Embryology Notes FcpsWorld
Embryology Notes FcpsWorld
Embryology Notes FcpsWorld
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Institute for Fcps & MD/MS
FcpsWorld Notes
Embryology
(General & Special)
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1. Early development
Week 1
Once the ovum has been fertilized by the spermatozoon, a
zygote (single cell) is formed. This undergoes a rapid succession
of mitotic divisions (cleavage) without an increase in size,
forming blastomeres, and eventually a morulla (12-32
blastomeres).
- A hollow cavity (blastocoele) forms at around day 3, marking the blastocyst stage.
- The centrally placed cells are called inner cell mass (embryonic pole, or embryonic stem cells) and
ultimately form tissues of the embryo (embryoblast).
- The outer cells, called the outer cell mass, form the trophoblast, which plays an important role in
the formation of the placenta and the embryonic membranes.
At around days 5-6, implantation of the blastocyst on the endometrial lining of the uterus occurs.
Ectopic Pregnancy
An ectopic pregnancy is a complication of pregnancy in which the fertilized ovum is implanted in any
other tissue other than the uterine wall. Most ectopic pregnancies occur in the Fallopian tubes (tubal
pregnancy), but implantation can also occur in the cervix (placenta praevia), ovaries, internal os, or
abdominal cavity. The fetus produces enzymes that allow it to implant in varied types of tissues, and
thus an embryo implanted elsewhere than the uterus can cause great tissue damage in its efforts to
reach a sufficient supply of blood.
Week 2
Trophoblast cells surrounding the embryonic cells
proliferate and invade deeper into the uterine lining.
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Week 3
Gastrulation occurs, in which distinct layers are
formed from within embryo, which will later grow into
different organs. The epiblast (embryonic cells)
flattens into a bilaminar embryonic disc, composed of
2 germ layers: the upper ectoderm and the lower
endoderm.
As growth proceeds, the embryonic disc becomes pear-shaped, and a narrow streak appears on its
dorsal surface formed of ectoderm, called the primitive streak. The further proliferation of the cells
of the primitive streak forms a layer of cells that will extend between the ectoderm and the
endoderm to form the mesoderm.
Further thickiening of the ectoderm gives rise to the neural plate on the dorsal surface of the
embryo. The plate sinkw beneath the surface of the embryo to form the neural tube, which
ultimately gives rise to the CNS.
A notochord, derived from mesoderm, forms in the centre of the embryonic disc and on the ventral
surface of the neural tube. This notochord will eventually develop to form the vertebral column.
The primitive yolk sac becomes modified to become the secondary yolk sac, while a chorionic cavity
develops between the 2 layers of mesoderm. Eventually, the placenta develops.
Embryonic Period
The initially flat embryonic disc develops into a “C-shaped”
cylindrical structure. Cephalocaudal flexion (in the
longitudinal direction) and lateral folding (in the
transversal folding) occur simultaneously, forming the
abdominal wall, permitting a delimitation of the embryo.
This also leads to enclosure of mesoderm and endoderm
by the ectoderm, which later forms the epidermis.
Fetal Period
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The foetal period (9th week to 9th month) is about continued differentiation of organs and tissues,
most importantly this period is about growth both in size and weight.
Organogenesis
- Early development: Any organ develops from a primordium (bud) derived from one or more
germ layers found in the germ disc during early development.
- Embryonic period: After folding is completed, the primordial of many organs become easily
recognizable as a simple shape. Primordium undergoes changes in shape, size and site to
become anatomically recognizable.
- Fetal period: Differentiation of cells in the developing organ into specific cell types help with
maturation whereby the organ becomes capable of normal function.
Germ layer:
- Lungs: Endoderm – Ventral wall of primitive foregut
- Pleura: Mesoderm surrounding diverticulum
Primordium: Laryngotracheal diverticulum
Embryonic Period
1. The diverticulum is partially partitioned off by the formation of the
tracheoesophagal septum from the tracheoesophagal ridges/grooves on
either side. This divides the foregut into the laryngotracheal tube (ventral)
and the esophagus (dorsal).
2. The partitioned portion of the laryngotracheal diverticulum separates off by
splitting along the septum from the esophagus. The caudal end enlarges to
form the lung bud, which is surrounded by splanchnic mesoderm.
3. Several generations of branching progressively increases the surface area
for gas exchange. This branching takes place mostly dichotomously except
after the formation of the primary when the R. divides into 3 and L. into 2. By the end of the
embryonic period, the lungs have the correct appearance but are still immature.
Fetal Period
- Cells lining terminal sacs become progressively flattened (increase efficiency of gas exchange)
- Rich vasculature develops around the terminal sacs (increase perfusion of alveoli)
- Type 2 cells in terminal sacs secrete increasing amounts of surfactant (reduces surface tension
in the fluid in the sacs to facilitate easy expansion of lungs at birth. Hence premature birth
predisposes to respiratory distress syndrome)
- Endodermal cells differentiate into respiratory epithelium and glands
- Mesodermal cells give rise to cartilaginous plates, smooth muscles and connective tissue.
o Splanchnic mesoderm forms visceral pleura
o Somatic mesoderm forms parietal pleura
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Germ Layer: Mesoderm formed in neck by fusion of myotomes of 3rd, 4th and 5th cervical segments.
Hence, the diaphragm’s nerve supply is derived from the phrenic nerve (C3, C4, C5).
Primordium: Septum Transversum – An incomplete mesodermal partition on ventral aspect of
embryo caudal to developing heart. The incompleteness is due to 2 pleuroperitoneal canals dorsal
to it (one on each side) which allows communication between the pleural and peritoneal cavities.
Development
1. Pleuroperitoneal folds develop from the dorsolateral body wall growing ventromedially to fuse
with the septum transversum and the dorsal meso-oesophagus, thereby forming the
pleuroperitoneal membranes. This effectively closes the pleuroperitoneal canals.
2. The developing lungs growing caudally (especially at the periphery) helps add the peripheral
portions of the diaphragm from the body wall, as well as create the dome shape. Hence, the
periphery of the diaphragm shares nerve supply with the thoracic nerves.
3. Progressive caudal migration of the diaphragm results in the phrenic nerve taking a course more
in line with the body axis.
Diaphragmatic Hernia
Congenital hernia can occur as the result of incomplete fusion of
the 3 components. Abdominal contents can then be pushed up
through the hiatus into the thoracic cavity. The herniae occur at
the following sites:
- Pleuroperitoneal canal (caused by incomplete fusion of
pleuroperitoneal folds with septum transversum)
- Opening between xiphoid and costal origins of the diaphragm
- Esophageal hiatus
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The heart tube starts to bulge into the pericardial cavity. Meanwhile, the endocardial tube becomes
surrounded by a thick layer of mesenchyme, which will differentiate into myocardium (cardiac
muscle) and visceral layer of the serious pericardium. The
primitive heart has been established, and the cephalic end is
the arterial end and the caudal end is the venous end. The
arterial end is continuous beyond the pericardium with a large
vessel, the aortic sac.
5. Before birth, the foramen ovale allows oxygenated blood that has entered the R. atrium from
the IVC to pass into the L. atrium. At birth, however, owing to the raised BP in the R. atrium, the
septum primum is pressed against the septum secundum and fuses with it, and the foramen
ovale is closed, separating the atria. The lower edge of the septum secundum seen in the R.
atrium becomes the annulus ovalis, and the depression below this is the fossa ovalis. The R. and
L. auricles later develop as small diverticula from the R. and L. atria.
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Development of the Ventricles
1. A muscular ventricular septum projects upward from the
floor of the primitive ventricle. The space bounded by the
upper edge of the septum and the septum intermedium is
the interventricular foramen.
2. Bulbar ridges (spiral endocardial thickenings) appear in the
distal part of the bulbus cordis grow and fuse to form a
spiral aorticopulmonary septum. The proliferation of
bulbar edges and septum intermedium results in the
closure of the interventricular foramen.
3. The aorticopulmonary septum grows down and fuses with
the upper edge of the muscular ventricular septum to form
the membranous part of the septum. This effectively shuts
off interventricular communication; while ensuring R.
ventricular communication with the pulmonary trunk and L.
ventricular communication with the aorta.
Tetralogy of Fallot
This occurs when the bulbar ridges fail to fuse correctly to form the aorticopulmonary septum,
resulting in unequal division of the bulbus cordis, and consequent narrowing of the pulmonary trunk
resulting in interference with R. ventricular outflow. The anatomic abnormalities include large
ventricular septal defect; stenosis of pulmonary trunk; exit of aorta immediately above the
ventricular septal defect; and severe hypertrophy of the R. ventricle.
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Development of the GIT
The components of the GIT develop from the primitive
gut which is an endodermal tube surrounded by
mesoderm resulting from folding of the trilaminar germ
disc.
- Endoderm: Gives rise to lining epithelium and
parenchyma of glands in the form of tubular
outgrowths (e.g. liver, pancreas)
- (Splanchnic) Mesoderm: Differentiates into muscular
wall (typical 4 layers), blood vessels and connective
tissue in gut wall.
Germ layer:
- Stomach Walls: Endoderm of primitive foregut
- Greater momentum: Mesoderm – Dorsal and
Ventral Mesentery
Primordium: Fusiform swelling (dilatation in caudal
part of foregut, dorsal to septum transversum)
3. The dorsal mesogastrium grows and projects ‘sac-like’ towards the left-side and helps form the
lesser sac of the peritoneal cavity and the greater omentum in its caudal part.
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Development of Liver
1. The liver diverticulum appears on the ventral side of the foregut just caudal to the septum
transversum. It forms the gall bladder component (cystic) caudally and the liver (hepatic)
component cranially.
2. The hepatic part grows into the septum transversum and divides in a dichotomous fashion
repeatedly. The terminal (distal) parts of this branching system differentiate into the
hepatocytes, which secrete bile into the more proximal parts which will form the bile ducts.
3. As the liver becomes too large for the septum transversum, it grows out caudally into the
abdominal cavity and separates the ventral mesogastrium into the falciform ligament and the
lesser omentum.
Biliary Atresia
Failure of the bile ducts to canalize during development causes atresia (lack of a lumen). Jaundice
soon appears after birth; clay-coloured stools and very dark coloured urine is produced.
1. Loop formation
2. Coiling (cranial segment)
3. Physiological Herniation with
associated 90: counterclockwise
rotation. This occurs in the umbilical
cord which contains a space that is a
continuation of the primitive
peritoneal cavity.
4. Return to the abdominal cavity along
with a further 180: counterclockwise
rotation. This results in the sup.
mesenteric artery occupying a position
between the duodenum and the
transverse colon.
5. Fixation: Parts of the original
mesentery (all midgut viscera except
transverse colon) become attached to
the posterior abdominal wall,
rendering these associated segments
retroperitoneal.
6. Vitellointestinal duct is obliterated.
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Potential Complications
1. Failure to return will result in hernia in the umbilical region
2. Incomplete rotation (e.g. during return will result in coon being on the left side). Abnormal
adhesions form, which run across the anterior surface of the duodenum and cause obstruction
in the second part.
3. Reverse rotation (i.e. clockwise) results in duodenum lying anterior to the transverse colon. Also
causes duodenal obstruction, leading to vomiting.
4. Inadequate fixation gives abnormal motility to the gut which could predispose to complications
like volvulus (a loop getting twisted around itself and getting strangulated)
Meckel’s Diverticulum
This represents a persistent portion of the vitellointestinal duct. It may possess a small area of
gastric mucosa, and bleeding may occur from a “gastric” ulcer in its mucous membrane. Moreover,
the pain from this ulcer may be confused with pain from appendicitis. Should a fibrous band connect
the diverticulum to the umbilicus, a loop of small bowel may become wrapped around it, causing
intestinal obstruction.
Germ layer: Endoderm of the caudal end of the dorsal and ventral foregut
Primordia: Dorsal and Ventral Diverticula
- The ventral diverticulum which appears immediately caudal to the liver diverticulum.
- The dorsal diverticulum is located slightly cranial to the ventral diverticulum.
The duodenum develops from the caudal end of the foregut as well
as the cranial-most part of the midgut; hence its blood supply is from
both the celiac trunk (splenic artery and hepatic artery --- sup.
pancreaticoduodenal branch) and the sup. mesenteric artery (inf.
pancreaticoduodenal branch)
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Development of the Kidney
- Metanephros: Forms the permanent kidney. It appears in the 5th week and becomes functional
at the end of the 1st trimester. However, it is not responsible for excretion of waste products,
which is achieved by the placenta. Urine passed into the amniotic cavity mixes with the amniotic
fluid and is swallowed by the fetus to enter the intestinal tract and absorbed by the bloodstream.
The process then repeats.
o Nephrons (the excretory system) develop from the metanephric mesoderm in a similar
way as the mesonephric system. The mesodermal intermediate cell mass of the lower
lumbar and sacral regions develops into the metanephric tissue cap. Upon contact with
the elongating ureteric bud, it is induced to condense around the ureteric bud, forming
small renal vesicles, and becoming comma-shaped bodies, followed by S-shaped bodies,
and finally metanephric tubules.
The proximal end forms the Bowman’s capsule, which is deeply indented by
glomerulus
The distal end is in open connection with collecting tubules.
As the nephron lengthens, the PCT, DCT, and LoH develops.
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o The collecting system develops from the ureteric bud, an
outgrowth of the mesonephric duct. The bud penetrates
metanephric tissue, dilating to form the renal pelvis and the
branches repeatedly, into the major and minor calyces and finally
the collecting tubules.
Ascent of kidneys
The kidneys were initially located in the pelvic region and supplied by the pelvic
branch of the aorta. However, due to diminution of body curvature and
growth of body in the lumbar and sacral regions, the kidneys shift to a more
cranial position in the abdomen and becomes supplied by the arteries
originating from the abdominal aorta. The lower vessels then degenerate.
Renal Agenesis
This condition refers to the failure of development of one or both kidneys.
- Unilateral renal agenesis: Usually not of any major concern as long
as the other kidney is healthy. However, people with this condition
have considerably higher chances of hypertension.
- Bilateral renal agenesis: The absence of kidneys causes a deficiency
of amniotic fluid (oligohydramnios) in pregnant women. Normally,
the amniotic fluid acts as a cushion for the developing fetus.
Insufficient amniotic fluid may result in compression of the fetus,
resulting in further malformations. Most infants that are born alive
do not live beyond 4 hrs.
Ectopic/Pelvic Kidney
The kidney is arrested in some part of its normal ascent and usually
found at the pelvic brim. Such a kidney may present with no signs or symptoms and may function
normally. However, should it be inflamed, it may, because of its unusual position, give rise to a
mistaken diagnosis.
Horseshoe Kidney
This condition is the result of the fusion of the caudal ends of
both kidneys as they develop. Both kidneys commence to
ascend from the pelvis, but the interconnecting bridge becomes
trapped behind the inf. mesenteric artery so that the kidneys
come to rest in the low lumbar region. Both ureters are kinked
as they pass inferiorly over the bridge of renal tissue, producing
urinary stasis, which may result in infection and stone
formation. Surgical division of the bridge corrects the condition.
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Ectopic ureter
Instead of opening into the bladder, the ureter may open into the urethra, vagina or uterus. The
result is constant dribbling of urine (urinary incontinence).
A urorectal septum divides the cloaca into the anorectal canal and
urogenital sinus between the 4th and 7th weeks. The cloaca membrane
is divided into the urogenital membrane and the anal membrane.
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The mucosa of the bladder is formed by incorporation of the mesonephric ducts and ureters in the
trigone region, and is hence of mesodermal origin. However, the mesodermal lining is replaced by
endodermal epithelium with time, and eventually, the entire bladder is lined by epithelium of
endodermal origin.
The urethra is of endodermal origin from the urogenital sinus. In males, the distal (penile) part is
derived from the urethral plate. The surrounding connective tissue and smooth muscle tissues are
derived from splanchnic mesoderm.
Testis
Under the Y chromosome influence (SRY gene), the
primitive sex cords proliferate and penetrate deep
into the medulla to form the testis/medullary cords.
The testis cords develop and become horseshoe shaped in the 4th month. They comprise primitive
germ cells and sustentacular/Sertoli cells derived from the gonadal surface epithelium. Meanwhile
the cords near the testis hilum break up to form the rete testis, a network of tiny cell strands. At
puberty, the solid testis cords acquire a lumen to form seminiferous tubules which connect to the
rete testis. The mesenchyme of the gonadal ridge develop shortly after the onset of testis cord
differentiation to form the interstitial Leydig cells which lie between the testis cords. These cells
produce testosterone from the 8th week onwards to influence differentiation of genital ducts and
external genitalia.
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Ovary
The primitive sex cords dissociate into irregular
cell clusters containing groups of primitive
germ cells and occupy the medullary part of
the ovary. The medullary cords later disappear,
and are replaced by vascular stroma to form
the ovarian medulla.
Origin Structure
Processus Parietal and visceral
vaginalis layers of tunica vaginalis
Transversalis Internal spermatic fascia
fascia
Int. oblique Cremasteric fascia and
muscle
Ext. oblique External spermatic fascia
Transversus (does not cover path of
abdominis migration)
The processus vaginalis is an evagination of peritoneum into the ventral abdominal wall. It follows
the course of the gubernaculums into the scrotal swellings and forms the inguinal canal together
with the muscular and fascial layers of abdominal wall. Its connection with the peritoneal cavity is
obliterated at or shortly after birth.
The descent of the testis is controlled by the outgrowth or regression of the extra-abdominal portion
of the gubernaculums, increase in intra-abdominal pressure due to organ growth and hormonal
influences, e.g. androgens and Mullerian-inhibiting substances.
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Congenital Inguinal Hernia
This occurs when the processus vaginalis is unobliterated, and intestinal loops descend into the
scrotum via the inguinal canal from the deep inguinal ring through the superficial ring. The remains
of the processus vaginalis form the hernial sac.
Cryptorchidism
This refers to imperfect descent of the testis, which could be due to abnormal androgen production.
This results in inability to produce mature spermatozoa as the temperature within the body retards
spermatogenesis. The descent may be incomplete, and the testis fails to reach the floor of the
scrotum and may be found within the abdomen, within the inguinal canal at the superficial inguinal
ring, or high up in the scrotum. Maldescent, in which the testis travels down an abnormal path, and
may be found in the superficial fascia of the ant. abd. wall above the inguinal ligament, in front of
the pubis, in the perineum or in the thigh.
Genital Ducts
2 pairs of indifferent genital ducts, the mesonephric/Wolffian and paramesonephric/Mullerian
ducts, are initially present in both males and females. Their development is influenced by hormones.
Male Female
Mesonephric / Testosterone, major androgen Absence of testosterone causes
Wolffian ducts produced by Leydig cells, causes regression of these ducts
virilisation of these ducts
Paramesonephric Mullerian-inhibiting substance Oestrogens (maternal, placental, foetal)
/ Mullerian ducts (MIS) / Anti-mullerian hormone and absence of MIS causes ducts to
(AMH) produced by Sertoli cells develop into uterine tubes, uterus, and
causes regression of these ducts upper part of the vagina
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Male Genital Ducts
- Efferent ductules: Arise from mesonephric
excretory tubules. Connect to rete testis.
- Mesonephric duct: Main genital duct
o Elongate and become highly
convoluted near efferent ductules to
form epididymis
o Obtain thick muscular coat to form
vas deferens from tail of epididymis to seminal vesicles
o Forms the ejaculatory ducts beyond the seminal vesicles
Vagina
The vagina is of dual origin:
- Sinovaginal bulbs: These are evaginations from the pelvic
part of the urogenital sinus which proliferate to form a solid
vaginal plate. By the 5th month, it will be completely
canalized to from the lower part of the vagina. The lumen
is separated from the urogenital sinus by the hymen.
- Vaginal fornices: These wing-like expansions of the upper
part of the vagina form around the end of the uterus.
These are of paramesonephric origin.
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Agenesis of the Uterus
This is a rare condition where the uterus is absent as the result of a failure of the paramesonephric
ducts to develop.
Infantile Uterus
This is a condition in which the uterus is much smaller than normal and resembles that present
before puberty. Amenorrhea is present, but the vagina and ovaries may be normal.
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Male Female
Development Influenced by androgens Stimulated by oestrogens
Genital - Initially located in inguinal region Enlarge to form the labia majora
swellings - Move caudally and fuse, each making
up half the scrotum
- Halves separated by scrotal septum
Genital - Rapidly elongates, pulling urethral Elongates slightly to form the clitoris
tubercle folds forward to form urethral groove
Urogenital - Extends along the caudal aspect of Remains open to form vestibule
groove the elongated genital tubercle
- Lined by endodermal cells to form a
urethral plate
Urethral folds - Fuse over urethral plate to form Do not fuse; Forms the labia minora
penile urethra at end of 3rd month.
- The canal does not extend to the tip
of the phallus
- Ectodermal cells from the tip of the
glans penetrate inward to form
epithelial cord at the 4th month
- Canalizes to form the external
urethral meatus.
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