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USMLE

®

STEP 1
Lecture Notes
2016

Anatomy


USMLE® is a joint program of the Federation of State Medical Boards (FSMB) and the National Board of
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© 2016 by Kaplan, Inc.
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Editors
James White, Ph.D.
Assistant Professor of Cell Biology
School of Osteopathic Medicine
Rowan University
Stratford, NJ
Adjunct Assistant Professor of Cell and Developmental Biology
University of Pennsylvania School of Medicine
Philadelphia, PA

David Seiden, Ph.D.
Professor of Neuroscience and Cell Biology
Rutgers-Robert Wood Johnson Medical School
Piscataway, NJ



Contents

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii

Section I: Early Embryology and Histology: Epithelia



Chapter 1: Gonad Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3



Chapter 2: Week 1: Beginning of Development . . . . . . . . . . . . . . . . . . 9



Chapter 3: Week 2: Formation of the Bilaminar Embryo . . . . . . . . . . 13



Chapter 4: Embryonic Period (Weeks 3–8) . . . . . . . . . . . . . . . . . . . . . 15



Chapter 5: Histology: Epithelia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Section II: Gross Anatomy


Chapter 1: Back and Autonomic Nervous System . . . . . . . . . . . . . . . 33



Chapter 2: Thorax . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47



Chapter 3: Abdomen, Pelvis, and Perineum . . . . . . . . . . . . . . . . . . . 101




Chapter 4: Upper Limb . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201



Chapter 5: Lower Limb . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217



Chapter 6: Head and Neck . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231

Section III: Neuroscience


Chapter 1: Nervous System Organization and Development . . . . . . . 251



Chapter 2: Histology of the Nervous System . . . . . . . . . . . . . . . . . . 261



Chapter 3: Ventricular System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273



Chapter 4: The Spinal Cord . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279




Chapter 5: The Brain Stem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
v




Chapter 6: The Cerebellum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345



Chapter 7: Basal Ganglia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353



Chapter 8: Visual Pathways . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361



Chapter 9: Diencephalon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371



Chapter 10: Cerebral Cortex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379



Chapter 11: Limbic System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399


Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 405

vi


Preface

These volumes of Lecture Notes represent the most-likely-to-be-tested material
on the current USMLE Step 1 exam.
We want to hear what you think. What do you like about the Notes? What could be
improved? Please share your feedback by e-mailing us at
Best of luck on your Step 1 exam!
Kaplan Medical

vii



SECTION

I

Early Embryology
and Histology:
Epithelia



Gonad Development


1

Learning Objectives
❏❏ Explain information related to indifferent gonad
❏❏ Interpret scenarios on testis and ovary
❏❏ Answer questions about meiosis
❏❏ Interpret scenarios on spermatogenesis
❏❏ Solve problems concerning oogenesis

INDIFFERENT GONAD
Although sex is determined at fertilization, the gonads initially go through an
indifferent stage between weeks 4 and 7 when there are no specific ovarian or
testicular characteristics.
The indifferent gonads develop in a longitudinal elevation or ridge of intermediate mesoderm called the urogenital ridge.

Primordial Germ Cells
Primordial germ cells arise from the lining cells in the wall of the yolk sac.
At week 4, primordial germ cells migrate into the indifferent gonad.

Components of the Indifferent Gonad
l

l

l

Primordial germ cells migrate into the gonad from the yolk sac and
provide a critical inductive influence on gonad development.
Primary sex cords are fingerlike extensions of the surface epithelium
that grow into the gonad that are populated by the migrating primordial

germ cells.
Mesonephric (Wolffian) and the paramesonephric (Mullerian) ducts
of the indifferent gonad contribute to the male and female genital tracts,
respectively.

3


Section I

l

Early Embryology and Histology: Epithelia

Yolk sac

Primordial
germ cells
Primordial
germ cells
Urogenital ridge

Yolk sac

Mesonephric
Urogenital
ridgeduct (Wolffian)

MIF: Müllerian-inhibiting factor


Paramesonephric
duct
Mesonephric
duct (Wolffian)
(Müllerian)
Paramesonephric duct
Indifferent gonad
(Müllerian)

TDF: testis-determining factor
MIF: Müllerian-inhibiting factor
TDF: testis-determining factor

Indifferent gonad
TDF
No factors
Testosterone
MIF
TDF
No factors
Testosterone
Testis
Ovary
MIF
and male
and female
genital
genital
Testissystem
Ovarysystem

and male
and female
genital system
genital system
Figure I-1-1. Development of Testis and Ovary
Figure I-1-1. Development of Testis and Ovary

TESTIS AND OVARY
The indifferent gonad will develop into either the testis or ovary (Figure I-1-1).

Testis
Development of the testis and male reproductive system is directed by:
l

The Sry gene on the short arm of the Y chromosome, which encodes
for testis-determining factor (TDF)

l

Testosterone, which is secreted by the Leydig cells

l

Müllerian-inhibiting factor (MIF), which is secreted by the Sertoli cells

l

Dihydrotestosterone (DHT): external genitalia

Ovary

Development of the female reproductive system requires estrogen.

4


Chapter 1

l

Gonad Development

MEIOSIS
Meiosis occurs within the testis and ovary. This is a specialized process of cell
division that produces the male gamete (spermatogenesis) and female gamete
(oogenesis). There are notable differences between spermatogenesis and oogenesis, discussed below.
Meiosis consists of 2 cell divisions, meiosis I and meiosis II (Figure I-1-2).

Meiosis I
In meiosis I, the following events occur:
l

Synapsis—the pairing of 46 homologous chromosomes

l

Crossing over—the exchange of segments of DNA

l

D

 isjunction—the separation of 46 homologous chromosome pairs
(no centromere-splitting) into 2 daughter cells, each containing
23 chromosome pairs

Meiosis II
In meiosis II:
l

Synapsis does not occur.

l

Crossing over does not occur.

l

Disjunction occurs with centromere-splitting.

5


Section I

l

Early Embryology and Histology: Epithelia

Type B
Spermatogonia
Oogonia


(46, 2n) (Diploid)

Meiosis I
Primary
spermatocyte

DNA replication
(46, 4n)

Primary
oocyte

Synapsis

Crossover

Cell division
Alignment and disjunction
Centromeres do not split
Secondary
spermatocyte

(23, 2n)

Secondary
oocyte
Meiosis II
Cell division
Alignment and

disjunction
Centromeres split

Gamete

(23, 1n)
(Haploid)
Figure I-1-2. Meiosis

6


Chapter 1

l

Gonad Development

SPERMATOGENESIS
l

l

Primordial germ cells arrive in the indifferent gonad at week 4 and
remain dormant until puberty.
When a boy reaches puberty, primordial germ cells differentiate into
type A spermatogonia, which serve as stem cells throughout adult life.

l


Some type A spermatogonia differentiate into type B spermatogonia.

l

Type B spermatogonia enter meiosis I to form primary spermatocytes.

l

Primary spermatocytes form 2 secondary spermatocytes.

l

Secondary spermatocytes enter meiosis II to form 2 spermatids.

l

Spermatids undergo spermiogenesis, which is a series of morphological
changes resulting in the mature spermatozoa.

OOGENESIS
l

l

l
l

l

l


Primordial germ cells arrive in the indifferent gonad at week 4 and differentiate into oogonia.
Oogonia enter meiosis I to form primary oocytes. All primary oocytes
are formed by month 5 of fetal life and are arrested the first time in
prophase (diplotene) of meiosis I and remain arrested until puberty.
Primary oocyte arrested in meiosis I are present at birth.
When a girl reaches puberty, during each monthly cycle a primary
oocyte becomes unarrested and completes meiosis I to form a secondary
oocyte and polar body.
The secondary oocyte becomes arrested the second time in metaphase
of meiosis II and is ovulated.
At fertilization within the uterine tube, the secondary oocyte completes
meiosis II to form a mature oocyte and polar body.

7


Section I

l

Early Embryology and Histology: Epithelia

Chapter Summary
lThe

indifferent gonad begins development in a column of intermediate
mesoderm called the urogenital ridge during week 4. Primordial germ cells
arise in the wall of the yolk sac and migrate to the indifferent gonad.




–In the male, a testis develops from the indifferent gonad due to the
presence of testis-determining factor (TDF), which is produced on the
short arm of the Y chromosome. Testosterone secreted by the Leydig cells
and Müllerian-inhibiting factor (MIF) secreted by the Sertoli cells also
contribute to the development of the genital system.


– In the female, an ovary develops in the absence of any factors.

lMeiosis

is a specialized type of cell division that produces the male and
female gametes during spermatogenesis and oogenesis, respectively.
Meiosis consists of 2 cell divisions: meiosis I and meiosis II.



–In meiosis I, the events include synapsis, exchange of DNA, and
disjunction, resulting in a reduction from 46 to 23 chromosomes.



– In meiosis II, there is a reduction of DNA from 2n to 1n.

lOogenesis

begins in the female during the early weeks of development, and
by month 5 of fetal life all of the primary oocytes are formed and become

arrested in prophase of meiosis I until puberty. After puberty, during each
monthly menstrual cycle, a secondary oocyte develops in the Graafian follicle
and is then arrested a second time in metaphase of meiosis II, which is then
ovulated. Meiosis II is completed only if there is fertilization.

lIn

the male, spermatogenesis begins after puberty in the seminiferous tubules
and moves through meiosis I and II without any arrested phases to produce
spermatids. Spermatids undergo spermiogenesis to develop into the adult
spermatozoa.

8


Week 1: Beginning of Development

2

Learning Objectives
❏❏ Solve problems concerning beginning of development

BEGINNING OF DEVELOPMENT
sis
mito
:
e
g
va
ea

l
C
Day 2
2-cell Blastula

Day 3

Embryoblast (forms embryo)

4-cell Blastula
Day 4
Morula

Trophoblast (forms placenta)
Day 5

(46, 2N) Zygote

Blastocyst

Day 1
Day 6 (Implantation
begins)

Fertilization

Ovary
Zona
pellucida


Corona
radiata cells

Ampulla
of oviduct

Secondary oocyte arrested
in metaphase of meiosis II

Cytotrophoblast
Blastocyst cavity
Embryoblast
Syncytiotrophoblast

Figure I-2-1. Week 1

Fertilization occurs in the ampulla of the uterine tube when the male and female pronuclei fuse to form a zygote. At fertilization, the secondary oocyte rapidly completes meiosis II.
Prior to fertilization, spermatozoa undergo 2 changes in the female genital tract:
1.Capacitation: Occurs over about 7 hours in the female reproductive tract
and consists of the removal of several proteins from the plasma membrane
of the acrosome of the spermatozoa.

9


Section I

l

Early Embryology and Histology: Epithelia


2.Acrosome Reaction: Release of hydrolytic enzymes from the acrosome
used by the sperm to penetrate the zona pellucida. This results in a cortical
reaction that prevents other spermatozoa penetrating the zona pellucida
thus preventing polyspermy.
During the first 4 to 5 days of the first week, the zygote undergoes rapid mitotic
division (cleavage) in the oviduct to form a blastula, consisting of increasingly
smaller blastomeres. This becomes the morula (32-cell stage).
A blastocyst forms as fluid develops in the morula. The blastocyst consists of an
inner cell mass known as the embryoblast, and the outer cell mass known as the
trophoblast, which becomes the placenta.
At the end of the first week, the trophoblast differentiates into the cytotrophoblast and syncytiotrophoblast and then implantation begins (see below).

Clinical Correlate
Ectopic Pregnancy
Tubal
most common form of ectopic pregnancy; usually occurs when the
blastocyst implants within the ampulla of the uterine tube because of
delayed transport

lThe

l
Risk

factors: endometriosis, pelvic inflammatory disease (PID), tubular
pelvic surgery, or exposure to diethylstilbestrol (DES)

l
Clinical signs:


abnormal or brisk uterine bleeding, sudden onset of
abdominal pain that may be confused with appendicitis, missed menstrual
period (e.g., LMP 60 days ago), positive human chorionic gonadotropin
(hCG) test, culdocentesis showing intraperitoneal blood, positive sonogram

Abdominal
l

Most commonly occurs in the rectouterine pouch (pouch of Douglas)

Implantation
The zona pellucida must degenerate for implantation to occur.
The blastocyst usually implants within the posterior wall of the uterus.
The embryonic pole of blastocyst implants first.
The blastocyst implants within the functional layer of the endometrium during
the progestational phase of the menstrual cycle.

10


Chapter 9

l

Urinary System

Chapter Summary
lFertilization


occurs in the ampulla of the uterine tube with the fusion of the
male and female pronuclei to form a zygote. During the first 4–5 days of
the first week, the zygote undergoes rapid mitotic division (cleavage) in the
oviduct to form a morula before entering the cavity of the uterus.

lA

blastocyst forms as fluid develops in the morula, resulting in a blastocyst
that consists of an inner cell mass known as the embryoblast (becomes the
embryo) and the outer cell mass known as the trophoblast (becomes the
placenta). At the end of the first week, the trophoblast differentiates into the
cytotrophoblast and syncytiotrophoblast and then implantation begins.

11



Week 2:
Formation of the Bilaminar Embryo

3

Learning Objectives
❏❏ Demonstrate understanding of the formation of the bilaminar embryo

Hypoblast
Epiblast

Bilaminar disk
Endometrial

blood vessel
Lacuna spaces
Endometrial
gland
Syncytiotrophoblast
• Implantation
• hCG

Prechordal
plate
Chorionic
cavity
Yolk sac

Connecting
stalk

Amniotic cavity

Primary villi
Chorion
Extraembryonic mesoderm
Cytotrophoblast
Figure I-3-1. Week 2

l

l

l


The embryoblast differentiates into the epiblast and hypoblast, forming
a bilaminar embryonic disk.
The epiblast forms the amniotic cavity and hypoblast cells migrate to form
the primary yolk sac.
The prechordal plate, formed from fusion of epiblast and hypoblast
cells, is the site of the future mouth.

13


Section I

l

Early Embryology and Histology: Epithelia

Extraembryonic mesoderm is derived from the epiblast. Extraembryonic somatic
mesoderm lines the cytotrophoblast, forms the connecting stalk, and covers the amnion. Extraembryonic visceral mesoderm covers the yolk sac.
The connecting stalk suspends the conceptus within the chorionic cavity. The wall
of the chorionic cavity is called the chorion, consisting of extraembryonic somatic
mesoderm, the cytotrophoblast, and the syncytiotrophoblast.
The syncytiotrophoblast continues its growth into the endometrium to make contact with endometrial blood vessels and glands. No mitosis occurs in the syncytiotrophoblast. The cytotrophoblast is mitotically active.
Hematopoiesis occurs initially in the mesoderm surrounding the yolk sac (up to
6 weeks) and later in the fetal liver, spleen, thymus (6 weeks to third trimester),
and bone marrow.

Clinical Correlate
Human chorionic gonadotropin (hCG) is a glycoprotein produced by the
syncytiotrophoblast. It stimulates progesterone production by the corpus

luteum. hCG can be assayed in maternal blood or urine and is the basis for early
pregnancy testing. hCG is detectable throughout pregnancy.
l

Low hCG levels may predict a spontaneous abortion or ectopic pregnancy.

l High

hCG levels may predict a multiple pregnancy, hydatidiform mole, or
gestational trophoblastic disease.

Chapter Summary
lIn

the second week, implantation is completed with the rapid growth and
erosion of the syncytiotrophoblast into the endometrium of the uterus where
early utero-placental circulation is established. The inner cell mass of the
first week differentiates into the epiblast and hypoblast cells and forms a
bilaminar embryonic disk. An amniotic cavity develops from the epiblast and
the primary yolk sac replaces the blastocyst cavity.

l

14

The extraembryonic mesoderm and chorion are formed in the second week.


Embryonic Period (Weeks 3–8)


4

Learning Objectives
❏❏ Solve problems concerning embryonic period

Dorsal View
Cranial
Prechordal plate
Primitive node
Primitive pit

B

Primitive streak
Cloacal membrane
Caudal

A

Sectional View
Cranial

Primitive node & streak
Epiblast
(ectoderm)
Amnion
Notochord
Yolk sac

Mesoderm

B

Hypoblast
Endoderm

Figure I-4-1. Week 3

15


Section I

l

Early Embryology and Histology: Epithelia
l

l
l

l

l

Gastrulation ⎯process that produces the 3 primary germ layers: ectoderm, mesoderm, and endoderm; begins with the formation of the
primitive streak within the epiblast
Ectoderm forms neuroectoderm and neural crest cells.
Mesoderm forms paraxial mesoderm (35 pairs of somites), intermediate mesoderm, and lateral mesoderm.
All major organ systems begin to develop during the embryonic period
(weeks 3–8). By the end of this period, the embryo begins to look human.

Third week: Gastrulation and early development of nervous and cardiovascular systems; corresponds to first missed period.

Clinical Correlate
Sacrococcygeal teratoma: a tumor that arises from remnants of the primitive
streak; often contains various types of tissue (bone, nerve, hair, etc)
Chordoma: a tumor that arises from remnants of the notochord, found either
intracranially or in the sacral region
Hydatidiform mole: results from the partial or complete replacement of the
trophoblast by dilated villi
a complete mole, there is no embryo; a haploid sperm fertilizes a blighted
ovum and reduplicates so that the karyotype is 46,XX, with all chromosomes
of paternal origin. In a partial mole, there is a haploid set of maternal
chromosomes and usually 2 sets of paternal chromosomes so that the typical
karyotype is 69,XXY.

lIn

l
Molar

pregnancies have high levels of hCG, and 20% develop into a
malignant trophoblastic disease, including choriocarcinoma.

16


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