Lecture 6 & 7 - Urogenital System I & II Flashcards
1
Q
What germ layers gives rise to the urogenital organs?
A
Almost only mesoderm, except:
- Adrenal medulla: ectoderm
- Labioscrotal swelling and urogenital sinus: endoderm
2
Q
Embryological origin of the male parts and trigone? 3 names.
What does this include?
A
Mesonephric duct = Wolffian duct = male duct
Trigone Efferent ducts of the testes Epididymis Vas deferens Seminal vesicles Ejaculatory ducts
3
Q
Embryological origin of the female parts? 3 names
What does this include?
A
Paramesonephric duct = Mullerian duct = female duct
Fallopian tubes
Uterus
Cervix
Upper 2/3rds of vagina
4
Q
Embryological origin of the ureters and collecting system? Describe the development of this structure
A
Ureteric bud
Most caudal mesonephric tubule is surrounded by metanephric blastema => differentiates into ureteric bud arising as a diverticulum of the mesonephric duct (bud grows laterally/dorsally and induces the metanephros)
5
Q
Embryological origin of urogenital system from the bladder down (excluding gonads and their tubing)?
A
Urogenital sinus
6
Q
What is the cloaca?
A
Common chamber into which urinary, genital, and GIT converge
7
Q
What is Potter syndrome? Pathology?
A
P = pulmonary hypoplasia O = oligohydramnios T = twisted face T = twister skin E = extermity defects R = renal failure
Pathology: oligohydramnios => not enough amniotic fluid => fetus does not produce urine => compression of developing fetus
8
Q
5 causes of Potter syndrome?
A
- PCKD
- Obstructive uropathy (valves)
- Esophageal atresia
- Bilateral UPJO
- Megaureter
9
Q
List 7 potential renal congenital abnormalities?
A
- Horseshoe kidney
- Renal agenesis
- MCDK = Multicystic dysplastic kidney
- Duplicated Collecting System
- UPJO = Ureteropelvic Junction Obstruction
- Pelvic kidney
- ARPKD = Autosomal Recessive Polycystic Kidney Disease
10
Q
What is the trigone’s embryological origin?
A
Connection between the mesonephros to the cloaca through the mesonephric ducts
11
Q
When does the pronephros disappear during embryological development?
A
Gone after week 4
12
Q
When does the mesonephros disappear during embryological development?
A
Gone after 1st trimester
13
Q
What does the pronephros give rise to when it disappears?
A
Mesonephric ducts
14
Q
What gives rise to the trigone in females?
A
Mesonephric ducts
15
Q
From what germ layer do the kidneys develop?
A
Anterior intermediate mesoderm
16
Q
When does the metanephros develop?
A
After 8 weeks
17
Q
What connects the metanephros to the ureteric bud?
A
Ureteropelvic junction
18
Q
What connects the ureteric bud to the UG sinus/cloaca?
A
Ureteral orifice of trigone
19
Q
What is UPJO (Ureteropelvic Junction Obstruction)?
A
Abnormal placement of the ureteropelvic junction leading to obstruction
20
Q
What induces the metanephros to become the kidney?
A
Ureteric bud
21
Q
What is MCDK (Multicystic dysplastic kidney)?
A
Failure of ureteric bud to get to and induce the metanephros to become the kidney causing failure of formation of the kidney as a functional set of glomeruli
22
Q
What connects the gonad to the mesonephric duct in the male?
A
Efferent Ducts => epididymus => vas Deferens
23
Q
What connects the gonad to the paramesonephric duct in the female?
A
Fallopian tube => uterus => cervix
24
Q
Describe the steps of kidney formation.
A
- Step 1: ureteric bud and metanephros induce each other to create the kidney and collecting system
- Step 2: ascendance of kidney from sacrum up the chest while ureteric bud bifurcates/branches 14-15 times into calyces, infundibula, and collecting ducts
- Rotation/Revascularization: as the kidney ascends it gains and loses blood supplies: iliacs => aorta
25
What EXACTLY does the metanephros develop into?
1. Glomerulus
2. Proximal tubule
3. Loop of Henle
4. Distal tubule
26
What EXACTLY does the ureteric bud develop into?
1. Collecting ducts
2. Calyces
3. Renal pelvis
4. Ureter
27
What are the 2 insertions of the ureteric bud?
1. Cloaca
| 2. Metanephros
28
What is the most common cause of an abdominal mass in a child?
MCDK = multicystic dysplastic kidney
29
What is hydronephrosis?
Swelling of a kidney due to a build-up of urine
30
What does MCDK look like on an ultrasound?
Beehive
31
What is the renal infundibulum?
Passage from the calyx to the renal pelvis
32
What anomalies can result from abnormal step 2 of kidney development, aka ascendance?
Duplications of collecting system if ureteric bud bifurcation happens too soon:
1. Complete duplication: 2 ureters on one side
2. Partial duplication: split ureter half-way between kidney and bladder
3. Bifid pelvis: split ureter at the renal pelvis
33
What are 3 potential road blocks to the kidney's ascendance?
1. Vasculature
2. Malformation: horseshoe kidney, where the inferior poles of the kidneys fuse, forming a horseshoe kidney that crosses over the ventral side of the aorta until it is blocked by the IMA
3. Masses
34
Consequence of horseshoe kidney on collecting system?
Ureteropelvic junction obstruction due to abnormal angle between the 2
35
In a person with a right pelvic kidney, where is the right adrenal located?
Normal spot
36
What anomalies can result from abnormal step 3 of kidney development, aka revascularization? How common is this? What happens exactly?
Kidneys have multiple arteries/veins
15% of people
When the vessels do not involute along the way, you get multiple arteries/veins
37
How does the urogenital sinus form? When?
At 30 days the urorectal septum splits the cloaca into the urogenital sinus and the anorectal canal
38
How does the trigone of the bladder form?
Urogenital sinus grows and absorbs part of the Wolffian duct distal to the ureteric bud - this part of the Wolffian duct becomes the trigone
39
Where is the trigone of the bladder located?
Middle bottom
40
What does the connection between the Wolffian duct and the ureteric bud become? Does this occur laterally or medially?
Ureteral orifice
Laterally
41
What does the insertion of the mesonephric ducts into the urogenital sinus become? Does this occur laterally or medially?
Ejaculatory duct
Medially
42
What is vesicoureteral reflux? What can this lead to?
Urine moves from bladder to ureter
Can lead to hydronephrosis, cystitis, or pyelonephritis
43
What is cystitis?
Bladder infection
44
What are UVJ obstructions?
Ureterovesicular junction obstructions
45
What is a ureterocele?
Obstruction of the ureteral orifice during embryogenesis, with incomplete dissolution of the Chwalla membrane, which is a primitive, thin membrane that separates the ureteral bud from the developing urogenital sinus
46
What is special about the trigone of the bladder?
Develops, looks, and acts differently compared to the rest of the bladder
Full of receptors and is where the ureter plugs into the bladder
47
What is an ectopic ureter? In this more prominent in males or females?
Uterer does not insert into the trigone:
- ureter inserts distal to the bladder neck (e.g. in UG sinus), leading to incontinence (continence mechanism in neck of bladder)
- ureter inserts in a more obstructed region than the trigone => obstruction of urethral orifice
More common in females
48
What rule do ectopic ureters follow? Explain.
Weigert-Meyer rule: when a collecting system is duplicated, ureters insert separately into the bladder and the upper pole is the ectopic one that inserts medially and is obstructed
49
Do ectopic ureters in men often result in incontinence? Explain.
NOPE because their continence mechanism is the external urinary sphincter in the penile urethra
50
6 potential causes of hydronephrosis in children?
1. Vesicoureteral reflux
2. UPJO
3. Megaureter
4. Ureterocele
5. Urinary obstruction with posterior urethral valves
6. MCDK/ARPKD
51
What is a megaureter?
Congenital abnormality in which the ureter is very big and distended and cannot conduct peristalsis, therefore cannot eject urine
52
What is ARPKD?
Genetic disease with abnormal cyst growth in kidneys
53
What would bilateral UPJO or megaureter cause?
Potter syndrome
54
Most common cause of Potter syndrome?
Posterior urethral valve leading to obstruction => obstructing membrane in the posterior urethra, which causes the ENTIRE urinary system to be obstructed
55
2 potential causes of hydronephrosis in adults?
1. Kidney stones
| 2. Cancer
56
4 most common places where kidney stones lodge?
1. UPJ
2. Over the iliacs
3. UVJ
4. Ureteral orifice
57
What are the first 2 steps in the differentiation of the genitals? When does each occur? What are the next steps dependent on?
1. 5 weeks: genital ridges next to the developing mesonephros (by having primordial germ cells migrate from yolk sac) and the primitive sex cord from mesenchymal cells
2. 6 weeks: paramesonephric ducts form lateral to the nephric ducts
Next steps depend on the presence or absence of the SRY gene on the Y chromosome = sex-determining region Y
58
Describe the genital development in the presence of the SRY gene in males. 4 steps
1. Primitive sex cord enlarge and are populated by Sertoli cells/germ cells and the genital ridges become testes
2. Sex chords are separated further from their surface by tunica albuginea => become the seminiferous tubules, which eventually join the efferent ducts
3. Sertoli cells secrete Mullerian Inhibiting Substance (MIS) starting at week 8 => Mullerian duct involutes and its cells undergo apoptosis + keeps Wolffian duct intact
4. Leydig cells differentiate within the sex chords and produce testosterone by week 8 and shut down at week 18 until puberty
5. 5-alpha reductase makes DHT from testosterone => DHT causes the development of the external genitalia: penis, scrotum, penile urethra
59
Timing of Leydig cells development in males?
Week 8-10
60
Describe the genital development in the absence of the SRY gene in females. 4 steps
1. Primitive sex cord (mesothelium) develop into ovarian follicles and ridges becomes ovaries
2. In the absence of MIS the Mullerian ducts develops and the Wolffian ones regress with cell apoptosis
3. Mullerian ducts develop into: fallopian tubes, uterus, and upper 2/3rds of vagina + 3 ligaments develop from mesoderm
4. In the absence of DHT, the female phenotype develops: clitoris, labia majora and minora
61
Timing of Mullerian duct differentiation in males?
Week 8-10
62
Until when are the male and female genitalia indistinguishable? Describe the early indifferentiated state. What does each become? Is growth of these tissues dependent on hormones?
Weeks 7-9
1. Genital eminance => genital tubercle
2. Clocal membrane => urogenital membrane
3. Cloacal folds => urogenital folds
4. Labioscrotal swellings
GROWTH OF THESE IS INDEPENDENT OF SEX HORMONES
63
What do the external genitalia develop from? What does each give rise to in both males and females?
Mesodermal tissue located around the cloaca
1. Pair of labioscrotal swellings: scrotum and labia majora
2. Pair of urogenital folds: penile urethra and labia minora
3. Anterior genital tubercle: penis and clitoris
4. Urogenital groove: lumen of penile urethra and vulvar vestibule
64
What does the presence or absence of MIS determine?
Which INTERNAL genitalia will develop
65
What does the presence or absence of DHT/testosterone determine?
Which EXTERNAL genitalia will develop
66
What do we call the remnant of the Mullerian duct? Other name?
Appendix testis = hydatid of Morgagni
67
What do we call the remnant of the Wolffian duct? 2 names
Appendix epidydimus = appendix vesiculosis
68
What is the default sex?
Female
69
Other name for urogenital groove?
Urogenital membrane
70
How does the penis develop in males?
Urogenital folds fuse and the genital tubercle elongates to form the penile shaft and glans
71
How does the clitoris develop in females?
Genital tubercle bends inferiorly to form the clitoris
72
What does the surface epithelial tag of the penis form? How?
Forms small region of the distal urethra in the glans via invagination
73
What is 5-alpha reductase deficiency?
Congenital disease in which an XY male lacks DHT so appears male internally but is externally female
74
What are hypospadias? Treatment?
Improper fusion of urethral folds to form the penile urethra => improper position of the urethral opening anywhere along the underside of the penis
Treatment: retubularization surgery using buccal mucosa from cheeks
75
In what patients are hypospadias common?
Patients with 5-alpha reductase deficiency
76
What does the pronephric duct develop into in both males and females?
Degenerates in both
77
What regulates the differentiation of the genital ridge?
SRY gene
78
What do the genital ridges develop into in both males and females?
1. Males: testis
| 2. Females: ovaries
79
What regulates the differentiation of the Wolffian ducts?
Testosterone
80
What do the Wolffian ducts develop into in both males and females?
1. Males: trigone, epididymis, ductus deferens, seminal vesicles, ejaculatory duct
2. Females: trigone, Gartner's duct (rest degenerates)
81
What regulates the differentiation of the ureteric bud?
Nada
82
What does the ureteric bud develop into in both males and females?
In both:
1. Ureters
2. Renal pelvis
3. Calyces
4. Distal collecting ducts
83
What regulates the differentiation of the metanephros?
Ureteric ingrowth
84
What does the metanephros develop into in both males and females?
Kidney nephrons in both
85
What regulates the differentiation of the UG sinus?
DHT
86
What does the UG sinus develop into in both males and females?
MALES:
1. Prostatic urethra
2. Cowper's glands
3. Prostate
4. Part of bladder
FEMALES:
1. Urethra
2. Bartholin's glands
3. Skene's glands
4. Part of bladder
5. Hymen
6. Lower 1/3rd of vagina
87
What regulates the differentiation of the Mullerian ducts?
MIF
88
What do the Mullerian ducts develop into in both males and females?
1. Males: degenerate
| 2. Females: fallopian tubes, uterus, cervix, upper 2/3rds of vagina
89
What is the male counterpart of Skene's glands?
Prostate
90
What is the male counterpart to the vagina and uterus?
Prostatic utricle
91
What is the male counter part to the female urethra?
Prostatic urethra
92
What is the female counterpart to the vas deferens and ejaculatory duct?
Gartner's duct
93
What is Gartner's duct?
Embryological remnant in human female development of the mesonephric duct
94
What is the male counterpart to the labia majora?
Scrotum
95
What is the female counterpart to Cowper's glands?
Bartholin's glands
96
What is the male counterpart to the round ligament of the uterus and the ovarian ligament?
Gubernaculum
97
3 types of hypospadias? Which are more common?
1. Anterior***
2. Middle
3. Posterior
98
What is the 2nd most common pediatric urologic procedure after circumcision?
Orchidopexy
99
Why is orchidopexy performed? 6 reasons
1. Decreases chance of malignancy
2. Allows surveillance for malignancy
3. Less prone to trauma
4. May enhance fertility potential
5. Can fix associated hernia
6. Improves cosmesis
100
Describe the steps of testicular descent. What to note?
1. Testicle starts in upper abdomen
2. Descends through retroperitoneum to inguinal canal
3. Passes through patent processus vaginalis
4. Processus vaginalis closes
Note: gubernaculum guides descent
101
What happens if the processus vaginalis fails to close?
Communicating hydrocele or hernia
102
What are the 9 risk factors of cryptorchidism?
1. Advanced maternal age
2. Maternal obesity
3. Breech presentation
4. C-section
5. Coke during pregnancy (the legal kind)
6. Pre term birth (30%)
7. Low birth weight (100% in wt <900gm)
8. Family history
9. Hypospadias
103
What is cryptorchidism linked to?
Deficiency in gonadotropins
104
What is congenital adrenal hypoplasia? What to note?
Inborn error in metabolism and is a pediatric emergency because these patients do not have functioning aldosterone, cortisone, and sex hormones => overproduction of ACTH and adrenal androgens that can lead to body growth, virilization, and ambiguous external genitalia (clitoral enlargement), degrees of labial fusion, and normal Mullerian structures
Note: variable presentation
105
3 types of CAH? List in order of prevalence.
1. 21-α-hydroxylase deficiency (95%)
2. 11-β-hydroxylase deficiency
3. 3-β-hydroxysteroid dehydrogenase deficiency (very rare)
106
3 types of patients with 21-α-hydroxylase deficiency? Describe each.
1. Salt wasters: patients with virilization and aldosterone deficiency
2. Simple virilizers: patients with virilization, but without salt wasting
3. Nonclassic patients: those without evidence of virilization or salt wasting
107
What % of patients with 21-α-hydroxylase deficiency show salt-wasting? Virilization?
75% have salt wasting
25% have simple virilization
108
Are the Mullerian structures affectes by 21-α-hydroxylase deficiency?
NOPE
109
Characteristic symptom of patients with 11-β-hydroxylase deficiency? Explain.
Hypertension because secondary to increased serum levels of deoxycorticosterone (DOC)
110
Role of aromatase enzyme in sex hormone production?
Converts testosterone to estradiol
111
What would an aromatase deficiency lead to? What can cause it?
Lack of estrogen leading to atypical feminization
Causes: aromatase inhibitors during breast cancer treatments, congenital causes, PCOS
112
What tissue has its own version of the enzyme aromatase?
Fat in obese patients
113
How are testosterone levels in patients with 21-α-hydroxylase deficiency?
Increased
114
What is the electrolyte profile that you would expect to see in salt-wasting patients with 21-α-hydroxylase deficiency?
1. Low sodium
2. High potassium
3. Very elevated 17 OH progesterone
115
Treatment goals of steroid hormone deficiency?
1. To supply the deficient hormone
2. To suppress pituitary ACTH secretion and hence adrenal androgens and clinical virilization
3. To forestall abnormally rapid somatic growth and osseous advance
4. To permit normal gonadal development
5. To correct salt-water loss or hypertension in the complicated forms
116
What is 46XX Externally Virilized? What causes this? Treatment?
Increased exposure to androgens
Causes: increased exposure to maternal androgens or androgen secreting tumors, progestational androgens and aromatase deficiency
Treatment: Danazol is prescribed for endometriosis
117
What is Turner syndrome? What renal abnormalities is it associated with?
45 X: infertile females with short stature, webbed neck, nuchal translucency, cystic hygroma, streak gonad (between embryological precursor of gonad and ovary)
Associated with renal abnormalities like horseshoe kidneys or duplication and agenesis
118
What is XXY Kleinfelter's syndrome? What are these patients at risk for?
Males with high levels of estradiol, which leads to gynecomastia, small testes, aspermatogenesis, long legs, intelligence deficit
8-fold increase in breast cancer risk
119
Direction of development of pronephros?
Cranial to caudal
120
What part of the cloaca is the UG sinus?
Ventral/anterior part
121
Embryological origin of the anal membrane?
Urogenital folds
122
Which happens first: urinary or genital development?
Urinary (3 weeks prior)
123
When should we start testing for fertility?
After 12 months of trying to get pregnant
124
What are 2 possible causes of lack of vas deferens?
1. Cystic fibrosis
| 2. Genetic abnormalities
125
What could trigger diagnosis of UPJO?
Beer and coffee because block ADH so lots of urine being dumped all at once in the collecting system of the kidney
126
How is anterior intermediate mesoderm differentiated first in urogenital development?
1. HOX genes 4-11 relying on retinoic acid for their proper expression
2. Epithelial cords called nephrotomes connect laterally to a pair of primary pronephric ducts => primary nephric ducts which grow caudally and attach to the cloaca
3. Over few days nephrotomes grow in size and number and become equivalent to mesonephric tubules found in fish: vascularized glomerulus partially surrounded by a capsule of epithelial cells and lined by capillaries from the aorta, which empty into the mesonephric ducts which connect to the cloaca
4. Concurrently primary nephric duct => mesonephric duct => destined to become Wolfian duct
5. Concurrently pronephros disentegrates cranially to caudally
127
When does the development of the metanephros start?
Week 5
128
When the kidney ascends is it considered a kidney or a metanephros?
Metanephros
129
What is the prostatic utricle?
Small indentation in the prostatic urethra laterally flanked by openings of the ejaculatory ducts
130
Does the metanephros start developing before the mesonephros disappears to give rise to the mesonephric ducts?
YUP
131
What marks the metanephric phase of kidney development?
Growth of ureteric bud
132
In what directions does the metanephros grow? What is this called?
Dorsally and cranially = kidney ascencion
133
Describe nephron development.
Relies on 3 cell lineages:
1. Epithelial cells of ureteric bud
2. Mesenchymal cells of metanephros
3. Ingrowing capillaries within slits beneath podocyte precursors => will form glomeruli + endothelial cells/podocyte lay down a thick basement membrane that is important for filtration
By week 8: loops of Henle form and epithelium within forms a mature brush border producing Tamm-Horsfall glycoproteins
134
Describe bladder formation.
1. Epithelial cells in allantois expand to form the urachus of the urinary bladder => as it expands it incorporates the mesonephric ducts and ureter buds which eventually empty separately into the bladder
2. Trigone develops from mesonephric duct
3. UG sinus forms most of the bladder
135
Is the SRY gene the only gene that guide germ cells to their final destination?
Nope, other genes involved too
136
Describe formation of the genital ridges at week 6 of development.
Primordial germ cells originate in definitive yolk sac => cells migrate by chemotaxis through the vitelline duct and allantois into the hindgut and up the dorsal mesentery => 1,000-2,000 primordial germ cells enter the genital ridges where a new set of genes are activated =>
- in males PGCs begin to exit the cell cycle
- in females they form cell nests, surrounded by follicle cells and are considered oogonia which proceed through meiosis and do not exit the cell cycle
137
Embryological origin of Sertoli cells?
Non-germ cell mesenchyme within the genital ridges in which the SRY gene is activated
138
Embryological origin of the male accessory organs?
Epithelium on ductal system
139
What do the seminal vesicles emanate from?
Ductus deferens
140
Where does the prostate emanate from?
Cranial end of urethral epithelium
141
Where do the bulbo-urethral glands emanate?
Along the length of the urethral epithelium
142
When are oogonia considered oocytes? Explain.
Week 22, they are primary oocytes in prophase I of meiosis and are arrested as such until puberty
143
Describe the development of the 3 ligaments of the female reproductive system.
1. Suspensory ligament of the ovary: cranial to ovary
2. Round ligament of ovary: caudal to ovary
3. Round ligament of uterus:
144
What are the 3 types of cells in the genital ridges and what does each give rise to?
1. Primordial germ cells: spermatogonia and oogonia
2. Mesothelial cells: seminiferous tubules and ovarian follicles
3. Mesenchymal cells: Leydig and Sertoli cells and ovarian support stroma
145
When does the gubernaculum develop?
Right after the Mullerian ducts
146
What are streak gonads? Example of patients with streak gonads?
Hypoplastic (underdeveloped) and dysfunctioning gonads mainly composed of fibrous tissue that lead to gonadoblastomas (TBD)
147
What are 2 remnants of the metanephric ducts?
1. Epoophoron
| 2. Paraophoron
