The Renal System

Overview of Renal Function

The kidneys are paired retroperitoneal organs that perform several essential functions: filtration of blood plasma, regulation of extracellular fluid volume and composition, acid-base homeostasis, excretion of metabolic waste products (urea, creatinine, uric acid), production of erythropoietin, activation of vitamin D (to calcitriol), and gluconeogenesis during prolonged fasting.

Nephron Anatomy

Each kidney contains approximately one million nephrons — the functional units of the kidney. Each nephron consists of: (1) the renal corpuscle (glomerulus + Bowman's capsule), where filtration occurs; (2) the proximal convoluted tubule (PCT); (3) the loop of Henle (descending and ascending limbs); (4) the distal convoluted tubule (DCT); and (5) the collecting duct, which empties into the renal pelvis.

Two nephron types exist: cortical nephrons (85%) have short loops of Henle that do not penetrate deep into the medulla; juxtamedullary nephrons (15%) have long loops that extend deep into the inner medulla, enabling the generation of a concentrated urine.

Glomerular Filtration

Glomerular filtration rate (GFR) is the volume of filtrate formed per unit time across all nephrons, normally ~125 mL/min (~180 L/day). The glomerular filtration barrier consists of three layers: the fenestrated endothelium of glomerular capillaries, the glomerular basement membrane (GBM), and the foot processes (podocytes) of visceral epithelial cells, separated by filtration slits bridged by nephrin.

Filtration is driven by the Starling forces across the glomerular capillary. Net filtration pressure = (P_GC − P_BS) − π_GC, where P_GC is glomerular capillary hydrostatic pressure (~55 mmHg), P_BS is Bowman's space pressure (~15 mmHg), and π_GC is glomerular oncotic pressure (~30 mmHg), giving net filtration pressure ≈ 10 mmHg. GFR = Kf × NFP, where Kf is the filtration coefficient.

GFR is autoregulated between MAP 80–180 mmHg via myogenic response and tubuloglomerular feedback (TGF). TGF: increased tubular NaCl delivery to the macula densa triggers afferent arteriolar constriction, reducing GFR. Sympathetic stimulation and angiotensin II constrict the afferent arteriole and reduce GFR.

Tubular Handling of Sodium, Potassium, and Water

PCT reabsorbs ~67% of filtered Na⁺, Cl⁻, K⁺, HCO₃⁻, glucose, and amino acids. Water follows osmotically. The Na⁺/K⁺-ATPase on the basolateral membrane drives active Na⁺ reabsorption, creating a low intracellular Na⁺ concentration that enables luminal entry via co-transporters (SGLT2, NHE3) and channels.

Descending limb of Henle is permeable to water but not NaCl. Water leaves by osmosis into the hyperosmotic medullary interstitium, concentrating tubular fluid.

Thick ascending limb (TAL) reabsorbs NaCl via the Na⁺-K⁺-2Cl⁻ cotransporter (NKCC2, target of furosemide) but is impermeable to water, diluting the tubular fluid. This segment generates and maintains the medullary concentration gradient (countercurrent multiplication).

DCT reabsorbs NaCl via NCC (target of thiazides) under aldosterone control. Fine-tuning of Ca²⁺ reabsorption also occurs here (regulated by PTH and calcitriol).

Collecting duct is the site of final regulation: aldosterone increases principal cell Na⁺ reabsorption (via ENaC) and K⁺ secretion; ADH (vasopressin) inserts aquaporin-2 (AQP2) channels, increasing water permeability and enabling concentration of urine up to ~1200 mOsm/kg.

Renin-Angiotensin-Aldosterone System (RAAS)

When renal perfusion pressure falls, NaCl delivery to the macula densa decreases, or sympathetic tone rises, juxtaglomerular cells release renin. Renin cleaves angiotensinogen (produced by the liver) to angiotensin I (Ang I). Ang I is converted to angiotensin II (Ang II) by ACE (angiotensin-converting enzyme), predominantly in the pulmonary endothelium. Ang II: (1) constricts efferent arterioles (maintaining GFR); (2) stimulates aldosterone secretion from the adrenal zona glomerulosa; (3) promotes Na⁺ and water reabsorption in the PCT; (4) acts on the hypothalamus to stimulate thirst and ADH release; and (5) is a potent systemic vasoconstrictor (raises MAP).

Acid-Base Regulation

The kidneys maintain arterial pH 7.35–7.45 by: (1) reabsorbing all filtered HCO₃⁻ (primarily in the PCT via NHE3); (2) excreting titratable acid (H₂PO₄⁻); and (3) synthesising and excreting NH₄⁺. The PCT secretes H⁺ via NHE3; intercalated cells of the collecting duct secrete H⁺ via H⁺-ATPase or H⁺/K⁺-ATPase. Type A intercalated cells secrete H⁺ (acidosis response); Type B intercalated cells secrete HCO₃⁻ (alkalosis response).