5 questions · Kidney development, anomalies, & Potter sequence
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07:30
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Instructions: Select the single best answer for each question. Review your answers at the end of the block before proceeding.
Question 1 of 5 — Kidney Development
A 32-year-old pregnant woman undergoes a routine second-trimester fetal ultrasound at 22 weeks. The fetus has severe oligohydramnios, no visible renal tissue bilaterally, and a small bladder that does not fill. On autopsy after intrauterine fetal demise at 26 weeks, the fetus has flattened facial features, low-set ears, and pulmonary hypoplasia. Which of the following embryologic structures is essential for definitive kidney formation, and failure of which event in its development best explains this case?
APronephros regression failure
BFailure of mesonephros to drain into the cloaca
CAbsence of ureteric bud interaction with metanephric blastema bilaterally
DPersistence of the allantois between the umbilicus and bladder
EFailure of the urorectal septum to divide the cloaca
C — Absent ureteric bud/metanephric blastema interaction. The definitive kidney forms from reciprocal induction between the ureteric bud (from the mesonephric duct) and the metanephric blastema (intermediate mesoderm). Metanephric blastema → NEPHRON; ureteric bud → COLLECTING system. Bilateral failure of this interaction (bilateral renal agenesis or bilateral MCDK) → no fetal urine → oligohydramnios → Potter sequence: flattened facies, twisted limbs, pulmonary hypoplasia. Death occurs from pulmonary hypoplasia, NOT renal failure. Options A, B, D, and E describe other anomalies that don't produce bilateral kidney absence.
Question 2 of 5 — Horseshoe Kidney
A 15-year-old girl is evaluated for short stature, webbed neck, and primary amenorrhea. Physical exam reveals a shield-shaped chest, wide carrying angle, and a soft systolic murmur consistent with bicuspid aortic valve. Abdominal imaging incidentally demonstrates fusion of the lower poles of both kidneys across the midline at the L3 vertebral level, with the renal pelves anteriorly positioned. Which of the following best explains why the fused kidney is NOT in its usual anatomic location in this patient?
AThe kidneys migrated too far cephalad because the SMA pushes them upward
BNormal cephalad migration is arrested because the fused mass catches on the inferior mesenteric artery
CFailure of reciprocal induction between ureteric bud and metanephric blastema
DPersistence of the mesonephric duct prevents kidney movement
EAbnormal rotation during ascent reverses kidney orientation
B — Arrest at the IMA. In this horseshoe kidney (associated with Turner syndrome, 45 XO), the two metanephric blastemas fuse in the midline during initial kidney formation. As the fused kidney ascends, it catches on the inferior mesenteric artery at about L3–L4 level. The kidney cannot ascend further because the IMA physically blocks movement. Note: don't conflate with a "pelvic kidney," which is a separate anomaly — a unilateral kidney that completely fails to ascend. The clues to Turner here are short stature, webbed neck, shield chest, primary amenorrhea, and bicuspid aortic valve.
Question 3 of 5 — Trigone Origin
A first-year medical student is studying the embryologic origins of the bladder. On histologic examination, the smooth triangular region between the openings of the two ureters and the urethra appears distinct from the rugated dome of the bladder. Which of the following embryonic structures forms this smooth triangular region?
AUrogenital sinus endoderm
BCloacal membrane ectoderm
CAbsorbed mesonephric (Wolffian) ducts — mesoderm
DParamesonephric (Müllerian) duct remnants
EUreteric bud proper
C — Absorbed Wolffian ducts (mesoderm). The bladder has a dual embryologic origin: the dome and walls are endodermal (from urogenital sinus), while the smooth trigone — the triangular region containing the ureteric orifices and internal urethral meatus — is mesodermal, derived from the distal portions of the mesonephric (Wolffian) ducts absorbed into the bladder wall during weeks 5–6. This mixed origin explains why the trigone appears smooth while the bladder dome is rugated. Clinical relevance: the trigone is more fixed and less distensible, contributing to the typical location of bladder cancers and the sensation of fullness.
Question 4 of 5 — Ectopic Ureter
A 4-year-old girl presents with a lifelong history of continuous dribbling of urine despite also voiding normally at intervals. Her mother reports she has never been "dry" and has had multiple UTIs. Renal ultrasound shows a duplicated collecting system on the right kidney with dilation of the upper pole. MR urography reveals an ectopic ureter from the upper pole entering the vaginal vestibule below the level of the external urethral sphincter. This ectopic position is best explained by which of the following embryologic failures?
AFailure of the ureteric bud to form
BPersistence of the urachus
CIncomplete/abnormal absorption of the mesonephric duct into the developing bladder
DFailure of urorectal septum formation
ERegression of the paramesonephric duct
C — Abnormal mesonephric duct absorption. Normally, the mesonephric ducts are absorbed into the bladder, positioning the ureteric orifices at the corners of the trigone. When absorption is incomplete or too low, the ureteric bud implants ectopically below the trigone. In girls, the ectopic ureter commonly drains into structures derived from the urogenital sinus or Müllerian duct — vagina, cervix, vestibule, or urethra distal to the external sphincter — producing continuous dribbling with preserved normal voiding (the other kidney-bladder unit works normally). The Weigert-Meyer rule states that in a duplex system, the upper pole ureter is the ectopic one. Boys rarely have this picture because male ectopic ureters drain above the sphincter (into vas, seminal vesicle).
Question 5 of 5 — ADPKD + Berry Aneurysm
A 46-year-old man with long-standing hypertension presents to the ED with the sudden onset of "the worst headache of my life," photophobia, and nausea. Non-contrast head CT shows subarachnoid blood in the basal cisterns. He has a history of renal failure: serum creatinine is 2.8 mg/dL. His father required renal transplantation at age 58 and died of a cerebral hemorrhage. Abdominal imaging reveals bilateral enlarged kidneys with multiple cysts of varying sizes and several hepatic cysts. Which of the following genes is most likely mutated in this patient?
APKD1 on chromosome 16
BPKHD1 on chromosome 6
CVHL on chromosome 3
DWT1 on chromosome 11
ENPHS1 on chromosome 19
A — PKD1 on chromosome 16. This is Autosomal Dominant Polycystic Kidney Disease (ADPKD), most commonly caused by mutations in PKD1 (85%) or PKD2. Classic associations include berry aneurysms in the Circle of Willis (→ SAH, the "worst headache of my life"), mitral valve prolapse, hepatic and pancreatic cysts, and diverticulosis. Adult-onset presentation with HTN is earliest finding. Family history is typical (AD inheritance). PKHD1 (B) → ARPKD (infantile, Potter sequence + congenital hepatic fibrosis). VHL (C) → renal cell carcinoma + hemangioblastomas. WT1 (D) → Wilms tumor. NPHS1 (E) → congenital nephrotic syndrome.
Block 2 — Sexual Differentiation & Genital Development
Instructions: Select the single best answer for each question. Review your answers at the end of the block before proceeding.
Question 6 of 15 — Complete AIS
A 17-year-old tall, well-developed adolescent presents to a gynecologist for primary amenorrhea. She has Tanner V breast development, scant pubic and axillary hair, and is 5'10" tall. Pelvic exam reveals a blind-ending vagina of normal length. Pelvic MRI shows no uterus, no ovaries, and bilateral inguinal masses consistent with undescended testes. Karyotype is 46,XY. Labs: testosterone 710 ng/dL, LH 52 mIU/mL (elevated), estradiol 95 pg/mL (elevated). Which of the following best explains both the absence of uterus AND the female external genitalia?
C — Defective androgen receptor (CAIS). In complete androgen insensitivity syndrome, the androgen receptor cannot respond to testosterone or DHT, BUT the testes produce normal MIS/AMH from Sertoli cells — this is INDEPENDENT of the androgen receptor. Therefore: Müllerian ducts regress → no uterus, no upper vagina (blind vagina). Wolffian ducts need T signaling → no epididymis or vas. External genitalia also can't respond to DHT → default female appearance. Breasts develop from peripheral aromatization of testosterone to estradiol. Gonadectomy is typically delayed until after puberty to allow spontaneous feminization (malignancy risk rises later).
Question 7 of 15 — 5α-Reductase Deficiency
A child was raised as a girl since birth because of apparently female external genitalia. At age 12, she presents with progressive voice deepening, growth of a phallus, and descent of testes into the labioscrotal folds. Karyotype is 46,XY. Pelvic exam demonstrates normal epididymides, vasa deferentia, and seminal vesicles bilaterally, but no uterus. Serum testosterone is elevated, and DHT is low. Which of the following best explains why this patient has normal internal male structures but was born with female-appearing external genitalia?
ATestosterone is required only for external masculinization
BTestosterone alone maintains the Wolffian ducts; DHT is required for external genital masculinization
CThe SRY gene was never expressed
DMüllerian inhibiting substance was never secreted
EThe androgen receptor is nonfunctional
B — T maintains internal (Wolffian) structures; DHT is required for external masculinization. This is classic 5α-reductase deficiency. The enzyme converts testosterone → DHT. Without DHT, external genitalia develop along the default (female) pathway at birth, but internal Wolffian derivatives (epididymis, vas deferens, seminal vesicles) develop normally because they depend on testosterone, which is high. Sertoli cells still produce MIS, so Müllerian ducts regress (no uterus). At puberty, massive testosterone surge partially masculinizes external genitalia — dramatic phenotype change ("penis at 12" / "guevedoces"). Diagnostic marker: elevated T:DHT ratio. CAIS (E) would have absent Wolffian derivatives AND breast development at puberty.
Question 8 of 15 — 21-Hydroxylase Deficiency
A 2-week-old phenotypically female infant presents to the ED in shock. She has been vomiting and feeding poorly for the past 4 days. Physical exam shows ambiguous genitalia with clitoromegaly and rugated, hyperpigmented labia. Vital signs: HR 180, BP 55/30 mmHg, capillary refill 4 seconds. Labs: Na⁺ 118 mEq/L, K⁺ 7.1 mEq/L, glucose 42 mg/dL. Newborn screen returns with markedly elevated 17-hydroxyprogesterone. Which of the following is the most appropriate immediate intervention?
AUrgent genitoplasty to reconstruct external genitalia
BSodium bicarbonate infusion alone
CIV normal saline bolus, IV hydrocortisone, and fludrocortisone
DOral dexamethasone only
ESpironolactone for hyperkalemia
C — IV saline + hydrocortisone + fludrocortisone. This is the classic salt-wasting crisis of 21-hydroxylase deficiency CAH (95% of CAH cases). The enzymatic block impairs both cortisol and aldosterone synthesis, shunting precursors to the androgen pathway → virilization of XX females. The clinical tetrad: hypotension + hyponatremia + hyperkalemia + hypoglycemia — reflects combined gluco + mineralocorticoid deficiency. Immediate priorities: (1) volume resuscitation (saline), (2) hydrocortisone (replaces cortisol; also has some mineralocorticoid activity), (3) fludrocortisone (potent mineralocorticoid, replaces aldosterone). Screening marker: 17-OH-progesterone. Contrast 11β and 17α deficiencies, which cause HTN instead.
Question 9 of 15 — Wolffian vs Müllerian
A 46-year-old woman undergoes hysterectomy for fibroids. During surgery, the pathologist identifies a small (1.5 cm) fluid-filled cyst in the broad ligament of the uterus, near its lateral attachment to the uterus. Histology shows a cuboidal-lined cyst with clear fluid. The surgeon explains this is a "Gartner's duct cyst." From which embryonic structure does this cyst derive?
AParamesonephric (Müllerian) duct remnant
BMesonephric (Wolffian) duct remnant
CUreteric bud remnant
DUrogenital sinus invagination
ENeural crest derivative
B — Mesonephric (Wolffian) duct remnant. In females, the Wolffian ducts regress due to lack of testosterone, but small remnants may persist. These remnants can become cystic and are called Gartner's duct cysts, typically found in the lateral vaginal wall or broad ligament. They are usually asymptomatic. The male equivalent of the Müllerian remnant is the prostatic utricle (a small midline blind pouch in the prostate — homolog of the uterus/upper vagina) and the appendix testis (upper pole of the testis). Knowing this duct anatomy is testable: if the cyst is in a male at the prostate midline → Müllerian remnant; if in a female lateral to the uterus/vagina → Wolffian remnant.
Question 10 of 15 — Hypospadias
A newborn boy is examined in the nursery. His penis has a urethral opening on the ventral (underside) surface of the shaft, approximately at the midshaft level. The foreskin is noted to be dorsally hooded. His parents inquire about circumcision. Which of the following is the most appropriate recommendation, and why?
APerform routine circumcision at 2 weeks of age, as usual
BDefer circumcision; the foreskin is needed for surgical urethroplasty
CPerform immediate surgical correction within 24 hours of birth
DCircumcise the baby to prevent infection of the abnormal urethra
EDelay all intervention until after puberty
B — Defer circumcision; foreskin is needed for urethroplasty. This is hypospadias, caused by failure of urethral (urogenital) folds to fuse ventrally during week 12. DHT drives fusion; partial androgen insensitivity or insufficient DHT production can contribute. The distal urethra opens on the ventral shaft instead of the glans tip. The characteristic dorsal "hooded" foreskin reflects incomplete ventral development. Definitive surgical repair (urethroplasty) uses the intact foreskin as a tissue graft to construct a new urethra — this is usually performed at 6–12 months. Circumcision would remove the graft material. Contrast with epispadias (dorsal opening), which is rarer and classically associated with bladder exstrophy.
Instructions: Select the single best answer for each question. These questions integrate multiple concepts from urogenital embryology.
Question 11 of 15 — 17α-Hydroxylase Deficiency
A 16-year-old phenotypically female presents with primary amenorrhea, no breast development, and hypertension. She is admitted with BP 176/108 mmHg. Labs: K⁺ 2.9 mEq/L, aldosterone suppressed, renin suppressed, low estradiol and testosterone. Further workup reveals 46,XY karyotype with bilateral inguinal testes but no uterus. Which of the following enzyme deficiencies best explains all of her findings?
A21-hydroxylase deficiency
B11β-hydroxylase deficiency
C17α-hydroxylase deficiency
D5α-reductase deficiency
EAromatase deficiency
C — 17α-hydroxylase deficiency. This rare form of CAH blocks synthesis of both cortisol AND all sex hormones (testosterone, estradiol, DHEA). The mineralocorticoid pathway is INTACT and actually overactive from ACTH stimulation → HTN + hypokalemia (from 11-deoxycorticosterone). In 46 XY patients, the testis can't make testosterone → no Wolffian derivatives AND no external masculinization → female phenotype. Sertoli cells still produce MIS → no uterus. At "puberty," no sex steroids = no breast development or menstrual function. Mnemonic: "17 = HTN + NO sex hormones". Distinguish from CAIS (female phenotype but ↑T, no HTN) and 5α-reductase def (normal Wolffian structures, virilization at puberty). Contrast with 11β (HTN + virilization) and 21 (hypoTN + virilization).
Question 12 of 15 — Klinefelter Syndrome
A 22-year-old male presents to a fertility clinic after 2 years of trying to conceive with his wife. He is 6'5" tall with long extremities (eunuchoid proportions), mild gynecomastia, and small, firm testes bilaterally. Semen analysis shows azoospermia. Labs: testosterone 220 ng/dL (low), LH 28 mIU/mL (high), FSH 42 mIU/mL (very high), estradiol 62 pg/mL (elevated). Which of the following best explains the hormonal pattern?
C — Klinefelter syndrome (47 XXY). Buzzwords: tall, eunuchoid body habitus, gynecomastia, small firm testes, azoospermia. Pathophysiology: the extra X chromosome causes seminiferous tubule dysgenesis → ↓ inhibin B → ↑ FSH (no feedback). Leydig cell dysfunction → ↓ testosterone → ↑ LH (no feedback). Remaining testosterone is aromatized peripherally → ↑ estradiol → gynecomastia. Treatment: testosterone replacement; fertility possible with sperm extraction + ICSI in some cases. Increased risk of breast cancer, extragonadal germ cell tumors, autoimmune disease. Kallmann (B) is hypogonadotropic (↓ LH/FSH) + anosmia.
Question 13 of 15 — Testicular Descent & Hydrocele
A 3-month-old male infant is brought to clinic with a fluctuating left scrotal swelling that transilluminates. The swelling enlarges when the infant cries and partially empties when he lies flat. Exam reveals a nontender, smooth left hemiscrotum and an easily palpable left testis within a fluid-filled sac. Which of the following embryologic events best explains this finding?
AFailure of the testis to descend through the inguinal canal
BIncomplete regression of the paramesonephric ducts
CFailure of the processus vaginalis to obliterate after testicular descent
DPersistence of the urachus between the bladder and umbilicus
EMalformation of the gubernaculum
C — Patent processus vaginalis. This is a communicating hydrocele. During testicular descent, the testis follows an outpouching of peritoneum called the processus vaginalis into the scrotum. Normally, after descent, the processus obliterates, leaving only the tunica vaginalis around the testis. If the processus remains patent, peritoneal fluid communicates with the scrotum → hydrocele that fluctuates with position (larger when upright/crying, smaller when supine). Most close spontaneously by age 1–2; if persistent, surgical correction is needed. A patent processus can also allow abdominal viscera to herniate → indirect inguinal hernia (passes through the deep inguinal ring, through the canal, into the scrotum). Failure of testicular descent itself = cryptorchidism (A).
Question 14 of 15 — Male/Female Homologues
A 52-year-old woman presents with recurrent painful vulvar swellings. Examination reveals a 2-cm tender cystic mass at the 5 o'clock position of the vaginal introitus, just inside the posterior labium majus. The mass is draining purulent fluid. The physician diagnoses a Bartholin gland abscess. Which of the following male structures is the embryologic homolog of the Bartholin (greater vestibular) glands?
AProstate gland
BSeminal vesicles
CBulbourethral (Cowper) glands
DProstatic utricle
ETunica vaginalis
C — Bulbourethral (Cowper) glands. Both the Bartholin glands (♀) and Cowper glands (♂) are derived from the urogenital sinus and function as mucous-secreting lubricating glands. Other key embryologic homologues to know: Genital tubercle → clitoris (♀) / glans penis (♂); Labioscrotal swellings → labia majora / scrotum; Urogenital folds → labia minora / penile urethra (fused); Gubernaculum → round lig. of uterus + ovarian lig. / gubernaculum testis; Skene glands → prostate; Gartner's duct (♀ Wolffian remnant) ↔ SEED (♂ Wolffian derivatives); Prostatic utricle (♂ Müllerian remnant) ↔ uterus/upper vagina (♀). The prostate (A) is homologous to the Skene glands, not Bartholin.
Question 15 of 15 — Comprehensive Synthesis
A 28-year-old woman (G1P0) at 20 weeks gestation is informed that her fetus has a 46,XY karyotype but female-appearing external genitalia on anatomic survey. No internal uterus or ovaries are visible. The fetus has normal-appearing intra-abdominal testes. Amniotic fluid volume is normal (no Potter sequence). If this karyotype-phenotype discordance is due to a single enzyme or receptor defect, which of the following best describes the MOST LIKELY diagnosis and the predicted appearance at puberty?
A21-hydroxylase deficiency; will develop salt-wasting crisis and virilize externally
BComplete androgen insensitivity syndrome; will develop breasts at puberty from peripheral aromatization but will have primary amenorrhea (no uterus), scant pubic hair, and a blind vagina
C5α-reductase deficiency; will virilize at puberty with normal internal male structures
DSwyer syndrome; will have a functional uterus but streak gonads, allowing donor-egg pregnancy
ETurner syndrome; will have short stature, webbed neck, and horseshoe kidney
B — Complete Androgen Insensitivity Syndrome (CAIS). Integrating everything: 46 XY with female external genitalia but NO uterus and functioning testes points to CAIS. Sertoli cells still make MIS → Müllerian ducts regress → no uterus/upper vagina. But the androgen receptor is defective, so Wolffian ducts don't develop AND external genitalia remain default female. At puberty, elevated testosterone is aromatized peripherally to estradiol → breast development. No menses (no uterus). Pubic/axillary hair requires androgen action → scant. Differentiate from other options: (A) 21-OH def is XX with virilized XX external genitalia. (C) 5α-red def has normal Wolffian structures and virilizes dramatically at puberty. (D) Swyer has a uterus (no MIS from streak gonads). (E) Turner is 45 XO — incompatible with XY karyotype. Key diagnostic question for any 46 XY with female phenotype: Is there a uterus? Is there an ↑T? What's the T:DHT ratio?
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