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Histology of the Urinary System

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Overview

• Regulating water, electrolyte, and acid-base balance
• Excreting metabolic waste products and drugs
• Secreting renin (blood pressure regulation) and erythropoietin (RBC production)
• Converting vitamin D prohormone to active calcitriol
• Performing gluconeogenesis during fasting

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1. Kidney - Gross Histological Organization

• Renal columns (of Bertin): cortical tissue extending between pyramids
• Renal lobe: one pyramid + its associated cortical tissue
• Renal lobule: a medullary ray + surrounding cortical labyrinth
• Renal papilla: apex of each pyramid, which inserts into a minor calyx
• Hilum: concave medial border where artery enters, vein/ureter/lymphatics exit

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2. Blood Supply (Critical for Function)

• Renal artery → interlobar arteries → arcuate arteries (at corticomedullary junction) → interlobular arteries → afferent arterioles
• Afferent arterioles supply glomerular capillaries
• Drained by efferent arterioles (not venules) - maintaining HIGH hydrostatic pressure for filtration
• Efferent arterioles from cortical nephrons → peritubular capillaries
• Efferent arterioles from juxtamedullary nephrons → long vasa recta (loops into medulla, essential for concentrating urine)

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3. The Nephron

1. Renal corpuscle
2. Proximal convoluted tubule (PCT)
3. Loop of Henle
4. Distal convoluted tubule (DCT)
5. Connecting tubule → Collecting duct

Types of Nephrons:

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4. Renal Corpuscle

Glomerulus

Bowman's Capsule

• Parietal layer: simple squamous epithelium; continuous with the proximal tubule at the urinary pole
• Visceral layer: podocytes - highly specialized cells that wrap around capillaries

Podocytes

• Large primary processes that curve around capillaries
• Short interdigitating secondary processes (pedicels)
• Between pedicels: narrow filtration slits (slit pores), covered by thin filtration slit diaphragms (composed of nephrin protein)

The Glomerular Filtration Barrier (3 layers):

1. Fenestrated capillary endothelium - pores ~70-100 nm; negatively charged; allows passage of small molecules
2. Fused basal lamina (330 nm thick) - type IV collagen + laminin + heparan sulfate; acts as main size and charge barrier
3. Filtration slit diaphragms between pedicels - final selective barrier

Mesangium

• Mesangial cells: modified smooth muscle cells located between glomerular capillaries
• Functions: structural support, phagocytosis of trapped proteins/debris, regulation of GFR by contraction, secretion of cytokines
• Surrounded by mesangial matrix (type IV collagen, fibronectin)

Juxtaglomerular Apparatus (JGA)

• Macula densa: a plaque of tall, closely packed epithelial cells in the thick ascending limb (TAL) where it contacts the afferent arteriole; acts as a flow/NaCl sensor
• Juxtaglomerular (granular) cells: modified smooth muscle cells in the afferent arteriole wall; contain renin-secreting granules; secrete renin in response to low blood pressure or low NaCl
• Extraglomerular mesangial cells (lacis cells): between macula densa and glomerulus; role in signal transduction

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5. Proximal Convoluted Tubule (PCT)

• Location: cortex (most prominent tubule in cortical sections)
• Epithelium: simple cuboidal to low columnar
• Brush border (abundant microvilli, ~1 µm long) greatly increases apical surface area
• Abundant mitochondria (basal striations) power active transport
• Large interdigitating basolateral folds - increase basolateral membrane area
• Lumen appears narrow and irregular due to brush border
• Nucleus: large, round, centrally placed; cytoplasm is eosinophilic

• Reabsorbs 100% of glucose and amino acids
• Reabsorbs ~65-70% of filtered Na+, Cl-, water
• Reabsorbs all small proteins (pinocytosis → lysosomal degradation)
• Secretes H+, organic acids (uric acid, drugs)

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6. Loop of Henle (Nephron Loop)

• Thin segments have flat nuclei that bulge into the lumen and are easy to confuse with capillaries (but have no RBCs)
• The TAL is impermeable to water - dilutes the filtrate and generates the medullary concentration gradient
• TAL extends into cortex as the distal straight tubule

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7. Distal Convoluted Tubule (DCT)

• Location: cortex (returns to its parent glomerulus)
• Epithelium: simple cuboidal
• No brush border (distinguishes it from PCT; lumen appears wider)
• Fewer mitochondria than PCT; less eosinophilic
• Basal striations still present (basolateral infoldings)
• Responds to aldosterone (increases Na+ reabsorption)
• Responds to PTH (increases Ca2+ reabsorption)

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8. Collecting Ducts and Collecting Tubules

• Arise from the connecting tubule; pass from cortex into medulla
• Lined by simple cuboidal epithelium (cortical); becomes simple columnar in medulla
• Two cell types:
  • Principal cells (light cells): pale cytoplasm; respond to ADH (water channels/aquaporin-2 insertion) and aldosterone (Na+ reabsorption)
  • Intercalated cells (dark cells): abundant mitochondria; regulate acid-base balance (secrete H+ or HCO3-)
• Cell borders are distinct ("cobblestone" appearance)
• Multiple collecting ducts merge to form ducts of Bellini, which drain at the area cribrosa of the renal papilla

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9. Interstitial Cells

• Type I interstitial cells (fibroblast-like): in cortex and medulla; produce prostaglandins; in medulla, store lipid droplets and have antihypertensive function
• Type II and III interstitial cells (pericyte-like): near blood vessels

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10. Ureter

1. Mucosa: transitional epithelium (urothelium) + lamina propria (loose CT with lymphocytes, blood vessels)
2. Muscularis: inner longitudinal + outer circular smooth muscle (upper 2/3); inner longitudinal + middle circular + outer longitudinal (lower 1/3, near bladder)
3. Adventitia: loose CT blending with surrounding tissue

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11. Urinary Bladder

Transitional Epithelium (Urothelium)

• Stratified; 4-6 cell layers thick when relaxed; thins to 2-3 layers when distended
• Three layers:
  • Basal layer: stem cells attached to basement membrane
  • Intermediate layer: cells of variable thickness; can differentiate to replace surface cells
  • Superficial (umbrella/dome) cells: large polyhedral cells (25-250 µm); often binucleated; bulge into lumen

• Fusiform vesicles (discoid vesicles): unique cytoplasmic vesicles that fuse with apical membrane during bladder distension, adding extra membrane area
• Asymmetric unit membranes (AUM): thickened lipid-rich apical plaques (uroplakins) making the epithelium essentially impermeable to urine

Bladder Wall Layers:

1. Mucosa: transitional epithelium + lamina propria
2. Submucosa: dense irregular CT
3. Muscularis (detrusor muscle): three interlacing layers of smooth muscle (inner longitudinal, middle circular, outer longitudinal) - these merge at the bladder neck as the internal urethral sphincter
4. Serosa/Adventitia: peritoneum covers the superior surface; elsewhere = adventitia

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12. Urethra

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Quick Summary Table

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