The Renal System

The kidneys maintain body fluid homeostasis by filtering blood, reabsorbing needed substances, and excreting waste. Each kidney contains approximately one million nephrons — the functional unit consisting of the glomerulus, proximal convoluted tubule (PCT), loop of Henle, distal convoluted tubule (DCT), and collecting duct.

Glomerular filtration produces ~180 L/day of ultrafiltrate at a glomerular filtration rate (GFR) of ~125 mL/min. The filtration barrier has three layers: fenestrated capillary endothelium, the glomerular basement membrane (negatively charged, repels albumin), and podocyte filtration slits. GFR is governed by Starling forces; net filtration pressure is ~10 mmHg. Roughly 99% of the ultrafiltrate is reabsorbed.

The PCT reabsorbs ~67% of filtered Na+, water, glucose (via SGLT2), amino acids, and bicarbonate. Glucose reabsorption is saturable; plasma glucose >10 mmol/L saturates transporters, causing glucosuria (as in diabetes mellitus). The loop of Henle generates the medullary osmotic gradient essential for urine concentration. The thin descending limb is permeable to water; water exits osmotically, concentrating the tubular fluid. The thick ascending limb actively reabsorbs NaCl via NKCC2 (target of loop diuretics like furosemide) without water, making fluid hypotonic and building the medullary gradient (up to ~1200 mOsm).

In the DCT and collecting duct, aldosterone (from adrenal cortex) binds mineralocorticoid receptors, increasing ENaC and Na+/K+-ATPase expression — promoting Na+ reabsorption and K+/H+ secretion. Antidiuretic hormone (ADH) from the posterior pituitary inserts aquaporin-2 (AQP2) water channels into the collecting duct apical membrane via a V2-receptor/cAMP/PKA pathway, allowing water reabsorption and urine concentration up to 1200 mOsm.

The renin-angiotensin-aldosterone system (RAAS) is the primary long-term blood pressure regulator. Juxtaglomerular cells release renin when renal perfusion pressure falls or sympathetic activity rises. Renin cleaves angiotensinogen → angiotensin I; ACE (lung) converts it to angiotensin II. Angiotensin II causes arteriolar vasoconstriction, stimulates aldosterone and ADH release, and promotes thirst — collectively raising blood pressure and blood volume. Atrial natriuretic peptide (ANP) opposes the RAAS by increasing GFR and promoting natriuresis.

The kidneys regulate acid-base balance by reabsorbing filtered HCO3−, excreting H+ via titratable acids (phosphate buffer) and ammonium (NH4+). For each NH4+ excreted, one new HCO3− is regenerated and added to the blood, correcting metabolic acidosis. In metabolic alkalosis, HCO3− reabsorption is reduced and excess is excreted in urine.