Flashcards in Embryology Deck (139)
What is the difference between embryological age and gestational age?
Embryological age is usually about 2 weeks less
Gestation starts after the beginning of the last menstrual period
What is oxygen tension at the third week?
What embryological changes have occurred by the 3rd week?
- Formation of trilaminar disc (mesoderm)
- CNS formation
- Somite formation
- Blood vessel initiation
What placental changes have occurred by the 3rd week?
Initiation of placental villi
What embryological changes have occurred by the 4th week?
- Closure of neural tube
- Heart, face and arm initiated
- Umbilical cord
What placental changes have occurred by the 4th week?
- Elaboration of placental villi
What embryological changed have occurred by the 5th week?
Face and limbs continue
What embryological changed have occurred by the 6th week?
Face, ears, hands, feet, liver, bladder, gut, pancreas
What embryological changed have occurred by the 7th week?
Face, ears, fingers, toes
What embryological changed have occurred by the 8th week?
Lungs, liver, kidneys
What other changes have occurred by the 8th week?
- Placental elaboration continues, development of villi
- Placental endocrinology becomes dominant
- Cytotrophoblast plugs in spiral arteries lost over next 2 weeks
How does O2 tension change by week 10?
What is the length of the foetus by the 3rd week?
What is the length of the foetus by the 4th week?
What is the length of the foetus by the 5th week?
What is the length of the foetus by the 6th week?
What is the length of the foetus by the 7th week?
What is the length of the foetus by the 8th week?
How does the weight of the foetus change over the three trimesters?
Epiblast and hypoblast present at ~9 days (~0.1cm wide)
Small developing conceptus present at ~5-6 weeks (~1cm wide)
- Can include everything from day 1 onwards, baby and placenta
Developing conceptus present at ~3 months (~7cm wide)
Anything derived from a fertilised egg
What are the 4 repeated processes which achieve embryology?
What is proliferation in response to in general?
GF, receptor expression, cell survival
All via para- or autocrine signalling
What is movement in response to in general?
Chemoattractants, cognate receptors, facilitated (via remodelling & proteases)
What is differentiation in response to in general?
Paracrine regulation, receptor expression, loss of proliferation
What is cell loss controlled by in general?
Programmed cell death controlled by mainly paracrine factors
What is concentration signalling?
The strongest signals are received by cells located closer to the source of the signalling molecules e.g. limb bud formation
What are HOX genes?
Establish A-P (anterior-posterior) axis, vertebral differences, CNS divisions, patterns in limbs
What activates HOX?
Retinoic acid (VitA derivative)
What is a blastocyst?
A bilaminar disc comprised of an epiblast and a hypoblast layer
What does gastrulation form?
A 3-layer conceptus comprised of the ectoderm, mesoderm and endoderm
Where does gastrulation occur?
Down the primitive streak
What are the three steps in gastrulation?
- Epiblast cells migrate towards the centre
- Epiblasts differentiate into mesoderm cells and move down into the new mesoderm layer
- Hypoblast cells apoptose and are replace by endoderm cells
What does the endoderm form?
Gut, liver and lungs
What does the mesoderm form?
Skeleton, muscles, kidneys, heart and blood
What does the ectoderm form?
Skin and CNS
What is formed after gastrulation?
How is the neural canal formed?
The ectoderm proliferates to form the neural plate, with no proliferation at the neural groove (negative stimulation of notochord)
What happens to the body cavity after day 21?
The body cavity closes
What happens to the yolk sac by day 28?
The yolk sac pinches off and becomes the umbilical cord (allantois)
What happens during the 2nd month of development?
The limbs develop (days 28-56)
Internal tissues develop - heart, lungs & gut
When will the conceptus look human (foetal)?
How does the CNS develop from days 22-23?
Tissues fuse down midline leaving anterior neuropore and posterior neuropore
When should the neuropores close by?
What is spina bifida?
Failure to complete neurulation
- Doesn't fuse completely, can occur towards top or bottom of spine
- Can result in faulty neurology in lower body
Which type of spina bifida has a better prognosis; top or bottom?
What is myelomeningocele?
Neural tissue is found in bulge
What is meningocele?
No neural tissue in bulge
What is spina bifida occulta?
Hair growth over area affected, no bulge
How are the vertebrae formed at the bulge?
No vertebral formation at bulge
Suggests bone growth dependent on neural tissue growth
What is the incidence of spina bifida?
1-2 per 1000
Does surgery help the anatomical and functional problems of spina bifida?
Anatomical not functional
What can be taken very early in pregnancy to prevent spina bifida and anencephaly?
What is anencephaly?
Reduced brain development
(Literally, lack of head)
What is the incidence of anencephaly?
1-8 per 10,000 births
F more than M
What is the embryological cause of anencephaly?
Failure of the anterior neuropore to close
What happens by day 21 in the development of the heart?
The two endocardial tubes fuse into a primitive heart tube
What layer do the endocardial tubes develop from?
What is MacDonald's arc shape?
The horseshoe shape formed by the joining of the primitive heart tube at the cranial end
What happens to the heart development between days 23-28?
Undergoes turning action (anti-clockwise) and the 4 chambers form
When does blood flow begin?
How do the atria and arteries rotate around each other?
Atria rotate behind the arteries
What happens to the heart development between days 17-28?
Head-tail folding -> aids heart rotation and heart movement more internally
What physiological changes result from the pressure of the folding head of the heart?
- Pushes the heart to the centre of the body
-Squashes the atria (less muscular than ventricles)
What heart changes occur at birth?
The ductus arteriosus and the foramen ovale close
What is the ductus arteriosus between?
Pulmonary artery and descending aorta
What is the foramen ovale between?
The right and left atria
When does the forelimb bud appear?
When does the hind limb bud appear?
Which layer do the limb buds grow from?
Lateral plate mesoderm
By what day are the limbs fully formed and patterned?
What is achondroplasia?
FGF23 gain of function mutation, which stops conversion of cartilage to bone
Concerns limb elongation not primary formation, so detail is there but the limbs aren't very long
What was thalidomide used to treat?
What did thalidomide affect in foetus'?
Limbs, eyes, heart, alimentary/urinary tracts, blindness, deafness
How many infants were affected?
~10,000 infants affected with a 50% survival rate
What is thalidomide currently used to treat?
Leprosy and other cancers
What genes regulate limb development?
Shh - Sonic Hedgehog protein - zone of polarising activity
FGF8 - fibroblast-like growth factor 8 - apical ectodermal ridge
How does thalidomide cause negative effects?
Interferes with blood vessel development which led to apoptosis and death of developing cells
What is amelia?
"Prolonged exposure" to thalidomide
Complete lack of limb growth
What is phocomelia?
"Short exposure" to thalidomide
Limbs are a lot shorter but hands and feet still develop
What is polydactyly?
Increased number of fingers or toes
What is the pronephros?
The first part of the urogenital system to develop
-Has no excretory function, solely developmental, degenerates as the mesonephros forms
What is the mesonephros?
Connects to the cloaca, has limited excretory function
What is the metanephros?
What happens after the mesonephros has formed?
-Metanephric ducts grow out of the cloaca and begin to form kidneys
- Mesonephric ducts begin to differentiate into testes/apoptose in F
How does the blood supply of the kidneys change as they develop?
Vascular buds initially grow from kidney and invade common illiac arteries
As the kidneys move cranially, form new vessels then induce regression of old vessels
What layer does the bladder form from?
Endoderm, apart from trigone (mesodermal) which forms from mesonephric duct
What is the trigone?
Signals filling of the bladder
What kidney developmental errors can occur?
- Renal agenesis (degeneration of ureteric bud): unilateral (1:1000, L > R); bilateral ("Potter's syndrome", oligohydramnios)
- Abnormal shaped kidneys
- Abnormal ureter - bifid ureter, double kidneys, supernumerary kidneys (extra kidney)
- Pelvic or horseshoe-shaped kidney - kidney doesn't ascend or kidneys fuse caudally to horseshoe shape
-Bladder exstrophy - protrusion of bladder through abdominal wall
What is the paramesonephric duct?
Mullerian ducts -> female ductal systems
What is the mesonephric duct?
Wolffian duct -> male ductal systems
How do the cells that make gametes develop?
Primordial germ cells found outside the embryo in the yolk sac -> move into embryo -> move into developing genital ridges
What is the difference between early male and female genital development?
Gonads are identical in both sexes and indifferent before primordial germ cells move in (week 7)
When does the urogenital ductal system develop?
What gene causes the male ductal system to form?
What happens to the mesonephric tubes in males and females?
M - become the testes
F - not connected to the ovaries and develops separately
What do the gonads arise from?
Intermediate mesoderm within urogenital ridges
How does urogenital development proceed in SRY -ve?
Female path (~9th week onwards)
What do the gonads develop into?
Testis containing spermatogonia, Leydig cells, Sertoli cells
What do the Leydig cells produce?
Testosterone -> supports growth of mesonephric ducts (absence -> regression)
What happens to some of the testosterone produced?
Converted to DHT -> supports development of prostate, penis and scrotum
What do the Sertoli cells produce?
AMH (anti-Mullerian hormone)/MIS (mullerian inhibiting substance) -> induces regression of paramesonephric ducts (absence -> persistance of paramesonephric ducts)
What forms the ureters?
What do the mesonephric ducts form?
Rete testes, efferent ducts, epididymis, vas deferens, seminal vesicle, trigone of bladder
(testes and trigone)
What does the urogenital sinus form?
- Bladder, prostate gland, bulbourethral gland, urethra
- Bulbourethral glands, lower 2/3rd of vagina
How do the testes move inside the abdominal/pelvic cavity?
Testes arise in lumbar region and descend into pelvic cavity via inguinal canal
Why is there this movement?
The testes are tethered to the anterior body wall by the gubernaculum
The growth and elongation of the embryo and shortening of the gubernaculum pulls testes through body wall
What do gonads develop into in SRY -ve?
Develop into ovary containing oogonia and stromal cells
What do the paramesonephric ducts form?
Oviducts, uterus, upper 1/3rd of vagina
What is hCG?
Human chorionic gonadotrophin
When is the hCG peak? Why is this significant?
8 weeks after last menstrual period
Drives testosterone production
What are the complications of undescended testes?
Increased risk of cancer
Do not function normally
What is hypospadias?
Incomplete fusion of urethral folds -> urethra exits penis early
What can Mullerian duct anomalies result in?
Abnormal fusion of ducts e.g. two uteruses
What is persistant Mullerian duct syndrome?
Occurs in M with mutations in AMH/MIS or receptor
No inhibition so paramesonephric ducts persist
Testis either sit by ovaries or one/both can descend
Testosterone/DHT produced so normal external genitalia/ducts
What is androgen insensitivity syndrome?
Occurs in genetic (XY) M with mutations in androgen receptor
Lack of virilisation (androgens have no effect)
Normal F external genitalia but undescended testes
Mesonephric ducts rudimentary due to testosterone loss
Normal MIS production causes Mullerian duct regression so no oviducts, uterus or upper 1/3rd of vagina
What is congenital adrenal hyperplasia?
Occurs in genetic females with no 21-OH enzyme (no cortisol) -> overproduction of ACTH and overactive adrenal glands
Leads to increased weak androgen production (DHEAS) -> weak virilisation -> enlarged clitoris, partial or complete labia majora fusion
Internal genitalia all F - testes absent
When does the face develop?
How does the face develop?
Mesenchyme apoptoses pulling eyes and nostrils towards midline
Grooves filled in by bulk tissue movement (clefting results if this doesn't happen)
Results in two different halves of face
When do the lungs start to develop?
How many primary bronchi are there?
3 right and 2 left
When is surfactant produced?
From week 25
What are the stages of lung development?
Embryonic - weeks 3-4
Pseudoglandular - weeks 5-16
Canalicular - weeks 16-26
Saccular - week 26-birth
Alveolar - month 8-childhood
What happens during the embryonic and pseudoglandular stages of lung development?
- Formation of major airways
- Formation of bronchial tree and portions of respiratory parenchyma
- First formation of acinus
What happens during the canalicular stage of lung development?
- Last generations of lung periphery formed
- Epithelial differentiation
- Air-blood barrier formed by blood capillaries migrating closer to bronchioles
What happens during the saccular stage of lung development?
- Expansion of air spaces
- Surfactant detectable in amnionic fluid
What happens during the alveolar stage of lung development?
What is respiratory distress syndrome?
Low physiological surfactant levels
Incidence ~1% of all births
How does premature birth affect RDS incidence?
24 weeks: 100%
26-28 weeks: 50%
30-31 weeks: 25%
What is surfactant composed of?
40-45% DPPC (reduces alveolar tension)
40-45% other phospholipids
5% other proteins
Trace cholesterol and other components
How can in utero production of surfactant be increased?
What is the half-life of surfactant?
What cells produce surfactant?
What is the function of surfactant?
Induce low surface tension in alveoli
What are teratogens?
Factors that dysregulate patterning
What can happen if teratogens are present earlier in development?