Embryology and CAH Flashcards
Origin of congenital sinus
Endodermal
Parts of urogenital system that are endodermal in origin are
Lower 1/3rd of Vagina and Vaginal epithelium
Intermediate mesoderm gives rise to
Genital ridge and ducts.
Genital ridge derivatives are
Gonads and Renal system.
Gonads develop at
5 wks
Sex of baby is decided by
SRY region or Testis determining factor.
SRY gene present means
Male
Medulla of gonads gives rise to
Testis
Cortex of gonads gives rise to
Ovary
Testis @ which week
7th week
Ovary @ which week
8th week
Genes associated with testis
SOX - 9
Genes associated with Ovary
RSPO - 4 and WnT - 4
1st feature to distinguish between Testis and ovary
Formation of testicular cords
Testis and ovary are indistinguishable till
10-11 wks
Blood - Testis barrier is formed by
Sertoli cells
For complete formation of ovaries _____ is required
Two X chromosome.
Turner’s syndrome
45XO - Gonads are ovary- No Y chromosome.
Streak ovaries - Coz of only one X chromosome.
Mesonephric Duct
Wolffian
Paramesonephric Duct
Mullerian
Ducts appear by
6 weeks
____ ducts disappear in Females
Wolffian
_____ ducts disappear in Males
Mullerian
Mullerian and wolffian ducts disappear by
9 weeks.
Sertoli cells secrete ____ at 7 th week.
Anti mullerian factor or Testis inhibiting Hormone.
Remnant of Mullerian duct in males.
Prostatic Utricle
Appendix of testis - Hydatid of Morgagni.
Leydig cells secrete _______
Testosterone.
Testosterone production begins @ ___
8 th week
Testosterone production is maximum @_____
15 weeks
_____ promotes wolffian duct production in males
Testosterone produced by leydig cells
Male internal genital organs formed from Wolffian ducts are
S - Seminal vesicle
E - Ejaculatory ducts
E - Epididymis
D - vas Deferens
_____ helps in formation of Male external genital organs from Lateral mesoderm
Testosterone from Leydig cells.
Appendix of testis
Remnant of mullerian duct
Appendix of Epididymis
From Wolffian duct or mesonephric duct
Efferent ductules of testis is derived from
Mesonephros.
Remnants of Pronephros
Kubelt tubercle or hydatid of morgagni
Remnant of caudal end Mesonephros
Paranephros
Remnant of Cranial end of Mesonephros
Epo-Nephros
Remnant of Mullerian duct in Females
Gartner’s duct.
After mesonephric duct gives rise to Ureteric bud it is called as
wolffian duct
Hydatid of morgagni in males
Remnant of Mullerian duct
Hydatid of Morgagni in females
Remnant of Pronephros or Kubelt tubercle
Anti mullerian Hormone deficiency
AMH is produced only in males to suppress MD
So in its absence - MD does not regress
MD form Female internal genital organs - FT, Uterus, Cervix and upper 2/3rd of vagina.
Wolffian duct - grows male internal and external genital organs .
Leads to Uterus herniation syndrome or Persistent Mullerian duct syndrome.
Persistent mullerian duct syndrome caused by
Deficiency of Anti mullerian hormone leading to non regression on Mullerian duct in male.
Not a cause of Ambiguous genitalia in males
AMH deficiency or persistent mullerian duct syndrome
Uterine herniation syndrome
Less space coz of both Male and Female internal genital organs being present. Cryptorchidism. Vas Deferens obstruction. Infertility Herniation of uterus .
Developments of ducts in females.
Since gonads are ovaries - no sertoli or leydig cells.
Since no Sertoli cells - no AMH or TIF so MD develops female Internal genital organs.
Since no leydig cells - no Testosterone - so Wolffian ducts regress and no Male Internal and external genitalia.
Remnants of Wolffian ducts in Females
Pronephros - Kubelt tubercle or hydatid of morgagni
Mesonephros - Cranial - Eponephros
Caudal - Paranephros.
Mesonephric duct - Gartner’s duct.
Lower 1/3 rd of vagina is derived from
Genital sinus / Sino-vaginal bulb
Sinovaginal bulb gives rise to
Lower 1/3rd of vagina
Vaginal epithelium is derived from
Endoderm - Genital sinus
Development of external genitalia
They develop from lateral plate mesoderm - Dorsal somatic part.
Depends on Testosterone levels.
If present - Male ext genitalia.
If absent - Female ext genitalia.
Genital tubercle
Penis / Clitoris
Genital Fold
Penile urethra / Labia minora
Genital Swelling
Scrotum / Labia majora
Sex of baby can be determined via USG by
14 weeks
Homologous organs
Same embryological origin
Homologous organ of Prostate
Skene or paraurethral glands
Homologous organ of Cowper or bulbourethral glands
Bartholin gland
Homologous organ of littre gland
Glands in labia majora and minora.
MCC of Ambiguous genitalia in male
Androgen Insensitivity syndrome or testicular feminizing syndrome
MCC of Ambiguous genitalia in females
CAH
MC structures affected in Ambiguous genitalia
Clitoromegaly.
Fusion of Labioscrotal folds.
Phallus (Penile Urethra)
True Hermaphroditism.
Both testis and ovary are present.
46XX is the most common stereotype.
Pseudohermaphroditism
Gonads of one sex and external genitalia of other.
Male Pseudohermaphroditism
Gonads - Testes - External genitalia of female
MCC- Androgen insensitivity syndrome
Female Pseudohermaphroditism
Gonads- Ovary - External genitalia - Male
MCC- CAH
DHEA - Steroid pathway
Pregnenolone to 17 hydroxypregnenolone to DHEA
Enzymes- 17 hydroxylase and 17,20 lyase
Pregnenolone to 17 hydroxypregnenolone.
Enzyme .?
17 hydroxylase.
Pregnenolone to aldosterone pathway
Pregnenolone to progesterone to deoxycortisone to cortisone to Aldosterone
Enzymes -3 beta HSD, 21 hydroxylase, 11 beta hydroxylase, 18 hydroxylase.
Pregnenolone to Progesterone. Enzyme
3 beta HSD
Progesterone to Deoxycortisone. Enzyme.
21 hydroxylase.
Deoxycortisone to Cortisone.
Enzyme
11 beta Hydroxylase.
Cortisone to Aldosterone. Enzyme.
18 Hydroxylase.
17- Hydroxypregnenolone to Cortisol pathway.
17- Hydroxypregnenolone to 17 OH Progesterone to Deoxycortisol to cortisol.
Enzymes- 3 beta HSD, 21 hydroxylase, 11 Beta Hydroxylase, 18 hydroxylase.
enzyme 3 beta HSD. which reaction’s.?
Pregnenolone to progesterone and 17 hydroxypregnenolone to 17 OH Progesterone.
21 Hydroxylase Enzyme. Which reaction’s.?
Progesterone to Deoxycortisone.
17 OH Progesterone to Deoxycortisol.
11 Beta Hydroxylase Enzyme. Which reaction.?
Deoxycortisone to Cortisone.
Deoxycortisol to Cortisol.
18 Hydroxylase Enzyme. Which reaction.?
Cortisone to Aldosterone.
Progesterone to Testosterone Pathway.
Progesterone to 17- OH Progesterone to Androsterone to Testosterone.
Enzymes- 17 hydroxylase and 17,20 lyase.
MC enzyme deficiency in CAH
21 hydroxylase
Progesterone to dexycortisone.
2nd MC Enzyme deficiency in CAH
11 Beta Hydroxylase.
Deoxycortisone to Cortisone.
Least common Enzyme deficiency in CAH
3 beta HSD- Hydroxysteroid dehydrogenase.
21 Hydroxylase is needed for production of ___ by Adrenals.
Cortico and mineralosteroids.
21 Hydroxylase is not needed for production of ____ by Adrenals
Progesterone and Androgens.
Pathogenesis of CAH - 21 hydroxylase.
21 hydroxylase is needed for production of Corticosteroids and mineralocorticoids by Adrenals.
Which provide negative feedback on ACTH.
Since no Cortico and mineralocorticoids - no negative feedback - inc ACTH - inc Progesterone and androgens.
Inc androgens causes _____ in CAH in females.
Ambiguous genitalia - Clitoromegaly, Labioscrotal fusion and phallus formation.
Precocious puberty - heterosexual.
Virilisation.
Short stature due to early epiphyseal fusion.
CAH in Males.
no ambiguous genitalia but other characteristics are present which are just normal male characteristics.
Heterosexual Precocious puberty in female causes
Virilisation, Hirsutism, Inc muscle mass, Deepening of voice and clitoromegaly.
Increased androgens effect + salt water wasting + Hyponatremia and hypokalemia + Hypotension=
CAH due to 21 hydroxylase deficiency
Increased Androgen effects + hypertension =
CAH due to 11 beta hydroxylase deficiency.
CAH with Hypertension.
11 beta Hydroxylase deficiency.
inc androgens- Ambiguous genitalia
inc deoxycortisone - hypertension.
Screening test for CAH
17 OH Progesterone.
if < 300 = not CAH
300 - 800 = do diagnostic test
> 800 = CAH
Diagnostic test for CAH
ACTH stimulation test.
Stimulate ACTH and check 17 OH Progesterone levels after 1/2 hr
if >1500 ng/dl = CAH
Mx of CAH
For Salt water wasting - Steroid of choice = Fludrocortisone.
Surgical removal of Phallus @ 4-5 yrs of age
For Corticosteroid deficiency = steroid of choice is age dependant
in Childhood - hydrocortisone - to prevent epiphyseal closure
@ puberty - Dexamethasone or prednisone
In pregnancy - Hydrocortisone - can not cross placental barrier.
Steroid of choice in CAH in childhood
Hydrocortisone - to prevent early epiphyseal closure
Steroid of choice @ puberty in CAH
Dexamethasone or Prednisone
Pregnancy in CAH females how to Mx.?
Steroid of choice is Hydrocortisone - does not cross placental barrier
@ 10 weeks - FISH - fluorescence In-Situ Hybridisation - If male or unaffected female - continue Hydrocortisone.
If affected female fetus - Give Dexamethasone to cross placenta.
Late onset CAH
@ puberty - inc androgens and progesterone.
normal genitalia but hirsutism, virilisation are present.
Dx is same as normal CAH
Pubertal woman with hirsutism - DDx
PCOS or late onset CAH
Virilisation Characteristics.
Female with secondary sexual characters resembling male. Hirsutism, inc muscle mass, Deep voice, Breast atrophy.
Gartner’s cyst
Tender, shiny No rugosities, not reducible, cough impulse is absent Well defined margins
Cystocele
Not shiny and tender Rugosities are present Reducible No clear margins Cough impulse is absent
MC cyst in vagina
inclusion cyst
MC cyst in Ovary
Follicular cyst