients.

Coccidioides Immitis
Grows as a white fluffy mold on most culture media and as a nonbudding spherical form (a spherule) in host tissue or under
special conditions
The organism reproduces in host tissue by forming small endospores within mature spherules
After rupture of the spherule, the released endospores enlarge, become spherules, and repeat the cycle. The fungus is identified by
its appearance and by the formation of thick-walled, barrel-shaped spores, called arthrospores, in the hyphae of the mold form
Causes: Valley fever/Desert Rheumatism.

Histoplasma Capsulatum
It is a dimorphic fungus
Hyphae bear both large and small spores, which are used for identification
H capsulatum grows as small budding yeast in host tissue and on enriched agar, such as blood cysteine glucose, at 37C
The fungus is unencapsulated
Grows in bird/bat enriched soil
Coculture of isolates with opposite mating types can produce different sporulating structures in which genetic recombination
occurs
When these structures, referred to as a teleomorph or the perfect state, are seen in culture, the name Ajellomyces capsulatus is
used
Causes: Histoplasmosis

USMLE Case Scenario


A 55-year-old HIV-positive male from Toledo complains of headache and blurred vision. Physical exam reveals papilledema
and ataxia. Head CT is normal but CSF obtained by lumbar puncture reveals encapsulated organisms observable with India
ink. Which is the organism implicated?
1. Cryptococcus
2. Histoplasmosis
3. Chromoblastomycosis
4. Blastomycosis
Ans. 1. Cryptococcus

USMLE Case Scenario


A 66-year-old farmer from rural area presents with chronic cough. Chest X-ray demonstrates a mass lesion with hilar
lymphadenopathy. Biopsy of the mass demonstrates multiple, tiny yeast forms within macrophages. Which of the following
is the most likely diagnosis?
1. Histoplasmosis
2. Chromoblastomycosis
3. Blastomycosis
4. Mucormycosis
Ans. 1. Histoplasmosis

Microbiology

315

Blastomyces Dermatitidis
It is a dimorphic fungus
Seen as broad, based, and budding, round yeast like cells with thick wall
Causes:
Blastomycosis
Have an indolent onset and a chronically progressive course. Fever, cough, weight loss, lassitude, skin lesions, and
chest ache are common
Skin lesions favor exposed areas and enlarge over many weeks from pimples to well-circumscribed, verrucous, crusted,
or ulcerated lesions
Pain and regional lymphadenopathy are minimal large chronic lesions may undergo central healing with scarring and
contracture. Mucous membrane lesions resemble squamous cell carcinoma
Chest X-ray findings are abnormal in two-thirds of patients, with one or more pneumonic or nodular infiltrate
Remember: Blasts skin, lungs.

USMLE Case Scenario


A pathogen is found to be present in the respiratory tract of a 36-year-old patient from Honduras as an opportunistic
pathogen; Fungus balls are also seen. Patient previously had Tuberculosis. Most likely organism is.
1. Blastomyces dermatitidis
2. Pneumocystis carinii
3. Aspergillus
4. Mycobacterium tuberculosis
Ans. 3. Aspergillus

Aspergillus: (USMLE Favorite)

It is the most common cause of aspergillosis, but A flavus, A niger, and several other species can also cause disease
Has branching hyphae. (septate)
Mc disease caused: otomycosis
Aspergillus is a mold with septate hyphae about 2 to 4 mm in diameter
Portal of entry is lungs
Aspergillus can colonize the damaged bronchial tree, pulmonary cysts, or cavities of patients with underlying lung disease
Causes:
Aspergillomas: Balls of hyphae within cysts or cavities usually in the upper lobe, may reach several centimeters in
diameter and maybe visible on chest X-ray. Tissue invasion does not occur
Allergic bronchopulmonary aspergillosis denotes the condition of patients with pre-existing asthma who have
eosinophilia, IgE antibody to Aspergillus and fleeting pulmonary infiltrates from bronchial plugging.

Mucormycosis: (USMLE Favorite)


Species of Rhizopus, Rhizomucor, are the most common causes of mucormycosis
It is angio invasive

Zygomycosis is a term that includes mucormycosis and entomophthoromycosis


Rhizopus and Rhizomucor species are ubiquitous, appearing on decaying vegetation, dung, and foods of high sugar content
Mucormycosis is uncommon and is largely confined to patients with serious pre existing diseases. (Diabetic ketoacidosis)
Mucormycosis originating in the paranasal sinuses and nose predominantly affects patients with poorly controlled diabetes
mellitus
Patients who have undergone organ transplantation, who have a hematologic malignancy, or who are receiving long-term
deferoxamine therapy are predisposed to mucormycosis of either sinus or lung
Gastrointestinal mucormycosis occurs in a variety of conditions, including uremia, severe malnutrition, and diarrheal diseases
Pulmonary mucormycosis manifests as progressive severe pneumonia accompanied by high fever and toxicity. The necrotic
center of large infiltrates may cavitate.

316

USMLE Step 1 Platinum Notes

USMLE Case Scenario


A fungal infection begins in the nasal passages, extends into the paranasal sinuses and spreads through the cribiform plate
to the frontal lobes of the brain. Patients typically complain of headache, facial pain and orbital swelling. Most likely cause is:
1. Chromoblastomycosis
2. Aspergillus
3. Mucormycosis
4. Blastomycosis
Ans. 3. Mucormycosis

USMLE Case Scenario


A mold with septate hyphae in immunocompromised patients, aspergillosis presenting with acute pneumonia with
cavitation is:
1. Chromoblastomycosis
2. Aspergillus
3. Mucormycosis
4. Blastomycosis
Ans. 2. Aspergillus

USMLE Case Scenario


An 85-year-old diabetic woman, on dialysis for chronic renal failure, develops bilateral orbital and facial pain, headache, and
sudden loss of vision in the right eye. When examined 2 days later, she is found to have the right eyelids red and swollen, and
she has complete loss of vision and motion on the right eye and partial loss of vision on the left eye. The mucosa of the nasal
passages is swollen and necrotic, with a black discoloration. MRI shows soft-tissue swelling of the nasal mucosa, sinuses, and
orbital tissues, with no evidence of cavernous sinus thrombosis or retro-orbital cellulitis. Biopsy of the temporal artery is
negative for giant cell arteritis. Biopsy of the nasal and sinuses mucosa demonstrates thrombosed vessels and multiple broad
nonseptate hyphae with right-angle branches. Which of the following is the most appropriate treatment?
1. Amphotericin B and surgical debridement
2. Corticosteroids
3. Heparin anticoagulation
4. Metronidazole and drainage of the paranasal sinuses
5. Surgical decompression of both orbits
Ans. 1. Amphotericin B and surgical debridement

Chromoblastomycosis
Chronic subcutaneous mycosis, presents as a verrucoid, ulcerated, or crusted skin lesion
Cladosporium is causative organism
The disease follows the introduction of any of several fungi into subcutaneous tissue by thorns or bits of vegetation
The appearance of thick-walled, dark-colored, rounded forms (copper pennies) in histopathologic section is diagnostic. Sclerotic
bodies
Surgical excision is the treatment of choice.

USMLE Case Scenario


A 66-years-old AIDS patient with pneumonia has a bronchoalveolar lavage that demonstrates small, hat-shaped structures
in alveoli that are about the size of an erythrocyte and stain with silver stains. The microorganism involved is most likely which
of the following?
1. Blastomyces dermatitidis
2. Mycobacterium avium
3. Mycobacterium tuberculosis
4. Pneumocystis carinii
Ans. 4. Pneumocystis carinii

Microbiology

317

USMLE Case Scenario


A 44-year-old HIV-positive mancomes to Immunology clinic complaining of dyspnea mild cough and fever. Physical
examination is remarkable for oral thrush and a few small, nontender cervical lymphnodes. A chest X-ray film reveals bilateral
interstitial infiltrates, and bronchoalveolar lavage reveals small silver-staining cysts. Most likely organism is:
1. Blastomyces dermatitidis
2. Pneumocystis carinii
3. Mycobacterium avium
4. Mycobacterium tuberculosis
Ans. 2. Pneumocystis carinii

Pneumocystis Carinii: (USMLE Favorite)


Obligate extracellular fungus
Present in patients with defects in cell-mediated immunity as with hematologic malignancies, lymphoproliferative diseases,
cancer chemotherapy, and AIDS
Causes interstitial pneumonia
Traditional stains have included reagents such as methenamine silver, toluidine blue, and cresyl violet, which selectively stain
the wall of P carinii cysts, and reagents such as Wright-Giemsa, which stain the nuclei of all developmental stages. Other reagents
include nonspecific fluorochrome stains (calcofluor white) and Papanicolaous stain.

Clinical Case Scenarios of USMLE (Important Guiding Features)


An organism is found to be a pleomorphic, gram-negative rod that causes a localized skin Erysipelothrix
infection and seems to be a cause of an occupational disease of fishermen, fish handlers, and
butchers. Most likely disease is caused by:
A nematode infection is caused by taking undercooked Pork with symptoms of diarrhea, periorbital Trichinella
edema, myositis, fever, and eosinophilia. Most likely organism is:
An organism occurs in the immunocompromised population and may cause severe diarrhea. Cryptosporodiosis
The organism presents as minute (2-5 mm) intracellular spheres or arc-shaped merozoites
under normal mucosa. Most likely disease is
A 44-year-old patient presents with facial edema and nodules, fever, lymphadenopathy, and Chagas disease
hepatosplenomegaly. The disease also affects cardiac muscle most severely. It is most prevalent
in Central and South America; with rare cases in the southern US. The disease is:
A 35-year-old female says she had a protozoan infection and used to eat undercooked Toxoplasmosis
meat and had exposure to cat feces. The organisms can also cause a heterophile-negative,
mononucleosis-like syndrome. In patients with AIDS, it causes ring-enhanced focal brain
lesions and pneumonia. Most likely the disease is
An African child develops massive unilateral enlargement of his lower face in the vicinity of Burkitts Lymphoma
the mandible. Biopsy demonstrates sheets of medium-sized blast cells with admixed larger
macrophages. This type of tumor has been associated with viral infection. Most likely
disease is
A Disease is found to be due to reactivation of epidemic typhus infection caused by Rickettsia Brill Zinsser disease
prowazekii. It can occur many years after an infection that was not treated with antibiotics.
The most likely disease is:
A gram-positive coco bacillus is causing Infection during pregnancy that may result in Listerosis
sepsis, abortion or premature delivery. Infection in the neonate may produce meningitis. In
immunocompromised adults, either meningitis or sepsis may occur. The organism is
A 3-year-old boy from rural America is brought to the ENT emergency room in extreme Epiglottitis
respiratory distress, with a temperature of 104 degrees Fahrenheit. He is drooling and
has great difficulty swallowing, and on physical examination, an inspiratory stridoris noted.
An immediate lateral X-ray done shows swelling of the epiglottis. He has had no previous
vaccinations. Most likely disease is

318

USMLE Step 1 Platinum Notes

An highly encapsulated organism is found to cause a bronchopneumonia with patchy infiltrates Klebsiella pneumoniae
involving one or more lobes with red sputum in a debilitated alcoholic. Most likely disease is:
A 8-year-old girl is bitten in the leg by a dog. She presents the next day with fever and bone Pasteurella
pain localized to her right calf. X-ray reveals a lytic lesion of the left femur. Results of the bone
culture are pending. Infecting organism is most likely to be:
An organism is causing urinary tract infections. It has ability to breakdown urea and is thought to Proteus species.
contribute to the development of struvite kidney stones due to the elevation of urine pH by production
of ammonia. The said organism is also having swarming motility. The organism is identified
A 44-year-old man from rural Indian village is brought to a rural hospital with severe Plague
bronchopneumonia. He suffered sudden onset of chills, fever, and headache several days ago.
Two day later, he complained of chest pain and difficulty breathing, and coughed up bloodtinged sputum. Chest X-ray reveals patchy infiltrates and segmental consolidation. The most
likely cause of this mans pneumonia and the disease itself is due to yersinia. Disease itself is:
A disease is caused the organism enters through skin breaks in the fingers or hands, causing Sporotrichosis
a chancre, papule, or subcutaneous nodule with erythema and fluctuance. Ulcerating lesions
appear along lymphatic channels, but the lymph nodes are not commonly infected. Potassium
iodide isused for the treatment for the subcutaneous manifestations. The disease is common in
gardeners. Most likely disease is:
A 66-year-old alcoholic man with brain and pulmonary abscess and is treated with antibiotics Clostridium difficile
for last two weeks. He develops nausea, vomiting, abdominal pain, and voluminous green
diarrhea. The condition is diarrhea due to:
An organism identified on dark ground microscopy caused testicular involvement with gumma Syphilis
formation, endarteritis, and/or a prominent plasma cell infiltrate. Most likely disease is:
A disease which maybe spread by handling rabbits or rabbit skins, or by bites from ticks that feed Tularemia
on the blood of wild rabbits, a gram-negative coccobacillus. The disease begins as a rupturing
pustule followed by an ulcer, with involvement of regional lymph nodes. More serious cases
can be complicated by bacteremia, splenomegaly, rash, pneumonia, or endotoxemic shock.
Most likely disease is:
A gram-positive spore-forming anaerobic rod causing (a spastic paralysis caused by toxin Tetanus caused by clostridia
which blocks the release of the inhibitory neurotransmitters glycine and gamma-aminobutyric tetani
acid [GABA]) is most likely:
A gram-negative rod that is a zoonotic agent causing an undulating febrile disease with Brucellosis
malaise, lymphadenopathy and hepatosplenomegaly. The normal route of exposure is via
ingestion of the organism. Most likely disease is:

Microbiology

319

USMLE Case Scenario


A minority of cases of infective endocarditis are caused by a number of normal commensals in the oral cavity, i.e. the HACEK
group. Hacek Means.
1. Hemophilus, Actinobacillus, Corynebacterium, Eikenella, and Kingella
2. Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Klebsiella
3. Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella
4. Hemophilus, Actinobacillus, Cardiobacterium, E coli, and Kingella
Ans. 3. Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella

USMLE Case Scenario


ADP-ribosylation of an elongation factor is a mechanism of action of:
1. Pseudomonas exotoxins
2. Clostrodial toxin
3. Streptococcal toxin
4. Staphylococcal toxin
Ans.1. Pseudomonas exotoxins

USMLE Case Scenario


An organism is found to be a pleomorphic, gram-negative rod that causes a localized skin infection and seems to be a cause
of an occupational disease of fishermen, fish handlers and butchers. Most likely organism is:
1. Erysipelothrix
2. Brucella
3. Salmonella
4. Leptospira
Ans. 1. Erysipelothrix

USMLE Case Scenario


Stalacite growth is a feature of:
1. Hemophilus
2. Pasteurella
3. Corynebacterium
4. Mycoplasma
5. Klebsiella
6. Pseudomonas
Ans. 2. Pasteurella

USMLE Case Scenario


A Virus produces neonatal infections and infections in immunocompromised patients such as AIDS patients and most common
clinical presentation is producing floaters, visual field deficits, and painless loss of vision. It also produces encephalitis and
may produce calcifying lesions in the CNS. Virus most likely is:
1. CMV
2. EBV
3. HSV
4. HHV
Ans. 1. CMV

320

USMLE Step 1 Platinum Notes

USMLE Case Scenario


Staphylococcus aureus is present in mayonnaise. The patient presents with nausea, vomiting, and abdominal pain, followed
by diarrhea beginning 16 hours after ingestion of the toxin. The toxin is:
1. Not a Preformed enterotoxin
2. Preformed enterotoxin
3. Preformed non enterotoxin
4. Non Preformed non enterotoxin
Ans. 2. Preformed enterotoxin

USMLE Case Scenario


An obligate intracellular parasite that induces endocytosis and resides in the phagosome of infected epithelial cell is:
1. Rickettsia
2. Mycoplasma
3. Mycobacteria
4. Chlamydia
Ans. 4. Chlamydia

USMLE Case Scenario


Lucio phenomenon is a widespread diffuse infiltration of the skin with secondary alopecia of the hair, eyebrows and eyelashes,
and generalized sensory loss. The patients are systemically ill with fever, chills, malaise, arthralgias, myalgias, and tender
cutaneous lesions that are responsive to steroids but not to thalidomide. Lucio phenomenon is usually associated with:
1. Mycoplasma
2. Chlamydia
3. Mycobacterium avium
4. Mycobacterium africanum
5. Mycobacterium tuberculosis
6. Mycobacterium leprae
Ans. 6. Mycobacterium leprae

USMLE Case Scenario


Overall, 3040% of all infections contracted in the post renal transplant period are viral. The most common viral infections
are by:
1. DNA viruses
2. RNA Viruses
3. Retroviruses
4. Arboviruses
Ans. 1. DNA viruses
The most common viral infections are DNA viruses of the herpes virus family and include cytomegalovirus (CMV), Epstein-Barr
virus, herpes simplex virus, and varicella zoster virus.

USMLE Case Scenario


An 66-years-old AIDS patient with pneumonia has a bronchoalveolar lavage that demonstrates small, hat- shaped structures
in alveoli that are about the size of an erythrocyte and stain with silver stains. The microorganism involved is most likely which
of the following?
1. Blastomyces dermatitidis
2. Mycobacterium avium
3. Mycobacterium tuberculosis
4. Pneumocystis carinii
Ans. 4. Pneumocystis carinii

Microbiology

321

USMLE Case Scenario


An 85-year-old diabetic woman from Chicago develops orbital and facial pain, headache. When examined 2 days later, she is
found to have the right eyelids red and swollen, and she has complete loss of vision and motion on the right eye. The mucosa
of the nasal passages is swollen and necrotic, with a black discoloration. Biopsy of the temporal artery is negative for giant cell
arteritis. Biopsy of the nasal and sinuses mucosa demonstrates thrombosed vessels and multiple broad nonseptate hyphae
with right-angle branches. Most likely cause is:
1. Histoplasmosis
2. Blastomycosis
3. Mucormycosis
4. Aspergellosis
Ans. 3. Mucormycosis

USMLE Case Scenario


A child after playing with a pet injured while playing with a pet has a local abscess. A gram-negative rod that is normal flora
of the oral cavity of dogs and cats is found to be causative. Most likely organism is:
1. Pasteurella
2. Pseudomonas
3. Francisella
4. Bartonella
Ans. 1. Pasteurella

USMLE Case Scenario


Visceral larva migrans is due to:
1. Ascariasis
2. Toxocaria
3. Schistosomiasis
4. Clonorchis
5. Trichomonas
6. Plasmodium
Ans. 2. Toxocaria

USMLE Case Scenario


An organism is causing urinary tract infections. It has ability to breakdown urea and is thought to contribute to the
development of struvite kidney stones due to the elevation of urine pH by production of ammonia. The said organim is also
having swarming motility. The organism is identified as:
1. Brucella
2. Proteus
3. Pseudomonas
4. Anthrax bacillus
5. Clostridia
Ans. 2. Proteus

USMLE Case Scenario


Botulin toxin acts by:
1. Secretion of Ach
2. Synthesis of Ach
3. Muscle nerve block
4. Inhibits Ach release
Ans. 4. Inhibits Ach release

322

USMLE Step 1 Platinum Notes

USMLE Case Scenario


A 33-year-old HIV-positive male from New York complains of pain on swallowing. Physical examination is remarkable for white
plaque-like material on his tongue and buccal mucosa, which is scraped and sent to the laboratory. The man is diagnosed with
acquired immunodeficiency syndrome (AIDS). With which of the following agents is the man most likely infected?
1. EBV
2. HSV
3. Candida
4. CMV
Ans. 3. Candida

USMLE Case Scenario


A 55-year-old man presents with an episode of shaking chills the previous night. He has now developed right-sided pleuritic
chest pain, fever, sweats, malaise, purulent sputum, and mild hemoptysis. On examination, the patient is diaphoretic but
alert, with right basilar rales. Chest X-ray films show a right lower lobe infiltrate with blunting of the right costophrenic angle.
The causative organism implicated is:
1. Streptococcus agalactiae
2. Streptococcus pneumonia
3. Streptococcus viridians
4. Streptococcus pyogenes
Ans. 2. Streptococcus pneumonia

USMLE Case Scenario


A 22-year-old veterinary surgeon presents with a 2 week history of high fevers, night sweats. He also had dry cough, and
myalgia. On examination, the patient had a palpable splenic tip. Blood films for malaria parasites were negative. Liver function
tests showed a raised serum alkaline phosphatase, raised serum aspartate aminotransferase concentration, serum bilirubin
concentration. Likely cause is:
1. Salmonella
2. Chlamydia
3. Bartonella
4. Francisella
5. Mycoplasma
6. Brucella
7. Legionella
Ans. 6. Brucella

USMLE Case Scenario


Erythema infectiosum is caused by:
1. Parvovirus B19
2. Papova virus
3. Human herpes virus type 8
4. Measles virus
Ans. 1. Parvovirus B19

USMLE Case Scenario


A Virus produces neonatal infections and infections in immunocompromised patients such as AIDS patients and most common
clinical presentation is producing floaters, visual field deficits, and painless loss of vision. It also produces encephalitis and
may produce calcifying lesions in the CNS. Virus most likely is:
1. CMV
2. EBV

Microbiology

323

3. HSV
4. HHV
Ans. 1. CMV

USMLE Case Scenario


Lipopolysaccharide is an important component of:
1. Gram-positive cells
2. Gram-negative cells
3. Neither Gram-positive nor Gram-negative cells
4. Both Gram-positive and Gram-negative cells
Ans. 2. Gram-negative cells

USMLE Case Scenario


Encephalitis typically affects the inferomedial temporal lobes and orbitofrontal gyri. Most likely double stranded DNA virus
implicated is:
1. EBV
2. HSV
3. CMV
4. Pox
Ans. 2. HSV

USMLE Case Scenario


Chagas disease is characterized by facial edema and nodules, fever, lymphadenopathy, and hepatosplenomegaly. It affects
cardiac muscle most severely. It is most prevalent in Central and South America; with rare cases in the southern US. The
causative organism is:
1. Trypanosoma cruzi
2. Trypanosoma brucei
3. Toxoplasma gondii
4. Babesia microti
Ans. 1. Trypanosoma cruzi

USMLE Case Scenario


Epidemic keratocojunctivitis is caused by:
1. Coronavirus
2. Epstien-Barr virus
3. Picornavirus
4. Adenovirus
Ans. 4. Adenovirus

USMLE Case Scenario


A pregnant 18-year-old woman came to the clinic with a low-grade fever, malaise and headache. Few days later she presented
with a macular rash on her trunk, arms, hands, and feet. Further examination revealed that 1 month previously, she had a
painless ulcer on her vagina that healed spontaneously. Most likely diagnosis is:
1. Lyme disease
2. Lymphogranuloma venereum
3. Behcets disease
4. Endocarditis
5. Syphilis by treponema
Ans. 5. Syphilis by treponema

324

USMLE Step 1 Platinum Notes

USMLE Case Scenario


Madura foot is caused by:
1. Blastomycosis
2. Nocardia
3. Candida albicans
4. Tenia versicolor
Ans. 2. Nocardia

USMLE Case Scenario


A Bullet shaped virus spreading along peripheral nerves to the central nervous system causing hydrophobia and copious
salivation. Most likely virus is:
1. Toga virus
2. EBV
3. Rabies virus
4. Influenza virus
Ans. 3. Rabies virus

USMLE Case Scenario


A 18-year-old, ill-appearing woman comes OPD with a fever. She notes the recent development of nausea, diarrhea, and a
rash. Her last menstrual period began 3 days ago. Physical examination is remarkable for blood pressure of 90/40 mm Hg and
heart rate of 120 beats per minute. A diffuse erythematous rash with desquamation over feet is noted. Infection with which of
the following toxin is the most likely cause of these signs and symptoms?
1. Clostridium perfringens toxin
2. Shigella dysenteriae toxin
3. Staphylococcus aureus toxin
4. Staphylococcus epidermidis toxin
Ans. 3. Staphylococcus aureus toxin

USMLE Case Scenario


A 26-year-old male complains of a severe headache and weakness. His condition rapidly deteriorates over a period of hours. A
lumbar puncture is performed and a Grams stain of spinal fluid reveals Neisseria meningococcus. The organism is:
1. Gram-negative diplococci
2. Gram-positive cocci
3. Gram-positive bacillus
4. Obligate intracellular organism
Ans. 1. Gram-negative diplococci

USMLE Case Scenario


HTLV-1, or human T-cell lymphotrophic virus 1 can lead to T-cell leukemia 2030 years after the infection. The virus is:
1. A nonenveloped, single-stranded, RNA retrovirus
2. An enveloped, double-stranded, RNA retrovirus
3. An enveloped, single-stranded, DNA retrovirus
4. An enveloped, single-stranded, RNA retrovirus
Ans. 4. An enveloped, single-stranded, RNA retrovirus

USMLE Case Scenario


A 64-year-old man from New Jersy presents with severe hemoptysis. An organism is isolated and found that it has a tendency
to invade pre-existing pulmonary cavities and form a rounded necrotic mass of matted hyphae, fibrin, and inflammatory cells.
A filamentous organism with coarse, septate, fragmented hyphae is isolated. Most likely organism is:

Microbiology

325

1. Cryptococcus neoformans
2. Candida albicans
3. Blastomyces dermatitidis
4. Paracoccidioides brasiliensis
5. Coccidioidomycosis
6. Aspergillus fumigatus
Ans. 6. Aspergillus fumigatus

USMLE Case Scenario


HTLV-1, or human T-cell lymphotrophic virus 1 can lead to T-cell leukemia 2030 years after the infection. The virus is:
1. A nonenveloped, single-stranded, RNA retrovirus
2. An enveloped, double-stranded, RNA retrovirus
3. An enveloped, single-stranded, DNA retrovirus
4. An enveloped, single-stranded, RNA retrovirus
Ans. 4. An enveloped, single-stranded, RNA retrovirus

USMLE Case Scenario


A 40-year-old man has been to Malaysia for 6 months. He has an erythematous, serpiginous, pruritic, cutaneous eruption on
the medial side of the ankle. What is the diagnosis?
1. Lyme disease
2. Cutaneous larval migrans
3. Leishmaniasis
4. Sarcoidosis
5. Tuberculosis
Ans. 2. Cutaneous larval migrans
Cutaneous larva migrans is caused by the penetration through intact skin of larval animal hookworms

USMLE Case Scenario


A 44-year-old man from rural Indian village is brought to a rural hospital with severe bronchopneumonia. He suffered sudden
onset of chills, fever, and headache several days ago. Two day later, he complained of chest pain and difficulty breathing, and
coughed up blood-tinged sputum. Chest X-ray reveals patchy infiltrates and segmental consolidation. The most likely cause
of this mans pneumonia and the disease itself is due to yersinia. Disease itself is:
1. Leprosy
2. Tuberculosis
3. Listerosis
4. Legionella pneumoniae
5. Tularemia
6. Psittacosis
7. Plague
Ans. 7. Plague

USMLE Case Scenario


The sulfur granules in the wound are diagnostic of:
1. Nocardia
2. Actinomyces
3. Clostridium welchii
4. Aspergillus flavusm
Ans. 2. Actinomyces

326

USMLE Step 1 Platinum Notes

USMLE Case Scenario


An organism inhabits the large intestine migrates at night into the perianal region to lay eggs, and can be identified by placing
cellophane tape on the perianal skin and then looking at the tape with a microscope. The most likely cause is:
1. Tenia solium
2. Tenia saginatum
3. H nana
4. F hepatica
5. T vaginalis
6. Enterobius vermicularis
Ans. 6. Enterobius vermicularis

USMLE Case Scenario


A 66-year-old patient from wales presents to a physician because of pain during defecation accompanied by blood in the stool.
Physical examination demonstrates a large perianal mass. Pathologic examination of the rectal mass following resection
demonstrates a condyloma in which transformation to frank carcinoma has occurred. Which of the following viruses would
most likely be associated with these lesions?
1. EBV
2. CMV
3. HSV
4. HPV
Ans. 4. HPV

USMLE Case Scenario


Which virus reactive and involves the eyes?
1. Herpes-Zoster
2. CMV
3. EB virus
4. Enterovirus-70
Ans. 1. Herpes-Zoster

USMLE Case Scenario


A pathogen is found to be present in the respiratory tract of a 36-year-old patient from Honduras as an opportunistic pathogen;
Fungus balls are also seen. Patient previously had Tuberculosis. Most likely organism is:
1. Blastomyces dermatitidis
2. Pneumocystis carinii
3. Aspergillus
4. Mycobacterium tuberculosis
Ans. 3. Aspergillus

USMLE Case Scenario


A 36-year-old female from Washington presents with a 2-day history of fever, chills, chest pain, and cough productive of rusty
sputum. Past medical history includes a splenectomy 1 year ago. A chest X-ray film indicates consolidation of the right lower
lobe. Blood cultures are positive for and alpha; hemolytic gram-positive diplococcic. Most likely organism is:
1. Pneumococcus
2. Meningococcus
3. Staphylococcus
4. Gonococcus
Ans. 1. Pneumococcus

Microbiology

327

USMLE Case Scenario


A 24-year-old AIDS patient develops chronic abdominal pain, low-grade fever, diarrhea, and malabsorption. Oocysts are
demonstrated in the stool. Which of the following organisms is most likely to be the cause of the patients diarrhea?
1. Diphyllobothrium latum
2. Entamoeba histolytica
3. Giardia lamblia
4. Isospora belli
5. Microsporidia
Ans. 4. Isospora belli

USMLE Case Scenario


Friable Nasal polyps and subcutaneous nodules are characteristically associated with the infection of:
1. Histoplasma
2. Sporothrix
3. Rhinosporidium
4. Cryptococcus
Ans. 3. Rhinosporidium

USMLE Case Scenario


Gastric ulcers are associated with malignancy, and therefore biopsy should be performed when they are discovered. This
association with malignancy is not found with duodenal ulcers. The increased risk for malignancy with gastric ulcers is a good
reason to test patients for H pylori and initiate treatment if it is found. H pylori is a:
1. Aerobe
2. Anaerobe
3. Obligate aerobe
4. Microaerophilic
Ans. 4. Microaerophilic

USMLE Case Scenario


A 66-year-old farmer from rural area presents with chronic cough. Chest X-ray demonstrates a mass lesion with hilar
lymphadenopathy. Biopsy of the mass demonstrates multiple, tiny yeast forms within macrophages. Which of the following
is the most likely diagnosis?
1. Histoplasmosis
2. Chromoblastomycosis
3. Blastomycosis
4. Mucormycosis
Ans. 1. Histoplasmosis

USMLE Case Scenario


A child presents with chronic enteritis, failure to thrive, hypoalbuminemia, and hypokalemia. Other findings include acute
right lower quadrant abdominal pain, tenderness, nausea, and vomiting. The infection mimics appendicitis or Crohns disease.
Most likely organism is:
1. Yersinia enterocolitica
2. Haemophilus aegyptius
3. Borrelia duttonii
4. Haemophilus ducreyi
Ans. 1. Yersinia enterocolitica

328

USMLE Step 1 Platinum Notes

USMLE Case Scenario


Torres bodies are seen in:
1. Kala-Azar
2. Q-fever
3. Yellow fever
4. LGV
5. Malaria
6. Hepatitis
7. Babeiosis
Ans. 3. Yellow fever

USMLE Case Scenario


An organism produces cutaneous disease (malignant pustule or eschar) at the site of inoculation in handlers of animal skins.
Most likely organism is:
1. Bacillus anthracus
2. Pseudomonas Aeruginosa
3. Neisseria meningitides
4. Cryptococcus neoformans
Ans. 1. Bacillus anthracus

USMLE Case Scenario


A viral organism was isolated from a painful blister on the lip of a girl. The agent was found to double-stranded, linear DNA
and was enveloped. Most likely causative organism is:
1. EBV
2. HSV
3. CMV
4. Pox
Ans. 2. HSV

USMLE Case Scenario


Donovan bodies are:
1. Leukocytes that contain the organism, Calymmatobacterium granulomatis
2. Eosinophils that contain the organism, Calymmatobacterium granulomatis
3. Monocytes that contain the organism, Hemophilus influenza
4. Monocytes that contain the organism, Calymmatobacterium granulomatis
Ans. 4. Monocytes that contain the organism, Calymmatobacterium granulomatis

USMLE Case Scenario


Chagas disease is an important cause of cardiac failure in some Latin American countries, and Brazilian cases can be associated
with megaesophagus and megacolon. The disease is Chagas disease, which is caused by:
1. Bacteria
2. Mycoplasma
3. Protozoa
4. Virus
Ans. 3. Protozoa

Microbiology

329

USMLE Case Scenario


A 55-year-old HIV-positive male from Toledo complains of headache and blurred vision. Physical exam reveals papilledema
and ataxia. Head CT is normal but CSF obtained by lumbar puncture reveals encapsulated organisms observable with India
ink. Which is the organism implicated?
1. Cryptococcus
2. Histoplasmosis
3. Chromoblastomycosis
4. Blastomycosis
Ans. 1. Cryptococcus

USMLE Case Scenario


A 4 year-old girl with a history of hydrocephalus is brought to the neurologist by her parents with a severe headache and
fever. The girl underwent a surgery for a ventricular-peritoneal shunt 2 months ago and the neurologist suspects that an
infection has occurred. Organisms would most likely be isolated from the shunt tubing is:
1. Staph aureus
2. Streptococcus
3. Staphylococcus epidermidis
4. Meningococcus
Ans. 3. Staphylococcus epidermidis

USMLE Case Scenario


A disease is seen mainly in the desert parts of the Southwest US. In the lungs, spherules containing endospores are seen. Most
likely disease is:
1. Coccidioidomycosis
2. Sporotrichosis
3. Paracoccidioidomycosis
4. Blastomycosis
Ans. 1. Coccidioidomycosis

USMLE Case Scenario


Among the choices mentioned below is a member of family Herpes viridae. It is an enveloped virus with an icosahedral
nucleocapsid that contains a double-stranded linear DNA genome.
1. CMV
2. Polio
3. HPV
4. Influenza
Ans. 1. CMV

USMLE Case Scenario


A 33-year-old woman in New Jersy presented with a 1 day history of fever and chills. On examination, she was febrile with
a blood pressure of 70/40 mm Hg. Over several hours, a widespread erythrodermic rash developed. The female collapses.
Further questioning revealed that the patient had removed a tampon shortly before presentation, as she had just ceased
menstruating.
1. Streptoccus Bovis infection
2. Hemolytic uremic syndrome
3. E coli sepsis
4. Fungal infection
5. Toxic shock syndrome
6. Meningococcal septicemia

330

USMLE Step 1 Platinum Notes

7. Staph epidermis infection


8. Pseudomonas induced shock
Ans. 5. Toxic shock syndrome
Toxic shock syndrome is due to toxin-1 (TSST-1), a protein secreted by S aureus or streptococci, was the first of many toxins
associated with the syndrome to be identified.

USMLE Case Scenario


Pinta is caused by:
1. Treponema pertenue
2. Treponema cerateum
3. Treponema pallidum
4. Treponema endemicum
Ans. 2. Treponema cerateum

USMLE Case Scenario


The organism that is strongly urease positive:
1. Proteus species
2. Klebsiella species
3. Helicobacter pylori
4. Staphylococcus
Ans. 1. Proteus species

USMLE Case Scenario


A 34 years old person has rapidly developing cough, dyspnea, expectoration and blood-tinged sputum. He is febrile, cyanosed,
and toxic. Chest examination reveals crepitations and ronchi. The most likely diagnosis is:
1. Legionella
2. Pneumonic plague
3. Septicemic plague
4. Pulmonary tuberculosis
Ans. 2. Pneumonic plague

USMLE Case Scenario


Satellitism is seen in cultures of:
1. Hamophilus
2. Streptococcus
3. Klebsiella
4. Proteus
5. Salmonella
Ans. 1. Hamophilus

USMLE Case Scenario


A patient (pigeon handler) presents with interstitial pneumonitis accompanied by headache, backache and a dry, hacking
cough. A pale, macular rash is also found on the trunk (Horders spots). Likely organism is:
1. Histoplasma
2. Chlamydiae
3. Mycoplasma
4. Aspergillus
Ans. 2. Chlamydiae

Microbiology

331

USMLE Case Scenario


In a 40-year-old man following tooth extraction developed oral local infection with draining discharge, which on examination
showed Gram-positive branching roads and leucocytes. Anaerobic growth was absent. The most likely organism responsible
for this is:
1. Fusobacterium
2. Nocardia
3. Bacteroids fragilis
4. Actinomyces
Ans. 4. Actinomyces

USMLE Case Scenario


A-65-year-old man presents to the hospital unwell with diarrhea. He has a BP of 110/70, heart rate 120 and Temp 38C. A
diastolic murmur is heard in aortic area. Which organism is likely to grow in the blood cultures?
1. MRSA
2. Listeria
3. Streptococcus mitis
4. Staphylococcus aureus
5. Streptococcus bovis
6. Escherichia coli
7. Brucella melitensis
Ans. 5. Streptococcus bovis usually enters the bloodstream via the gastrointestinal tract. There is also an association with
malignancy of the GI tract

USMLE Case Scenario


In a poultry farm, many chickens developed diarrhea, emaciation and mucopurulent discharge. After about 2 hours the farmer
developed fever, chills, headache, and Breathlessness. The most likely diagnosis is:
1. Anthrax b
2. Q fever
3. Relapsing fever
4. Ornithosis
Ans. 4. Ornithosis

USMLE Case Scenario


Fungal meningitis in an immunocompromised individual is most commonly caused by:
1. Candida albicans
2. Cryptococcus neoformans
3. Penicillium
4. Aspergillus
Ans. 2. Cryptococcus neoformans

USMLE Case Scenario


Transplacental transfer of antibodies from immunized mother to her newborn is:
1. Natural active immunity
2. Natural passive immunity
3. Acquired active immunity
4. Acquired passive immunity
Ans. 2. Natural passive immunity

332

USMLE Step 1 Platinum Notes

USMLE Case Scenario


A severely ill 44 years old HIV affected patient from New york has evidence of destruction of myelin at multiple sites in the CNS
pointing to a diagnosis of progressive multifocal leukoencephalopathy (PML). PML is caused by:
1. JC virus which is a papovavirus
2. JC virus which is a parvovirus
3. HTLV1 virus which is a Rhabdovirus
4. HTLV2 virus which is a papovavirus
Ans. 1. JC virus which is a papovavirus

USMLE Case Scenario


A farmer developed a swelling in the inguinal region which later ulcerated. What stain can be used to detect bipolar stained
organisms?
1. Alberts stain
2. Waysons stain
3. Ziehl neelsen stain
4. Nigrosin stain
Ans. 2. Wayson stain

PATHOLOGY

Pathology

CELL INJURY/CELL DEATH


Terminology frequently asked in USMLE
Hypertrophy: Increased cell and organ size, often in response to increased workload; induced by mechanical stress and by growth
factors; occurs in tissues incapable of cell division
Hyperplasia: Increased cell numbers in response to hormones and other growth factors; occurs in tissues whose cells are able
to divide
Atrophy: Decreased cell and organ size, as a result of decreased nutrient supply or disuse; associated with decreased synthesis
and increased proteolytic breakdown of cellular organelles
Metaplasia: Change in phenotype of differentiated cells, often a response to chronic irritation that makes cells better able to
withstand the stress; usually induced by altered differentiation pathway of tissue stem cells; may result in reduced functions or
increased propensity for malignant transformation.

Different Cell Types: (Commonly asked)


Cell proliferation is regulated by cyclins that, when complexed with cyclin-dependent kinases, regulate the phosphorylation of
proteins involved in cell cycle progression leading to DNA replication and mitosis
The cell cycle is tightly regulated by stimulators and inhibitors, and contains intrinsic checkpoint controls to prevent replication of
abnormal cells
Tissues are divided into labile, stable and permanent, according to the proliferative capacity of their cells
Continuously dividing tissues (labile tissues) contain stem cells that differentiate to replenish lost cells and maintain tissue
homeostasis

High Yield USMLE Points

Labile cells
Stable cells
Permanent cells
Totipotent cells
Pleuropotent cells

Regenerate throughout life. (Surface Epithelial Cells, Stem cells, Blood Cells)
Replicate at low levels. (Hepatocytes, Proximal tubule Cells)
Dont Replicate (Neurons)
They can develop into any cell type, e.g. Germ cells
They are primitive cells and can develop into multiple cell types

Growth Factors
Growth Factors, Receptors and Signal Transduction Polypeptide growth factors act in autocrine, paracrine, or endocrine manner
Growth factors are produced transiently in response to an external stimulus and act by binding to cellular receptors
Different classes of growth factor receptors include receptors with intrinsic kinase activity, G-protein-coupled receptors and
receptors without intrinsic kinase activity
Growth factors such as EGF and HGF bind to receptors with intrinsic kinase activity, and trigger a cascade of phosphorylating
events through MAP kinases, which culminate in transcription factor activation and DNA replication
Cytokines generally bind to receptors without kinase activity; such receptors interact with cytoplasmic transcription factors that
move into the nucleus
Most growth factors have multiple effects, such as cell migration, differentiation, stimulation of angiogenesis and fibrogenesis in
addition to cell proliferation.

336

USMLE Step 1 Platinum Notes

Difference in Calcifications: (High Yield Topic)


Dystrophic calcification

Metastatic calcification

Occurs in Dying tissues

Occurs in Normal tissues

Serum calcium levels are usually Normal

Serum calcium levels are usually elevated

Seen in
Atherosclerosis
Damaged heart valves
Psammoma bodies

Seen in
Kidneys
Lungs
Gastric mucosa

An elevated calcium phosphate product, as in secondary hyperparathyroidism, can lead to nodules of metastatic calcinosis cutis,
which tend to be subcutaneous and periarticular. This form is often accompanied by calcification of muscular arteries and subsequent
ischemic necrosis (calciphylaxis).

Types of Infarcts
Red Infarct

Pale Infarct

Hemorraghic infarct

White Infarct

Seen in venous occlusion

Occurs in arterial occlusion

Area of infarct usually has double blood supply

Area of infarct usually has single blood supply

Seen in
Brain
Gut
Liver

Seen in
Kidney
Myocardium
Spleen

Septic Infarctions
Occur when bacterial vegetations from a heart valve embolize or when microbes seed an area of necrotic tissue. In these cases the
infarct is converted into an abscess, with a correspondingly greater inflammatory response.

INFLAMMATION
Positive Acute Phase Reactants
CRP
Mannose binding protein
Complement factors
Ferritin
Cerruloplasmin
Serum amyloid A
Haptoglobin
Alpha 1 antitrypsin
Alpha 2 macroglobulin

Negative Acute Phase Reactants


Albumin
Transferrin
Transthyretin
Transcortin
Retinol Binding Protein

Pathology

337

Types of Necrosis: (Very Important Topic)


Coagulation Necrosis

Liquefaction Necrosis

Fat Necrosis

Caseous Necrosis

Gangrenous Necrosis

Most Common Type


(Kerala 96)

Seen in Brain

Seen in adipose
Tissues

Combination of
Coagulation and
Liquefaction

Due to Ischemia
especially to Lower Limb

Severe ischemia Predisposes

Due to Hydrolytic
enzymes

Due to Lipases

Cottage cheese
appearance

Examples:
Thermal injury
Myocardial infarction
Tuberculosis

Bacterial infections

Acute Pancreatic
Necrosis
Trauma to Breast
Retroperitoneal fat

Seen in centre of
Tuberculous Lesions

More of coagulation leads


to Dry gangrene
More of Liquefaction
leads to Wet Gangrene

Reversible Cell Injury

Cellular swelling
Loss of microvilli
Formation of cytoplasmic blebs
ER swelling
Ribosomal detachment
Myelin figures
Clumping of nuclear chromatin

Irreversible Cell Injury


Flocculent, amorphous densities in mitochondria
Swelling and disruption of lysosomes
Plasma membrane damage
Nuclear changes:
Pyknosis (nuclear condensation)
Karryorex his (nuclear fragmentation)
Karyolysis (nuclear dissolution)

Mechanisms of Cell Injury


ATP depletion: Failure of energy-dependent functions reversible injury necrosis Mitochondrial damage: ATP
depletion failure of energy-dependent cellular functions ultimately, necrosis; under some conditions, leakage of
proteins that cause apoptosis
Influx of calcium: activation of enzymes that damage cellular components and may also trigger apoptosis
Accumulation of reactive oxygen species: covalent modification of cellular proteins, lipids, nucleic acids
Increased permeability of cellular membranes: may affect plasma membrane, lysosomal membranes, mitochondrial
membranes; typically culminates in necrosis. Accumulation of damaged DNA and misfolded proteins: triggers apoptosis.

USMLE Case Scenario


Earliest transient change following tissue injury will be:
1. Neutropenia
2. Neutrophilia
3. Monocytosis
4. Lymphocytosis
Ans. 2. Neutrophilia

338

USMLE Step 1 Platinum Notes

USMLE Case Scenario


Oxygen dependent killing is done through:
1. NADPH oxidase
2. Superoxide dismutase
3. Catalase
4. Glutathione peroxidase
Ans. 1. NADPH oxidase

USMLE Case Scenario


Reactive oxygen intermediates are released by:
1. Catalase
2. NADPH oxidase
3. Glutathione peroxidase
4. Superoxide dismutase
Ans. 2. NADPH oxidase

USMLE Case Scenario


The epitheloid cell and multinucleated gaint cells of Granulomatous inflammation are derived from:
1. Basophils
2. Eosinophils
3. CD4-T lymphocytes
4. Monocytes Macrophages
Ans. 4. Monocytes Macrophages

USMLE Case Scenario


Degeneration of the basement membrane is mediated by:
1. Oxidases
2. Elastases
3. Hydroxylases
4. Metallo proteinase
5. Protease
Ans. 4. Metallo proteinase

USMLE Case Scenario


Most characteristic feature of acute inflammation is:
1. Vasoconstriction
2. Vascular stasis
3. Vasodilatation and Increased vascular permeability
4. Vasoconstriction and decreased vascular permeability
5. Margination of Leucocytes
Ans. 3. Vasodilatation and Increased vascular permeability

USMLE Case scenario


Most effective bactericidal system within phagocytes is:
1. Lysozyme mediated
2. Lactoferrin mediated
3. Reactive oxygen metabolite mediated
4. Cationic basic protein mediated
Ans. 3. Reactive oxygen metabolite mediated

Pathology

339

Apoptosis: (USMLE Favorite)


Regulated mechanism of cell death that serves to eliminate unwanted and irreparably damaged cells, with the least
possible host reaction
Characterized by: enzymatic degradation of proteins and DNA, initiated by caspases; and recognition and removal of dead
cells by phagocytes
Initiated by two major pathways:
1. Mitochondrial (intrinsic) pathway is triggered by loss of survival signals, DNA damage and accumulation of misfolded
proteins (ER stress); associated with leakage of pro-apoptotic proteins from mitochondrial membrane into the cytoplasm,
where they trigger caspase activation; inhibited by anti-apoptotic members of the Bcl family, which are induced by survival
signals including growth factors
2. Death receptor (extrinsic) pathway is responsible for elimination of self-reactive lymphocytes and damage by cytotoxic
T-lymphocytes; is initiated by engagement of death receptors (members of the TNF receptor family) by ligands on adjacent
cells.

Nutshell of Programmed Cell Death

Lack of Inflammation
Cell shrinkage
Condensation of nuclear chromatin followed by fragmentation
Intranucleosomal cleavage of DNA is characteristic
Formation of cytoplasmic/Membrane blebs
Cytoplasmic chromophilia is a feature
Apoptotic bodies
bcl2 inhibits Phagocytosis
p53 stimulates phagocytosis

Proapoptotic Factors

Apaf 1
Cytochrome C
AIF
p53
Caspaces
TNFRI
FAS (CD 95)

Apoptosis inhibiting gene is: bcl2


Detection of Apoptosis is by:
DNA fragmentation analysis
Capsase activity assays
Annexin V Assay
Propium Iodide assay

USMLE Case Scenario


Which of the following organelles plays a pivotal role in Apoptosis:
1. Mitochondria
2. Endoplasmic Reticulum
3. Nucleus
4. Golgi Apparatus
Ans. 1. Mitochondria

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USMLE Step 1 Platinum Notes

USMLE Case Scenario


Caspases are involved in:
1. Cell division
2. Necrosis
3. Apoptosis
4. Inflammation
Ans. 3. Apoptosis

USMLE Case Scenario


Irreversible cell injury is indicated by:
1. Accumulation of calcium in mitochondria
2. Myelin figures
3. ATP depletion
4. Shifting of ribosomes
Ans. 1. Accumulation of calcium in mitochondria

USMLE Case Scenario


Wound contraction is mediated by:
1. Myofibroblasts
2. Epithelial cells
3. Collagen
4. Elastin
Ans. 1. Myofibroblasts

USMLE Case Scenario


Gene inhibiting apoptosis is:
1. bcl2
2. p53
3. ras
4. n-myc
Ans. 1. bcl2

Systemic Effects of Inflammation


Fever: cytokines (TNF, IL-1) stimulate production of prostaglandins in hypothalamus
Production of acute-phase proteins: C-reactive protein, others; synthesis stimulated by cytokines (IL-6, others) acting on
liver cells
Leukocytosis: cytokines (colony-stimulating factors) stimulate production of leukocytes from precursors in the bone
marrow
In some severe infections, septic shock: fall in blood pressure, disseminated intravascular coagulation, metabolic
abnormalities; induced by high levels of TNF.

Sepsis, Severe Sepsis, Septic Shock, Systemic Inflammatory Response Syndrome (SIRS)
The hosts reaction to invading microbes involves a rapidly amplifying polyphony of signals and responses that may spread beyond
the invaded tissue. Fever or hypothermia, tachypnea, and tachycardia often herald the onset of sepsis.
The systemic response to microbial invasion. When counter regulatory control mechanisms are overwhelmed, homeostasis may fail,
and dysfunction of major organs may supervene (severe sepsis).

Pathology

341

Further regulatory imbalance leads to septic shock, which is characterized by hypotension as well as organ dysfunction. As sepsis
progresses to septic shock, the risk of dying increases substantially. Sepsis is usually reversible, whereas patients with septic shock
often succumb despite aggressive therapy.
Systemic inflammatory response syndrome (SIRS):
Temp > 38C or < 36C
HR > 90 bpm
RR > 20 breaths/min
WBC > 12000 cells/mm3 or < 4000 cells/mm3

Monocytes-Macrophages: (USMLE Favorite)


Monocytes arise from precursor cells within bone marrow and circulate with a half-life ranging from 1 to 3 days
Common locations where tissue macrophages (and certain of their specialized forms) are found are lymph node, spleen, bone
marrow, perivascular connective tissue, serous cavities such as the peritoneum, pleura, skin connective tissue, lung (alveolar
macrophage),
Liver (Kupffer cell)
Bone (osteoclast)
Central nervous system (microglia)
And synovium (type A lining cell)

Specific Cell Types


Lymphocytes are the mediators of adaptive immunity and the only cells that produce specific and diverse receptors for antigens
T (Thymus-derived) lymphocytes express antigen receptors called T cell receptors (TCRs) that recognize peptide fragments of
protein antigens that are displayed by MHC molecules on the surface of antigen-presenting cells
B (Bone marrow-derived) lymphocytes express membrane-bound antibodies that recognize a wide variety of antigens. B cells
are activated to become plasma cells, which secrete antibodies
Natural killer (NK) cells kill cells that are infected by some microbes, or are stressed and damaged beyond repair. NK cells express
inhibitory receptors that recognize MHC molecules that are normally expressed on healthy cells, and are thus prevented from
killing normal cells
Antigen-presenting cells (APCs) capture microbes and other antigens, transport them to lymphoid organs, and display them
for recognition by lymphocytes. The most efficient APCs are dendritic cells, which live in epithelia and most tissues. The cells of
the immune system are organized in tissues, some of which are the sites of production of mature lymphocytes (the generative
lymphoid organs, the bone marrow and thymus), and others are the sites of immune responses (the peripheral lymphoid organs,
including lymph nodes, spleen, and mucosal lymphoid tissues).

Types of immunity

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USMLE Step 1 Platinum Notes

Dendritic/Langerhans Cells

Dendritic/Langerhans cells are bone marrow-derived


They generally lack the standard T, B, NK, and monocyte cell markers but do express CD83
CD 1 is the marker
Dendritic cells are referred to as Langerhans cells when they are present in the skin and beneath the mucosal surface.

Mediators of Shock
Clinical finding

Mediator

Fever

Interleukin 1

Hypotension

Bradykinin, Nitric Oxide

Inflammation

C3a, C5a

DIC

Hageman Factor

Remember Bradykinin also causes pain, Vasodilation and cough


CVC Lungs: Brown induration of lungs
CVC Liver: Nut meg liver
CVC Spleen: Gamma Gandy bodies

Cytokines
Cytokines are soluble proteins produced by a wide variety of hematopoietic and nonhematopoietic cell types
Cytokines are involved in the regulation of the growth, development, and activation of immune system cells and in the mediation of
the inflammatory response
Immunoregulatory cytokines involved in the activation, growth, and differentiation of lymphocytes and monocytes, e.g. IL-2,
IL-4, IL-10 and transforming growth factor (TGF)
Proinflammatory cytokines produced predominantly by mononuclear phagocytes in response to infectious agents (e.g. IL1, TNF- and IL-6) and the chemokine family of inflammatory cytokines, within which are included IL-8, monocyte chemotactic
protein (MCP)-1, MCP-2, MCP-3, macrophage inflammatory protein and regulation-upon-activation, normal T expressed and
secreted (RANTES)
Cytokines that regulate immature leukocyte growth and differentiation, e.g. IL-3, IL-7, and GM-CSF.

Prostaglandins: (USMLE Favorite)


LTA4:
Produced in leucocytes, platelets, mast cells, vascular tissue
LTC4, LTD4, LTE4:
Contraction of smooth muscle
Bronchoconstriction
Vasoconstriction
vascular permeability
Components of SRSA
LTB4:
Chemotaxis
Adhesion of WBC
Release of lysosomal enzymes
Thromboxanes:
Produced mainly in platelets
Promotes platelet aggregation

Pathology

343

Vasoconstriction
Smooth muscle contraction
Prostacyclins:
Produced by endothelium of vessels
Vasodilation
Inhibits platelet aggregation
Cortisol inhibits Phospholipase A2
Aspirin, Indomethacin, Phenylbutazone inhibit Both COX 1 and COX 2
Coxibs are selective COX 2 inhibitors (Celecoxib)

USMLE Case Scenario


Which of the following cells play a crucial role in the pathogenesis of alveolar-capillary damage in adults respiratory distress
syndrome (ARDS)?
1. Basophils
2. CD4-positive lymphocytes
3. CD8-positive lymphocytes
4. Eosinophils
5. Mast cells
6. Neutrophils
Ans. 6. Neutrophils
Neutrophils release chemokines that attract histiocytes and produce oxygen radicals, prostaglandins, and proteases that damage
alveolar epithelium. Formation of hyaline membranes is due to a combination of plasma fluid extravasation and alveolar cell necrosis.

Procoagulant States

Factor V (Leidein mutation)


Protein C deficiency
Protein S deficiency
Homocystenemia
Antiphospholipid antibody

Thrombus Development
Depends on the relative contribution of the components of Virchows triad:
Endothelial injury (e.g. by toxins, hypertension, inflammation, or metabolic products)
Abnormal blood flow stasis or turbulence (e.g. due to aneurysms, atherosclerotic plaque)
Hypercoagulability, which can be either primary (e.g. factor V Leiden, increased prothrombin synthesis, antithrombin III
deficiency) or secondary (e.g. bed rest, tissue damage, malignancy)
Thrombi may propagate, resolve, become organized, or embolize. Thrombosis causes tissue injury by local vascular occlusion or by
distal embolization.

Anticoagulant Factors

Antithrombin III
Protein C
Protein S
Prostacyclin
Nitric oxide

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USMLE Step 1 Platinum Notes

Hyperviscosity
Multiple myeloma
Cryoglobinemia
Myeloproliferative disorders

Remember: Virchows Triad


Endothelial injury
Alteration in blood flow
Hypercoagulability

Stains
Von kossa: calcium
Toluidine blue: mast cells
Alician blue: mucins
Congo red: amyloid
Masons trichome: collagen, connective tissue
Orcein: elastic fibers

USMLE Case Scenario


Which one of the following stains is specific for Amyloid?
1. Periodic Acid schif (PAS)
2. Alzerian red
3. Congo red
4. Von-Kossa
Ans. 3 Congo red

Major Histocompatibility Complex


The human major histocompatibility complex (MHC), commonly called the human leukocyte antigen (HLA) complex, is a 4-megabase
(Mb) region on chromosome 6
Class I MHC
They are glycoproteins
Present on surface of all nucleated cells
Presents antigen to CD 8 positive cells
Have only one chain encoded by MHC locus
Antigen binding site on MHC I is proximal end of alpha subunit of one and two
Class II MHC
They are glycoproteins present on the surface of Macrophages, B cells, dendritic cells of spleen and Langerhans cells
Presents antigen to CD 4 positive cells
Not Present on surface of nucleated cells
Have both chains encoded by MHC locus

Important HLA Associations: (Frequently asked)


A3 Hemachromatosis
B5 Behcets Disease
B 27 Ankylosing Spondylitis, Rieters Syndrome, Psoriatic Arthritis

Pathology

345

DR 2 Multiple Sclerosis, Narcolepsy


DR 3 Dermatitis Herpetiformis, Sjogrens Syndrome, Myasthenia Gravis, Iddm
DR 4 Iddm, Rheumatoid Arthritis
DR 5 Pernicious Anemia
DR 7 Coeliac Disease

HLA B-27 associations

USMLE Case Scenario


Rheumatoid arthritis is characterized by Rheumatoid nodules which develop in 20 to 30 percent of patients, usually on or
around joints, on extensor surfaces, or on other areas subjected to mechanical trauma. The most important HLA association
is with:
1. HLA-DR2
2. HLA-DR3
3. HLA-DR4
4. HLA B 27
Ans. 3. HLA-DR4

USMLE Case Scenario


A 24-year-old man presented to an ophthalmologist with a severe painful left eye for 38 hours. There is redness around the
cornea which developed into a iritis. Three days later the right eye also became involved. One week after the onset of the eye
symptoms, the patient complained of dysuria. No chlamydia, viruses or bacteria were isolated from this discharge. He was
treated with oxytetracycline and his eye signs gradually cleared. At about this time, however, his right first metatarsophalangeal
joint became inflamed and, subsequently, several joints were similarly involved. He was found to be HLA-B27-positive. Most
likely diagnosis would be:
1. Behcets Disease
2. Ankylosing Spondylitis
3. Reiters Disease
4. Gonococcal arthritis
5. Rheumatoid arthritis
6. Gouty Arthritis
Ans. 3. Reiters Disease

Natural Killer Cells


Are part of innate immunity
Are large granular lymphocytes
Lack T cell receptor, surface IgM and IgD

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USMLE Step 1 Platinum Notes

Express CD 16 and CD 56
The classic NK cells are CD2+, CD3+, CD4+, CD56+, and CD16+
Thymus is not required for their development
Activity not enhanced by prior sensitization. NK cells do not require sensitization to express the killer function
NK cells constitute 2 to 10% of normal peripheral blood lymphocytes
Contain Azurophilic granules
Kill virus infected cells and cancer cells
Kill by producing perforins, granzymes

Killing is non specific


NK cells are not MHC-restrictedthey will kill certain autologous, allogeneic, and even xenogeneic tumor cells whether or not
these targets express MHC
NK cells do not use the TCR, CD3 complex to recognize target cells
Killing is not dependent on foreign antigen presentation. (MHC Independent)

Graft Rejection
The graft rejection response is initiated mainly by host T cells that recognize the foreign HLA antigens of the graft, either directly (on
APCs in the graft) or indirectly (after uptake and presentation by host APCs)
Types and mechanisms of rejection:
Hyperacute rejection. Preformed antidonor antibodies bind to graft endothelium immediately after transplantation, leading to
thrombosis, ischemic damage, and rapid graft failure
Acute cellular rejection. T-cells destroy graft parenchyma by cytotoxicity and DTH reaction
Acute vascular rejection. T-cells and antibodies damage graft vasculature
Chronic rejection. Dominated by arteriosclerosis, this type is probably caused by T-cell reaction and secretion of cytokines that
induce proliferation of vascular smooth muscle cells, associated with parenchymal fibrosis.

Molecular Basis of Carcinogenesis

Self-sufficiency in growth signals


Insensitivity to growth-inhibitory signals
Evasion of apoptosis
Limitless replicative potential, (i.e. overcoming cellular senescence and avoiding mitotic catastrophe)
Development of sustained angiogenesis
Ability to invade and metastasize
Genomic instability resulting from defects in DNA repair

Oncogenes that Promote Unregulated Proliferation (Self-sufficiency in Growth Signals)


Proto-oncogenes: normal cellular genes whose products promote cell proliferation
Oncogenes: mutant versions of proto-oncogenes that function autonomously without a requirement for normal growthpromoting signals.

Insensitivity to Growth-Inhibitory Signals


Tumor suppressor genes encode proteins that inhibit cellular proliferation by regulating the cell cycle. Unlike oncogenes,
both copies of the gene must be lost for tumor development, leading to loss of heterozygosity at the gene locus. In cases
with familial predisposition to develop tumors, the affected individuals inherit one defective (nonfunctional) copy of a tumor
suppressor gene and lose the second one through somatic mutation. In sporadic cases both copies are lost through somatic
mutations.

Pathology

347

USMLE Case Scenario


An example of a tumor suppressor gene is:
1. myc
2. fos
3. ras
4. Rb
Ans. 4. Rb

Oncogenic Organisms
HPV has been associated with benign warts, as well as cervical cancer.The oncogenic ability of HPV is related to the expression of
two viral oncoproteins, E6 and E7; they bind to RB and p53, respectively, neutralizing their function; they also activate cyclins
E6 and E7 from high-risk HPV (that give rise to cancers) have higher affinity for their targets than E6 and E7 from low-risk HPV (that give
rise to low-grade tumors).
EBV has been implicated in the pathogenesis of Burkitt lymphomas, lymphomas in immunosuppressed individuals with
HIV infection or organ transplantation, some forms of Hodgkin lymphoma, and nasopharyngeal carcinoma. All except the
nasopharyngeal cancers are B-cell tumors.
The oncogenic effects of HBV and HCV are multifactorial, but the dominant effect seems to be immunologically mediated chronic
inflammation, hepatocellular injury, stimulation of hepatocyte proliferation, and production of reactive oxygen species that can
damage DNA. The HBx protein of HBV and the HCV core protein can activate a variety of signal transduction pathways that may
also contribute to carcinogenesis.
H pylori infection has been implicated in both gastric adenocarcinoma and MALT lymphoma. The mechanism of H pylori-induced
gastric cancers is multifactorial, including immunologically mediated chronic inflammation, stimulation of gastric cell proliferation,
and production of reactive oxygen species that damage DNA. H pylori pathogenicity genes, such as CagA, may also contribute by
stimulating growth factor pathways. It is thought that H pylori infection leads to polyclonal B-cell proliferations and that eventually a
monoclonal B-cell tumor (MALT lymphoma) emerges as a result of accumulation of mutations.

Important Translocations: (USMLE Favorite)


t(8;14) Burkitts Lymphoma
t(9;22) CML
t(15;17) AML
t(11;22) Ewings sarcoma
t(X;18) Synovial cell Ca

USMLE Case Scenario


A sarcoma appears like a malignant melanoma, which arises in the soft tissue. It usually is found on the tendons of extremities
of young patients. Histologically, the cells can have pigment or clear cytoplasm. It is associated with t(12,22). The sarcoma is:
1. Synovial cell sarcoma
2. Clear Cell sarcoma
3. Leiomyosarcoma
4. Rhabdomyosarcoma
Ans. 2. Clear Cell sarcoma
Burkitts Lympohoma is associated with:
1. t (8:14)
2. t (11:14)
3. t (15:17)
4. t (14:18)
Ans. 1. t (8:14)

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USMLE Step 1 Platinum Notes

Atrophy: Decreae in cell size/function


Hypertrophy: Increase in cell size/function
Hyperplasia: Increase in number of cells in tissues/organs
Metaplasia: Reversible change of epithelial transformation
Anaplasia: Hallmark of malignant transformation
Dysplasia: Reversible abnormal proliferation of cells. Intact basement membrane

Premalignant forms of SCC: (USMLE Favorite)

Actinic keratosis, or solar keratoses


Actinic cheilitis
Bowens disease
Erythroplasia of Queyrat
DLE
Xeroderma Pigmentosa
UV Radiation UV B
Hypertrophic lichen planus

Actinic keratoses and cheilitis are hyperkeratotic papules and plaques that occur on sun-exposed areas. While the potential for
malignant degeneration is low in any individual lesion, the risk of SCC increases with larger numbers of lesions
Bowens disease presents as a scaling, erythematous plaque, which may develop into invasive SCC in up to 20% of cases. Treatment
of premalignant and in situ lesions reduces the subsequent risk of invasive disease.

The following oral lesions are Premalignant Lesions


Leucoplakia
Erythroplakia
Chronic hyperplastic candidiasis
Oral submucous fibrosis
Syphilitic glossitis
Sideropenic dysphagia
Cancer Type Environmental Risk Factor
Lung: Smoking, Asbestos, Nickel, Radon, Coal, Arsenic, Chromium, Uranium
Mesothilioma: Asbestos
Bladder Ca: Smoking, Aniline dyes, Schistomiasis
Skin Ca: UV light exposure, coal, Tar, Arsenic
Liver: Alcohol, Vinyl chloride, Aflatoxins
Pancreas: Smoking
Renal Cell Carcinoma: Smoking
Stomach: Alcohol, Nitrosamines

Chemical Carcinogens
Chemical carcinogens have highly reactive eletrophile groups that directly damage DNA, leading to mutations and eventually
cancer
Direct-acting agents do not require metabolic conversion to become carcinogenic, while indirect-acting agents are not active until
converted to an ultimate carcinogen by endogenous metabolic pathways.

Pathology

349

Hence polymorphisms of endogenous enzymes like cytochrome P-450 may influence carcinogenesis. Following exposure of a
cell to a mutagen or an initiator; tumorigenesis can be enhanced by exposure to promoters, which stimulate proliferation of the
mutated cells
Examples of human carcinogens include direct-acting (e.g. alkylating agents used for chemotherapy), indirect-acting (e.g.
benzopyrene, azo dyes, and aflatoxin), and promoters/agents that cause pathologic hyperplasias of liver, endometrium.

Immune Surveillance
Tumor cells can be recognized by the immune system as nonself and destroyed. Antitumor activity is mediated by
predominantly cell-mediated mechanisms. Tumor antigens are presented on the cell surface by MHC class I molecules and are
recognized by CD8+ CTLs
The different classes of tumor antigens include products of mutated proto-oncogenes, tumor suppressor genes, overexpressed or
aberrantly expressed proteins, tumor antigens produced by oncogenic viruses, oncofetal antigens, altered glycolipids and glycoproteins,
and cell type-specific differentiation antigens. Immunosuppressed patients have an increased risk of cancer. In immunocompetent
patients, tumors may avoid the immune system by several mechanisms, including selective outgrowth of antigennegative variants,
loss or reduced expression of histocompatibility antigens, and immunosuppression mediated by secretion of factors (e.g. TGF-) from
the tumor.

Hereditary DNA Repair Disorders: (USMLE Favorite)


Xeroderma pigmentosum:
Hypersensitivity to sunlight/UV, resulting in increased skin cancer
Incidence and premature aging
Cockayne syndrome:
Hypersensitivity to UV and chemical agents
Trichothiodystrophy:
Sensitive skin, brittle hair and nails
Werners syndrome:
Premature aging and retarded growth
Blooms syndrome:
Sunlight hypersensitivity, high incidence of malignancies (especially leukemias)
Ataxia telangiectasia:
Sensitivity to ionizing radiation and some chemical agents.
All of the above diseases are often called segmental progerias (accelerated aging diseases) because their victims appear elderly
and suffer from aging-related diseases at an abnormally young age
Other diseases associated with reduced DNA repair function include:
Fanconis anemia
Hereditary breast cancer and
Hereditary colon cancer

Important Tumor Markers


Alpha fetoprotein

Hepato cellular carcinoma


Endodermal sinus tumor

PSA

Prostate cancer

Neuron specific enolase

Small cell lung cancer, Neuroblastoma

LDH

Lymphoma

Cathecolamines

Pheochromocytoma

350

USMLE Step 1 Platinum Notes

Beta 2 microglobulin

Multiple Myeloma
Lymphoma

Gastrin

Pancreatic neuroendocrine tumors

Bladder Tumor Antigen

Bladder Tumor, UTI, Renal Calculi

CA 27.29

Breast Cancer

CA 72.4

Ovarian and Pancreatic Cancer

LASA P (Lipid Associated Sialic Acid)

Ovarian Cancer

Keratin

Ca cervix

NMP 22

Bladder Cancer

HCG

Gestational Trophoblastic Disorders

CA 125

Ovarian Cancer

Placental Alkaline Phosphatase

Seminoma

S100

Melanoma, Neural Tumors

APUD omas: (CAPITALS)


C- Carcinoid tumor
A- Adrenal pheochromocytoma
P- Pancreatic endocrine tumors
I- Islet-cell tumor
T- Thyroid medullary carcinoma
A- Additional: Ganglioblastoma, neuroblastoma, paragangliomas
L- Lung: Small-cell carcinoma
S- Skin: Melanoma

USMLE Case Scenario


Serous papillary cystadenocarcinomas of the ovaries express:
1. CA-125
2. CA-19
3. CEA
4. AFP
Ans. 1. CA-125

USMLE Case Scenario


A 25-year-old man has a testicular mass, which on orchiectomy shows a malignant tumor with yolk sac differentiation. Which
of the following tumor markers would probably be most useful in monitoring the patient for recurrent or metastatic disease?
1. Alpha-fetoprotein
2. Carcinoembryonic antigen (CEA)
3. Prostate-specific antigen (PSA)
4. S-100
Ans. 1. Alpha-fetoprotein
Serum alpha-fetoprotein is a fetal serum protein produced by the yolk sac and liver. Increased serum levels in adults are seen
in tumors (hepatocellular carcinoma, neuroblastomas and teratoma) and acute hepatitis and colitis. In patients with tumors,
serum levels often correlate with tumor size. Resection is usually associated with a fall in serum levels. Serum levels are useful
in assessing response to treatment.

Pathology

Mesenchymal Tumors
Endothelial tumors
Melanoma
Fibrohistiocytic tumors
Muscle tumors

HYPERSENSITIVITY REACTIONS: (USMLE FAVORITE)


Type I Hypersensitivity reactions: IgE Mediated
Theobald phenomenon
Prusnitz reaction (PK)
Casonis Test
Anaphylaxis
Local: Asthma, Hay fever, Angioedema, Eczema, Urticaria

Type II Hypersensitivity reactions: IgG or IgM Mediated


Graves disease (ALSO TYPE V)
Goodpastures Syndrome
Myasthenia Gravis
Blood transfusion reactions
Immune hemolytic anemia
Immune Thrombocytopenic purpura

Type III Hypersensitivity Reactions: Immune Complex Mediated


Arthus reaction
Serum Sickness
SLE
Schiks test
Post Streptococcal Glomerulonephritis

Type IV Hypersensitivity Reactions: Delayed Hypersensitivity


Tuberculin test
Lepromin Test
Contact dermatitis
Pernicious anemia

Immune-Complex-Dependent Reactions/Serum Sickness


Serum sickness is produced by circulating immune complexes and is characterized by:
Fever
Arthritis
Nephritis
Neuritis
Edema, and an Urticarial, papular, or purpuric rash
Serum sickness was first described following administration of foreign sera, but drugs are now the usual cause

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USMLE Step 1 Platinum Notes

TYPE III hypersensitivity reaction


Drugs that produce serum sickness include the
Penicillins
Sulfonamides
Thiouracils
Cholecystographic dyes
Phenytoin, aminosalicylic acid
Heparin and antilymphocyte globulin
In classic serum sickness, symptoms develop 6 days or more after exposure to a drug, the latent period representing the time
needed to synthesize antibody. The antibodies responsible for immune-complex-dependent drug reactions are largely of the IgG
or IgM class
Vasculitis, may also be a result of immune complex deposition.

Collagen
Collagen is the main protein of connective tissue in animals and
The most abundant protein in mammals, making up about 25 to 35% of the whole-body protein content
In muscle tissue it serves as a major component of Endomysiun.
Type I
This is the most abundant collagen of the human body
It is present in scar tissue, the end product when tissue heals by repair. It is found in
Tendons
Skin
Artery walls
The endomysium of myofibrils
Fibrocartilage and the organic part of bones and teeth.
Type II
Hyaline cartilage makes up 50% of all cartilage protein
Vitreous humor of the eye.
Type III
This is the collagen of granulation tissue, and is produced quickly by young fibroblasts before the tougher type I collagen is synthesized.
Also found in:
Artery walls
Skin
Intestines and the
Uterus
Reticular fiber.
Type IV
Present in
Basal lamina
Eye lens
Filtration system in capillaries and the
Glomeruli of nephron in the kidney.

Amyloidosis: (USMLE Favorite)


Amyloidosis is a disorder characterized by the extracellular deposits of misfolded proteins that aggregate to form insoluble
fibrils. The deposition of these proteins may result from: excessive production of proteins that are prone to misfolding and
aggregation; mutations that produce proteins that cannot fold properly and tend to aggregate; defective or incomplete
proteolytic degradation of extracellular proteins
Amyloidosis maybe localized or systemic.

Pathology

Remember the type of Amyloidosis and the Protein type associated


Type of Amyloidosis

Amyloid protein

Primary Amyloidosis, Myeloma

AL

Secondary Amyloidosis
Tuberculosis
Rheumatoid arthritis
Hodgkins lymphoma

AA

Familial Medittarean Fever

AA

Hemodialysis associated Amyloidosis

A2M

Cerebral (Alzhiemers) Amyloidosis

Cardiac Amyloidosis

ATTR

Amyloidosis is deposition of an extracellular protein


Individual subunits form pleated sheets.
Kidney followed by liver is the commonest sites involved
Deposits stain red with Congo red
Apple green birefrigerence is seen on Congo red stain under polarized light
Amyloid is composed of fibrillary protein, amyloid P Component and Glycosaminoglycans
Thyroid cancer with amyloid stroma: MTC (Medullary ca thyroid)
Rectal biopsy is the best diagnostic method.

On light microscopy: Eosinophilic amorphous substance


Congo red in ordinary light: Pink color
Congo red on polarizing microscope: Yellow green birefringence
Electron microscopy: Nonbranching fibrils
X-ray crystallography: Crossed pleated configuration

Pathology and Genetics: (USMLE Favorite)


The following conditions are inherited as
Asked innumerable times in
Autosomal Dominant

Autosomal Recessive

Huntingtons disease
Marfans syndrome
Adult polycystic kidney disease
Familial hypercholestremia
Osteogenesis imperfecta
Neurofibromatosis
Achondroplasia
Myotonic dystrophy
Von Willebrands disease
HNPCC
BRCA1, BRCA2 Breast cancer
Otosclerosis
Tuberous sclerosis
MC group of mendelian disorders

Cystic fibrosis
Ataxia telengectasia
Freidrechs ataxia
Infantile polycystic kidney disease
Wilsons disease
Alkaptonuria
Hemochromatosis
Sickle cell anemia
phenyl ketonuria
beta thalessemia
alpha 1 antitrypsin deficency

X-linked recessive
Becker
Colour blindness
Duchenne muscular dystrophy
Fabrys disease
G6PD deficiency
Hemophilia A, B
Hunters disease
Lesch-Nyhan syndrome
Nephrogenic diabetes insipidus
Ocular albinism
Retinitis pigmentosa
Testicular feminization syndrome
Wiskott-Aldrich syndrome
Color blindness
Affects males more

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USMLE Step 1 Platinum Notes

Autosomal Dominant Traits


Are fully manifest in the presence of a gene in the heterozygous state, i.e. when only one abnormal gene (mutant allele) is present and
the corresponding partner allele on the homologous chromosome is normal. The following features are characteristic:
Each affected individual has an affected parent (unless the condition arose by a new mutation in a germ cell that formed
the individual);
An affected individual usually bears an equal number of affected and unaffected offspring;
Males and females are affected in equal numbers;
Each gender can transmit the trait to male and female;
Normal children of an affected individual have only normal off spring;
When the trait does not impair viability or reproductive capacity, vertical transmission of the trait occurs through
successive generations. Three or more generations of male-to-male transmission argues against X-linkage of a rare gene.

Autosomal Recessive Traits


Autosomal recessive conditions are clinically apparent only in the homozygous state, i.e. when both alleles at a particular
genetic locus are mutant alleles. The following features are characteristic:
The parents are clinically normal
Only siblings are affected
Males and females are affected in equal proportions
If an affected individual marries a homozygous normal person, none of the children is affected but all are heterozygous carriers
If an affected individual marries a heterozygous carrier, one half of the children are affected, and the pedigree pattern superficially
suggests a dominant trait
If two individuals who are homozygous for the same mutant gene marry, all of their children are affected
If both parents are heterozygous at the same genetic locus, one fourth of their children are homozygous affected, on average one
fourth are homozygous normal, and one half are heterozygous carriers of the same mutant gene; and
The less frequent the mutant gene is in the population, the greater the likelihood that the affected individual is the product of
consanguineous parents.

X-Linked Recessive Traits


Diseases or traits that result from genes located on the X chromosome are termed X-linked. Because the female has two
X chromosomes, she maybe either heterozygous or homozygous for the mutant gene, and the trait may exhibit recessive or
dominant expression. The terms X-linked dominant and X-linked recessive refer only to expression of the trait in females. The
male has only one X chromosome and therefore is hemizygous for X-linked traits. Males can be expected to express X-linked traits
regardless of their recessive or dominant behavior in the female. This accounts for the large numbers of X-linked diseases.
Males transmit their X chromosome to all of their daughters, making them all obligate carriers of an X-linked disease trait
Affected males do not transmit an X chromosome to their sons; thus, an important feature of X-linked inheritance is the
absence of male-to-male transmission.

X-Linked Dominant Traits


This mode of inheritance is uncommon. Its characteristic features are as follows:
Females are affected about twice as often as males;
Heterozygous females transmit the trait to both genders with a frequency of 50%;
Hemizygous affected males transmit the trait to all of their daughters and none of their sons; and
The expression is more variable and generally less severe in heterozygous females than in hemizygous affected males. Examples
of X-linked dominant inheritance include the vitamin D-resistant (hypophosphatemic) rickets and pseudohypoparathyroidism.

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355

USMLE Case Scenario


The BRCA-1 gene associated with breast cancer and ovarian cancer, is located on:
1. 17q
2. 17 p
3. 22q
4. 18q
Ans. 1. 17q
The NF-1 gene is, associated with neurofibromatosis type I, is on 17q
The NF-2 gene associated with neurofibromatosis type II, is on 22q
The p53 gene associated with many cancers, is on 17p
The DCC oncogene located on the long arm of chromosome 18q

USMLE Case Scenario


Ophthalmoscopic examination of a 7-year-old child from Washington DC demonstrates a retinal angioma. This finding should
raise the possibility of which of the following syndromes?
1. Neurofibromatosis type I
2. Neurofibromatosis type II
3. Tuberous sclerosis
4. von Hippel-Lindau disease
Ans. 4. von Hippel-Lindau disease

USMLE Case Scenario


Subependymal giant cell astrocytoma is a peculiar astrocytic tumor that grows from the walls of the lateral ventricles. It is
caused by mutations of TS1 or TS2 genes. It is usually seen in:
1. von Hippel-Lindau syndrome
2. Neurofibromatosis 1
3. Neurofibromatosis 2
4. Tuberous Sclerosis
Ans. 4. Tuberous Sclerosis

USMLE Case Scenario


Kinky hair disease is a disorder where an affected child has peculiar white stubby hair, does not grow, brain degenration is
seen and dies by age of two years. A lady is hesitant about having children because her two sisters had sons who had died
from kinky hair disease. Her mothers brother also died of the same condition. Which of the following is the possible mode of
inheritence in her family?
1. X-linked recessive
2. X-linked dominant
3. Autosomal recessive
4. Autosomal dominant
Ans. 1. X-linked recessive

USMLE Case Scenario


The chances of having an unaffected baby, when both parents have achondroplasia, are:
1. 0%
2. 25%
3. 50%
4. 100%
Ans. 2. 25%

356

USMLE Step 1 Platinum Notes

X-Linked Dominant
Hypophosphatemic type of vitamin D resistant rickets
Incontenentia pigmentii
Orofaciodigital syndrome
Hereditary spherocytosis is AD
Achondroplasia is AD
Familial hypercholestrelemia is AD
Retinoblastoma is AD
von Villebrands disease is AD
Homocystinuria is AR

Y-Linked Disorders
Only a few genes are known on the Y chromosome
One such gene, the sex-region determining Y factor (SRY), or testis-determining factor (TDF), is crucial for normal male
development
Men with oligospermia/azoospermia frequently have microdeletions on the long arm of the Y chromosome that involve one or
more of the azoospermia factor (AZF) genes.

Trinucleotide Repeat Disorders


A number of diseases are caused by a mutation that is an expansion of a repetitive sequence of three nucleotides
which is genetically unstable
When repeat length increases from one generation to the next, disease manifestations may worsen or be observed atan earlier
age; this phenomenon is referred to as anticipation
Conditions Include:
Huntingtons disease
Myotonic dystrophy
Fragile X Syndrome
Kennedys Syndrome
Some forms of Spino cerebellar Ataxia
Huntingtons disease is transmitted in an autosomal dominant fashion. The age at which the patient becomes symptomatic
is variable and has no effect on the probability of transmitting the disease. The defect underlying this degenerative disease
is an abnormal expansion of a region of chromosome 4 containing a triplicate repeat (CAG) sequence. Normal individuals
have between 6 and 34 copies of this CAG section; patients with Huntingtons disease may have from 37 to more than 100
repeats. Once expanded beyond 40 copies, the repeats are unstable and may further increase as they are passed on from one
generation to the next. An increased number of repeats leads to a phenomenon known as anticipation, by which successive
generations have earlier disease onset.

Fragile X-Syndrome: (USMLE Favorite)


Pathologic amplification of trinucleotide repeats causes loss-of-function (fragile X-syndrome) or gain-of-function mutations
(Huntington disease). Most such mutations produce neurodegenerative disorders. Fragile X-syndrome results from loss of
FMR1 gene function and is characterized by mental retardation, macroorchidism, and abnormal facial features. In the normal
population there are about 29 CGG repeats in the FMR1 gene. Carrier males and females carry permutations with 52 to 200
CGG repeats that can expand to 4000 repeats (full mutations) during oogenesis. When full mutations are transmitted to
progeny, fragile X-syndrome occurs.

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357

Genomic Imprinting
Imprinting involves transcriptional silencing of the paternal or maternal copies of certain genes during gametogenesis. For such genes
only one functional copy exists in the individual. Loss of the functional allele (not imprinted) by deletions gives rise to diseases
Prader-Willi syndrome results from deletion of paternal chromosome 15q12 and is characterized by mental retardation, short stature,
hypotonia, obesity and hypogonadism
Angelman syndrome results from deletion of maternal chromosome 15q12 and is characterized by mental retardation, ataxia,
seizures and inappropriate laughter.

Mitochondrial DNA/Mitochondriopathies: (USMLE Favorite)


Mutation rate about ten times greater than nuclear DNA
This is because there are no introns and a mutation invariably strikes a coding sequence (axon)
Tissues with greatest ATP requirement (CNS, Skeletal muscle, Heart muscle, Kidney, Liver) are most affected
Mitochondrial DNA is maternally inherited because mitochondria from sperms do not enter the fertilized egg
Mitochondrial DNA is Closed and circular and 16.5 kb in length
MELAS (Mitochondrial Encephalopathy, Lactic Acidosis and Stroke like episodes) are attributed to
Mitochondrial mutations. Other diseases associated with mt DNA are:
Lebers Hereditary Optic Neuropathy
MELAS (mitochondrial encephalopathy with lactic acidosis and stroke like episodes)
Myopathy
MERRF Syndrome: (myoclonic epilepsy and ragged red fibers.)
Cardiomyopathy
Strokes
Lactic acidosis
External Ophthalmoplegia
Optic atrophy
NARP (Neuropathy, ataxia and retinitis pigmentosa)
Pearsons syndrome
Sensorineural deafness
Diabetes mellitus

Gene Frequency
The distribution of a mutant gene in the general population maybe calculated on the basis of the Hardy-Weinberg equation. If the
frequency of a particular gene A is p, then that of its alternative allele is (1 p) = q. Three genotypes are found in the population:
Those who are homozygous AA
Those who are heterozygous Aa and
Those who are homozygous aa
In a randomly mating population, the frequencies of these genotypes are in the proportion p2 (AA), 2 pq (Aa), and q2 (aa)
An important consequence of this distribution is that irrespective of the initial frequency of the genes A and a in the
population, the proportion of the three genotypes tends to remain constant in succeeding generations, provided that
there is no difference in biologic fitness of any of the genotypes. If viability or fertility among the three genotypes is
unequal, if individuals migrate into or out of the population, or if mating is not random, the frequency calculations require
considerable correction. In small populations major changes in gene frequency can occur on the basis of chance alone
If the frequency of a recessive disease in a particular population is known, the frequency of heterozygous carriers and
of the abnormal gene can be calculated. Thus for a recessively inherited disease aa (q2) with a frequency of 1 per 10,000
(e.g. albinism), the frequency of the gene a (q) is 1 per 100, and that of heterozygous carriers is 2 p q = 2 99/100 1/100
= approximately 1 in 50

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USMLE Step 1 Platinum Notes

Commonly asked Terminology: (USMLE Favorite)


Allelic Heterogeneityrefers to the fact that different mutations in the same genetic locus can cause an identical or similar
phenotype. For example, many different mutations of the b-globin locus can cause b-thalassemia.
Phenotypic Heterogeneityoccurs when more than one phenotype is caused by allelic mutations (e.g. different mutations
in the same gene). e.g. Similarly, identical mutations in the FGFR2 gene can result in very distinct phenotypes: Crouzon syndrome
(craniofacial synostosis), or Pfeiffer syndrome (acrocephalo polysyndactyly).
Locus or Nonallelic Heterogeneity and Phenocopies: Refers to the situation in which a similar disease phenotype results
from mutations at different genetic loci. For example, osteogenesis imperfecta can arise from mutations in two different
procollagen genes (COL1A1 or COL1A2) that are located on different chromosomes.
Variable Expressivity and Incomplete Penetrance: The same genetic mutation causes a phenotypic spectrum illustrating
the phenomenon of variable expressivity. MEN-1 illustrates several of these features. Families with this autosomal dominant
disorder develop tumors of the parathyroid gland, endocrine pancreas, and the pituitary gland. However, the pattern of tumors
in the different glands, the age at which tumors develop, and the types of hormones produced vary among affected individuals,
even within a given family.
Penetrance: It is the probability of expressing the phenotype given a defined genotype; it can be complete or incomplete. For
example, hypertrophic obstructive cardiomyopathy (HOCM) caused by mutations in the myosin heavy chain b gene is a dominant
disorder with clinical features in only a subset of patients who carry the mutation. Patients who have the mutation but no
evidence of the disease can still transmit the disorder to subsequent generations. In this situation, the disorder is said to be
nonpenetrant or incompletely penetrant.

USMLE Case Scenario


Differential expression of same gene depending on parent of origin is referred to as:
1. Genomic imprinting
2. Mosaicism
3. Anticipation
4. Nonpenetrance
Ans. 1. Genomic imprinting

USMLE Case Scenario


Males are more commonly affected than females in:
1. Autosomal Dominant
2. Autosomal Recessive
3. X- Linked Dominant
4. X- Linked recessive
Ans. 4. X- Linked recessive

Cluster Designation (CD) Markers

CD 3
CD 10
CD 19
CD 20, 21, 22
CD 16 and CD 56

Pan T-cell marker


Immature B-cell marker
Pan B-cell marker
B-cell markers
NK-cells

USMLE Case Scenario


Which of the following markers is specific for Gastrointestinal stromal tumors (GIST):
1. CD 117
2. CD 34

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359

3. CD 23
4. S 100
Ans. 1. CD 117

USMLE Case Scenario


Which of the following are characteristic markers for Hodgkins Lymphoma?
1. CD15 and CD30
2. CD15 and CD45
3. CD30 and CD68
4. CD15 and CD3
Ans. 1. CD15 and CD30

USMLE Case Scenario


Which of the following is a marker for Langerhans cell histiocytosis:
1. CD 1a
2. CD 10
3. CD 30
4. CD 56
Ans. 1. CD 1a

Chromosomal Involvements: (USMLE Favorite)


Chromosome 1

Neuroblastoma

Chromosome 2

Cystinuria

Chromosome 3

RCC

Chromosome 4

Huntingtons Chorea

Chromosome 5

FAP, Cri Du Chat

Chromosome 6

HLA/MHC Antigens

Chromosome 7

Cystic Fibrosis

Chromosome 8

Osteopetrosis

Chromosome 9

Freidreichs Ataxia

Chromosome 11

Wilms Tumor

Chromosome 13

Retinoblastoma

The c-Ki-ras and the c-myc genes are the oncogenes most frequently altered in colorectal cancer
Antigen presenting cells (APC) gene, a tumor suppressor gene located on chromosome 5q, is a inactivated by a point mutation
in FAP
The p53 gene is also implicated in colorectal cancer. It checks the integrity of the genome prior to mitosis
BRCA1 gene is associated with familial breast cancer.

USMLE Case Scenario


Familial polyposis coli is a rare condition inherited as autosomal dominant, with equal sex incidence. Hundreds of adenomas
develop throughout the colon and rectum. The gene responsible for FAP is:
1. On the short arm of chromosome 5
2. On the long arm of chromosome 5
3. On the short arm of chromosome 15
4. On the long arm of chromosome 15
Ans. 1. On the short arm of chromosome 5

360

USMLE Step 1 Platinum Notes

USMLE Case Scenario


Cowden syndrome is due to:
1. Mutations of a gene on chromosome 9
2. Mutations of a gene on chromosome 10
3. Mutations of a gene on chromosome 11
4. Mutations of a gene on chromosome 12
Ans. 2. Mutations of a gene on chromosome 10

Remember

Gene for Major Histocompatibility is carried on chromosome 6


Gene for Folate carrier protein is carried on chromosome 21
Cystic fibrosis transmembrane conductance regulator gene is carried onchromosome 7
Short arm of chromosome is p arm
Long arm of chromosome is q arm
Genes regulating morphogenesis: homeobox genes (HOX)
APC gene is located on chromosome 5
BRCA 1 gene is located on chromosome 17

Important Points about Antibodies

Immunoglobulin
IgM
The first Ab formed after primary immunization (exposure to new Ag)
Exists in a monomeric or pentameric form and protects the intravascular space from disease.
The large IgM molecules readily activate complement and serve as opsonizers and agglutinators to assist the phagocytic system
to eliminate many kinds of microorganisms
Fixes complement
Isohemagglutinins and many Abs to gram-negative organisms are IgM.

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361

IgG
The most prevalent type of Ab is found in plasma and extravascular spaces; it is produced when IgM titers begin to decrease after
primary immunization.
IgG is the major Ig produced after reimmunization (the memory immune response or secondary immune response).
IgG is the prime mediator of the memory response and protects the tissues from bacteria, viruses and toxins.
It is the only Ig that crosses the placenta.
IgG subclasses neutralize bacterial toxins, activate complement and enhance phagocytosis by opsonization.
Commercial gamma globulin is almost entirely IgG, with small amounts of other Igs.
IgA (secretory Ab)
It is found in mucous secretions (saliva, tears, respiratory, GU and GI tracts, and colostrum), where it provides an early
antibacterial and antiviral defense.
Secretory IgA is synthesized in the subepithelial regions of the GI and respiratory tracts and is present in combination with locally
produced secretory component (SC).
IgD
It is not known to have much biologic activity. Present in serum in extremely low concentrations, it appears on the surface of
developing B cells and maybe important in their growth and development.
IgE
(Reaginic, skin-sensitizing, or anaphylactic Ab), like IgA, is found primarily in respiratory and GI mucous secretions.
In serum, IgE is present in very low concentrations
IgE is elevated in atopic diseases (e.g. allergic asthma, hay fever and atopic dermatitis), parasitic diseases, far-advanced
Hodgkins disease, and IgE-monoclonal myeloma
IgE may also have a beneficial role in the defense against parasites.
IgE -mediates reagenic hypersensitivity
IgG
IgG: This is major serum immunoglobulin
IgG: It is only maternal immunoglobulin that is normally transported across the placenta and provides natural passive immunity
in newborn
IgA: It is the second most abundant class of immunoglobulin seen in body fluids such as colostrums, saliva and tears
IgM: It is called millionaire molecule. It is not transported across the placenta hence presence of IgM in the fetus or newborn
indicates diagnosis of congenital infection such as syphilis, rubella, HIV and toxoplasmosis
IgM: Antibodies are short lived; hence their presence in serum indicates recent infection
IgE: Greatly elevated in atopic (Type I allergy) conditions such as asthma, hay fever, eczema, and also in children having high
load of intestinal parasites.

Interferons
IFN-alpha
Produced by leucocytes
Antiviral action
Useful in hepatitis B and C, Kaposis sarcoma, metastatic renal cell cancer, hairy cell leukemia

IFN-beta
Produced by fibroblasts
Antiviral action
Reduces the frequency of exacerbations in patients with relapsing-remitting MS

362

USMLE Step 1 Platinum Notes

IFN-gamma
Produced by T-lymphocytes and NK-cells
Weaker antiviral action, more of a role in immunomodulation particularly macrophage activation
Maybe useful in Chronic granulomatous disease.

Interleukins: (USMLE Favorite)


IL1 causes Fever
IL2T cell stimulation
IL3 Bone Marrow stimulation
IL4IgE Stimulation
IL5IgA Stimulation

Functions of Different Complement Components


Opsonization (C3b)
Chemotaxis (C5a)
Anaphylotoxin (C3a, C4a, C5a)
Cytolysis (insertion of C5b, 6,7,8,9 into the cell membrane)
Enhancement of antibody production (C3b)

Oncogenes
Oncogenes are regulatory genes
Activity is abnormally increased after a genetic alteration
Oncogene activation may occur after
Chromosomal translocation
Gene amplification
Mutation within coding sequence of oncogene
Oncogenes act in a dominant fashion
Examples of oncogenes include:
Ras on chromosome 11 mediates signal transduction
ErbB2 on chromosome 7 growth factor receptor
Src on chromosome 20 tyrosine kinase
Myc on chromosome 8 transcription factor.

Tumor Suppressor Genes

Code for inhibitory proteins


Normal function is to prevent cell growth
In cancer, suppressor function is lost
Most tumor suppressor genes are recessive
Inactivation of tumor suppressor genes can occur by
Gene mutation causing loss of gene product
Prevention of binding of a gene product to its target site
Inactivation by other proteins

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363

Examples of tumor suppressor genes include


Rb on chromosome 13 control of cell cycle
p53 on chromosome 17 DNA repair and apoptosis
Bcl2 on chromosome 18 apoptosis
APC on chromosome 5 regulation of co-transcriptional activators
Mutation of tumor suppressor genes is seen in many familial cancers
Rb childhood retinoblastoma
p53 Li-Fraumeni syndrome
APC familial colon cancer
BRCA1/2 familial breast cancer

Tumor Suppressor Genes: (Nutshell)


Tumor suppressor gene
VHL
WT 1 and 2
Rb
P53 (Guardian of genome)
BRCA1
BRCA2
APC
DCC
NF1 and NF2

Tumors
von Hippel-Lindau disease
Wilms tumor
Retinoblastoma, Osteosarcoma
Lung, colon, breat Ca
Hereditary breast and ovarian Ca
Hereditary breast Ca
Adenomatous polyps and colon Ca
Colon Ca
Neurofibromas

Protein 53: (USMLE Favorite)


p53 also known as protein 53 or tumor protein 53 is a transcription factor which in humans is encoded by the TP53 gene.
p53 is important in multicellular organisms, where it regulates the cell cycle and thus functions as a tumor suppressor that is
involved in preventing cancer
Acts at G1 S Phase.
As such, p53 has been described as
The guardian of the genome,
The guardian angel gene, and the
Master watchman, referring to its role in conserving stability by preventing genome mutation.
The name p53 is in reference to its apparent molecular mass: it runs as a 53 kilodalton (kDa) protein on SDS-PAGE.
In humans, p53 is encoded by the TP53 gene (guardian of the cell) located on the short arm of chromosome 17 (17p13.1).
p53 has many anti-cancer mechanisms:
It can activate DNA repair proteins when DNA has sustained damage.
It can induce growth arrest by holding the cell cycle at the G1/S regulation point on DNA damage recognition
(if it holds the cell here for long enough, the DNA repair proteins will have time to fix the damage and the cell will be allowed to
continue the cell cycle.)
It can initiate apoptosis, the programmed cell death, if the DNA damage proves to be irreparable.

Oncogenes: (USMLE Favorite)


RAS:
K-RAS: colon, lung, pancreatic tumors
N-RAS: melanoma, AML
H-RAS: Bladder, kidney tumors

364

USMLE Step 1 Platinum Notes

ABL
MYC
C-MYC: Burkitts lymphoma
N-MYC: Neuroblastoma
L-MYC: Small cell lung cancer
WNT 1
ERB B2
FOS
JUN
AKTI, AKT2
BRAF

Immunology: (USMLE Favorite)


Primary immunodeficiency disorders maybe classified according to which component of the immune system they affect:
Neutrophil disorders
Chronic granulomatous disease
Chediak-Higashi syndrome
Leukocyte adhesion deficiency
B-cell disorders
Common variable immunodeficiency
Brutons congenital agammaglobulinemia
IgA deficiency
T-cell disorders
Di George syndrome (Thymic and Parathroid aplasia)
Combined B-and T-cell disorders
Severe combined immunodeficiency
Ataxic telangiectasia
Wiskott-Aldrich syndrome

Jobs Syndrome/Hyperimmunoglobulin E-recurrent Infection Syndrome


The hyperimmunoglobulin E-recurrent infection (HIE) syndrome or Jobs syndrome
It is a rare multisystem disease in which the immune system, bone, teeth, lung and skin are affected. Abnormal chemotaxis is a
variable feature
The cold abscesses have been considered a reflection of impaired chemotaxis with too few phagocytes arriving too late, perhaps
due to a lymphocyte factor inhibiting chemotaxis
Serum IgE elevated. Other immunoglobulins normal.

ABNORMAL NEUTROPHIL FUNCTION


Disorders of Adhesion (Leukocyte adhesion deficiency (LAD))
Two types of leukocyte adhesion deficiency (LAD) have been described
Both are autosomal recessive traits and result in the inability of neutrophils to exit the circulation to sites of infection, leading
to leukocytosis and increased susceptibility to infection Neutrophils (and monocytes) from patients with LAD 1 adhere poorly to
endothelial cells and protein-coated surfaces and exhibit defective spreading, aggregation and chemotaxis
LAD 1 Patients have recurrent bacterial and fungal infections involving skin, oral and genital mucosa, and respiratory and intestinal
tracts; persistent leukocytosis (neutrophil counts of 15,000 to 20,000/uL) because cells do not marginate; and in severe cases
A history of delayed separation of the umbilical stump
Infections, especially of the skin, may become necrotic with progressively enlarging borders

Pathology

365

Slow healing and development of dysplastic scars


The most common bacteria are Staphylococcus aureus and enteric gram-negative bacteria
LAD 2 is caused by an abnormality of CD15, the ligand on neutrophils that interacts with selectins on endothelial cells.

Disorders of Neutrophil Granules


The most common neutrophil defect is Myeloperoxidase deficiency, a primary granule defect inherited as an autosomal
recessive trait
Microbicidal activity of neutrophils is delayed but not absent
Myeloperoxidase deficiency may make other acquired host defense defects more serious
An acquired form of myeloperoxidase deficiency occurs in myelomonocytic leukemia and acute myeloid leukemia.

Chediak-Higashi Syndrome (CHS)


Autosomal recessive inheritance due to defects in the lysosomal transport protein LYST, encoded by the gene CHS1 at 1q42.
This protein is required for normal packaging and disbursement of granules
Neutrophils (and all cells containing lysosomes) from patients with CHS characteristically have large granules Patients with CHS
have an increased number of infections resulting from many agents
CHS neutrophils and monocytes have impaired chemotaxis and abnormal rates of microbial killing due to slow rates of
fusion of the lysosomal granules with phagosomes
NK cell function is also impaired
Specific granule deficiency is a rare autosomal recessive disease in which the production of secondary granules and their contents,
as well as primary granule component defensins, is defective
The defect in bacterial killing leads to severe bacterial infections.

Chronic Granulomatous Disease


Disorders of granulocyte and monocyte oxidative metabolism
There is defective neutrophil oxidative metabolism
Most often CGD is inherited as an X-linked recessive trait; 30% of patients inherit the disease in an autosomal recessive pattern
Leukocytes from patients with CGD have severely diminished hydrogen peroxide production
Patients with CGD characteristically have increased numbers of infections due to catalase-positive microorganisms (organisms
that destroy their own hydrogen peroxide)
When patients with CGD become infected, they often have extensive inflammatory reactions, and lymph node suppuration is
common despite the administration of appropriate antibiotics.
Persistent Neutrophilia with cell counts of 30,000 to 50,000/microliter or higher is called Leukemoid reaction
In leukemoid reaction the circulating neutrophils are mature and not clonally derived.
Cyclic Neutropenia:
It is decrease in neutrophils counts at intervals of 3 weeks (1345) days with normal periods in between
Patients develop overwhelming infections
It is inherited as Autosomal Dominant trait
It is due to Neutrophil elastase gene defect.
Hereditary neutropenias:
Are rare and may manifest in early childhood as a profound constant neutropenia or agranulocytosis
Congenital forms of neutropenia include:
Kostmanns syndrome (neutrophil count <100/uL), which is often fatal; more benign chronic idiopathic neutropenia (neutrophil
count of 300 to 1500/uL);

366

USMLE Step 1 Platinum Notes

Cartilage-hair hypoplasia syndrome; Shwachmans syndrome associated with pancreatic insufficiency; myelokathexis, a
congenital disorder characterized by neutrophil degeneration, hypersegmentation, and myeloid hyperplasia in the marrow
associated with decreased expression of bcl-XL in myeloid precursors and accelerated apoptosis
Neutropenias associated with other immune defects (X-linked agammaglobulinemia, ataxia telangiectasia, IgA deficiency)
The presence of immunoglobulin directed toward neutrophils is seen in Feltys syndrome: a triad of rheumatoid arthritis,
splenomegaly and Neutropenia.

Vessel Disorders: (USMLE Favorite)


Large Vessel Arteritis
Giant cell arteritis
Takayasus arteritis

Medium Sized Vessel Arteritis


Poly arteritis nodosa
Kawasaki disease

Small Sized Vessel Arteritis

Essential cryoglobinemia
Churg strauss syndrome
HSP
Microscopic poly angitis
Wegners Granulomatosis

Takayasus Arteritis
Also called as Pulseless Disease or Aortic Arch Syndrome
It is a vasculitis common in Asia especially in young and middle aged females, affecting medium to large size arteries including
Aorta and its branches
Characterized by granulomatous Inflammation leading to arterial thrombosis, stenosis or aneurysm
Clinical features are:
Loss of pulse in upper extremities. (Radial Pulse not felt)
Systemic features: fever, weight loss, arthalgias, fatigue
Anemia and increased ESR
Visual loss or field defects, retinal hemorrhages
Neurological abnormalities like Headache, plus Chest Pain, Hypertension

Polymyositis/Dermatomyositis
A systemic connective tissue disease characterized by inflammatory and degenerative changes in the muscles (polymyositis) and
frequently also in the skin (dermatomyositis), leading to symmetric weakness and some degree of muscle atrophy, principally
of the limb girdles.

USMLE Case Scenario


A 32-year-old woman with a past history of ulcerative colitis (quiescent for the last 7 years), presented with a dry cough.
Increasing dyspnea, myalgia and arthralgia. A clinical diagnosis of fibrosing alveolitis was made and confirmed by
transbronchial biopsy. She had a severe proximal myopathy. Serum creatine kinase was found to be very high and a muscle
biopsy showed necrosis and a cellular infiltrate. She had a circulating autoantibody to Jo1 antigen
Ans. Diagnosis is: Polymyositis

Pathology

367

Reiters Syndrome (RS)


Arthritis associated with nonbacterial urethritis or cervicitis, conjunctivitis and mucocutaneous lesions
RS is classified with the seronegative spondyloarthropathies
Joint involvement generally is asymmetric and polyarticular, occurring in the large joints of the lower extremities as well as the
toes. Back pain may occur, usually with more severe disease
Enthesopathy (inflammation at tendinous insertion into bone) is common in RS and other seronegative arthritides, e.g. plantar
fasciitis, digital periostitis, Achilles tendinitis
Mucocutaneous lesionssmall, painless superficial ulcersare commonly seen on the oral mucosa, tongue, and glans penis
(balanitis circinata)
Patients may also develop hyperkeratotic skin lesions of the palms and soles and around the nails (keratoderma blennorrhagica)
Cardiovascular involvement with aortitis, aortic insufficiency and conduction defects occurs rarely.

Temporal Arteritis
(Giant Cell Arteritis; Cranial Arteritis)
A chronic inflammatory disease of large blood vessels, particularly those with a prominent elastica, occurring primarily in the elderly
Giant cell arteritis most often involves arteries of the carotid system, particularly the cranial arteries
Segments of the aorta, its branches, the coronary arteries, and the peripheral arteries may also be affected
The disease has a predilection for arteries containing elastic tissue; it is rarely seen in veins
The histologic reaction is a granulomatous inflammation of the intima and inner part of the media
Presentations are diverse, depending on the distribution of the arteritis, but typically include:
Severe headache (especially temporal and occipital)
Scalp tenderness
Visual disturbances (amaurosis fugax, diplopia, scotomata, ptosis and vision blurring)
Claudication of the masseter, temporalis and tongue muscles are characteristic
Blindness due to ischemic optic neuropathy probably occurs in < = 20% of patients but is infrequent after high dose corticosteroid
treatment. On physical examination, there maybe swelling and tenderness with nodularity over the temporal arteries and bruits
over the large vessels
ESR is usually markedly elevated (often > 100 mm/h, Westergren) during the active phase, but is normal in about 1% of patients
Normochromic and normocytic anemia is often present and, at times, profound. Alkaline phosphatase maybe elevated. Other
nonspecific findings include polyclonal hyperglobulinemia and leukocytosis.

High Yield USMLE


Wegners granulomatosis: necrotizing lesions in upper respiratory tract and kidney
Henon scholein purpura: IgA deposits with vasculitis
Churg strauss syndrome: asthma plus blood eosinophilia
Kawasakis disease: in children
Takayasus arteritis: in young patients
Giant cell arteritis: in older patients

USMLE Case Scenario


Giant cell arteritis involves the cranial arteries (branches of the carotid system). Biopsying 2 cm lengths of each temporal
artery are indicated because the process can be patchy. Biopsy can reveal.
1. Granulomatous inflammation
2. Fibrinoid necrosis
3. Hyperplastic necrosis
4. Leukocytoclastic vasculitis
Ans. 1. Granulomatous inflammation

368

USMLE Step 1 Platinum Notes

USMLE Case Scenario


A 48-year-old male from Ohio presents with sinus pain and drainage, bloody nasal discharge and nasal mucosal ulceration.
On laboratory examination, the man is found to have hematuria, and red blood cell casts. A biopsy of the upper airway tissue
reveals granulomatous inflammation with necrosis. Blood tests show the presence of antineutrophil cytoplasmic antibodies
(c-ANCA). Most likely diagnosis is:
1. Goodpastures syndrome
2. Noninfectious granulomatous disease
3. Wegeners granulomatosis
4. Bergers Disease
Ans. 3. Wegeners granulomatosis

Atherosclerosis
Complicated lesions indicate advanced atherosclerotic disease. They arise in atherosclerotic plaques, and render them more
susceptible to sudden occlusion and acute infarction of the supplied tissues. Commonly, the plaque ulcerates or ruptures, and
the exposed surfaces, being highly thrombogenic, precipitate thrombus formation
Thrombi are typified by the lines of Zahn, alternating layers of platelets and fibrin (the pale lines) and layers of blood (the dark lines).
Beyond thrombus formation, other features of a complicated plaque include hemorrhage into the lesion itself, and microembolism
by cholesterol crystals or calcified debris. Furthermore, the weakened media underlying the plaque may develop an aneurysmal
dilatation. In general, the clinical significance of atherosclerosis is related to the consequences of complicated lesions.

Aneurysms
Pseudoaneurysm also known as false aneurysm is usually as a result of trauma to all the three layers of the artery resulting in hematoma
This hematoma must communicate with artery to be considered as a pseudoaneurysm
Pseudoaneurysm differs from true aneurysm in that it does not contain any vessel wall
Penetrating trauma is the most common cause of pseudoaneurysm.

Other Causes are


Marfans syndrome
Fibromuscular Dysplasia
Vasculitis

Pulsatile mass is the most common manifestation. Locations of Pseudoaneurysms


Femoral artery
Left Ventricular Pseudoaneurysm
Abdominal Aorta Pseudoaneurysm
Carotid Pseudoaneurysm

Important Points about Aneurysms

The most common type of true aneurysm is fusiform type


The most common site of arterial aneurysm is Infrarenal part of Abdominal Aorta
Popliteal Aneurysms are the most common Peripheral aneurysms
The most common site for dissecting aneurysms is Ascending Aorta
Cirsoid aneurysms are common in superficial temporal artery
Atherosclerosis is the mc cause of Abdominal aneurysms
Atherosclerosis is the mc cause of any aneurysm.

Pathology

369

Types of aneurysms:
Berry aneurysm: occurs in circle of willis
Microaneurysms: seen in Diabetes and Hypertension
Mycotic aneurysms: are seen in bacterial infections
Aortic dissecting Aneurysms: Due to degeneration of tunica media
Occur in Marfans Syndrome and Hypertension
Syphilitic aneurysms or Luetic aneurysms: involve ascending Aorta
Tree bark calcification is seen in syphilis.

Developmental or Berry, Aneurysms


Occur in cerebral vessels. These are small, spherical dilatations typically in the circle of Willis; when ruptured, they can causes fatal
intracerebral hemorrhage.
Arteriovenous fistulas
Are abnormal, typically small, direct connections between arteries and veins that bypass the intervening capillaries. They occur most
commonly as developmental defects but can also result from rupture of an arterial aneurysm into the adjacent vein, from penetrating
injuries that pierce arteries and veins or from inflammatory necrosis of adjacent vessels; intentionally created arteriovenous fistulas are
used to provide vascular access for chronic hemodialysis. When arteriovenous fistulas are large or extensive, they can become clinically
significant by shunting blood from the arterial to the venous circulations. This forces the heart to pump additional volume, and highoutput cardiac failure can ensue.
Fibromuscular dysplasia
It is a focal irregular thickening of the walls of medium and large muscular arteries, including renal, carotid, splanchnic and vertebral
vessels. The cause is developmental. Segments of the vessel wall are focally thickened by some combination of irregular medial and
intimal hyperplasia and fibrosis; this results in luminal stenosis and in the renal arteries maybe a cause of renovascular hypertension.

Aortic Dissection
In the vast majority of spontaneous dissections, the intimal tear marking the point of origin of the dissection is found in the
ascending aorta, usually within 10 cm of the aortic valve
The dissection can extend along the aorta retrograde toward the heart as well as distally, sometimes all the way into the
iliac and femoral arteries. The dissecting hematoma spreads characteristically along the laminar planes of the aorta, usually
approximately between the middle and outer thirds
It often ruptures out through the adventitia, causing massive hemorrhage. In some instances, the dissecting hematoma reenters
the lumen of the aorta, producing a second distal intimal tear and a new vascular channel within the media of the aortic wall (and
resulting in a double-barreled aorta with a false channel). This averts a fatal extra-aortic hemorrhage. In the course of time,
false channels may become endothelialized and can be recognized as chronic dissections.

Abnormal structural proteins produce inborn errors such as

Marfan syndrome (fibrillin)


Osteogenesis imperfecta (collagen type I)
Spondyloepiphyseal dysplasia (collagen type II), and
Sack syndrome (collagen type III)

Marfan Syndrome: (USMLE Favorite)


It is characterized by skeletal, ocular and cardiovascular abnormalities. Typically, Marfan patients are tall with very long legs and
tapering fingers. Laxity of joints is present, so that the thumb can be extended back to the wrist. Chest and spinal column deformities
maybe present as well. The most frequent cardiovascular anomalies are incompetence of the aortic valve, aortic dissection and mitral
valve prolapse (floppy valve). The latter may give rise to mitral regurgitation with the typical auscultatory phenomenon of a systolic
click followed by a murmur. The most characteristic ocular change is ectopia lentis, i.e. dislocation of the lens. Most deaths are due to
rupture of aortic dissections. The gene mutated in Marfan syndrome encodes fibrillin, a 350-kD protein that serves as scaffolding for
the deposition of elastin and formation of elastic fibers.

370

USMLE Step 1 Platinum Notes

USMLE Case Scenario


It is seen that vasa vasorum of the aorta undergoes obliterative endarteritis, leading to atrophy of the muscularis and elastic
tissues of the aorta and dilatation. Linear calcifications are often seen in the ascending aorta by X-ray. The intimal wrinkling is
seen. The disease most likely represents:
1. Marfans syndrome
2. Syphilis infection
3. Aortic dissection
4. Takayasus arteritis
Ans. 2. Syphilis Infection (The intimal wrinkling or tree barking is also a common feature.)

USMLE Case Scenario


A 35-year-old tall male from New Jersey has Marfan syndrome, an autosomal dominant disorder with features of subluxated
lens of the eye, mitral valve prolapsed. The defect lies in:
1. Gene on chromosome 15 encoding fibrillin
2. Gene on chromosome 16 encoding fibrillin
3. Gene on chromosome 17 encoding fibrillin
4. Gene on chromosome 18 encoding fibrillin
Ans. 1. Gene on chromosome 15 encoding fibrillin

Rheumatic Heart Disease

Preceded by streptococcal pharyngitis


Aschoff bodies are a feature
Anitschkow cells/caterpillar cells are seen
Pancarditis
Bread and butter pericarditis
Vegitation along line of closure of valves
Sub endocardial Mc Callums patches present
Mc cause of mitral stenosis
ASLO titers used in diagnosis
Tricuspid valve is least commonly involved
MC cause of MS is rheumatic fever

Mc Callums Patch

Lesions of Mural endocardium


Deposition of Aschoff Bodies occurs here
Site of Thrombus formation

Aschoff Bodies

Present in Perivascular connective tissue


Feature of Rheumatic heart disease

Anitschkow myocytes

Modified cardiac mesenchymal cells with caterpillar nuclei, cytoplasm.

Aschoff cells

Multinucleated giant cells

USMLE Case Scenario


Aschoffs nodules are seen in:
1. Subacute bacterial endocarditis
2. Libman-Sacks endocarditis
3. Rheumatic carditis
4. Nonbacterial Thrombotic endocarditis
Ans. 3. Rheumatic carditis

Pathology

371

Myocarditis
Can be caused by a variety of conditions such as a virus, sarcoidosis and immune diseases (such as systemic lupus, etc.), pregnancy,
and others. The most common cause of myocarditis is infection of the heart muscle by a virus. Coxsackievirus B is the most common
culprit in the United States. Viruses capable of causing myocarditis include.
Coxsackievirus types A and B (especially type B)
Adenovirus (most commonly types 2 and 5)
Cytomegalovirus
Echovirus
Epstein-Barr virus
Hepatitis C virus
Herpes virus
Human immunodeficiency virus
Influenza and parainfluenza
Measles
Mumps, associated with endocardial fibroelastosis (EFE)
Parvovirus B19
Poliomyelitis virus
Rubella
Varicella
HIV infection: About 10 percent of people with HIV develop myocarditis
Bacterial infection: Rarely, myocarditis occurs as a complication of endocarditis, an infection of the heart valves and the lining
inside the hearts chambers caused by bacteria. Some common bacteria responsible for myocarditis include Staphylococcus aureus,
enterococci and Corynebacterium diphtheriae
Chagas disease: This infection, caused by the protozoan Trypanosoma cruzi, is transmitted by an insect bite. In the United States,
myocarditis caused by Chagas disease is most common among travelers or immigrants from Central and South America. In up to
one-third of people with Chagas disease, a form of chronic myocarditis develops many years after the initial infection. This chronic
myocarditis leads to significant destruction of heart muscle with progressive heart failure
Lyme myocarditis: Lyme disease, an infection caused by the tick-borne bacterium Borrelia burgdorferi, causes myocarditis or other
heart problems in about 10 percent of patients
Giant cell myocarditis: This rare form of myocarditis takes its name from large, abnormal giant cells that are found when a piece of
the affected heart muscle is examined under a microscope. Giant-cell myocarditis is most common among patients suffering from
thymoma, systemic lupus erythematosus (SLE or lupus), or thyrotoxicosis
Other agents: Myocarditis also can be caused by:
Alcohol, radiation, chemicals (hydrocarbons and arsenic) and drugs, including doxorubicin Adriamycin, cyclophosphamide
emetine, chloroquine and sulfonamides
Diphtheria causes myocarditis by virtue of it exotoxin. The flabby, stretched out heart muscle is characteristic of diphtheria.
Because of flabby nature of heart muscle; the myocardial pumping activity is significantly reduced as a result if which congestive
heart failure occurs within three weeks of illness.

Myxoma

Myxomas are the most common type of primary cardiac tumor in all age groups
Female predilection
Most myxomas are sporadic
NAME syndrome (nevi, atrial myxoma, myxoid neurofibroma and ephelides)
LAMB syndrome (lentigines, atrial myxoma and blue nevi)
Carney complex

372

USMLE Step 1 Platinum Notes

Pathologically, myxomas are gelatinous structures consisting of myxoma cells imbedded in a stroma rich in glycosaminoglycans
The majority are solitary and located in the atria
Myxomas commonly present with obstructive, embolic, or constitutional signs and symptoms.

USMLE Case Scenario


A 68-year-old woman who is normotensive presents to hercardiac physician after several episodes of syncope. Physical
examination is remarkable for alow-pitched plopping sound during mid-systole. Two-dimensional echocardiography
demonstrates aball-valve type obstruction of the mitral valve. Which of the following would most likely be observed if the
cause of the obstruction were biopsied?
1. Benign glandular tissue
2. Myxomatous degeneration of valves
3. Dense calcification in tricuspid area
4. Densely packed smooth muscle
5. Densely packed striated muscle
6. Malignant glandular tissue
7. Scattered mesenchymal cells in a myxoid background
Ans. 7. Scattered mesenchymal cells in a myxoid background
Atrial myxoma may intermittently obstruct the mitral valve. Histologically, these tumors are composed of scattered
mesenchymal cells in a prominent myxoid background.

Myocardial Infarction

LAD is the mc artery involved


Enzyme elevated in first two hours is CPK MB
Waviness of fibers is the earliest change
Coagulation necrosis and neutrophilic infiltration is seen within 13 days
Granulation tissue is seen within 1 week
Scarring in MI is completed by 3 months
Troponin T is a marker of MI.

Hyaline arteriosclerosis: benign hypertension


Hyperplastic arteriosclerosis: malignant hypertension
MC Primary tumor of heart myxoma
Libman sacks endocarditis is found in SLE
Dresselers syndrome is autoimmune.

Respiratory Pathology

Pores of Kohn are present in Alveoli


Charcoat layden crystals: Feature of asthma
Curschmanns spirals: Feature of asthma
Creola bodies: Feature of asthma
Reid index is used for Chronic bronchitis
Blue bloaters: Chronic bronchitis
Pink puffers: Emphysema.

ARDS
In the acute phase of ARDS the lungs are dark red, firm, airless and heavy
Microscopically, there is capillary congestion, necrosis of alveolar epithelial cells, interstitial and intra-alveolar edema and hemorrhage,
and (particularly with sepsis) caollections of neutrophils in capillaries
The most characteristic finding is the presence of hyaline membranes, particularly lining the distended alveolar ducts
Such membranes consist of fibrin-rich edema fluid admixed with remnants of necrotic epithelial cells.

Pathology

373

Emphysema
Emphysema is defined anatomically as a permanent and destructive enlargement of airspaces distal to the terminal bronchioles
without obvious fibrosis and with loss of normal architecture
1 antitrypsin (1AT) deficency is associated with panacinar emphysema
Smoking is a cause of emphysema.
The diagnosis and classification of emphysema depend largely on the macroscopic appearance of the lung
Panacinar emphysema, when well developed, produces pale, voluminous lungs that often obscure the heart when the anterior chest
wall is removed at autopsy
With advanced disease, adjacent alveoli become confluent creating large airs paces. In addition to alveolar loss, the number of alveolar
capillaries is diminished.

Chronic Bronchitis: (USMLE Favorite)


Grossly, the mucosal lining of the larger airways is usually hyperemic and swollen by edema fluid
It is often covered by a layer of mucinous or mucopurulent secretions
The smaller bronchi and bronchioles may also be filled with similar secretions. Histologically, the diagnostic feature of chronic
bronchitis in the trachea and larger bronchi is enlargement of the mucus-secreting glands The magnitude of the increase in size is
assessed by the ratio of the thickness of the submucosal gland layer to that of the bronchial wall (Reid index; normally 0.4)
Chronic bronchiolitis (small airway disease), characterized by:
Goblet cell metaplasia
Mucus plugging
Inflammation, and
Fibrosis

Asthma
Grossly, the lungs are overdistended because of overinflation, and there maybe small areas of atelectasis. The most striking
macroscopic finding is occlusion of bronchi and bronchioles by thick, tenacious mucus plugs. Histologically, the mucus plugs
contain whorls of shed epithelium (Curschmann spirals)
Numerous eosinophils and Charcot-Leyden crystals (collections of crystalloids made-up of eosinophil proteins) are also present.

Bronchiectasis: (USMLE Favorite)


When tumors or aspiration of foreign bodies lead to bronchiectasis, involvement maybe sharply localized to a single segment of
the lungs
In the full-blown active case, an intense acute and chronic inflammatory exudate within the walls of the bronchi and bronchioles
and the desquamation of lining epithelium cause extensive areas of ulceration. In the usual case, a mixed flora can be cultured from
the involved bronchi, including staphylococci, streptococci, pneumococci, enteric organisms, anaerobic and microaerophilic
bacteria, and (particularly in children) Hemophilus influenzae and Pseudomonas aeruginosa.

Pulmonary Anthracosis
It is coal-induced pulmonary lesion in coal miners, urban dwellers and tobacco smokers. Inhaled carbon pigment is engulfed by
alveolar or interstitial macrophages, which then accumulate in the connective tissue along the lymphatics, including the pleural
lymphatics or in lymph nodes.

Coal Workers Pneumoconiosis (Cwp)


Coal dust is associated with CWP
Much of the symptomatology associated with simple CWP appears to be similar and additive to the effects of cigarette smoking
on the development of chronic bronchitis and obstructive lung disease

374

USMLE Step 1 Platinum Notes

With prolonged exposure, small, rounded, regular opacities, 1 to 5 mm in diameter (nodular pattern). Calcification is generally not
seen
Complicated CWP is manifested by the appearance on the chest radiograph of nodules ranging from 1 cm in diameter to the size
of an entire lobe, generally confined to the upper half of the lungs
Particle size of 15 micrometer is dangerous dor pneumoconiosis.

Caplans Syndrome: (USMLE Favorite)


First described in coal miners but subsequently found in patients with a variety of
Pneumoconioses
Seropositive Rheumatoid arthritis with
Characteristic progressive massive fibrosis

Simple CWP
It is characterized by coal macules and the somewhat larger coal nodule
The coal macule consists of dust-laden macrophages; in addition the nodule contains small amounts of a delicate network of
collagen fibers
Although these lesions are scattered throughout the lung, the upper lobes and upper zones of the lower lobes are more
heavily involved.

Complicated CWP (PMF)


Occurs on a background of simple CWP by coalescence of coal nodules and generally requires many years to develop
It is characterized by intensely blackened scars larger than 2 cm, sometimes up to 10 cm in greatest diameter
They are usually multiple.

Beryllium may produce an acute pneumonitis or, far more commonly, a chronic interstitial pneumonitis. (BERYLLIOSIS)
Radiodense dusts include iron and iron oxides from welding or silver finishing (Siderosis)
Tin oxide used in metallurgy, color stabilization, printing, and the manufacture of porcelain, glass, and fabric (Stannosis)
And barium sulfate used as a catalyst for organic reactions, drilling mud components, and electroplating (Baritosis).

Silicosis: (USMLE Favorite)

Mc occupational disorder
Crystalline form most common cause
Upper lobes involved
Eggshell pattern
Patients with silicosis are at greater risk of acquiring Mycobacterium tuberculosis infections (silicotuberculosis) and atypical
mycobacterial infections.

Silicotic nodules are characterized grossly in their early stages by tiny, barely palpable, discrete, pale-to-blackened nodules in the
upper zones of the lungs
Microscopically, the silicotic nodule demonstrates concentrically arranged hyalinized collagen fibers surrounding an amorphous
center
The whorled appearance of the collagen fibers is quite distinctive for sometimes, thin sheets of calcification occur in the lymph
nodes and are appreciated radiographically as eggshell calcification (e.g. calcium surrounding a zone lacking calcification).

Asbestosis: (USMLE Favorite)


Asbestos is a generic term for several different mineral silicates, including chrysolite, amosite, anthophyllite and crocidolite
Asbestosis is a diffuse interstitial fibrosing disease of the lung
Physiologic studies reveal a restrictive pattern with a decrease in lung volumes

Pathology

375

Lower lobes affected commonly


Asbestos bodies
Ferruginous bodies
Laryngeal and colonic cancers associated
Mesotheliomas, both pleural and peritoneal, are also associated with asbestos exposure
Intense fibrosis is a pathological feature of mesotheliomas.
It is marked by diffuse pulmonary interstitial fibrosis
These changes are indistinguishable from those resulting from other causes of diffuse interstitial fibrosis, except for the presence
of asbestos bodies, which are seen as golden brown, fusiform or beaded rods with a translucent center. They consist of asbestos
fibers coated with an iron-containing proteinaceous material
Asbestosis begins in the lower lobes and subpleurally, but the middle and upper lobes of the lungs become affected as fibrosis
progresses. Pleural plaques are the most common manifestation of asbestos exposure and are well-circumscribed plaques of
dense collagen.

Sarcoidosis: (USMLE Favorite)

Noncaseating granulomas with bilateral hilar lymphadenopathy


Berylium inhalation mimicks sarcoidosis
It is an end stage lung disease
Epitheloid cells with no caseation Seen
Sarcoidosis does not involves brain
Kveim test is used for sarcoidosis
Schaumann bodies (conchlike structures)
Asteroid bodies (stellate-like structures), and
Residual bodies (refractile calcium-containing inclusions)
Two syndromes have been identified in the acute group
Lofgrens syndrome includes the complex of Erythema nodosum and X-ray findings of bilateral hilar adenopathy, often
accompanied by joint symptoms, including arthritis at the ankles, knees, wrists, or elbows
The Heerfordt-Waldenstrom syndrome describes individuals with fever, parotid enlargement, anterior uveitis and facial
nerve palsy.
Feature is the noncaseating epithelioid granuloma
This is a discrete, compact collection of epithelioid cells rimmed by an outer zone of largely CD4 + T-cells. The epithelioid cells are
derived from macrophages and are characterized by abundant eosinophilic cytoplasm and vesicular nuclei. Two other microscopic
features are sometimes seen in the granulomas: (1) Schaumann bodies: laminated concretions composed of calcium and
proteins; and (2) Asteroid bodies: stellate inclusions enclosed within giant cells
Intrathoracic hilar and paratracheal lymph nodes are enlarged 75 to 90% of patients, while a third present with peripheral
lymphadenopathy. The nodes are characteristically painless and have a firm, rubbery texture
Erythema nodosum, the hallmark of acute sarcoidosis, consists of raised, red, tender nodules on the anterior aspects of the legs.
In contrast, discrete painless subcutaneous nodules can also occur in sarcoidosis, and these usually reveal abundant noncaseating
granulomas. Another characteristic skin lesion of sarcoidosis consists of indurated plaques associated with a violaceous discoloration in
the region of the nose, cheeks and lips (lupus pernio)
Involvement of the eye and lacrimal glands occurs in about one-fifth to one-half of patients. The ocular involvement takes the
form of iritis or iridocyclitis and maybe unilateral or bilateral. The posterior uveal tract is also affected with resultant choroiditis,
retinitis and optic nerve involvement. These ocular lesions are frequently accompanied by inflammation in the lacrimal glands,
with suppression of lacrimation (sicca syndrome)
Unilateral or bilateral parotitis with painful enlargement of the parotid glands occurs in less than 10% of the individuals
with sarcoidosis; some go onto develop xerostomia (dry mouth). Combined uveoparotid involvement is designated Mikulicz
syndrome.

376

USMLE Step 1 Platinum Notes

Acute Pneumonias
S pneumoniae (pneumococcus) is the most common cause of community-acquired acute pneumonia, and the distribution of
inflammation is usually lobar
Morphologically, lobar pneumonias evolve through four stages: congestion, red hepatization, gray hepatization and resolution
Other common causes of acute pneumonias in the community include H influenzae and M catarrhalis (both associated with acute
exacerbations of COPD)
S aureus (usually secondary to viral respiratory infections)
K pneumoniae (observed in chronic alcoholics)
P aeruginosa (seen in individuals with cystic fibrosis, in burn patients and in neutropenics) and L pneumophila, seen
particularly in individuals who have undergone organ transplants.

Lung Abscess: (USMLE Favorite)


Abscesses vary in diameter from a few millimeters to large cavities of 5 to 6 cm
The localization and number of abscesses depend on their mode of development
Pulmonary abscesses resulting from aspiration of infective material are much more common on the right side (more
vertical airways) than on the left and most are single
On the right side, they tend to occur in the posterior segment of the upper lobe and in the apical segments of the lower
lobe, because these locations reflect the probable course of aspirated material when the patient is recumbent
Abscesses that develop in the course of pneumonia or bronchiectasis are commonly multiple, basal and diffusely scattered. Septic
emboli and abscesses arising from hematogenous seeding are commonly multiple and may affect any region of the lungs.

Tuberculosis: (USMLE Favorite)


The initial lesion is usually a small focus of consolidation, less than 2 cm in diameter, within 1 to 2 cm of the apical pleura. Localized,
apical, secondary pulmonary tuberculosis may heal with fibrosis either spontaneously or after therapy, or the disease may progress
and extend along several different pathways:
Progressive pulmonary tuberculosis may ensue. The apical lesion enlarges with expansion of the area of caseation. Erosion into a
bronchus evacuates the caseous center, creating a ragged, irregular cavity lined by caseous material that is poorly walled off by fibrous
tissue
Erosion of blood vessels results in hemoptysis. If the treatment is inadequate, or if host defenses are impaired, the infection may
spread by direct expansion, via dissemination through airways, lymphatic channels, or the vascular system.
Miliary pulmonary disease occurs when organisms drain through lymphatics into the lymphatic ducts, which empty into the
venous return to the right side of the heart and thence into the pulmonary arteries
Miliary lesions may expand and coalesce to yield almost total consolidation of large regions or even whole lobes of the lung. With
progressive pulmonary tuberculosis, the pleural cavity is invariably involved and serous pleural effusions, tuberculous empyema,
or obliterative fibrous pleuritis may develop
Endobronchial, endotracheal and laryngeal tuberculosis may develop when infective material is spread either through
lymphatic channels or from expectorated infectious material. The mucosal lining maybe studded with minute granulomatous
lesions, sometimes apparent only on microscopic examination
Systemic miliary tuberculosis ensues when infective foci in the lungs seed the pulmonary venous return to the heart; the
organisms subsequently disseminate through the systemic arterial system. Almost every organ in the body maybe seeded. Lesions
resemble those in the lung. Miliary tuberculosis is most prominent in the liver, bone marrow, spleen, adrenals, meninges, kidneys,
fallopian tubes and epididymis
Isolated-organ tuberculosis may appear in any one of the organs or tissues seeded hematogenously and maybe the
presenting manifestation of tuberculosis. Organs typically involved include the :
Meninges (tuberculous meningitis)
Kidneys (renal tuberculosis)
Adrenals (formerly an important cause of Addison disease)
Bones (osteomyelitis), and
Fallopian tubes (salpingitis)
When the vertebrae are affected, the disease is referred to as Pott disease.

Pathology

377

Paraspinal cold abscesses in persons with this disorder may track along the tissue planes to present as an abdominal or
pelvic mass
Lymphadenitis is the most frequent form of extrapulmonary tuberculosis, usually occurring in the cervical region (scrofula).
In HIV-negative individuals, lymphadenopathy tends to be unifocal, and most individuals do not have evidence of ongoing
extranodal disease
Intestinal tuberculosis is more often a complication of protracted advanced secondary tuberculosis, secondary to the swallowing
of coughed-up infective material. Typically, the organisms are trapped in mucosal lymphoid aggregates of the small and large
bowel, which then undergo inflammatory enlargement with ulceration of the overlying mucosa, particularly in the ileum.

Malignant Mesotheliomas: (USMLE Favorite)


Are often preceded by extensive pleural fibrosis and plaque formation
These tumors begin in a localized area and in the course of time spread widely, either by contiguous growth or by diffusely seeding
the pleural surfaces
The neoplasm may directly invade the thoracic wall or the subpleural lung tissue. Normal mesothelial cells are biphasic, giving rise
to pleural lining cells as well as the underlying fibrous tissue.

USMLE Case Scenario


(PAS)-positive cytoplasmic granules in hepatocytes are seen in:
1. Wilsons disease
2. Hepatitis B
3. Alpha1-antitrypsin deficiency
4. Alcoholic hepatitis
Ans. 3. Alpha1-antitrypsin deficiency

USMLE Case Scenario


A 34-year-old male from Africa in New York Chest clinic as a pathology characterized by noncaseating granulomata in lungs.
The disease was discovered incidentally when chest X-ray reveals bilateral hilar adenopathy. Definitive diagnosis is based
on biopsy, which reveals noncaseating granulomata that are negative for fungi or acid-fast bacilli. The disease most likely is:
1. Cat scratch disease
2. Sarcoidosis
3. Scleroderma
4. Systemic lupus erythematosus
Ans. 2. Sarcoidosis

378

USMLE Step 1 Platinum Notes

USMLE Case Scenario


A 38-year-old man from Washington complained of breathlessness on examination, he had no clubbing and no abnormal
chest signs. A chest X-ray showed fine, diffuse radiological shadows, predominantly in the mid zones, and bilateral hilar
lymphadenopathy. Lung function tests were normal and a Mantoux test was negative. ACE levels and calcium levels are
increased. A clinical diagnosis suggests:
1. Pneumonia
2. Tuberculosis
3. Sarcoidosis
4. Cat scratch disease
5. Coal workers lung
6. Caplans syndrome
Ans. 3. Sarcoidosis

USMLE Case Scenario


A disease occurs with prolonged exposure to dust during glass production which can progress to respiratory failure and death,
and is associated with increased risk for tuberculosis. Classic X-ray findings include calcified lymph nodes that produce an
eggshell pattern. Pleural involvement creates dense fibrous plaques and adhesions that may obliterate the pleural cavities.
Most likely disease is:
1. Byssinosis
2. Berylliosis
3. Silicosis
4. Anthracosis
Ans. 3. Silicosis

USMLE Case Scenario


A 35-year-old occupational worker presents to his primary care physician complaining of dyspnea and chronic dry cough.
Chest X-ray reveals pulmonary hyperinflation with honeycombing and calcified parietal pleural plaques. The most likely
diagnosis is:
1. Anthracosis
2. Asbestosis
3. Histoplasmosis
4. Tuberculosis
5. Berylliosis
6. Byssinosis
7. Silicosis
Ans. 2. Asbestosis

GIT PATHOLOGY
Esophagus
The metaplasia of esophageal squamous epithelium to columnar epithelium (Barretts esophagus) is a complication of severe reflux
esophagitis, and it is a risk factor for esophageal adenocarcinoma
Barretts epithelium progresses through a dysplastic stage before developing into adenocarcinoma
The etiology of squamous cell esophageal cancer is related to
Excess alcohol consumption and/or cigarette smoking
Ingestion of nitrites, smoked opiates and fungal toxins in pickled vegetables, as well as mucosal damage caused by such physical
insults as long-term exposure to extremely hot tea, the ingestion of lye, radiation-induced strictures, and chronic achalasia
The presence of an esophageal web in association with glossitis and iron deficiency (i.e. Plummer-Vinson or Paterson-Kelly
syndrome) and congenital hyperkeratosis and pitting of the palms and soles (i.e. tylosis palmaris et plantaris) have each been
linked with squamous cell esophageal cancer
Dietary deficiencies of molybdenum, zinc and vitamin A
Viral Esophagitis Herpes simplex virus (HSV) type 1 occasionally causes esophagitis in immunocompetent individuals, but
either HSV type 1 or HSV type 2 may afflict patients who are immunosuppressed.

Pathology

379

Herpetic vesicles on the nose and lips may provide a clue to the diagnosis. Barium swallow is inadequate to detect early lesions and
cannot reliably distinguish HSV infection from other types of infections. Endoscopy shows vesicles and small, discrete, punched-out
superficial ulcerations with or without a fibrinous exudate. In later stages, a diffuse erosive esophagitis develops from enlargement
and coalescence of the ulcers. Mucosal cells from a biopsy sample taken at the edge of an ulcer or from a cytologic smear show
ballooning degeneration, ground-glass changes in the nuclei with eosinophilic intranuclear inclusions (Cowdry type A), and giant
cell formation on routine stains
Viruses causing esophagitis:
HSV1
HSV2
Varicella zoster
CMV
HIV
Varicella-zoster virus (VZV) sometimes produces esophagitis in children with chickenpox and adults with herpes zoster.
Esophageal VZV also can be the source of disseminated VZV infection without skin involvement. In an immunocompromised host,
VZV esophagitis causes vesicles and confluent ulcers and usually resolves spontaneously, but it may cause necrotizing esophagitis in
a severely compromised host.
Cytomegalovirus (CMV) infections occur only in immunocompromised patients. CMV is usually activated from a latent stage or
maybe acquired from blood product transfusions
CMV lesions initially appear as serpiginous ulcers in an otherwise normal mucosa
These may coalesce to form giant ulcers, particularly in the distal esophagus.

Barretts Esophagus: (USMLE Favorite)


May occur in a small number of patients who have gastroesophageal reflux disease (GERD). This condition is a metaplasia of
the normal squamous mucosa of the esophagus to a columnar (glandular) type of epithelium, and is usually seen as a response
to repeated acid exposure to the distal esophagus. Tobacco and alcohol use are also thought to contribute to the process. The
significance of Barretts esophagus is that it may lead to the development of low-grade dysplasia, high-grade dysplasia, or esophageal
adenocarcinoma.

H pylori
H pylori colonization induces chronic superficial gastritis, which includes both mononuclear and polymorphonuclear cell
infiltration of the mucosa
Progression to atrophy when H pylori is present
Most H pylori-colonized persons do not develop clinical sequelae
The two major disease-associated H pylori virulence factors are a vacuolating cytotoxin, VacA, and a group of genes termed the
cag pathogenicity island (cag PaI)
H pylori colonization diminishes the number of somatostatin-producing cells; somatostatin-mediated inhibition of gastrin release
leads to hypergastrinemia.

380

USMLE Step 1 Platinum Notes

Gastric Carcinoma
Gastric carcinoma is classified on the basis of depth of invasion, macroscopic growth pattern and histologic subtype. The
morphologic feature having the greatest impact on clinical outcome is the depth of invasion
Early gastric carcinoma is defined as a lesion confined to the mucosa and submucosa, regardless of the presence or absence
of perigastric lymph node metastases
Advanced gastric carcinoma is a neoplasm that has extended below the submucosa into the muscular wall and has perhaps
spread more widely. Gastric mucosal dysplasia is the presumed precursor lesion of early gastric cancer, which then in turn
progresses to advanced lesio