Urinary System – Kidney Structure & Function

Core Physiologic Roles of the Urinary System

• Not merely for waste removal
  • Maintains water–electrolyte balance (osmoregulation)
  • Regulates systemic blood pressure via juxtaglomerular (JG) apparatus and renin release
  • Endocrine synthesis/activation of:
  • Vitamin D (final hydroxylation step → 1,25\text{-}(OH)2\text{D}3)
  • Erythropoietin (EPO) for bone-marrow erythropoiesis
  • Contributes to acid–base buffering and excretion of metabolic toxins (urea, creatinine, xenobiotics)

Integration With Other Organ Systems

• Skeletal / GI: Active vitamin D from kidney ↑ intestinal Ca^{2+} & PO_4^{3-} absorption
• Cardiovascular:
  • Renin–angiotensin cascade raises BP; opposed by cardiac atrial natriuretic peptide (ANP)
  • Close feedback between renal perfusion & systemic arterial pressure
• Hematologic: Chronic kidney disease (CKD) ↓ EPO → normocytic normochromic anemia
• Endocrine / Electrolyte: Estrogen, parathyroid hormone (PTH), and adrenal steroids modify renal Na^+, K^+, Ca^{2+} handling

Major Homeostatic Processes

• Glomerular filtration ≈ 180\;\text{L plasma filtrate·day}^{-1} (ultrafiltration)
• Tubular reabsorption
  • Nearly all filtered glucose & amino acids reclaimed
  • Variable reclamation of Na^+, H2O, HCO3^- under hormonal influence (ADH, aldosterone)
• Tubular secretion of K^+, H^+, organic acids/bases
• Net urine volume ≈ 1!–!2\;\text{L day}^{-1}

Gross Anatomy & Spatial Orientation

• Location: Retroperitoneal, T12–L3; right kidney slightly lower due to liver
• Hilum contents (antero-posterior): renal vein, renal artery, pelvis → ureter; plus lymphatics & nerves
• Two concentric regions:
  • Cortex (outer granular region)
  • Medulla (inner striated region of pyramids)
• Capsule
  • Outer fibrous layer (dense collagen)
  • Inner myofibroblastic layer (smooth-muscle–like cells permitting slight contractility)

Renal Sinus & Collecting System

• Minor calyces surround papillae → major calyces → renal pelvis → ureter
• Area cribrosa on papilla: sieve-like zone where collecting ducts empty

Sub-gross Units

• Renal pyramid = medulla segment with base toward cortex, apex (papilla) toward sinus
• Medullary rays: Cortical extensions of straight tubules & collecting ducts; appear as radial stripes
• Renal columns (of Bertin): Cortical tissue between adjacent pyramids; house vessels & connective tissue
• Renal lobe = pyramid + overlying cortical cap; ≈ 8–10 per kidney (visible in fetus)
• Renal lobule = group of nephrons draining into a single collecting duct (microscopic, 3-D concept)

Nephron Architecture

• Renal corpuscle (in cortex)
  • Glomerulus of fenestrated capillaries
  • Bowman’s capsule
  • Visceral layer → podocytes (modified epithelial cells)
  • Parietal layer → simple squamous epithelium continuous with PCT
• Proximal convoluted tubule (PCT)
  • Tall microvillus (brush-border) cells → bulk reabsorption (≈ 65–70 % filtrate)
• Loop of Henle
  • Descending limb: thin segment \rightarrow permeable to H_2O
  • Ascending limb: thin + thick segments; thick ascending limb (TAL) actively pumps Na^+/K^+/2Cl^- (diluting segment)
• Distal convoluted tubule (DCT)
  • Macula densa region senses tubular NaCl to modulate renin release
  • Principal site for aldosterone-dependent Na^+ reabsorption & K^+ secretion
• Connecting/Collecting tubules & ducts (of Bellini)
  • Responsive to antidiuretic hormone (ADH) → aquaporin-2 insertion; determine final urine osmolality

Two Physiologic Classes of Nephrons

• Cortical (superficial) nephrons
  • Short loops; remain in outer medulla → limited concentrating ability
• Juxtamedullary nephrons
  • Corpuscles near corticomedullary junction; very long loops projecting to inner medulla/papilla
  • Generate corticomedullary osmotic gradient essential for urine concentration

Juxtaglomerular Apparatus (JGA)

• Components
  • Macula densa (DCT epithelial sensor of filtrate NaCl)
  • JG (granular) cells: modified afferent-arteriole smooth muscle storing renin
  • Extraglomerular mesangial cells (Lacis cells): paracrine signaling
• Functions
  • Renin release → \rightarrow Angiotensin II → systemic vasoconstriction & aldosterone secretion
  • Tubuloglomerular feedback stabilizes single-nephron GFR despite BP fluctuations

Histologic Identification Guide

• Cortex
  • Presence of numerous round glomeruli
  • PCTs (eosinophilic, fuzzy lumina) vs. DCTs (paler, clearer lumina)
• Medulla
  • No glomeruli; parallel arrays of thin limbs, thick limbs, vasa recta & collecting ducts
• Interstitium
  • Fibroblasts & pericytes; secrete medullipin I → II (hypotensive lipid mediators)
  • Houses capillaries for reabsorbed solutes & water return

Renal Blood Supply (from hilum to microcirculation)

1. Renal artery
2. Segmental arteries (multiple)
3. Interlobar arteries (within renal columns)
4. Arcuate arteries (arch along corticomedullary junction)
5. Interlobular (cortical radial) arteries (extend into cortex)
6. Afferent arterioles → glomerular capillaries → efferent arterioles
   • Cortical nephrons: efferent arterioles → peritubular capillary plexus
   • Juxtamedullary nephrons: efferent arterioles → vasa recta (hair-pin capillaries paralleling loop) for counter-current exchange
7. Venous return mirrors arteries (interlobular → arcuate → interlobar → renal vein)

Basement-Membrane & Filtration Barrier Details

• Trilaminar glomerular basement membrane (GBM)
  1. Lamina rara interna
  2. Lamina densa (type IV collagen, heparan sulfate)
  3. Lamina rara externa
• Surfaces flanked by:
  • Fenestrated endothelial cells (charge-selective filter)
  • Podocyte foot processes with slit diaphragms (nephrin zipper-like proteins)
• Pathology correlation: defects → proteinuria (e.g., minimal-change, Alport, diabetic nephropathy)

Connective-Tissue & Hormonal Microenvironment

• Myofibroblasts in capsule provide limited contractility accommodating pressure/volume oscillations
• Pericytes in vasa recta regulate medullary blood flow; potential source of fibroblasts in CKD fibrosis
• Interstitial hormones
  • Medullipin I/II: vasodilatory, BP-lowering
  • Prostaglandins (PGE_2), nitric oxide: modulate renal hemodynamics and renin release

Developmental Notes

• Fetal kidney shows external lobulation (medulla + cortical cap) → smooths post-natally
• Each adult kidney retains ≈ 8!–!10 lobes internally (surgical relevance for segmental resections)

Clinical Correlations & Pathophysiologic Highlights

• CKD
  • ↓ EPO → anemia requiring recombinant EPO
  • ↓ 1,25\text{-}(OH)2\text{D}3 → secondary hyperparathyroidism, renal osteodystrophy
• Hypertension
  • Overactive RAAS (e.g., renal artery stenosis) ↑ systemic BP; ACE inhibitors mitigate
• Diuretic pharmacology
  • Loop diuretics target TAL Na^+/K^+/2Cl^- cotransporter
  • Thiazides act on DCT Na^+/Cl^- cotransporter
• Glomerular diseases: structural injury to filtration barrier → hematuria/proteinuria; localized to cortex because glomeruli reside there
• Acute tubular injury: ischemic or toxic damage to PCT/TAL; manifests in medulla (high metabolic demand/low O_2)

Summary Checklist

• Kidney functions = filtration, reabsorption, secretion + endocrine
• Understand gross regions (cortex, medulla, pyramids, columns, rays) and microscopic landmarks (glomeruli, tubules)
• Distinguish cortical vs. juxtamedullary nephrons & their vascular supply (peritubular capillaries vs. vasa recta)
• JGA integrates tubular feedback with systemic BP control (renin)
• Activation of vitamin D and synthesis of EPO couple renal health to bone & blood physiology
• Interstitial cells, medullipin, and capsule myofibroblasts add nuanced regulation of renal hemodynamics