Lecture 04: Male Reproductive System

HoyaDocs β€” Repro Block | USMLE Step 1 Preparation

Lecture 04 β€” Overview

Male Reproductive System Β· HoyaDocs Repro Block

Page Summaries

♂️ Testis & Spermatogenesis
Descent & cryptorchidism Β· Pampiniform plexus & torsion Β· Three tunicas Β· Leydig/Sertoli Β· Blood-testis barrier Β· HPG axis Β· 74-day spermatogenesis Β· Spermiogenesis
Practice Qs: 1–4
πŸ”€ Excurrent Ducts
Tubulus rectus β†’ Rete testis β†’ Efferent ductules β†’ Epididymis β†’ Vas deferens β†’ Ampulla Β· Distinguishing histology Β· Vasectomy
Practice Qs: 5–7
πŸ’§ Accessory Glands & Penis
Seminal vesicles (fructose) Β· Prostate zones Β· BPH vs. cancer Β· PSA Β· Cowper's glands Β· Penile erectile tissue Β· Erection/ejaculation autonomics
Practice Qs: 8–11
🚿 Urethra
Prostatic (transitional) Β· Membranous (pseudostratified + external sphincter) Β· Penile/spongy (pseudostrat β†’ squamous) Β· Urethritis Β· Trauma
Practice Qs: 12–14

Official Learning Objectives Map

1 Know the structure and function of the testis. Understand the process of spermatogenesis. Testis ▼
2 Know the different components of the excurrent ducts, how to distinguish between them, and their function. Ducts ▼
3 Know the structure and function of the accessory glands and penis. Glands & Penis ▼
4 Know the structure of the different components of the urethra. Urethra ▼

LO 1 β€” Testis & Spermatogenesis

Structure Β· Descent Β· Leydig/Sertoli Β· HPG Axis Β· Spermatogenesis Β· HoyaDocs Repro Block

Learning Objectives Covered
  • LO 1: Know the structure and function of the testis. Understand the process of spermatogenesis.
On This Page
  1. Testicular Descent & Cryptorchidism
  2. Pampiniform Plexus & Torsion
  3. Testis Coverings β€” Three Tunicas
  4. Leydig & Sertoli Cells
  5.   β†³ Blood-Testis Barrier
  6. Hypothalamus-Pituitary-Gonadal Axis
  7. Spermatogenesis (74-Day Timeline)
  8. Spermiogenesis & Mature Sperm Anatomy

🧠 Testing Your Understanding!

Testing Your Understanding β€” LO 1, Question 1

A 28-year-old man with a history of unilateral cryptorchidism treated with orchidopexy at age 8 presents with infertility. Semen analysis shows azoospermia. Labs: testosterone 420 ng/dL (normal), LH 9 mIU/mL (normal-high), FSH 28 mIU/mL (high), inhibin B 20 pg/mL (low). Explain the hormonal pattern in terms of Leydig vs. Sertoli cell heat sensitivity.

Consider: heat-resistant Leydig cells, heat-sensitive Sertoli/germ cells, negative feedback loops, inhibin B

βœ“ Answer: Selective Sertoli/germ cell damage from prolonged heat exposure β€” Leydig function preserved.

The scrotal position of the testis normally keeps the testes ~2–4Β°C cooler than core body temperature. With cryptorchidism, the abdominal environment damages heat-sensitive seminiferous tubules β€” specifically the Sertoli cells and germ cells. Leydig cells are heat-resistant, so testosterone production continues normally (normal T, normal-high LH). The Sertoli-cell damage reduces inhibin B, which selectively inhibits FSH β†’ loss of this feedback causes isolated FSH elevation. Spermatogenesis is severely impaired β†’ azoospermia. The late orchidopexy (age 8) did not prevent the damage β€” intervention before age 1 preserves much more fertility and modestly decreases malignancy risk. Consider: what additional surveillance is warranted long-term? (↑ risk of seminoma β€” regular self-exam + clinical follow-up.)

Testing Your Understanding β€” LO 1, Question 2

A researcher uses electron microscopy to examine cells within the interstitium of the testis and identifies rectangular cytoplasmic inclusions, abundant smooth endoplasmic reticulum, and mitochondria with tubular cristae. Name the cell type, its principal hormone, and the transcriptional regulation that drives its secretion.

Consider: Reinke crystals, cholesterol side-chain cleavage, LH receptor pathway

βœ“ Answer: Leydig cells producing testosterone, stimulated by LH via the cAMP-PKA pathway.

The three ultrastructural features are the classic tip-off for Leydig cells: (1) Reinke crystals β€” rectangular eosinophilic cytoplasmic inclusions unique to Leydig cells; (2) abundant smooth ER reflecting active steroid synthesis (membranes for enzymes); (3) tubular cristae in mitochondria β€” a morphologic signature of steroid-producing cells (also seen in adrenal cortex). LH binds its GPCR on Leydig cells β†’ Gs β†’ adenylyl cyclase β†’ ↑ cAMP β†’ PKA activation β†’ phosphorylates StAR (steroidogenic acute regulatory protein), which moves cholesterol into the mitochondrion β†’ CYP11A1 (side-chain cleavage) converts cholesterol to pregnenolone β†’ subsequent enzymes generate testosterone. Consider: how would the histology differ in prolonged chronic LH stimulation (e.g., Klinefelter)? (Leydig cell hyperplasia β€” fewer tubules, more interstitial Leydig cells dominating the image.)

LO 2 β€” Excurrent Duct System

Tubulus Rectus β†’ Rete Testis β†’ Efferent Ductules β†’ Epididymis β†’ Vas Deferens β†’ Ampulla Β· HoyaDocs Repro Block

Learning Objectives Covered
  • LO 2: Know the different components of the excurrent ducts, how to distinguish between them, and their function.
On This Page
  1. Overview β€” Sperm's Exit Pathway
  2. Tubulus Rectus & Rete Testis
  3. Efferent Ductules
  4. Epididymis (Head, Body, Tail)
  5. Vas Deferens & Vasectomy
  6. Ampulla & Ejaculatory Duct
  7. Histologic Distinguishing Table

🧠 Testing Your Understanding!

Testing Your Understanding β€” LO 2, Question 1

A pathology resident is shown a high-magnification image of a male reproductive duct. The epithelium is characterized by alternating tall ciliated cells and short non-ciliated cells, producing a "scalloped" or "toothed" luminal profile. Name the structure, its embryologic origin, and its primary physiologic role in sperm handling.

Consider: mesonephric tubules, fluid reabsorption, ciliary transport, concentration of sperm

βœ“ Answer: Efferent ductules β€” mesonephric tubule origin; their role is to reabsorb testicular fluid and concentrate sperm.

The "scalloped" luminal profile is the single-best visual cue for the efferent ductules. These ~20 small ducts connect the rete testis to the head of the epididymis. Their key histologic feature is the alternation of tall ciliated cells (transport) and short non-ciliated resorptive cells (absorption), which creates the toothed/saw-tooth appearance. Embryologically, they derive from mesonephric tubules β€” the same tissue that forms kidney tubules, which is why they retain strong fluid-resorptive capacity. Functionally: testicular fluid arriving from the rete testis is ~90% reabsorbed here, concentrating sperm dramatically before they enter the epididymis for maturation and storage. Consider: what would happen with a selective efferent-ductule transport defect? (Accumulated fluid β†’ testicular fluid backup β†’ obstructive oligo/azoospermia.)

Testing Your Understanding β€” LO 2, Question 2

A 32-year-old man requests permanent contraception via vasectomy. After the procedure, he asks why he still needs backup contraception for the next 3 months and why his testosterone and ejaculate volume are expected to remain unchanged. Explain the anatomy and physiology that justify both points.

Consider: sperm storage distal to the vasectomy site, fluid contributions to ejaculate, Leydig cell testosterone production

βœ“ Answer: Residual sperm downstream of the ligation must be cleared; ejaculate volume and testosterone are dominated by accessory gland and Leydig-cell output, both unaffected by vasectomy.

Vasectomy cuts/ties the vas deferens, blocking sperm transit from the epididymis to the ejaculatory duct. However, downstream of the ligation site β€” in the ampulla, seminal vesicles, and ejaculatory duct β€” there are residual mature sperm. These take ~2–3 months (or ~20 ejaculations) to be cleared. Semen analysis is required to confirm azoospermia before discontinuing backup contraception. As for unchanged ejaculate/testosterone: (1) ~70% of ejaculate volume is from seminal vesicles (fructose-rich fluid), ~25% from prostate (PSA, zinc, acid phosphatase), and only a small percentage from the epididymis/vas. None of those glands are affected by vasectomy. (2) Testosterone is made by Leydig cells in the testicular interstitium β€” independent of ductal plumbing. Leydig function is preserved, as is LH/FSH feedback. Consider: what might cause infertility if the patient later tries to reverse the vasectomy? (Anti-sperm antibodies β€” leakage of sperm antigens post-vasectomy can cross the damaged blood-testis barrier, sensitizing the immune system.)

LO 3 β€” Accessory Glands & Penis

Seminal Vesicles Β· Prostate Β· Bulbourethral Glands Β· Penis Β· HoyaDocs Repro Block

Learning Objectives Covered
  • LO 3: Know the structure and function of the accessory glands and penis.
On This Page
  1. Accessory Glands Overview & Ejaculate Composition
  2. Seminal Vesicles
  3. Prostate Gland
  4.   β†³ BPH & Prostate Cancer
  5. Bulbourethral (Cowper's) Glands
  6. Penis β€” Structure & Erectile Tissue
  7.   β†³ Erection Physiology

🧠 Testing Your Understanding!

Testing Your Understanding β€” LO 3, Question 1

A 68-year-old man presents with urinary hesitancy, weak stream, and nocturia. DRE reveals a symmetrically enlarged, rubbery prostate. His PSA is mildly elevated. He is started on tamsulosin and finasteride. Explain how each drug targets a different component of the pathophysiology of the patient's condition, and why both are often used together.

Consider: which prostatic zone is enlarged, Ξ±1 receptors on smooth muscle, DHT-driven hyperplasia, 5Ξ±-reductase pharmacology

βœ“ Answer: BPH involves both static (bulk) and dynamic (tone) obstruction β€” finasteride addresses volume, tamsulosin addresses muscle tone.

BPH arises in the transition zone and causes obstruction via two mechanisms: (1) Static β€” bulk enlargement of glandular/stromal tissue compresses the prostatic urethra; this is DHT-driven. Finasteride (5Ξ±-reductase inhibitor) blocks testosterone β†’ DHT conversion, shrinking volume over several months (takes time). (2) Dynamic β€” Ξ±1-adrenergic tone of prostatic smooth muscle + bladder neck actively constricts urine flow. Tamsulosin (Ξ±1A-selective antagonist) relaxes this smooth muscle, giving immediate symptomatic relief. Combination therapy is standard because it addresses both components. Important teaching points: finasteride artificially lowers PSA by ~50% β€” must be accounted for in cancer screening; side effects include sexual dysfunction and gynecomastia. Tamsulosin can cause orthostatic hypotension and intraoperative floppy iris syndrome in cataract surgery. Consider: why would you avoid combining tamsulosin with sildenafil? (Additive vasodilation β†’ hypotension.)

Testing Your Understanding β€” LO 3, Question 2

A 42-year-old man presents with erectile dysfunction and infertility. Exam reveals bilateral absence of the vas deferens on palpation. Semen analysis shows azoospermia with a low ejaculate volume (0.5 mL) and absent fructose. Which underlying genetic disorder most likely explains all of these findings, and what developmental mechanism links them?

Consider: CFTR, Wolffian duct-derived structures, seminal vesicle function, fructose as a marker

βœ“ Answer: Congenital Bilateral Absence of the Vas Deferens (CBAVD) β€” associated with CFTR mutations.

CBAVD is strongly linked to CFTR mutations β€” it can occur in classic cystic fibrosis (>95% of CF males are infertile from CBAVD) and also in men with milder CFTR variants who lack overt pulmonary/pancreatic CF disease. Without the vas deferens, sperm cannot reach the ejaculate β†’ azoospermia. Because the vas deferens develops from the mesonephric (Wolffian) duct alongside the seminal vesicles, CBAVD is often accompanied by absent or hypoplastic seminal vesicles. This explains: (1) low ejaculate volume (seminal vesicles contribute ~70% of volume); (2) absent fructose (the seminal vesicles are the sole source). CFTR mutations are thought to cause fetal obstruction β†’ atresia of the developing duct. Work-up includes CFTR genotyping, partner genetic testing, and fertility via testicular sperm extraction + IVF/ICSI. Consider: why is Leydig function preserved in these patients? (Leydig cells are in the testicular interstitium and not derived from mesonephric ducts β€” testosterone, LH, and secondary sex characteristics are normal.)

LO 4 β€” Male Urethra

Prostatic Β· Membranous Β· Penile (Spongy) Segments Β· HoyaDocs Repro Block

Learning Objectives Covered
  • LO 4: Know the structure of the different components of the urethra.
On This Page
  1. Overview β€” Three Segments, Two Sphincters
  2. Prostatic Urethra
  3. Membranous Urethra
  4. Penile (Spongy) Urethra
  5. Histology Distinguishing Table
  6. Clinical Correlates

🧠 Testing Your Understanding!

Testing Your Understanding β€” LO 4, Question 1

A 72-year-old man with diabetes and BPH on tamsulosin reports that during intercourse he now has a barely perceptible ejaculate volume, but his post-coital urine is cloudy. Explain the underlying urethral and autonomic physiology, and why tamsulosin contributes to the problem.

Consider: internal urethral sphincter, sympathetic Ξ±1 tone, ejaculatory duct opening, mechanical vs. neural dysfunction

βœ“ Answer: Retrograde ejaculation β€” internal urethral sphincter fails to close β†’ semen enters the bladder.

Normally, during the emission phase of ejaculation, sympathetic Ξ±1-adrenergic tone closes the internal urethral sphincter at the bladder neck, ensuring that semen released into the prostatic urethra is propelled forward through the external meatus rather than backward into the bladder. Tamsulosin is a selective Ξ±1A-antagonist used to relax prostatic and bladder-neck smooth muscle in BPH β€” but it also disables the internal sphincter, causing retrograde ejaculation. Additive causes in this patient: diabetic autonomic neuropathy further impairs sympathetic function. Clinical findings: low-volume or anejaculation, orgasm preserved, post-coital urinalysis reveals sperm in urine (confirming the diagnosis). Management: if fertility is not desired, no treatment needed; if desired, switch off Ξ±1 blockers or use sympathomimetics (imipramine, pseudoephedrine) or perform sperm retrieval from post-orgasm urine for IVF/ICSI. Consider: why does tamsulosin NOT cause urinary incontinence? (The external urethral sphincter β€” skeletal muscle controlled by the pudendal nerve, independent of Ξ±1 tone.)

Testing Your Understanding β€” LO 4, Question 2

A 30-year-old man presents to the ED after a high-speed motorcycle accident with a displaced pelvic fracture. He is hemodynamically stable, unable to void, and has blood at the urethral meatus. The urology resident wants to place a Foley catheter to drain the bladder. What is the next appropriate step, and what is the underlying anatomic reason for this concern?

Consider: urethral segments and their vulnerability; what imaging rules out or localizes injury; which urethral segment is most fixed

βœ“ Answer: Obtain a retrograde urethrogram before attempting catheterization β€” pelvic fracture classically disrupts the membranous urethra.

The membranous urethra is the shortest and most fixed segment, passing through the urogenital diaphragm. In a pelvic fracture with diastasis of the pubic symphysis, the shearing forces disrupt the diaphragm and commonly rupture the membranous urethra. Signs that should stop any clinician from passing a blind Foley are: blood at the urethral meatus, inability to void, perineal bruising, and a "high-riding" prostate on DRE (prostate displaced superiorly due to loss of urethral continuity). Blind catheterization risks converting a partial tear into a complete tear and creating a false passage. The appropriate step is a retrograde urethrogram β€” contrast instilled at the meatus shows the site + extent of injury. If urgent bladder drainage is needed, a suprapubic cystostomy bypasses the urethra entirely. Consider: how would a straddle injury (bike crossbar) differ? (Straddle injury usually ruptures the bulbous (proximal penile) urethra β€” perineal ecchymosis in a "butterfly" pattern.)

Practice Questions

Lecture 04 β€” Male Reproductive System Β· HoyaDocs Repro Block

LO 1 β€” Testis & Spermatogenesis (Q1–Q4)

Question 1

A 34-year-old man is evaluated for infertility. History reveals a bout of mumps at age 16 complicated by bilateral orchitis. Semen analysis now shows azoospermia. Serum labs: testosterone 460 ng/dL (normal), LH 8 mIU/mL (normal), FSH 32 mIU/mL (elevated), inhibin B 18 pg/mL (low). Which structure or cell type is most severely damaged?

A. Leydig cells

B. Sertoli cells and germ cells within the seminiferous tubules

C. Anterior pituitary gonadotroph cells

D. Hypothalamic GnRH-producing neurons

E. Prostate gland

βœ“ Correct: B β€” Sertoli cells and germ cells (seminiferous tubule damage).

The hormonal pattern β€” normal testosterone + LH, elevated FSH, and low inhibin B β€” is classic for isolated Sertoli/germ cell damage. Mumps orchitis disrupts the blood-testis barrier and damages the thermally and immunologically sensitive seminiferous epithelium. Leydig cells are in the interstitium and relatively spared β†’ testosterone preserved. Because Sertoli cells make inhibin B (selective FSH inhibitor), their damage removes negative feedback on FSH β†’ ↑↑ FSH. LH remains normal because testosterone negative feedback is intact. A (Leydig) would show ↓ T, ↑ LH. C (pituitary) would show ↓ LH/FSH. D (hypothalamus) would show ↓ all gonadotropins. E (prostate) doesn't affect spermatogenesis or hormonal axis.

Question 2

A researcher performs electron microscopy on a cross-section of a seminiferous tubule. She identifies tight junctions between adjacent support cells, dividing the seminiferous epithelium into two compartments: a basal compartment containing mitotic cells and an adluminal compartment containing meiotic and post-meiotic cells. Which of the following best explains the physiologic purpose of this barrier?

A. To prevent bacterial translocation from the bloodstream

B. To sequester meiotic germ cells expressing novel surface antigens from immune surveillance

C. To concentrate FSH within the seminiferous lumen

D. To block testosterone diffusion into the tubule

E. To prevent sperm from entering the ductus epididymis prematurely

βœ“ Correct: B β€” Blood-testis barrier sequesters meiotic germ cells from the immune system.

The blood-testis barrier is formed by Sertoli-Sertoli tight junctions. Meiotic and post-meiotic germ cells express unique antigens (e.g., sperm-specific proteins) that the immune system never encountered during fetal development when self-tolerance was established. Without the barrier, these cells would be attacked β†’ autoimmune orchitis + infertility. The barrier also creates a specialized microenvironment with ~100Γ— higher testosterone (via Sertoli-secreted ABP), needed for spermatogenesis. A β€” the barrier isn't primarily antibacterial. C β€” FSH acts on Sertoli cell basal surface; it doesn't need to cross the barrier. D β€” testosterone actually DOES cross (paracrine from Leydig cells). E β€” sperm do enter the epididymis; that's their exit route.

Question 3

A 19-year-old bodybuilder has been taking high-dose anabolic steroids for 18 months. On exam, both testes appear small and soft. He complains of infertility and gynecomastia. Labs: testosterone 950 ng/dL (high; exogenous), LH 1.2 mIU/mL (low), FSH 0.8 mIU/mL (low), estradiol 60 pg/mL (high). Which of the following best explains the testicular atrophy and infertility?

A. Leydig cell hyperplasia from elevated LH

B. Exogenous testosterone suppresses GnRH/LH/FSH β†’ loss of intratesticular testosterone and FSH support

C. Direct anabolic steroid toxicity on germ cells

D. Autoimmune destruction of seminiferous tubules

E. Anti-sperm antibody formation from an abnormal blood-testis barrier

βœ“ Correct: B β€” Exogenous testosterone negatively feeds back on the hypothalamus/pituitary, suppressing LH and FSH β†’ testicular atrophy and infertility.

Although serum testosterone is elevated (from the exogenous source), the intratesticular testosterone concentration drops dramatically because Leydig cells are no longer being stimulated by LH. Spermatogenesis requires very high intratesticular testosterone (~100Γ— plasma levels, maintained by Sertoli-cell ABP and LH-driven Leydig production). Without endogenous Leydig stimulation + FSH support of Sertoli cells, spermatogenesis ceases β†’ infertility. The unused Leydig cells atrophy. Gynecomastia comes from peripheral aromatization of excess testosterone to estradiol. Similar pattern seen with any exogenous androgen abuse, transgender hormone therapy, or prostate cancer androgen-deprivation treatment. Management: stop steroids; fertility typically returns over 6–12 months; in severe cases, hCG + clomiphene or recombinant FSH can be used to restart spermatogenesis.

Question 4

A 4-year-old boy has chronic recurrent sinus and lung infections, was found to have dextrocardia on a preoperative chest X-ray, and now his parents are told he may have infertility when he grows up. A defect in which subcellular structure explains all of these findings?

A. Mitochondrial electron-transport chain

B. 9+2 microtubule axoneme / dynein arm

C. Actin-myosin crossbridges

D. Gap junction connexins

E. Intermediate filaments

βœ“ Correct: B β€” Dynein arm defect in the 9+2 axoneme (Kartagener syndrome / primary ciliary dyskinesia).

Kartagener syndrome (PCD) is caused by mutations affecting dynein arms of the 9+2 axoneme, which is the core motility apparatus of cilia AND sperm flagella (identical structure). The clinical triad: (1) situs inversus or heterotaxy (because ciliary beating of the embryonic node establishes L–R asymmetry during gastrulation); (2) chronic sinusitis + bronchiectasis (immotile respiratory cilia β†’ mucus stasis β†’ recurrent infection); (3) infertility in males (immotile sperm) and reduced fertility in females (reduced oviduct ciliary transport). The same 9+2 axoneme is shared by respiratory cilia, oviduct cilia, ependymal cilia, and sperm flagella β€” a classic Step 1 "one defect, many organs" question.

LO 2 β€” Excurrent Ducts (Q5–Q7)

Question 5

A pathology resident examines a histology image showing a small, coiled duct with a single-layered pseudostratified columnar epithelium bearing long, non-motile apical projections. The lumen contains numerous spermatozoa. The surrounding smooth-muscle coat is thin. Which structure is most likely shown?

A. Seminiferous tubule

B. Rete testis

C. Efferent ductule

D. Ductus epididymis

E. Vas deferens

βœ“ Correct: D β€” Ductus epididymis (pseudostratified columnar with stereocilia + thin muscle).

The combination of pseudostratified columnar epithelium with long non-motile apical projections (stereocilia), a lumen full of mature sperm, and a thin smooth-muscle coat is diagnostic of the ductus epididymis. Stereocilia are actually long actin-based microvilli (not true cilia β€” they have no 9+2 axoneme and are non-motile). Key distinguishers: (A) seminiferous tubules are multi-layered with developing germ cells + Sertoli cells; (B) rete testis has simple cuboidal epithelium in anastomosing channels; (C) efferent ductules have a "scalloped" luminal border from alternating tall ciliated and short resorptive cells; (E) vas deferens also has stereocilia but its wall is dominated by a massive three-layer smooth-muscle coat.

Question 6

A 16-year-old boy with recurrent pulmonary infections and pancreatic insufficiency is found to have a CFTR mutation. Which additional finding is most likely to be identified on reproductive-system evaluation in adulthood?

A. Klinefelter karyotype

B. Bilateral absence of the vas deferens

C. Hydrocele

D. Sertoli-cell-only syndrome

E. Testicular torsion

βœ“ Correct: B β€” Congenital Bilateral Absence of the Vas Deferens (CBAVD) β€” a CFTR-linked anomaly.

CFTR mutations (classic cystic fibrosis or milder variants) are strongly associated with CBAVD β€” fetal obstruction/atresia of the mesonephric (Wolffian) duct derivatives leads to absent vas deferens + often absent or hypoplastic seminal vesicles. Clinical findings: azoospermia (obstructive), low ejaculate volume (<1 mL), absent fructose in semen (seminal vesicles make it). Because Leydig cells and spermatogenesis are preserved, testosterone and FSH/LH are normal, and fertility can be achieved via testicular sperm extraction + IVF/ICSI. A β€” Klinefelter is unrelated. C β€” hydrocele is a tunica vaginalis fluid collection. D β€” Sertoli-cell-only is a different infertility cause. E β€” torsion is anatomic, not CFTR-related.

Question 7

A medical student is shown a histology slide that shows a small stellate lumen lined by pseudostratified columnar epithelium with stereocilia, surrounded by a disproportionately thick wall of three layers of smooth muscle. Which structure is being shown?

A. Ureter

B. Epididymis

C. Vas deferens

D. Ejaculatory duct

E. Penile urethra

βœ“ Correct: C β€” Vas deferens: pseudostratified columnar with stereocilia + three thick smooth-muscle layers around a small stellate lumen.

The absolutely-diagnostic feature is the disproportionately thick three-layer smooth-muscle wall (inner longitudinal, middle circular, outer longitudinal) surrounding a tiny stellate lumen. This muscular architecture drives powerful peristaltic contractions during ejaculation. The epithelium is similar to epididymis (pseudostratified columnar with stereocilia), but the epididymis has only a thin smooth-muscle layer. The ureter (A) has three muscular layers but transitional epithelium β€” not columnar with stereocilia. Ejaculatory duct (D) has less muscle. Penile urethra (E) is lined by columnar epithelium without stereocilia and has no surrounding thick muscle.

LO 3 β€” Accessory Glands & Penis (Q8–Q11)

Question 8

A 72-year-old man has been experiencing progressive lower back pain and difficulty walking. X-rays reveal multiple dense (sclerotic) lesions in the lumbar vertebrae and pelvis. His PSA is 120 ng/mL. Alkaline phosphatase is elevated. Biopsy confirms metastatic adenocarcinoma. Which zone of the prostate gland is the most likely origin, and what is the most appropriate initial treatment approach?

A. Transition zone; 5Ξ±-reductase inhibitors

B. Peripheral zone; androgen deprivation therapy (GnRH agonist)

C. Central zone; chemotherapy with doxorubicin

D. Anterior fibromuscular stroma; radical prostatectomy alone

E. Ejaculatory duct opening; radiation only

βœ“ Correct: B β€” Peripheral zone (posterior prostate, most cancers); androgen deprivation with GnRH agonist is first-line for metastatic disease.

Prostate adenocarcinoma arises predominantly in the peripheral zone (~70% of cancers) β€” posterior and thus palpable as a hard nodule on DRE. Osteoblastic (sclerotic) bone metastases to the lumbar spine and pelvis are classic for prostate cancer (vs. most other carcinomas which are osteolytic) β€” explaining the dense lesions and elevated alk phos. For advanced/metastatic disease, the backbone of therapy is androgen deprivation: options include GnRH agonists (leuprolide β€” causes initial flare; give with AR antagonist for first month), GnRH antagonists (degarelix β€” no flare), bilateral orchiectomy, AR antagonists (bicalutamide, enzalutamide), and CYP17 inhibitors (abiraterone). A (transition zone) is BPH territory. C β€” chemo is second-line. D (anterior stroma) has no glands. E β€” ED opening is the verumontanum.

Question 9

An infertility specialist performs a semen analysis on a 38-year-old man. Results: ejaculate volume 0.4 mL (low), sperm count essentially zero, absent fructose. Subsequent scrotal ultrasound is normal; transrectal ultrasound shows absent seminal vesicles bilaterally. What is the most likely underlying molecular diagnosis?

A. 46,XY karyotype with SRY deletion

B. Klinefelter syndrome (47,XXY)

C. CFTR gene mutation

D. Kallmann syndrome (anosmin mutation)

E. 5Ξ±-reductase deficiency

βœ“ Correct: C β€” CFTR mutation causing Congenital Bilateral Absence of the Vas Deferens (CBAVD) with concomitant seminal vesicle agenesis.

The triad of azoospermia + low ejaculate volume + absent seminal vesicles points to a mesonephric duct developmental failure. CFTR mutations produce luminal obstruction of developing Wolffian duct structures β†’ atresia of vas deferens AND seminal vesicles. Because the seminal vesicles are the source of fructose (~70% of ejaculate volume), their absence explains both the low volume and absent fructose. Testes, Leydig cells, and spermatogenesis are intact, so testosterone and gonadotropins are normal; the issue is purely transport/delivery. Management: CFTR genotyping of patient + partner; testicular sperm extraction + IVF/ICSI. A (Swyer) has a female phenotype. B (Klinefelter) has small testes, ↑ FSH, ↑ LH. D (Kallmann) causes hypogonadotropic hypogonadism + anosmia. E (5Ξ±-reductase) causes ambiguous external genitalia.

Question 10

A 55-year-old man on nitrates for stable angina takes a tablet of sildenafil before intercourse. He becomes severely hypotensive and develops chest pain. What is the mechanism of the drug interaction?

A. Additive effects on guanylate cyclase β†’ cGMP accumulation β†’ excessive vasodilation

B. Competitive antagonism at Ξ²1 receptors β†’ bradycardia

C. Inhibition of angiotensin-converting enzyme β†’ loss of vasopressor tone

D. Blockade of calcium channels β†’ decreased cardiac output

E. Direct myocardial toxicity from sildenafil

βœ“ Correct: A β€” Both drugs increase cGMP (nitrates via NO β†’ guanylate cyclase; sildenafil via PDE5 inhibition) β†’ additive, severe vasodilation.

During erection, parasympathetic nerves release NO β†’ activates guanylate cyclase β†’ ↑ cGMP β†’ smooth-muscle relaxation β†’ penile vasodilation. Phosphodiesterase-5 (PDE5) normally degrades cGMP. Sildenafil (and tadalafil, vardenafil) inhibit PDE5 β†’ more cGMP β†’ prolonged vasodilation. Nitrates (nitroglycerin, isosorbide) generate NO, which activates guanylate cyclase β†’ also ↑ cGMP. Combining these drugs produces additive cGMP accumulation β†’ profound systemic vasodilation β†’ severe hypotension, coronary hypoperfusion (especially in fixed coronary disease), and potentially MI. Sildenafil is also contraindicated or cautious with Ξ±1 blockers (additive hypotension). Teaching points: always screen for nitrate use before prescribing PDE5 inhibitors; they can be used 24 h after last nitrate dose (48 h for tadalafil due to longer half-life).

Question 11

A 68-year-old man with symptomatic BPH is prescribed finasteride. After 6 months, his PSA has decreased by 50% and his prostate has visibly shrunk on imaging. By what molecular mechanism does finasteride produce these effects?

A. Competitive antagonism at the androgen receptor

B. Inhibition of 5Ξ±-reductase β†’ decreased conversion of testosterone to DHT

C. Inhibition of aromatase β†’ reduced estradiol

D. GnRH receptor desensitization β†’ ↓ LH β†’ ↓ testosterone

E. Competitive binding to PSA active site

βœ“ Correct: B β€” Finasteride inhibits 5Ξ±-reductase, blocking testosterone β†’ DHT conversion.

DHT is the dominant androgen driving prostatic and external genital development (50Γ— more potent than T at the androgen receptor). Finasteride (type II selective) and dutasteride (both types) block 5Ξ±-reductase β†’ ↓ intraprostatic DHT β†’ prostate shrinks over months and PSA falls ~50%. This must be remembered when interpreting PSA during cancer screening (multiply by 2). Clinical notes: other 5Ξ±-reductase inhibitor uses include male-pattern baldness and hirsutism. Side effects: ↓ libido, erectile dysfunction, gynecomastia, and a controversial association with high-grade prostate cancer. A (AR antagonist) = flutamide/bicalutamide/enzalutamide. C (aromatase) = anastrozole/letrozole. D (GnRH desensitization) = leuprolide. E is not a real pharmacology.

LO 4 β€” Urethra (Q12–Q14)

Question 12

A 27-year-old man has sexual contact that results in dysuria and a thick, purulent yellow urethral discharge 4 days later. Gram stain reveals Gram-negative diplococci within neutrophils. Which of the following is the most appropriate empirical treatment regimen?

A. Doxycycline alone

B. Ceftriaxone alone

C. Ceftriaxone plus doxycycline

D. Acyclovir

E. Metronidazole

βœ“ Correct: C β€” Ceftriaxone + doxycycline (cover both gonorrhea and chlamydia).

The Gram-stain finding of Gram-negative diplococci within neutrophils is diagnostic of gonococcal urethritis (Neisseria gonorrhoeae). However, co-infection with Chlamydia trachomatis occurs in ~30% of patients, and chlamydia is often asymptomatic or presents with thinner discharge. Guidelines now recommend treating both whenever gonorrhea is diagnosed: ceftriaxone 500 mg IM (for GC, with dose increase due to Ξ²-lactamase resistance trends) PLUS doxycycline 100 mg PO BID Γ— 7 days (for Chlamydia). Azithromycin is no longer first-line for chlamydia per updated CDC guidelines. Partner tracing and HIV/syphilis testing are essential. A alone misses GC; B alone misses Chlamydia; D is for HSV; E is for trichomoniasis.

Question 13

A pathologist examines a biopsy from a mass at the distal penile urethra near the meatus. The tumor cells show keratin pearls, intercellular bridges, and a nest-like invasive pattern. Which epithelial type best accounts for this tumor's histology, and what is the most likely diagnosis?

A. Transitional epithelium β†’ urothelial (transitional cell) carcinoma

B. Pseudostratified columnar epithelium β†’ adenocarcinoma

C. Stratified squamous (non-keratinized) epithelium near the fossa navicularis β†’ squamous cell carcinoma

D. Simple cuboidal epithelium β†’ clear-cell carcinoma

E. Mesothelium β†’ mesothelioma

βœ“ Correct: C β€” Distal penile urethra has stratified squamous epithelium near the meatus β†’ squamous cell carcinoma (keratin pearls + intercellular bridges are classic SCC features).

The epithelium-predicts-malignancy rule applies along the length of the urethra:
β€’ Proximal urethra (prostatic, membranous, most of penile) β†’ transitional or pseudostratified columnar epithelium β†’ urothelial carcinoma
β€’ Distal urethra (near external meatus, fossa navicularis) β†’ stratified squamous non-keratinized epithelium β†’ squamous cell carcinoma
The histologic features described β€” keratin pearls (whorled keratin in tumor nests) and intercellular bridges (desmosomal connections between adjacent cells) β€” are pathognomonic for squamous cell carcinoma. Risk factors for distal urethral SCC include chronic inflammation (strictures, STIs), HPV infection, and poor hygiene. Proximal urothelial carcinomas are more common in smokers and occupational exposures (aromatic amines).

Question 14

A 25-year-old man is brought to the ED after a motorcycle crash with pelvic instability on imaging showing a diastasis of the pubic symphysis. On exam, he has blood at the urethral meatus, perineal ecchymosis, and is unable to void. The trauma team wants to place a Foley catheter. What is the single best next step?

A. Pass a Foley catheter gently; if resistance is met, withdraw

B. Obtain a retrograde urethrogram before attempting any urethral instrumentation

C. Place a suprapubic catheter immediately without imaging

D. Obtain a CT cystogram

E. Observe without drainage until the bladder is palpable

βœ“ Correct: B β€” Retrograde urethrogram (RUG) first β€” diagnose urethral injury before instrumentation.

The trio of findings β€” blood at the meatus, perineal ecchymosis, inability to void, in the setting of pelvic fracture β€” is highly suspicious for urethral injury, most likely at the membranous urethra as the urogenital diaphragm shears during pelvic disruption. Attempting to pass a Foley blindly can convert a partial tear into a complete one and create a false passage, making subsequent repair much harder. The correct algorithm is to obtain a retrograde urethrogram β€” contrast is instilled gently at the meatus under fluoroscopy. If the urethra is intact, the contrast flows smoothly to the bladder and Foley placement can proceed. If disrupted, contrast extravasates at the injury site. Definitive drainage is then achieved via suprapubic cystostomy, bypassing the urethra; urologic repair (primary realignment or delayed reconstruction) follows. A is dangerous. C is reasonable AFTER confirming injury but RUG is the standard first step. D (CT cystogram) assesses the bladder, not the urethra. E fails to address the urologic emergency.