Renal & Reproductive

Renal & Reproductive Systems

High‑yield concepts for clinical reasoning · USMLE Step 1

🧪 Renal Tubules & Countercurrent

Proximal convoluted tubule (PCT)

Tall epithelial cells with extensive apical microvilli and basal invaginations. Numerous mitochondria support active transport. The luminal brush border often appears clouded in histologic sections due to microvilli.

  • Function: bulk reabsorption of Na⁺, H₂O, glucose, amino acids, and HCO₃⁻.
  • Histology: eosinophilic cytoplasm, interdigitated lateral borders, prominent basal membrane infoldings.

Loop of Henle

Descending and ascending limbs with distinct permeability. Thin descending limb is water‑permeable; thick ascending limb actively transports Na⁺, K⁺, Cl⁻ (impermeable to water). This arrangement generates a medullary osmotic gradient — the countercurrent multiplier.

  • Thick ascending limb: resembles distal tubule, rich in Na⁺/K⁺/2Cl⁻ cotransporter (NKCC2).
  • Clinical: loop diuretics (e.g., furosemide) block NKCC2, impairing gradient formation.

Distal convoluted tubule (DCT)

Epithelium with fewer microvilli and less active transport compared to PCT. The DCT contacts its own glomerulus at the macula densa, then connects to collecting ducts.

  • Functions: fine‑tuning of Na⁺, Ca²⁺, and pH balance; regulated by aldosterone and PTH.
  • Macula densa: senses tubular fluid [Na⁺] and modulates renin release.

Collecting ducts

Lined by principal cells (aldosterone‑responsive, regulate Na⁺/K⁺ and water via aquaporins) and intercalated cells (acid‑base regulation).

  • ADH increases water permeability via aquaporin‑2 insertion.
  • Medullary interstitium fibroblasts produce erythropoietin in response to hypoxia.
Mesangial cells click

Located between glomerular capillaries, outside the endothelium, with phagocytic activity. Involved in basal lamina turnover. Abnormalities contribute to glomerular distortion in diseases like IgA nephropathy.

PCT Loop of Henle DCT Collecting duct

Diuretics inhibit Na⁺ reabsorption → increased natriuresis and diuresis.

⚙️ Juxtaglomerular complex

Specialized region where the afferent arteriole, macula densa (DCT), and mesangial cells meet.

  • JG cells: modified smooth muscle cells in afferent arteriole; secrete renin in response to decreased renal perfusion pressure, sympathetic stimulation, or low NaCl at macula densa.
  • Macula densa: tall cuboidal cells that detect luminal Na⁺ concentration and signal to JG cells.
  • Mesangial cells: provide structural support and may communicate between macula densa and JG cells.

🧬 Embryology & Congenital Anomalies

Gonadal differentiation

  • Indifferent stage: both mesonephric (Wolffian) and paramesonephric (Müllerian) ducts.
  • SRY (TDF) → testes → Sertoli cells secrete Müllerian inhibiting factor (MIF) → regression of Müllerian ducts; Leydig cells produce testosterone → stabilizes Wolffian ducts.
  • Female: absent TDF → Müllerian ducts persist → uterus, tubes, cervix; Wolffian ducts regress.

Anomalies

  • Female pseudohermaphroditism (46,XX): congenital adrenal hyperplasia → excess androgens → virilized external genitalia.
  • Male pseudohermaphroditism (46,XY): 5α‑reductase deficiency → inadequate DHT → ambiguous genitalia; at puberty virilization due to T surge.
  • Complete androgen insensitivity (CAIS): AR mutation → female phenotype, no uterus, testes in labia; risk of malignancy.

Penis & testis abnormalities

  • Hypospadias: urethral meatus on ventral penis; often with ventral curvature (chordee).
  • Epispadias: dorsal meatus; associated with bladder exstrophy.
  • Cryptorchidism: undescended testis; bilateral leads to infertility; increased malignancy risk.
  • Hydrocele: patent processus vaginalis → fluid accumulation.

⛰️ Pelvic & Urogenital Diaphragms

Pelvic diaphragm

Muscular floor (levator ani + coccygeus). Supports pelvic organs; puborectalis forms a sling at the anorectal junction, crucial for fecal continence.

Urogenital diaphragm

Thick muscular sheet (sphincter urethrae + deep transverse perineus) inferior to pelvic diaphragm. Contains the external urethral sphincter (voluntary control).

  • Innervation: pudendal nerve (S2–S4).

♂️ Male Pelvis & Prostate

Prostate hyperplasia (BPH)

Enlargement of the transition zone compresses the prostatic urethra → urinary frequency, hesitancy, weak stream. The dense fibroelastic capsule limits expansion, causing urethral compression.

  • Treatment: α‑blockers, 5α‑reductase inhibitors.

♀️ Female Pelvis & Ligaments

Ureter passes medial to the ovarian vessels (suspensory ligament) and under the uterine artery (“water under the bridge”) — critical during hysterectomy.

Prolapse: weakness of pelvic diaphragm, perineal body, cardinal/uterosacral ligaments may cause cystocele, rectocele, or uterine prolapse.

🌀 Perineum & Pouches

Superficial perineal pouch

  • Contains: crura of penis/clitoris, bulb (penis or vestibule), ischiocavernosus, bulbospongiosus, greater vestibular (Bartholin) glands (female).

Deep perineal pouch

  • Contains: sphincter urethrae, deep transverse perineus, bulbourethral (Cowper) glands (male).

Pudendal nerve block: as nerve crosses ischial spine, anesthetizes perineum.

Extravasation: injury to bulbar urethra → urine may track into scrotum, penis, and anterior abdominal wall (deep to Scarpa’s fascia).

🔬 External Genitalia

Male

Corpora cavernosa (crura) and corpus spongiosum (bulb) form the shaft. The spongiosum surrounds the urethra.

Female

Crura of clitoris → corpora cavernosa; bulbs of vestibule lie lateral to the vaginal introitus; greater vestibular glands drain into the vestibule.

🧫 Testis & Spermatogenesis

Seminiferous tubules

Coiled loops (150–200 µm diameter) lined by germinal epithelium and Sertoli cells. Spermatogonia lie on the basal lamina; primary spermatocytes and spermatids are more luminal.

Stages of spermatogenesis

  • Spermatogonium (2n): stem cell (type A → type B).
  • Primary spermatocyte (4n): enters meiosis I.
  • Secondary spermatocyte (2n): rapidly undergoes meiosis II → spermatids (1n).
  • Spermiogenesis: differentiation of spermatid into spermatozoon (acrosome formation, flagellum, cytoplasm loss).

Cytoplasmic bridges interconnect progeny until mature sperm are released.

🧪 Sertoli, Leydig, Blood‑Testis Barrier

Sertoli cells

  • Support, nourish, and phagocytize residual bodies.
  • Secrete androgen‑binding protein (ABP) – stimulated by FSH.
  • Secrete inhibin (suppresses FSH) and anti‑Müllerian hormone (fetal).
  • Form tight junctions → blood‑testis barrier (basal vs. adluminal compartment).

Leydig cells

  • Located in interstitium; produce testosterone under LH stimulation.
  • Essential for spermatogenesis and male secondary sex characteristics.

Barrier protects late spermatocytes and spermatids from blood‑borne agents; primary spermatocytes must cross the barrier via an unknown mechanism.

🔗 Genital Ducts & Accessory Glands

Rete testis → efferent ductules → epididymis

  • Efferent ductules: ciliated cells propel sperm; non‑ciliated reabsorb fluid.
  • Epididymis: pseudostratified columnar with stereocilia; sperm gain motility and are stored.
  • Vas deferens: thick smooth muscle (3 layers) – vasectomy interrupts sperm transport.

Seminal vesicles

  • Produce ~70% of ejaculate: fructose (energy), citrate, prostaglandins, proteins.
  • Pseudostratified columnar epithelium with secretory granules.

Prostate

  • 30–50 tubuloalveolar glands; periurethral and peripheral zones.
  • Secretes acid phosphatase, citric acid, fibrinolysin.

💥 Erection & Ejaculation

Erection (parasympathetic)

Pelvic splanchnic nerves → NO release → relaxation of cavernosal smooth muscle → increased blood inflow, engorgement.

Ejaculation (sympathetic + somatic)

  • Sympathetic (lumbar splanchnic): contraction of epididymis, vas deferens, and accessory glands.
  • Somatic (pudendal): bulbospongiosus and ischiocavernosus contractions → expulsion of semen.