Está en la página 1de 84

EMBRYOLOGY

Jahnavi Patel MD 1

Table of Contents

Chapter 1: Introduction.........1 9

Chapter 2: Chromosomal Anomalies. . 10 14

Chapter 3: Spermatogenesis...15 20

Chapter 4: Oogenesis...21 25

Chapter 5: Female Reproductive Cycle....26 28

Chapter 6: Formation of Germ Layers.....29 39

Chapter 7: Connecting Stalk & Placenta.....40 45

Chapter 8: Skeletal System..... 47 60

Chapter 9: Skin & Its Appendages..... 61 64

Chapter 10: The Pharyngeal Arches65 71

Chapter 11: Fetal Circulation..72 73

Chapter 12: Cardiovascular System

Chapter 13: Urogenital System

Chapter 14: Nervous System

Chapter 15: Digestive System

Chapter 16: Development of the Face

Chapter 17: Respiratory System

Chapter 18: Development of Eye and Ear


Chapter 1 Introduction

What is Embryology?

- Study of the formation and development of the embryo (fetus) from the moment of inception up to
the time when it is born as an infant
- Every individual spends first 9 months (266 days or 38 weeks) within the womb (uterus) of its mother
o During first two months its called an embryo
One cell billions of cells
Recognizable as a human
o From third month until birth its called a fetus

Overview of Gametogenesis

- Gametes: Cells that carry out special function of reproduction


o Male gamete (sperm/ spermatozoon) + Female gamete (ovum/oocyte) = Zygote
o Fertilization: The process of the fusion of male and female gametes
- Spermatozoa
o Produced in the male gonads Testes
o Formation of spermatozoa = spermatogenesis
- Ova
o Produced in the female gonads Ovaries
o Formation of ova = oogenesis

Chromosomes

- A very long DNA molecule and associated proteins, that carry portions of hereditary information of an
organism

Haploid & Diploid Chromosomes

- Number of chromosomes in each cell is fixed for a given species


o Human = 46 chromosomes (diploid) 2n
- Spermatozoa and ova have 23 chromosomes (haploid) 1n

Spermatozoa (23 Chromosomes) + Ova (23 Chromosomes) = Zygote (46 Chromosomes)

Autosomes & Sex Chromosomes

- 46 Chromosomes = 44 Autosomes + 2 Sex Chromosomes (X or Y) Homologous


o Women= 44 Autosomes + XX alleles at a
o Male = 44 Autosomes + XY specific locus
- 46 chromosomes are in pairs
o 22 pairs of exactly alike homologous chromosomes
o One comes from father, one from mother

3p 3m 1
Chapter 1 Introduction

Chromosomes Continued

Chromosome Structure

- Chromosomes are not visible when in rest due to their chromatin material being highly
dispersed
- However, during cell division the chromatin network in the nucleus becomes condensed into a
number of chromosomes

- Two rod shaped structures called chromatids


- A chromosomal DNA molecule contains specific nucleotide
sequences which are required for starting replication
(replication origin)
- Chromatids joined by centromere or kinetochore
o To attach the DNA to the mitotic spindle
- Telomere located at each end of the linear chromosome
- Each chromatid has 2 arms, one on either side of
centromere
- Chromosomes differ from one another in length and other
characteristics
o Allows to identify an individual chromosome
- Karyotyping
o Classification of chromosomes
o Allows to identify abnormalities in Chromosome
number and individual chromosomes
- The DNA molecule is highly condensed o
- The human DNA helix occupy too much space in the cell, so small proteins are responsible for packing
DNA into unites called nucleosomes
- Single & Double Structured Chromosomes
o Other names:
Single structured chromosome/ Unduplicated chromosome/ Chromosome with one
chromatid
Double structured chromosome/ Duplicated chromosome/ Chromosome with two
chromatids
o N Capital N is the notation used for the amount of DNA in a given cell
Not to be confused with n for number of chromosomes
1n = 23 chromosomes (haploid), 2n = 46 chromosomes (diploid)
2N = Pair of single structured chromosomes
4N = Pair of double structured chromosomes

**If youre referring to Dr. Vankateshs notes, n is same as N and N is same as C

2
Chapter 1 Introduction

Chromosomes Continued

Significance of Chromosomes

- Each chromosome has numerous genes


o Genes are made up of nucleic acid called deoxyribonucleic acid (DNA)
o All information is stored in genes
o Genes are involved in synthesis of proteins (enzymes, hormones, antibodies etc)
o Nature and functions of a cell depend on the protein synthesized by it
Cells differ from one another because of the differences in the proteins that constitute
it

Cell Division

- Mitosis
o Process of cell division which results in the production of two daughter cells from a single
parent cell (equal number of chromosomes)
o Daughter cells are identical to one another and to the original parent cell
- Meiosis
o Process that allows one diploid cell to divide in a special way to generate haploid cells in
eukaryotes
o Word meiosis comes from the Greek meioun, meaning to make smaller, since it results in a
reduction in chromosome number
- Interphase
o The period between two successive divisions

3
Chapter 1 Introduction

Interphase

- Gap 1 (G1) Phase


o Characterized by increasing cell size from accelerated manufacture of organelles, proteins and
other cellular matter
- Synthesis (S) Phase
o The genetic material is replicated
- Gap 2 (G2) Phase
o The cell continues to grow (increase in cytoplasmic contents)

- Mitosis: G1 S G2 Prophase Metaphase Anaphase Telophase


- Meiosis: G1 S G2 Meiosis I Interphase II Meiosis II

4
Chapter 1 Introduction

Mitosis

Prophase

- The chromatin diffuse in interphase and condenses into chromosomes


- Each chromosome has duplicated and now consists of two sister chromatids
- At the end of prophase, the nuclear envelope breaks down into vesicles

Metaphase

- The chromosomes align at the equatorial plate


- They are held in place by microtubules attached to the mitotic spindle and to part of the centromere

Anaphase

- The centromeres divide


- Sister chromatids separate and move toward the corresponding poles

Telophase

- Daughter chromosomes arrive at the poles and the microtubules disappear


- The condensed chromatin expands and the nuclear envelope reappears
- Cytokinesis
o The cytoplasm divides, the cell membrane pinches inward ultimately producing two daughter
cells

5
Chapter 1 Introduction

Meiosis I

Prophase I

- The cells genetic material, which is normally in a loosely arranged pile known as chromatin, condenses
into a visible threadlike structures
- Along the thread, centromeres are visible as small beads of tightly coiled chromatin
- 4 Stages of Chromosome in Prophase I
o Leptotene Stage
Individual chromosomes begin to condense into long strands within the nucleus
o Zygotene Stage
Chromosomes approximately line up with each other into homologous chromosomes
The combined homologous chromosomes are said to be bivalent
They are also referred to as a tetrad, a reference to the four sister chromatids
o Pachytene Stage
Heralds crossing over
Non-sister chromosomes of homologous chromosomes randomly exchange segments
of genetic information
o Diplotene Stage
The synaptonemal complex degrades
Homologous chromosomes fall apart and begin to repel each other
The chromosomes themselves uncoil a bit, allowing some transcription of DNA
They are held together by virtue of recombination nodules, betraying the sites of
previous crossing over, the chiasmata
- Diakinesis Stage
o Chromosomes re-condense
o Sites of crossing over entangle together, effectively overlapping, making chiasmata clearly
visible
o In general, every chromosome will have crossed over at least once
o The nucleoli disappears and the nuclear membrane disintegrates into vesicles
- During these stages, centrioles are migrating to the two poles of the cell
o These centrioles, which were duplicated during interphase, fucntion as microtubule
coordinating centers
- Centrioles sprout microtubules, essentially cellular ropes and poles, during crossing over
- They invade the nuclear membrane after it disintegrates, attaching to the chromosomes at the
kinetochore
- The kinetochore functions as functions as a motor, pulling the chromosome along the attached
microtubule toward the originating centriole, like a train on a track
- There are two kinetochores on each tetrad, one for each centrosome
- Prophase I is the longest phase in meiosis
- Microtubules that attach to the kinetochores are known as kinetochore microtubules
- Other microtubules will interact with microtubules from the opposite centriole these are called
nonkinetochore microtubules
6
Chapter 1 Introduction

Meiosis I Continued

Metaphase I

- As kinetochore microtubules from both centrioles attach to their respective kinetochores, the
homologous chromosomes align equidistant above and below an imaginary equatorial plane due to the
continuous counterbalancing forces exerted by the two kinetochores of the bivalent
- Because of independent assortment, the orientation of the bivalent along the plane is random
- Maternal or paternal homologues may point to either pole

Anaphase I

- Kinetochore microtubules shorten, severing the recombination nodules and pulling homologous
chromosomes apart
- Since each chromosomes are pulled toward opposing poles, forming two haploid sets
- Each chromosome still contains a pair of sister chromatids
- Nonkinetochore microtubules lengthen, pushing the centrioles further apart
- The cell elongates in preparation for division down the middle

Telophase I

- The first meiotic division effectively ends when the centromeres arrive at the poles
- Each daughter cell now has half the number of chromosomes but each chromosome consists of a pair
of chromatids
- The microtubules that make up the spindle network disappear and a new nuclear membrane surrounds
each haploid set
- The chromosomes uncoil back into chromatin
- Cytokinesis, the pinching of the cell membrane in animal cells or the formation of the cell wall in plant
cells occurs
- This completes the creation of two daughter cells

Interphase II

- Another name is interkinesis, this is a resting period for cells


- There is no DNA replication during this stage

7
Chapter 1 Introduction

Meiosis II

Prophase II

- There is a disappearance of the nucleoli and the nuclear envelope


- Chromatids shorten and thicken
- Centrioles move to the polar regions and are arranged by spindle fibers

Metaphase II

- Centromeres contain two kinetochores, organizing fibers from the centrosomes on each side

Anaphase II

- Centromeres are cleaved, allowing kinetochores to pull the sister chromatids apart
- The sister chromatids by convention are now called sister chromosomes and are pulled toward
opposing poles

Telophase II

- Marked by uncoiling, lengthening and disappearance of the chromosomes occur as the disappearance
of the microtubules
- Nuclear envelopes reform
- Cleavage or cell wall formation eventually produces a total of four daughter cells
o Each with a haploid set of chromosomes

8
9
Chapter 2 Chromosomal Anomalies
Introduction

- There are two types of chromosomal anomalies


o Structural
o Numerical
- Late pregnancies (age 35 and over) lead to anomalies
o Ova or oocyte is present in the ovaries for a long period of time (since IUF)
o They can be exposed to any type of teratogerms (chemical radiation) and can result in
mutation causing damage of the gametes
- Chromosomal anomalies cause spontaneous abortions
- How to diagnose an anomaly?
o Early Diagnosis
Amniocentesis
After 14 weeks an amniocentesis is performed (taking a sample of amniotic
fluid)
The fluid goes through the FISH analysis (Fluorescence in situ hybridization
Analysis)
The karyotyping determines the anomaly
Risk of amniocentesis
o Can introduce infection into the body if not properly sterilized
Chorionic Villus Sampling
o Late Diagnosis
Ultra sound

Structural Chromosomal Anomalies

- Occurs when there is damage to chromatid but the number of chromosomes is normal
- Types of structural changes
o Deletions (deficiencies)
o Duplications
o Inversions
o Translocations
- How can chromosomes break?
o Ionization radiation
Production of free radicals, which act like little atomic cannon balls blasting through
strands of DNA or chromosomes
o Chemical insult
- How do they rejoin?
o Break points of chromosomes are highly reactive (sticky), whereas normal ends of
chromosomes are capped by telomeres, which do not readily bond to other molecules

10
Chapter 2 Chromosomal Anomalies
Structural Chromosomal Anomalies Continued

- Cri-du-chat Syndrome
o Deletion of the short arm of chromosome number 5 (Deletion of 5p)

o Clinical Features
Mental retardation
Slow motor skill development
LBW (low birth weight) and slow growth
Microcephaly (small head)
Partial webbing of fingers or toes
Hypertelorism (wide-set eyes)
High-ptiched cry

Numerical Chromosomal Anomalies

- Occurs when there are abnormal numbers of chromosomes but structurally its normal
- Types of numerical changes
o Euploidy
true ploidy, meaning two members of each homologous pair
o Aneuploidy
not true ploidy, meaning more or fewer members than two of each homologous pair
Monosomy
One homolog; partner is missing
Trisomy
Three homologs
Nullisomy
One entire homologous pair is missing
- How do chromosomes have abnormal numbers?
o The normal separation of chromosomes in MI or sister chromatids in MII is termed disjunction
o When the separation is not normal nondisjunction
This results in the production of gametes which have either more or less of the usual
amount of genetic material
It can occur in MI, MII, or mitosis

11
Chapter 2 Chromosomal Anomalies
Numerical Chromosomal Anomalies Continued

- Patau Syndrome (Trisomy 13)


o Three homologs of chromosome 13
o 1/20 000 births

o Clinical Features
Severe mental retardation
Heart and organ defects
Polydactyly Extra finger
Death by the age of one year
- Edward Syndrome (Trisomy 18)
o Three homologs of chromosome 18
- Down Syndrome (Trisomy 21)
o Three homologs of chromosome 21, an error in meiosis
It has a recurrence risk of about 1/100
o 1/700 births
o >60% spontaneously aborted
o 20% stillborn

12
Chapter 2 Chromosomal Anomalies
Numerical Chromosomal Anomalies Continued

- Down Syndrome (Trisomy 21)


o Clinical Features
Head & Neck
Brachycephaly, broad face
Up-slanting palpebral fissures
Brushfield spots, Folded or dysplastic ears, open mouth, protruding tongue,
short neck, excessive skin at the nape of neck
Flat nasal bridge
Epicanthal folds
Extremities
Simian crease single palmar crease
Short broad hands, short fifth finger, incurved fifth finger
Space between first and second toe
Hyper flexibility of joints
Mental retardation
Low IQ (<50)
o IQ declines through the first 10 years of age, reaching a plateau in
adolescence that continues into adulthood
Almost all DS babies have MR (mildly to moderately retarded)
Average age of sitting is 11 months, walking is 26 months, first words at 18
months (twice the typical age)
Heart Disease
50% of DS have congenital heart disease
o Atrioventricular septal defect, VSD, Secundum ASD, PDA, Tetrology of
Fallot, Mitral valve prolapse, AR, MR
GI Abnormalities (intestinal blockage)
5% of the cases
o Duodenal atresia or stenosis, sometimes associated with annular
pancreas in 2.5% of cases
o Imperforate anus, esophageal atresia with TE fistula is less common
o Hirschsprungs disease
o Strong association with celiac disease between 5-16%, 5-16 fold
increase as compared to general population
Growth
BW, length and HC are less in DS, reduced growth rate
Prevalence of obesity is greater in DS
Weight is less than expected for length in infants with DS, and then increases
disproportionally so that they are obese by 3-4 years
Alzheimers disease adult with DS has earlier onset of symptoms
When diagnosing, thyroid disease/ depression should be excluded
13
Chapter 2 Chromosomal Anomalies
Numerical Chromosomal Anomalies Continued

- Klinefelter Syndrome (47, XXY)


o Clinical Features
Hypogonadism
Reduced testosterone levels
Testicular atrophy testicles are not developed properly and can result in infertility
Tall stature
Gynaecomastia enlargement of the male breast
Educational difficulties intelligence can be 10 15 points lower than siblings but
usually in normal range
Behavioural problems

- Turner Syndrome (45, X)


o Clinical Features
Possible neonatal features
Lymphedema
Webbed neck
CHD Coarctation of the aorta (narrowing of the aorta)
Renal anomalies
Other features include:
Short stature
Infertility due to streak gonads or premature ovarian failure (if mosaic TS)
Educational or behavioural problems
Wide spaced nipples
Puffy feet
Redundant skin at back of neck

14
Chapter 3 Spermatogenesis

Formation of Male Reproductive System in Embryo

Testes

- XY - Testes
- Testes develops in the posterior lumbar region
- Coelomic epithelium surrounds the testes in the posterior lumbar region
o At this point they are undifferentiating gonads (XY Y has TDF (testes determining factor)
- Coelomic epithelium burrows inside, sets septa into the gonads
o Septa are called sex cords or medullary cords
- These cords become canalized to become seminiferous tubules
o Not all are canalized, some remain as cord-like structures
They are broken down to interstitium
Function: keep seminiferous tubules apart and support them
- Within interstitium there are specialized cells
o Leydig cells
Secrete testosterone
- Within walls of tubules there are specialized cells
o Sertoli cells
They secrete MIF (Mullerian inhibiting factor)
Maintain blood testes barrier

Germ Cells

- Primordial germ cells are formed in the wall of yolk sac


- From the wall of yolk sac, migrate to testes in the posterior lumbar region
o Walls of testes rete testes mitosis meiosis morphological change

15
Chapter 3 Spermatogenesis

Seminal vesicles secrete


fructose nutrition for
sperm

Prostate gland
- phosphoric acid
- citric acid

16
Chapter 3 Spermatogenesis

Spermatogenesis

- Spermatogenesis happens in 64 days


- Initiated: Puberty (11 14 years)
- Terminated: Death
- Spermatocytogenesis PGC Spermatid
- Spermiogenesis Spermatid Spermatozoa

- Sperm comes out of rete testes tail-end first


- Goes to the epididymis
o They take rest and mature
Maturation: More layers on the acrosomal cap are added

17
Chapter 3 Spermatogenesis

18
Chapter 3 Spermatogenesis

Spermiogenesis
1. Elongation of nucleus
2. Golgi apparatus packaging the membrane
bound granules called the acrosomal
vesicles
3. Acrosomal vesciles takes a superior
nucleus position. When this happens, the
centrioles begin to elongate in the
opposite direction (to form the tail)
4. Mitochondria moves down on either sides
of the elongated centrioles
5. Macrophages (sertoli cells) take away the
residual cytoplasm
6. Mature sperm cell spermatozoa

- Main part of the tail is attached to the proximal centriole called axoneme
- Acrosomal Cap
o Contains enzyme acrosin and hyaluronidase
Important in the penetration of the ovum
- Extra Note: Cowpers gland helps in lubrication

19
Chapter 3 Semen Analysis

Infertility

- If a couple fails to produce a child, the first analysis is done by the male called semen analysis
- Commonly used normal semen parameters
o Volume of semen
o Sperm count
o Morphology
o Motility
o pH

Normal Abnormal (Causes infertility)


Normal volume of semen 2 5 ml Lower
Normal sperm count 20 million/ml Lower
Morphology >30% Dwarfism/ Gigantism/ Double head
Motility >50% Slow/ sluggish
pH 7.2 7.8

Definition of Terms
- Aspermia
o Absence of semen
- Azoopermia
o Absence of sperm
- Oligospermia
o Less sperm
- Asthenozoospermia
o Weak sperm (in motility)
Asthenic = weak

20
Chapter 4 Oogenesis

Female Reproductive System

Endometrium
- Inner wall of uterus
- Highly vascular
- Endometrial glands
- Responds to hormone levels in
the blood
Intra mural portion of FT
- The tube that still surrounded by
uterine wall

21
Chapter 4 Oogenesis

Formation of Female Reproductive System in Embryo

Ovaries

- XX - Ovary
- The undifferentiated gonads in the posterior lumbar region covered by coelomic epithelium sends
septa known as sex cords or medullary cords
- NONE are canalized, ALL are broken down
o They mostly form granulosa cells(they are descendants of coelomic epithelium)
o Some form interstitial cells

Germ Cell

- PGC formed in the wall yolk sac (around 4


- From the wall of yolk sac, PGC proliferate by mitosis and migrate to the undifferentiated cells
- PGC Cortex of ovaries oogonia (2n)

Oogenesis

- Initiated: Intrauterine life


- Terminated: Menopause
- Timeline of oogenesis
o 3rd moth 7th month of IUL
7 million oogonium
As development continues oogonium becomes atretic/degenerates
o End of 7th month
Dictyotene Stage
All primary oocytes at prophase I, diplotene stage are arrested
o At birth
2 million oogonium
Still arrested
o Puberty
Puberty age: 11 14 years
40 000 oogonium
Due to lack of hormones they degenerate even while at arrest
Complete Meiosis I
Change to secondary oocyte and arrest at Metaphase II
If sperm fertilizes ovary, meiosis II is completed
- Reproductive Period
o Menarche (11 14) Menopause (45 50)
o Total: 35 40 years
o 12 Ova/ year
o Total ova: 480 Ova released in a females lifetime

22
Chapter 4 Oogenesis

Prenatal Development

- PGC Oogonium Primary oocyte Primordial follicle


- Primary oocyte Diploid, 2N (Before 1st meiotic division)
- Primordial Follicle
o Primary oocyte surrounded by single layer of flat follicular cells derived coelomic epithelium
o Dictyotene stage
o 2 million at birth
o Diploid - 46 chromosomes (2n)
o 4N
- At birth, no oogonium present

23
Chapter 4 Oogenesis

Postnatal Development

- Primordial follicle Primary follicle Secondary follicle Graafian follicle


- Each month, 5 15 primordial follicles start growing to make primary follicles
- Primary Follicle
o Has primary oocyte in diplotene stage
o The flat follicular cells become circular or columnar
o They mature and become stratified granulosa cells
o Oocyte secrete glycoprotein outside and the follicle
cells secrete glycoprotein inside
Zona Pellucida
o Formation of Theca folliculi
Connective tissue derived from ovarian stroma
- Secondary Follicle
o Fluid-filled space formed between granulosa cells
Antrum
o Follicle increases rapidly and granulosa cells become thin. Oocyte now lies eccentrically in the
follicle surrounded by some granulosa cells called cumulus oophoricus
o Theca folliculi (interstitial cells) now have:
Thick layer inside Theca interna
Produce androgens which
Diffuse inside the granulosa
Cells to get converted into
estrogen
Thin layer outside Theca externa
o Still primary oocyte
24
Chapter 4 Oogenesis

Postnatal Development

- Graafian follicle
o Fully developed secondary follicle
o Secondary oocyte and polar body formed by completion of first meiotic
23 chromosomes, double structured (haploid)
DNA material 2N or 2C
o Secondary oocyte enters into 2nd meiotic division and arrests at metaphase II (3 hours before
ovulation)
o 14 days before menstrual cycle, graafian follicle is ready for ovulation
o During ovulation
One secondary oocyte is released
Cumulus oophoricus is also released and renamed corona radiata

Ovulation

- Definition: Discharge of mature ovum from the ovary


- 3 hours before ovulation, LH is at its peak
- High LH leads to increased activity of collagenase which digests the collagen fibers surrounding follicle

Fate of Ovum

- After release of secondary oocyte, it moves into the infundibulum by fimbriae, then goes to ampulla
(site of fertilization)
- Ovum will wait in the fallopian tube for 24 48 hours
- If sperm does not come
o Ovum will degenerate, become apoptotic and die in the fallopian tube
- If sperm comes
o Fertilization zygote

25
Chapter 5 Female Reproductive Cycle

Regulation of Hormones

Phases of the Ovarian Cycle

The ruptured follicle left behind after


ovulation becomes corpus luteum
- Cytoplasm of these cells accumulate
a yellow pigment
- Secretes progesterone to maintain
the thickened endometrium
Corpus Luteum of Menstruation
- Occurs when no implantation
- Dies after 10 14 days and is known
as corpus albicans (white body, lose
the yellow colour) which is shed in
menstrual blood
Corpus Luteum of Pregnancy
- Occurs when implantation
- Stays 2 months longer than CLofM

From birth till puberty ovary surface is smooth


From puberty scar tissue formed due to release of ovaries
26
Chapter 5 Female Reproductive Cycle
Phases of Uterine Cycle

- Menstrual Phase ( 1st day to 4/5th day)


o Degeneration of endometrium
o Menstruation actual blood loss
o Menses Period of menstrual cycle
o Mittelschmerz pain: abdominal pain due to ovulation
o Abnormal Menstrual cycle
Due to thyroid imbalance or abnormalities in ovaries can fluctuate hormonal levels
(FSH and LH)
- Proliferative Phase/ Estrogenic phase/ Follicular Phase (1st day to 14th day)
o Restoration of endometrium
o Hormones: Estrogen major hormone which acts on endometrium, FSH acts on follicles (follicles
mature to produce estrogen)
o Endometrium begins to proliferate to prepare for zygote
Interstitium and blood vessels also elongate
o Of 40 000 at puberty, only 15 20 mature (Primary Graafian)
10th day: 3 4 remain, others are discarded
13th day: 1 Graafian follicle

27
Chapter 5 Female Reproductive Cycle
Phases of Uterine/Ovarian Cycle

- Secretory Phase/ Luteal Phase/ Progestational Phase (14th day to 28th day)
o Endometrium glands enlarge (cork-screw shaped) and accelerate their rates of secretion
o Corpus luteum stimulated by LH secretes progesterone, estradiol
It stimulates development of gland and arteries of endometrium causing it to become
thick and spongy
Glands become watery mucous (assist spermatozoa through uterus and FT)
Estradiol exert negative feedback on hypothalamus
o LH, FSH levels are negligible atresia
o If fertilization takes place and implants in endometrium, placental HCG from the site of
implantation rescues CL, and secretes progesterone for another 2 months
Progesterone is responsible for the maintenance of pregnancy
o No progesterone no HCG Continues menstrual phase
o Threatened abortion
Continue giving progesterone (extra loading)
Can see spotting on the 2nd month
If female does not take proper care, complete abortion can take place
Summary

28
Chapter 6 Formation of Germ Layers
Contraception

- Oral contraceptive pills (OCP)


o Combined OCP estrogen and progesterone
o Action of OCP
Prevent ovulation by preventing maturation of follicles
Inhibits GnRH from releasing FSH
During ovulation, cervical fluid is less viscous, body temperature also rises
Also a form of natural contraception
Prevents implantation by altering the endometrium
o Adverse effects of OCP cause embolism
o Polycystic ovarian disease: OCP used as treatment

Fertilization

- 2 days before and 1 day after ovulation, fertilization is most likely


- Journey of Sperm
o When introduced to the female tract, it can survive for 72 hours
o Rhythmic contraction of uterine musculature and cervical canal allows the movement of sperm
inside the female tract
o Sperm rest in the intramural portion of the fallopian tube but the ovaries keep releasing chemo
attractants, so the sperm moves again to the ampullary region
o It takes the sperm 2 7 hours to reach the ampullary region, where fertilization occurs
o Sperms undergo capacitation when in the female genital tract
The layers that were put on in epididymis are removed here
o Enzymes in the acrosomal cap: acrosin and hyalurinidase perentrate corona radiate first
o The glycoprotein layer, zona pellucida is only permeable to one sperm
o Male nucleus is known as male pronucleus
- Journey of ovum
o After release of secondary oocyte, it moves into the infundibulum by fimbriae, then goes to
ampulla (site of fertilization)
o Epithelium of fallopian tube has hair-like projections (cilia) and the rhythmic contractions of FT
allow the oocyte to move through the FT
o Ovum will wait in the fallopian tube for 24 48 hours
o Female nucleus is known as female pronucleus
- Male pronucleus (haploid) + Female pronucleus (haploid) = Zygote (diploid)

29
Chapter 6 Formation of Germ Layers
Fertilization

- Abnormal Implantation
o Normal implantation occurs in the upper uterine segment
o Ectopic pregnancy: implantation occurs outside the uterine cavity
Abdominal pregnancy
A form of an ectopic pregnancy where the pregnancy is implanted within the
peritoneal cavity outside the fallopian tube or ovary and not located in the
broad ligament
Tubal pregnancy
Implantation in the fallopian tube
- Changes in Zygote
o Meiosis II is completed
o Sex Determined
Ova contains 22 + X
Spermatozoa are of 2 types:
Half are 22 + X
Half are 22 + Y
Sex of the child determined at the time of fertilization
o Cleavage initiated

Cleavage

- Cleavage is the rapid mitotic division of zygote after


fertilization
- All dividing cells are known as blastomere
- Morula: 16 cell stage
o Consists of inner cell mass
This gives rise to the embryo - embryoblast
o Outer layer - trophoblast
- Zygote is still surrounded by zona pellucida
o Prevents from sticking to the epithelium by its
glycoprotein characteristics, hence avoiding ectopic
pregnancy
- Quantity of fluid inside morula increases and a cyst is
formed
o The morula now has become blastocyst
- Timeline
o The process of entering the uterine cavity after
fertilization takes 2 -4 days
o Implantation = 3 days
o Total time from fertilization implantation
7 days (20th day of ovarian cycle)
30
Chapter 6 Formation of Germ Layers
Implantation

- Site of implantation: Upper uterine segment (posterior wall of decidua)


- Type of implantation in humans: interstitial implantation
- As soon as zygote enters uterine cavity, zona pellucida degenerates, thus exposing trophoblastic layer
which has high affinity to get attached or implanted with any tissue it comes in contact with (gets stuck
and burrows inside)
o Trophoblastic Layer Function
Nutrition
Implantation

- When the zygote enters the uterine cavity,


the entire uterinfe cavity is called Decidua
- When comes in contact, tries to burrow inside
then gets completely submerged in the
endometrium
- Decidua basalis The point where zygote comes in contact with endometrium
o One the maternal side
- Decidua capsularis When zygote is completely submerged, the capsule which covered it is known as
this
- Decidual Reaction Within endometrium this reaction takes place, accumulation of glycogen and lipid
material

31
Chapter 6 Formation of Germ Layers
Summary of the First Week of Development

Second Week of Development

- Trophoblast develops into cytotrophoblast


- Cytotrophoblast multiplies and all the cells lose their cell membrane
o This homogenous layer is called syncytiotrophoblast
Produces HCG, which sends signal to the corpus luteum to continue producing
progesterone for another 2 months
- Trophoblast synthesize a mass of cells all around the blastocyst going outside inner cell mass (embryo)
Extraembryonic mesoderm
o Within EEM, another cavity is formed Extraembryonic coelomic cavity
o By the formation of EE coelomic there is some mass of EEM outside and inside
Inside: Visceral/ Splanchnopleuric EEM
Outside: Parietal/ Somatopleuric EEM
- How does it get attached to the endometrium? Chorionic villi
o Comes from extraembryonic mesoderm
o There are 3 types of villi
Primary Villi
Syncytiotrophoblast + Cytotrophoblast
Secondary Villi
ST + CT + Extraembryonic mesoderm
Tertiary Villi
ST + CT + EEM + Blood capillaries

32
Chapter 6 Formation of Germ Layers
Second Week of Development Continued

- The inner cell mass arrange themselves into a 2 layered disk Bilaminar disk
o Ectoderm (Epiblast) columnar cells
o Endoderm (Hypoblast) cuboidal cells
- There is a small cavity within the mass of ectoderm called amniotic cavity
- Endoderm forms a membrane called Heusers membrane just beneath cytotrophoblast
- Formation of primary yolk sac
- AC later expands and completely surrounds the yolk sac
o Fetus in the AC
o As enlarges, all structured behind are compressed
o The primary yolk sad becomes smaller in side due to the pressure
Now called secondary yolk sac
o Because of the pressure, the EE coelomic cavity is obliterated
o As a result amniochorionic membrane is formed
Amnionic inside
Chorionic outside
During labour: amniochorionic fluid will rupture first, allowing the head to pass the
cervical canal
If doesnt rupture by itself
o ARM: Artificial rupture membrane
o Anoxia can be a result due to inability of the head to come out

33
Chapter 6 Formation of Germ Layers
Gastrulation - Formation of All Three Germ Layers (3rd Week of Development)

- Some cells (only at one corner) from endoderm and ectoderm proliferate and change shape
o Prochordal plate
Mass of proliferated endodermal cells
Appearance of this determines the head end of the development of embryo
o Primitive Streak
Mass of proliferated ectodermal cells
Tail end
rd
- During the 3 week:
o The primitive streak passes between ectoderm and endoderm to form intraembryonic
mesoderm
o The 3 layered disk (ectoderm, mesoderm and endoderm) is called trilaminar disk
34
Chapter 6 Formation of Germ Layers
What the Germ Layers Form

Endoderm Mesoderm Ectoderm


Respiratory tract (trachea, Axial mesoderm (prechordal All nervous tissue
bronchi, alveoli, lungs) plate, notochord)
Endocrine glands and organs Paraxial mesoderm (somites: Epidermis of skin
(thyroid glands, thymus) muscles, bones, cartilages)
Urinary system (urethra, urinary Intermediate mesoderm Tooth enamel
bladder) (gonads, kidney, adrenal cortex)
GIT (liver, pancreas, alimentary Lateral mesoderm (CV organs: Lining of mouth, anus, nostrils
canal except mouth, pharynx heart, blood vessels, CT,
and terminal part of rectum) mesenchymal cells, limb buds)
Auditory system (epithelium of Sweat glands
auditory tube and tympanic
cavity)
Hair, nails

Third Week of Development

Development of Notochordal Process

- Primitive streak cells still accumulate and become knob like structures called primitive node or
primitive knob
- The cells from this will move along the ectoderm from primitive node till the Prochordal plate
- The cells moving are called notochordal plate
o Notochordal process acts as a stimulant, instigator for ectoderm above it to change,
differentiate into special structure known as neural plate
Notochordal plate thickens neural plate
Remaining free space is filled with intraembryonic mesoderm
Which 3 places dont see intraembryonic mesoderm?
o Cloaca, Prochordal plate, notochordal process

Ectoderm and endoderm are firmly


attached

- At primitive streak there is


cloaca

35
Chapter 6 Formation of Germ Layers
Third Week of Development

Formation of Neural Tube

- The neural plate gets elevated to form neural folds


o Neural folds fuse to form neural tubes
Cranial end closes (anterior fold of neural tube) Forms brain
Caudal end (posterior fold) Forms the spinal cord
- From the edges of the neural folds, some cells differentiate, specialize and migrate to different parts of
the body
o Elevated folds at the edge are called crest
o Special cells are called neural crest cells
These cells derive
Adrenal medulla
Melanocytes
Dorsal nerve root ganglion
Odontoblast cells
Schwan cells

5r

36
Chapter 6 Formation of Germ Layers
Third Week of Development

Subdivisions of Intraembryonic Mesoderm

- Intraembryonic mesoderm gets divided into 3 important regions


o Paraxial Intraembryonic Mesoderm
PIM gets segmented:
Somites (each segment) they themselves get divided into 3 regions
o Sclerotome
Medial region of the somite vertebral bones
o Myotome
Muscles: back musculature
o Dermatome
Skin of the back (dermis)
o Intermediate Mesoderm
Gives rise to renal system: kidneys, gonads, except bladder (some mesoderm and some
ectoderm)
o Lateral Plate Mesoderm
Forms a cavity: Intraembryonic coelomic cavity
Another name: Horse-shoe shaped cavity
Does not get obliterated
The cavity forms:
o Pericardial cavity Apex of IECC
o Pleural cavity To hold both lungs
o Peritoneal cavity Fuses to form one huge cavity in abdomen
Lateral plate mesoderm splits into:
Parietal/somatopleuric IEM attached to ectoderm
Visceral/splanchnopleuric IEM attached to endoderm
- IEM above the apex of IECC is called septum transversum
o Within this, see the formation of liver and diaphragm
o Heart tubes are formed within the visceral IEM in front of septum transversum
o Cranio-caudal folding and lateral folding takes place which allows heart tubes, liver and
diaphragm to come to the middle region
- Due to lateral folding, IEM gives rise to the musculature of upper and lower limbs

37
Neurulation & Development of Somites

38
Embryonic Folding

39
Chapter 7 Connecting Stock & Placenta
Connecting Stock

- As amniotic cavity completely surround the blastocyst, portion of EEM remains


- It also migrates due to the movement of amniotic cavity
o Migrates to the tail end and comes to the ventral aspect
- Connecting stock: connection between mother and fetus
- When attached to the umbilical opening, blood vessels have been developed
o 2AV - 2 arteries and 2 veins
o The right vein disappears over time
o The EEM of the connective stock gets converted into a gelatinous substance called whartons
jelly (present in between 2AV)
Umbilical Cord
- Length = 50 55cm
- Increase in length = more dangerous
- UC is attached to the center of placenta
- Maternal cotyledon
o Maternal side of placenta
o It is divided into numerous lobes
Each lobe is known as cotyledon
- Fetal side of the placenta is smooth
- Anomalies of Umbilical Chord
o Nuchal chord: 75 100cm

Placenta
- Decidua basalis from the maternal aspect and villi from the embryonic side help to form placenta
(Refer for primary tertiary villi notes)
- Placenta is circular, disk in shape
- Diameter is 5 -7 inches
- Function of placenta
o Enables transport of oxygen, water, electrolytes and nutrition
o Provides excretion of carbon dioxide, urea and other waste products
o Maternal antibodies give fetus immunity against some infections
o Acts as barrier and prevents many bacteria and other harmful substances from reaching the
fetus
But, some pass through the placenta (rubella, measles, poliomyelitis)
Rubella can cause cataracts, deafness, congenital CVS anomalies
o Keeps blood separate, preventing antigenic reaction between them
o Syntheses many hormones produced in the syncytiotrophoblast
Estrogen development of mammary glands
Progesterone CL will secrete progesterone 2 3 months, after secreted by placenta
HCG main base for urine pregnancy test
Somatomammotropin hormone has anti-insulin effect

40
Chapter 7 Connecting Stock & Placenta
Placenta

- Villi develop blood capillaries


- Fetal blood within chorionic villi project into lacunae which unite to form intervillous spaces that bathe
the chorionic villi with maternal blood
- Blood seeps in intervillous space
o Only products of nutrition, oxygen and excretory products exchange
o NO blood, microorganisms, hormones (except thyroid hormones and synthetic hormones)
Formation of Chorionic Villi

Formation of Placenta

41
Chapter 7 Connecting Stock & Placenta
Placenta Continued

Anomalies of Placenta
- Anomalies in shape of placenta
o Bidiscoidal
o Fenestrated placenta hole in placenta
o Placenta succenturate extension of placenta
o Circumvallate placenta entire placenta is covered in
o Lobed placenta divided into lobes
o Diffuse placenta chorionic villi persists all around blastocyst
- Anomalies in attachment of placenta
o Placenta percreta sometimes the attachment of villi enters myometrium and perimetrium
o Placenta accrete attachment of villi to myometrium
o Placenta previae placenta attached anywhere other than upper uterine segment
Grade 1 (1st degree)
Attached in LUS away from IOS
Uterus grows, so the placenta can move to UUS
Grade 2
Attached in LUS, touching IOS
Grade 3
Attached in LUS, but edge covers the IOS
Can open if cervix dilates
Grade 4
Attach in LUS, completely covers IOS
Without use of ultra sound for early diagnosis, many death can occur by heavy
bleeding
o Abruptio Placenta
Premature detachment of placenta (before delivery)
Normal: 15 20 minutes placenta still hands and slowly constricts and removes it, this
prevents blood clots, hemorrhage
o Furcate placenta
Before attachment to placenta, arteries are divided
o Battledoor placenta
Umbilical cord is attached to the margin of placenta not the center

42
Chapter 7 Twins
Types of Twins

- Dyzygotic Twins
o 2 ova and 2 sperms
o Non-identical
o 2/3 of twins
- Manozygotic Twins
o 1 ova fertilizes by 1 sperm
o Identical
o 1/3 of twins

Monozygotic Twins

- Can develop during the blastomere stage


o There might be a division in middle of blastomere so they develop into different embryo
o 2 serperate mass of cells
Dichorionic diamniotic twin placenta - Each develops separately but identical
2 chorionic cavity
2 amniotic cavity
2 placenta
- Can develop during the blastocyst stage
o There is already chorionic cavity so only splits at the mass cells
Monochorionic diamniotic twins
1 chorionic cavity
2 amniotic cavity
Rarely 2 placenta

Siamese Twins

- Attachment near the cranial, mediastinum, abdomen or pelvic area


o Cephalipagus Cranium attachment
o Thoracopagus Thorax (mediastinum) attachment
o Omphalopagus Abdomen attachment
o Pyopagus Pelvic attachment

43
Chapter 7 Extra Notes
Anomalies & Prenatal Diagnostics Tests

- Amniogenic cells line the amniotic cavity


o Fluid enters the fetuss GIT absorbed in fetal circulation filtered by kidneys and excreted
by urine
o Amniotic fluid is in constant production, if in excess absorbed by fetus
o Normal amniotic fluid: 700 1200ml
If goes above 1500: Polyhydromions
If abnormality in GIT, the fetus regurgitates: trachea-esophageal fistula
o Fistula: Connection of two hollow structures
o Sinus: Has one opening
If goes below 700: Oligoamnions
It can result in a condition where kidneys cannot develop: renal agenesis

Amniocentesis

- Amniotic fluid also helps in diagnosis of chromosomal anomalies can do karyotyping (FISH)
- Can aspirate after the 14hth week
- Comes with risk: infection can occur
o Chorioamniotic membrane is first exposed, if any organisms enter can result in
chorioamnionitis
o Amniotic bands
Necrotic material in amniotic fluid can result in amniotic bands due to infection
These bands can surround structures in body and can result in abnormal structures or
death
- Amniocentesis analyzes alpha-fetoprotein level which is produced by hepatocytes
o Normal level: 40 microgram/L
o High alpha-fetoprotein level in: tumours and neural tube defect
Neural Tube Defect
Genetic defect Neural tube does not completely emerge
When pregnant, obstetricians give folic acid for nutrition if runs in fam

Ultrasound

- Any morphological changes are diagnosed

Chorionic Villus Biopsy

- Early diagnosis: 8th week onwards


- Disadvantage: cannot analyze alpha-fetoprotein level

44
Chapter 7 Extra Notes
Tests

IVG In vitro Fertilization

- Final answer to infertility


- Have to aspirate the oocyte
o Take graafian follicle
o When it reaches 8 cell stage, it is taken out from the petri dish and introduced in the uterine
cavity
o Success rate is 20 25%

GIFT Gamete Intra Fallopian Transfer

- Take out sperm and transfer to the fallopian tube

ICSI Intra Cytoplasmic Sperm Injection

- An in vitro fertilization where single sperm is injected directly into an egg

Elderly primi

- When women get pregnant after 35

45
Timeline
Overview of the Events

Age (in days) Development Events


2 - Embryo is at two-cell stage
3 - Morula is formed
4 - Blastocyst is formed
8 - Trophoblast differentiates into cytotrophoblast and
syncytiotrophoblast.
- Bilaminar disk is formed
9 - Lacunae appear in the syncytium
11 - Embry gets completely implanted in the endometrium
13 - Primary villi are formed
14 - Prochordal plate and primitive streak are seen
15 - Primitive streak appears.
- Definitive yolk sac is formed
16 - Intraembryonic mesoderm is formed trilaminar disk.
- Secondary and tertiary villi are seen.
17 - Notochordal process appears.
- Heart tube is seen in cardiogenic area.
- Allantoic diverticulum is seen.
19 - Intraembryonic Mesoderm is being formed.
- Connecting stalk can be distinguished
21 - Neural groove is seen.
- Head fold begins to form.
23 - Closure of neural tube is seen.
2nd month - Villi are seen all around the Trophoblast
4th month - A definitive placenta is formed
Full term - Placenta is shed about 15 20 minutes after birth of the baby

Oragnogenesis Week 4 8

46
Skeletal System

Introduction

- Remaining cells of intraembryonic mesoderm give rise to mesenchymal cells


o Meshwork of loosely organized embryonic connective tissue
o Has the ability to get transformed into any type of cell the body needs
o Its a stem cell
- Fate of cells
Blastocytes Differentiated cells
Cartilage Chondroblast Chondrocytes
Bone Osteoblast Osteocytes Osteoclast
Muscle Myoblast Myocytes
RBC Reticulocytes Erythrocytes
WBC Lymphoblast Lymphocyte
o Osteoclast: modelling and remodelling of the bone bone eating cells
Digests damaged or excess of bone

Development of Appendicular Skeleton

- All bone is of mesodermal origin


- Process of bone formation is called ossification
- There are two types of bone formation:
o Endochondral ossification/ Cartilage model
Cartilage bones
o Membranous ossification
A membrane folds itself, within membrane are mesenchymal cells, these get
transferred into osteoblast osteocytes
No cartilage used
Flat bones skull, clavicle and mandible

Endochondral Ossification

- Key steps in endochondral ossification


o At the site where the bone is to be formed, the mesenchymal cells become closely packed to
form a mesenchymal condensation
o Some mesenchymal cells become chondroblasts and lay down hyaline cartilage. Mesenchymal
cells on the surface of the cartilage form a membrane called perichondrium
This membrane is vascular and contains osteoprogenitor cells
Osteoblast and osteoclast
o Cells of the cartilage are at first small and irregularly arranged. However, in the area where
bone formation has to begin, the cells enlarge considerably

47
Skeletal System

Development of Appendicular Skeleton

Endochondral Ossification

- Key steps in endochondral ossification continued

o The intracellular substance between enlarged


cartilage cells becomes calcified under the
influence of an enzyme alkaline
phosphatase (secreted by cartilage cells)
When calcified, process of diffusion is
terminated and nutrition to
chondrocytes is cut off they die,
leaving behind empty spaces called
primary areola
o Some blood vessels of the perichondrium
(called periosteum as soon as bone is formed)
now invade the calcified cartilaginous matrix,
accompanied by osteoprogenitor cells
Osteoclasts eat away much of the
calcified matrix forming the walls of the
primary areola and formed the large
cavity called secondary areola

o Walls of secondary areola are formed by thin layers of


calcified matrix that have not been dissolved
o Osteoprogenitor cells become osteoblasts and arrange
themselves along the surfaces of these bars of calcified
cartilaginous matrix
o Osteoblasts now lay down a layer of ossein fibrils
embedded in a gelatinous intracellular matrix osteoid
(prebone)
Its calcified and a lamellus of a bone is formed
o Osteoblasts lay down another layer of osteoid over the
first lamellus calcifies 2 lamellus of bone formed
Some osteoblasts get caught between lamellae
which form osteocytes
As more lamellae are laid down, bony trabeculae
are formed
Haversian System Circular pattern of
osteoblast and osteoid forming is this

48
Skeletal System

Development of Appendicular Skeleton

Endochondral Ossification

- How bone grows in length:


o Calcified matrix of cartilage only acts as a support for the developing trabeculae and is not
itself converted into bone
o At this stage, the ossifying cartilage shows a central area where bone has been formed

o As we move away from this area, we see the following:


Zone 1
Region where cartilaginous matrix has been
calcified and surrounds dead and dying
cartilage cells
Zone 2
Proliferative or highly mitotic zone
o Cells are larger and dividing
Zone 3
Resting zone
o Cells are small and irregularly arranged
o When bone formed in zone 1, zone 2 becomes calcified zone,
zone 3 becomes mitotic zone, zone 4 becomes resting zone etc.
o Total effect = ossifying cartilage progressively increases in size
o During 2nd trimester, given calcium phosphate supplements
which is responsible for bone growth

Development of Long Bone

- Mesenchymal condensation is seen in the limb bud in the region where the bone is to be formed
- Long bone ossifies by 2 ossification centers
o Primary ossification (before birth)
Always for the diaphysis of the bone (shaft of bone)
Calcification starts at the center called primary ossification center in the diaphysis
Calcification is spread to the periphery
Appears during intra uterine life
o Secondary ossification
For the epiphysis
Appears after birth
Calcification starts in the center called secondary ossification center in the epiphysis
- Junction between epiphysis and diaphysis epiphyseal plate
o Stop ossification by 18 20 years of age

49
Skeletal System

Development of Appendicular Skeleton

Development of Long Bone

- How is medullary cavity formed?


o Medullary cavity
Recall: the empty space in the shaft is created by osteoclasts
Cavity is created right before metaphysis
Contains bone marrow Reticuloendothelial System = blood cells
Where are first blood cells formed?
o Yolk sac Spleen & liver bone marrow (end of 3rd month of IUL)
If serum blood calcium is low or needs calcium somewhere else, get it from metaphysis
- Characteristics of Metaphysis [4]
o Store house of calcium
o Attachment of ligaments
o Also rich vascular supply (more prone to infection)
o No marrow cavity

50
Skeletal System

Development of Appendicular Skeleton

Anomalies of Bone

- Osteoporosis or Brittle Bone Disease


o Brittle bone, increase porosity of the bone
o Seen in adults mostly (women > men)
o Supplement with calcium
- Rickets
o Increase porosity of bone
o Seen in children mostly
o Renal disease: vitamin D deficiency = Ca deficiency absorption leads to rickets
- Osteopetrosis or Marble Bone Disease
o More calcium deposition takes place = increase density
- Osteomyelitis
o Painful inflammatory disease of bone that is often of bacterial origin and may result in death
of bone tissue
- Exastosis
o Outgrowth, multiple or single
o Extra cartilage and extra bone
- Achondroplasia
o No chondroblasts = no chondrocytes, bone
o More commonely seen in epiphyseal region, can also occur in diaphysis
o Osteochondro Dystrophy or Chondro osteo Dystorphy
Type of achondroplasia
Vertebral column will be short but limb bones may be normal in length
- Cleidocranial Dysostosis
o Absence of clavicle with malformation of facial and skull bones
- Common sites for metastasis
o Bone, liver, lungs and brain

Formation of Limbs

- Limb buds form after 4th week


- There is thickening of the buds called ectodermal ridge
o Ectodermal ridge acts as an inducer or initiator to grow as proper limbs

51
Skeletal System

Development of Appendicular Skeleton

Formation of Limbs

- Upper limb buds or Forelimb buds


o Appear earlier
o All from mesoderm Forms the limb bones and muscles
o Each forelimb bud becomes subdivided by constrictions into arm, forearm and hand
Hand itself soon shows outlines of digits by cell death of interdigital areas
o Upper limb Rotation
Rotates laterally to come to anatomical position (90 degrees)
Preaxial bone is radius
- Lower limb buds or Hindlimb buds
o Everything similar
o Lower limb Rotation
Rotates medially to come to anatomical position (90 degrees)
Preaxial bone is tibia

Anomalies of Limbs
- Club foot Congenital Talipes Equinovarus
o Kids feet are inverted
- Amelia or Phocomelia
o Amelia: complete absence
o Phocomelia: Not formed properly
o Thalidomide prevent morning sickness during pregnancy, leads to these conditions
- Polydactyly
o Extra digits
- Sandytyly
o Digits are fused
- Synphalangia
o Interphalangeal joints are fused
52
Skeletal System

Development of Axial Skeleton

Formation of Vertebral Column

- Vertebral column is formed from the sclerotomes of the somites


o Cells of each sclerotome get converted into loose mesenchyme
o The mesenchyme migrates medially and surrounds the notochord
o The mesenchyme then extends backwards on either side of the neural tube and surrounds it
o Extensions of this mesenchyme also take place:
Laterally in the position to be occupied by the transverse process
Ventrally in the body wall, in the position to be occupied by the ribs

- The mesenchymal cells undergo compaction in the center perichordal disc


o This disc becomes intervertebral disc
o Fate of notochordal process
Perichordal disc surrounds the notochordal process
Since its a fibro-cartilage, it cannot completely destroy the notochordal process
Some portion of the NP remains in the intervertebral disc
Remnant of NP nucleus pulposus
o Interspinous and intertransverse ligament formed same way as intervertebral disc
- Above and below the perichordal disc are less condensed parts, which fuse Vertebral bodies
o Fate of notochordal process
Vertebral bodies surround the NP
NP degenerates where the vertebral bodies are being formed
o Neural arch, transverse process and costal elements formed same way as the body
Text

53
Skeletal System

Development of Axial Skeleton

Formation of Vertebral Column

- Vertebral bodies have 3 ossification centers


o Body
o 2 for each side of the neural arch
- Foramen transversarium seen in all the cervical
vertebrae, not in any other

Formation of Vertebral Column Overview

54
Skeletal System

Development of Axial Skeleton

Congenital Anomalies of Vertebral Column

- Hemivertebra
o Commonly seen when vertebrae ossifies by 2 ossification centers which fuse
o One of these parts may fail to develop, resulting in only half of the body
o Usually associated with absence of the corresponding rib
- Spinabifida Anterior
o 2 halves of the vertebral body form normally but fail to fuse = gap
Sometimes gap is large enough for meninges and nerves to bulge forward between
them
- Spinabifida
o Gap between neural arches
- Diastetomatomylia
o Small bony projection (spicule) coming out of neural canal
(there is a spinal cord running in bony canal), it can dissect
into the spinal cord
o Depending on the severity of the spicule, may have
neurological abnormalities
- Klipper Feil Syndrome
o Cervical vertebrae are fused Spinabifida
- Sacralization
o 5th lumbar vertebra partially or completely fused to the sacrum
- Lumarization
o 1st sacral vertebra attached with 5h lumbar vertebra
- Occipitilization
o 1st cervical vertebra attached with occipital bone
- Spondylolisthesis
o Articular facets are abnormal in orientation or are deficient
o When deficiency both inferior articular processes of the 5th lumbar vertebra and the body of
the vertebra may slip forwards over the sacrum

55
Skeletal System

Development of Axial Skeleton

Formation of Ribs

- Ribs are derived from ventral extension of the sclerotomic mesenchyme that forms the vertebral
arches
- Small projection from the transverse process is known as costal element
o It is present in transverse process of all vertebrae BUT formation of ribs takes place only in the
thoracic vertebra
o In thoracic vertebrae
The entire extension (primitive costal arch) undergoes chondrification followed by
ossification to form the ribs
o Other regions will not project forward and remain in the vertebrae

Formation of Sternum

- Sternum is formed by fusion of two sternal bars that develop on either side of the midline
o Fusion first occurs at their cranial end manubrium
o Fusion proceeds caudally
- Mesenchymal condensaions forming at these sites become cartilaginous in the 7th week of IUL
- Laterally, sternal bars are continuous with ribs
- Manubrium and body of sternum are ossified separately
- Xyphoid process ossifies only late in life

56
Skeletal System

Development of Axial Skeleton

Congenital Anomalies of Ribs & Sternum

- Cervical Ribs
o 7th cervical vertebrae has rib formation
May compress brachial plexus, resulting in a tingling sensation
o Treatment: surgically remove
- Funnel Chest
o Thoracic outlet forms a funnel shape
o Lower part of the sternum and the attached ribs are drawn inward into the thorax
o Primary defect is that the central tendon of the diaphragm is abnormally short
- Pigeon Chest
o When manubrium projects forward with a break shape appearance
o Thoracic inlet projecting forward

Facial & Skull Bones

- Skull is developed from the mesenchyme surrounding the developing brain


- Sutures
o Coronal suture Parietal to frontal
o Sagittal suture 2 parietal
o Lambdoid suture Occipital to parietal
- Fontanelle
o Soft spot on a babys head which, during birth enable the bony plates of the skull to flex and
overlap, allowing the childs head to pass through the birth canal
o Ossification of the bones of the skull causes:
Anterior fontanelle: fuses permanently 12 15 months after birth
Posterior fontanelle: 2 3 months
o In case of intracranial pressure, when palpate risen
o In case of severe diarrhea, when palpate sunken
- Bones
o Some bones are cartilaginous and some are membranous
o Frontal, Parietal, occipital
o Temporal 4 parts of the temporal bone:
Squamous (flat part of the temporal bone)
Tympanic (ear)
Petreous
Mastoid
o Sphenoid bone
Body
Wings Greater and lesser
Pterygoid laminae medial and lateral

57
Skeletal System

Development of Axial Skeleton

Facial & Skull Bones

- Bones & Cavities Front of Skull


o Occipital cavity
o Lacrimal cavity has lacrimal fluid stored in lacrimal sac
o Nasal cavity divided by cartilaginous nasal bone called vomer
Lateral wall of nose is a shelf-like structure (3 shelves)
Superior
Middle
Inferior also known as concha
o Zygomatic bone small projection going toward parietal bone is zygomatic process
o Maxillary bone under zygomatic bone
o Roof of oral cavity palate

58
Skeletal System

Development of Axial Skeleton

Facial & Skull Bones

- Recall: Some bones are cartilaginous and some are membranous


- Cartilaginous bones thick
o Derived from cartilage of nasal capsule
Ethmoid bone
Inferior nasal concha
- Membranous bones thin
o Formed in relation to mesenchyme covering the developing brain
Frontal
Parietal
o Formed by intramembranous ossification of the mesenchyme of maxillary process
Maxilla (excluding premaxilla)
Zygomatic
Palatine
Extra Note:
o Ossified in the membrane covering the nasal capsule
- Occipital & preoccipital somites
Nasal
o Sclerotomes of these two form
Lacrimal
the base of the skull near the
Vomer
occipital region
- Cartilaginous & Membranous bones
o Myotome of occipital somite
o Occipital
gives musculature of tongue
Membranous: Interparietal part
o Myotome of preoccipital somite
Cartilaginous: Rest
gives the extraoccular muslces (6
o Temporal
muscles of the eye)
Membranous: Squamous and tympanic
Supplied by 3rd, 4th and
Cartilaginous: Petrous and mastoid
6th cranial nerves
o Sphenoid
Membranous: Later part of great wing and pterygoid laminae
Cartilaginous: Wings and body
o Mandible
Membranous: Coronoid and condylar
Cartilaginous: Rest

Congenital Anomalies of Skull Bones

- Scaphocephaly Premature fusion of sagittal suture


- Acrocephaly Premature fusion of coronal suture
- Plagiocephaly Asymmetrical fusion
- Microcephaly Skull is small

59
Skeletal System

Timeline of Skeletal System

Age Development Events


4th week (26) - Forelimb bud appears
4th week (28) - Hindlimb appears
5th week - Limbs become paddle shaped
6th week (36) - Formation of future digits can be seen
- Cartilaginous model of bone start forming
7th week - Rotation of limb occurs
8th week (50) - Elbow and knee are established
- Finger and toes are free
- Primary centers of ossification are seen in many bones
12th week - Primary centers of ossification are seen in all the long bones

60
The Skin & Its Appendages

Skin

- Epidermis ectoderm
o Ectodermal cells proliferate to give rise to typical stratified squamous epithelium
o 5 layers of epidermis
Stratum basalis/ stratum germinatum
Stratum spinosum
Stratum granulosum
Stratum lucidem
Stratum corneum
- Dermis mesoderm
o Formed by condensation and differentiation of mesenchyme underlying the surface of
ectoderm
- Dermal papillae
o Line of junction between dermis and epidermis is at first straight
o Subsequently, the epidermis shows regularly spaced thickening hat project into dermis
o The portions of dermis intervening between these projections dermal papillae
- Colour of skin
o Melanin melanocytes neural crest cells neural folds
NCC enter into dermis and become melanoblasts, migrate to upper layer of dermis and
become melanocytes

61
The Skin & Its Appendages

Hair

- Ectoderm
- Stratum basalis dips into dermis and becomes a cup-shape (root of hair)
o This elongates by deposition of keratin
- Hair itself is formed by proliferation of germinal cells overlying the papilla
- Arrector pili
o Thin band of smooth muscle formed by mesodermal cells
o Gets attached to the root and a typical hair follicle is formed
- Primitive Hair Lanugo Hair
o Hair developed in IUL, even there at birth
o 1st year of life, this hair comes off and see formation of regular porous hair

Nail

- Nails develop from the surface ectoderm


- At the edge of the digits, a ridge is formed (nail ridge/ ectodermal ridge) which later on migrates to the
dorsal aspect of the distal phalanx where they form the nail matrix
- Deposition of keratin helps in formation of nail plate which is equivalent to stratum lucidem

62
The Skin & Its Appendages

Glands

- Formation of gland
o Ectoderm derivatives Sweat gland, mammary, sebaceous
o Mesoderm derivatives
o Endoderm derivatives Liver, pancreas
o Mixture Prostate gland (endoderm + mesoderm)
- Exocrine glands
o They have a duct, secretions are in a duct system
o How derived?
From epithelium there is a down growth divides terminal duct enlarges to form
the secretory portion canalized
- Endocrine glands
o Ductless glands pituitary, thyroid
o How derived?
Same, but down growth is disconnected

Sebaceous Gland

- Part of hair follicle


- Near root of hair, down growth again which branches out and opens in the root
- Secretes sebum depending on hormones
- Sometimes enlarges on its own, when see a lot of pollution, the dust constantly sits on face and blocks
pores and forms a cystic growth (sebaceous cyst)
- Vernix Caseosa
o Sebaceous secretion and lanugo hair form small coating over the skin of fetus (jelly-like)
o Protective in function

Mammary Gland

- During development there is milk line/ mammary line which is extending from axilla to inguinal region
- Gland is formed in the pectoral region
- From epidermis there is a down growth which dips in dermis, giving 7 8 lactiferous ducts and forming
secretory elements
- Anomalies of Mammary Gland
o Polythelia Extra nipples along milk line
o Athelia No nipple
o Amastia Absence of mammary gland
o Gynecomastia Enlargement of male breast (excess estrogen)

Anomalies of Skin
- Albinism Lack of pigment melanin
- Atrikia Absence of hair (Can have ulcers too incomplete epithelium)
- Hypertricosis More hair
63
The Skin & Its Appendages

Timeline of Skeletal System

Age Development Events


7th week - Mammary line is established
8th week - Melanoblasts start appeariing
1 3rd month
st
- NCC migrate to skin
2nd month - Surface ectoderm is single layered
2 4th month
nd
- Surface ectoderm becomes multi-layered
3rd 4th month - Dermal papillae are formed

64
The Pharyngeal Arches

Introduction

- Pharyngeal arches are mesodermal thickening in the wall of the cranial most part of foregut
- Another name: Branchial arches
- There are 6 of them, 5th arch degenerates

Name of Arch Cartilage


1 Mandibular Arch Meckels Cartilage
2 Hyoid Arch Hyoid Cartilage
3 No name No name
4 No name No name
6 No name No name

65
The Pharyngeal Arches

Bones & Ligaments Formed by Pharyngeal Arches

- Side note: Parts of the ear


o Outer ear
o Middle ear
Bones Malleus, Stapes, Incus
o Inner ear

Meckels Cartilage

- Meckels cartilage gets divided:


o Ventral portion Mandible
o Dorsal portion Malleus and Incus
o Central portion forms 2 ligaments:
Anterior ligament of malleus
Sphenomandibular ligament
- Contributes to some bones in the face
o Extra note: NCC also develop in the mesodermal arches and contribute to the bones
- Anomaly
o First Arch Syndrome or Mandibulofacial Disostosis or Ostosis Disorganize
Defective formation of the face and lower jaw inherited as an autosomal dominant
trait & characterized by bilateral malformations, deformities of the outer & middle ear

Hyoid Cartilage

- Bones formed
o Stapes
o Styloid process
o Stylogyoid ligament
o Superior part of the hyoid bone
o Lesser cornu

3rd Cartilage

- Bones formed
o Inferior part of hyoid bone
o Greater cornu

4th and 6th Cartilage

- Aid in the formation of laryngeal and tracheal cartilages

66
The Pharyngeal Arches

Overview of Pharyngeal Arches

Arch Cartilage Nerve Skeletal Structures Ligaments Muscles


1 Meckels Mandibular - Malleus - Anterior ligament - Medial and lateral pterygoids
Cartilage - Incus of malleus - Masseter
- Sphenomandibular - Temporalis
ligament - Mylohyoid
- Anterior belly of digastric
- Tensor tympani
- Tensor palati
2 Hyoid Facial - Stapes - Stylohyoid ligament - Muscles of facial expression
Cartilage - Styloid process - Stapedius
- Stylogyoid ligament - Stylohyoid
- Superior part of the - Posterior belly of digastric
hyoid bone - Occipitofrontalis
- Lesser cornu of hyoid - Platysma
bone - Auricular muscles

3 No name Glossopharyngeal - Greater cornu of hyoid - Stylopharyngeus


bone
- Inferior part of hyoid
bone
4 No name Superior - Laryngeal cartilage - Muscles of larynx and pharynx
laryngeal branch - Tracheal cartilage
of vagus
6 No name Recurrent Same as 4th arch Same as 4th arch
laryngeal branch
of vagus

67
The Pharyngeal Arches

Overview of Skeletal Structures Derived from PA

Overview of Muscles Derived from PA

68
The Pharyngeal Arches

Ectodermal Cleft

- First cleft between 1st and 2nd arch


o Helps in the formation of external auditory canal
- Second cleft between 2nd and 3rd arch
o This cleft will overgrow the remaining clefts and establish the smoothness of the neck
- During the development, there is a gap between arches and membrane, before 1st and 2nd month of
birth this gap gets obliterated
- Anomaly
o Branchial cyst or Cervical cyst
Born with a selling in the angle of the mandible, anterior border of
sternocleidomastoid
Sometimes might open to the outside and release fluid
Cervical sinus or branchial sinus
If it opens outside and inside its called a fistula

Endodermal Pouch

- 4 pouches are formed


- Eustachian tube connects to the middle ear cavity coming from the pharynx
- First pouch
o Ventral portion forms the tongue
o Dorsal portion 1st and 2nd pouch unit to form a tubular structure called tubotympanic
recess or pharyngotympanic tube
It expands to form the middle ear cavity
Tympanic membrane is made up of all 3 germs layers
Outside ectoderm
Middle SOME mesoderm
Inside endoderm
- Second pouch
o Ventral portion forms the tonsil
- Third pouch
o Origin of inferior parathyroid and thymus gland
- Fourth pouch
o Origin of superior parathyroid and may contribute to the thyroid gland
- Thymus starts descending during development and pull the inferior parathyroid gland and gets stuck to
the lower portion of thyroid gland

69
The Pharyngeal Arches

Formation of Tongue

- Tongue develops in relation to the pharyngeal arches in the floor of the developing mouth
- At the floor of the first pouch:
o Midline swelling tuberculum impar
o 2 lateral swellings lingual swellings
- Swelling in relation to the 2nd, 3rd and 4th pouch
o Midline swelling Hyperbronchial eminence
Lower portion of HE is left behind which contributes to the epiglottis
- Parts of the tongue
o Posterior most
Derived from hyperbronchial eminence in relation to 4th pouch
Nerve: mandibular nerve
o Posterior 1/3
Derived from hyperbronchial eminence in relation to 2nd and 3rd pouch
HE of 3rd portion overgrows over the HE of 2nd pouch, making 3rd pouch the most
dominant during the formation of posterior 1/3 of tongue
Nerve: Glossopharyngeal nerve
o Anterior 2/3
Derived from the fusion of tuberculumimpar and lingual swellings
Nerve: Superior laryngeal nerve
- Frenulum attaches to the tongue to the oral cavity
o Function: support
- Anomaly
o Ankyloglossia Tongue tie: tip of tongue attached to the floor of oral cavity
o Ankyloglossia superior Tip of the tongue is attached to the palate (roof of oral cavity)

70
Fetal Circulation

Thyroid Gland

- There are 2 lobes joined by isthmus of the thyroid gland


- Secretes thyroxin
- Within thyroid gland have follicles that store thyroxin
o Between the follicles are parafollicular cells
- Behind the tuberculum impar, the epithelium proliferates to form a downward growth
o Thyroglossal duct
This downward growth is marked by a depression called foramen cecum
The duct extends from foramen cecum 4th pouch
It becomes bifid and enlarges to form the follicles of thyroid gland
The pouch is made up of endoderm which contributes to the parafollicular cells
- Anomaly
o Anomalies of Position
Ectopic Thyroid
Thyroid outside, seen in ovaries stroma ovarii
Lingual Thyroid
Thyroid lies under the mucosa of the dorsum of the tongue and may form
swelling leading to difficulty swallowing
Intra-lingual thyroid
Thyroid embedded in the musculature substance of tongue
Suprahyoid thyroid
Gland may lie in the midline of the neck, above hyoid bone
Infrahyoid thyroid
Gland may lie below hyoid bone but above normal position
Intrathoracic thyroid
Entire gland or part of it lies in the thorax

Parathyroid Gland

- Above and below thyroid gland


- Important in regulating calcium

Thymus Gland

- Its present in the thorax and the site for T-lymphocytes


- Develop during childhood and undergo regression in adult life

71
Fetal Circulation

Intra-Uterine Life

- Oxygenated and nutrient-enriched blood returns to the fetus from the placenta via the left umbilical
vein (note: oxygenated blood is carried by the LUV, not by an artery as in the adult)
- Some blood percolates through the hepatic sinusoids; most of the blood bypasses the sinusoids passing
through the ductus venosus and enters the future IVC
o Note: Liver is formed in septum transversum, so that is present in that area as well
- From future IVC, blood enters the right atrium, where most of the blood bypasses the right ventricle
through the foramen ovale to the left atrium
- From the LA, blood enters the LV and is delivered to fetal tissues via aorta
o The aorta between LV and ductus arteriosus is OXYGENATED ONLY
This gives oxygenated blood to the cranial end
o After ductus arteriosus, it is a mixture of OXYGEN AND CARBON DIOXIDE
o Aorta branches into 2 arteries:
Poorly oxygenated and nutrient-poor fetal blood is sent back to the placenta via right
and left umbilical arteries
- Some blood in the RA enters the RV; blood in the RV enters the pulmonary trunk but most of the blood
bypasses the lungs through ductus arteriosus which is connected to the aorta because
o Fetal lungs are not capable of performing their adult respiratory function because they are
functionally immature and the fetus is underwater (amniotic fluid). The placenta provides
respiratory function

72
Fetal Circulation

Intra-Uterine Life

- Deoxygenated blood from the cranial end goes to RA RV


- Which chamber contains both oxygenated and deoxygenated blood? Right ventricle
o Deoxygenated from cranial end
o Oxygenated Some blood trickles down RA when oxygenated blood comes from placenta via
umbilical vein

After Birth

- When the baby comes out and cries, it takes in oxygen


- There is an increase in pressure in LA and the flap between RA and LA closes (foramen ovale)
- When the umbilical cord is cut
o Umbilical artery goes under constriction and gets obliterated so major amount of blood is not
lost and is conserved within the baby
- Within 24 hours, ductus arteriosus and venosus get obliterated
o The inner layers proliferate and thus completely obliterate and form ligamentum strucutes
Ductus venosus Ligamentum venosum
Ductus arteriosus Ligamentum arteriosum
Left umbilical vein Ligamentum teres of liver
Umbilical artery Medial umbilical ligament

Coarctation of Aorta

- Narrowing of the artery


- The proliferation of DA will enter the lumen of the aorta and thus narrowing the aorta
o Post ductal coarctation - after the DA and aorta joining
o Preductal coarctation - before the joining
- Because of the narrowing, there is back flow into the cranial branch from the aorta causing a higher
pressure in the upper limbs and lower in the lower limb
o Pulse volume is low in lower limb and high in upper

73
Cardiovascular System

Introduction

- Cardiovascular system is the first major system to function in the embryo


- The primordial heart and vascular system appear in the middle of the third week
o This precocious cardiac development is necessary because the embryo cannot satisfy its
nutritional and oxygen requirements by diffusion alone
- Heart is formed in the splanchnopleuric mesoderm lying cranial to the prochordal plate
o This mesoderm contributes the cardiogenic area
- Layers of the heart
o Pericardium
Outside: somatopleuric pericardium (parietal layer)
Inside: splanchnopleuric pericardium (visceral layer)
o Myocardium
Derived from splanchnopleuric mesoderm
o Endocardium
Derived from splanchnopleuric mesoderm

Formation of Heart Tube

- Earliest sign of the heart is the appearance of paired endothelial strands angioblastic cords
o Formation of blood vessels is called angiogenesis
Blood vessels have 3 layers
o Near the yolk sac, the mesenchymal cells get transferred into angioblastic cells
Angioblastic cells arrange in a tubular fashion, first layer is the endothelium, muscular
layer derived from mesoderm
- These cords are formed in the splanchnopleuric mesoderm
o Some portion is within the septum transversum
o They canalize to form two thin heart tubes
The two heart tubes fuse by the pressure initiated by lateral folding single heart
tube
Craniocaudal folding puts it in its right position
- Splanchnopleuric mesoderm forms myocardium before and surrounds the heart tubes called
myoepicardial mantle or epimyocardial mantle
- Heart tube invaginates inside the pericardial cavity and gets completely surrounded by it
- Heart tube is dorsal to the developing GUT and ventral to pericardial cavity
o When the craniocaudal folding takes place, there is a switch in position and the heart tube
becomes dorsal to the pericardial cavity and ventral to the gut

74
Cardiovascular System

Formation of Heart Tube

- After fusion of heart tube


o The tube forms series of dilation:
Bulbus cordis
It lies at the arterial end of the heart
Divided into 3 parts
o Proximal (1/3)
It is dilated and does not have a special nam
o Middle (1/3)
Conus
o Distal (1/3)
Truncus ateriosus (TA)
Continuous distally with aortic sac
o Aortic sac is continuous with right and left
pharyngeal arch arteries dorsal aorta
Primitive Ventricle (Common Ventricular Chamber CVC)
Primitive Atrium (Common Atrial Chamber CAC)
Sinus venosus
In the venous end of the heart tube
Two horns are formed (left and right horn of the sinus venosus)

Sinus venosus Primitive atrium Primitive ventricle Conus TA Future aortic sac

Arterial and Venous Ends


75
Cardiovascular System

Formation of Heat Tube

Development of Veins Associated with the Heart

- Both horns of the sinus venosus receive blood from 3 important regions of the body
o Oxygenated blood from placenta
Formation of 2 veins
Right umbilical vein
Left umbilical vein
Carry well-oxygenated blood from the chorion
o Yolk sac supplies nutrition rich blood
Formation of 2 veins
Right vetallineum
Left vetallineum
Return poorly oxygenated blood from the umbilical vesicle
o Blood from the body wall
Formation of 2 veins
Right common cardinal vein
Left common cardinal vein
Anterior and posterior cardinal vein fuse to form the common cardinal vein
Return poorly oxygenated blood from the body of the embryo

76
Cardiovascular System

Overview of Heart Tube

Partitioning of the Primordial Heart

- Partitioning of the atrioventricular canal, primitive atrium and ventricle begins around the middle of
the 4th week and is essentially completed by the end of the 8th week
- Although described separately, these processes occur concurrently
- Sinus venosus slowly gets released from septum transversum and moves superiorly and posteriorly
- Primitive atrium divides into 2 atrium
- Primitive ventricle divides into 2 ventricles
o Right ventricle is formed by major portion of conus
Left ventricle is formed by a bit of conus and some by primitive ventricle
- Truncus arteriosus is divided into aorta and pulmonary artery

Partitioning of Atrium

- SV and PA are first connected by a wide opening


- Left horn of the sinus venosus shifts to the right due to the growth in the wall of the atrium
o LH becomes narrowed and almost empties into the right horn, it wont get dislodge because of
the atrial wall
LH becomes tributaries for RH
LH is behind the atrium
LH forms a structure called coronary sinus
LH becomes a narrow slit which has right and left venous valves

77
Cardiovascular System
Partitioning of the Primordial Heart

Partitioning of Atrium Continued

- RVV and LVV


o A small septum is formed where the RVV is opening which is called septum spurium
Formed by the cranial fusion of RVV and LVV
o RVV gets divided into 3 different regions
Valve of IVC
Valve of coronary sinus
Valve of cristae terminalis (junction between SV and PA)
- SV gets absorbed into the RA
o Within RA there is a demarketing point which shows the junction between SV and primitive
atrium sinus venarum
o Smooth portion of the RA is derived from SV

ATRIOVENTRICULAR CANAL

o Joins atrium and ventricle


o Anterior and posterior walls of endocardial cells
proliferate proliferating cells are called
endocardial cushions (atrio-ventricular cushions)
Grow towards each other and fuse forming
Right atrio-ventricular canal
Left atrio-ventricular canal
o Endocardial cushions give rise to septum intermedium

78
Cardiovascular System
Partitioning of the Primordial Heart

Partitioning of Atrium Continued

FORMATION OF INTERATRIAL SEPTUM

- The atrial chamber undergoes division into right and left halves by formation of two septa

- Septum primum
o It arises from the roof of CAC, to the left of septum spurium
o It grows downward towards the septum intermedium but does not fuse initially
o Note: throughout fetal life oxygenated blood reaches the RA from the placenta, this blood has
to reach LA. So communication between RA and LA is essential
o During the formation of the septum, first there is an opening called foramen primum/ ostium
primum
Blood flows from RA to LA through this foramen
o After the first opening, septum primum fuses with septum intermedium BUT before it fuses
there is a small opening at the top (by the breakdown of the upper part of SP)
Foramen secundum/ ostium secundum
Second opening so blood enters from right to left
When this is formed, the foramen secundum is called foramen ovale
o Upper edge of septum primum is thin Fossa Ovalis
- Septum Secundum
o It arises from the roof of CAC and stops right after the second opening
o Lower edge of the septum secundum is thick Anulus Ovalis
When the blood comes, the thick later allows blood to flow from right to left but not
left to right
- After birth, pulmonary vasculature is established
o Pulmonary vein brings blood into LA and these is an increase pressure in LA
o This rise in pressure approximates septum primum and secundum so foramen ovale is closed
o Patent foramen ovale when foramen ovale is slightly open
79
Cardiovascular System
Partitioning of the Primordial Heart

FORMATION OF INTERATRIAL SEPTUM

80
Cardiovascular System
Partitioning of the Primordial Heart

Partition of Atrium Continued

STRUCTURES CONTRIBUTING TO THE RA [3]

- Right half of the CAC or primitive atrium


- RAVC
- SV (Right horn) is absorbed into the RA by the enlargement of the sinuatrial orfice

STRUCTURES CONTRIBUTING TO THE LA [3]

- Left half of the CAC


- LAVC
- Portion of pulmonary vein

Partition of Ventricles

FATE OF BULBUS CORDIS

- A spiral septum appears within the truncus arteriosus and subdivides it into the ascending aorta and
the pulmonary trunk
- It is formed by union of right superior and left inferior truncus swellings or cushions

FORMATION OF INTERVENTRICULAR SEPTUM

- Its made up of two parts


o Muscular part
Due to the concentric growth of the musculature of the myocardium, there is not much
space to grow
So, the muscular portion gets compressed and from the pressure gets elevated
o Membranous part
This portion fills the remaining portion of the septum contributed by
Encocardial swellings (cushions)
Trunco-conal swellings
o Derived from neural crest cells
o They fuse in a spiral pattern, a spiral septum is formed which results in
the partitioning of the TA
One goes to RV pulmonary artery
One goes to LV Aorta
If membranous not formed Membranous Ventricular Septal Defect
Why not formed?
o No migration of neural crest cells can result in ventricular septal defect
o Defect in the conal swellings or defect in the cushions
Defect accompanied by persistant truncus arteriorsus

81
Cardiovascular System
Partitioning of the Primordial Heart

Partition of Ventricle Continued

FORMATION OF VALVES IN PA AND AORA

- Endocardium proliferate to form the flaps


- Pulmonic aorta (P2A)
o 1 posterior
o 2 anterior
- Aortic (A2P)
o 1 anterior
o 2 posterior

Congenital Anomalies of the Heart

Anomalies of Position

- Dextrocardia
o Chambers and blood vessels of the heart are reversed from side to side
- Ectopia Cordis
o Heart lies exposed (front of the chest) due to defective development of the chest wall

Defective Formation of Septa

- Atrial Septal Defect


o Foramen primum defect/ Osteum primum defect - it does not close
Septum primum may fail to reach the atrio-ventricular endocardial cushions and as a
result, the foramen primum persists
It can be caused by defective formation of AV endocardial cushions
There is a mixture of blood (oxygenated and deoxygenated)
o Foramen secundum defect/ Osteum secundum defect
Septum secundum may fail to develop, causing foramen secundum to remain open
o Patent foramen ovale
Septum primum and secundum may develop normally but the oblique valvular passage
between them may remain patent
The patency is significant only if there is shunt of blood through it
Mostly asymptomatic, diagnosed when gap is big --> has to be corrected surgically
o Occasionally, there is a premature closure of the foramen ovale (before birth) causing RA and
RV to undergo hypertrophy, while the left side of the heart is underdeveloped
- Ventricular Septal Defect
o Defects of spiral septum not completely formed called patent TA
Seen in either membranous or in muscular part of the septum
o AV canal defect or persistent AV canal

82
Cardiovascular System
Congenital Anomalies of the Heart

Defective Formation of Septa

- Patent Truncus Arteriosus


o Spiral septum may not be formed at all or there is a partial absence the septum leading to
communication between aorta and the pulmonary trunk
- Atrio-ventricular canal defect/ Persistent AV canal
o Defective formation of the AV cushions
o Can lead to condition in which all four chambers communicate
o Interatrial and interventricular septa are incomplete (as the normal contribution to these septa
from the endocardial cushions are lacking)

Combined Defects

- Fallots Tetralogy
o Pulmonary stenosis
Myocardium extends toward the mitral valve leaflets, so outlet becomes narrowed
o RV hypertrophy
o Ventricular septal defect
o Overriding aorta

Other Defects

- Taussig-Bing Syndrome
o Ventricular septal defect
Aorta arises from RV
- Ebstein Anomaly
o Valve leaflets are pushed below
o RV volume is decreased
o Atrialization occurs: some of RV is fused with atrium
- Coarctation of Aorta
- Patent Ductus Arteriosus
o Blood enters the pulmonary artery and to the lungs if the DA is open
o Heart cardiac murmur
o If opening is big ligation
o If opening is small anti prostaglandins

83