RAAS is a critical hormonal system for regulating blood pressure, blood volume, and electrolyte balance. Trigger: fall in blood pressure or GFR, low blood sodium, or sympathetic nervous system activation. Juxtaglomerular (JG) cells (modified smooth muscle cells in afferent arteriole wall near glomerulus) detect reduced stretch (low blood pressure) or low Na+ delivery. JG cells secrete RENIN into bloodstream. Renin (protease from JG cells): cleaves angiotensinogen (alpha-2-globulin made by liver) → Angiotensin I (10 amino acid peptide). Angiotensin Converting Enzyme (ACE, located in lung endothelium): converts Angiotensin I → Angiotensin II (8 amino acid peptide, the active hormone). Angiotensin II actions: powerful vasoconstrictor (raises BP directly), stimulates aldosterone release from adrenal cortex, stimulates ADH from posterior pituitary, promotes Na+ reabsorption. Aldosterone: acts on DCT and collecting duct → Na+ reabsorption → water follows osmotically → increased blood volume → increased BP → GFR rises → homeostasis restored.

JGA is a specialised structure at the junction of afferent arteriole and distal convoluted tubule. Components: Juxtaglomerular (JG) cells: modified smooth muscle cells of afferent arteriole wall. Contain granules of renin. Sense stretch (blood pressure). Macula densa: specialised cells in the thick ascending limb of loop of Henle / early DCT, lying adjacent to the JG cells. Sense NaCl concentration of tubular fluid reaching DCT. Low NaCl → stimulates renin release. High NaCl → inhibits renin. Extraglomerular mesangial cells (lacis cells): between JG cells and macula densa. Possibly relay signals. Function: the JGA integrates information about blood pressure (from JG cells) and tubular fluid composition (from macula densa) to regulate renin release and thereby GFR and blood pressure — autoregulation of kidney function.

Multiple hormones regulate kidney function: ADH (Antidiuretic Hormone / Vasopressin): from posterior pituitary. Increases water reabsorption in collecting duct (by inserting aquaporin-2 channels). Triggered by: high plasma osmolarity (detected by hypothalamic osmoreceptors), low blood volume. Effect: concentrated urine, water retention. Aldosterone: from adrenal cortex (zona glomerulosa). Increases Na+ reabsorption + K+ secretion in DCT and collecting duct. Triggered by: angiotensin II, high K+, low Na+. Atrial Natriuretic Peptide (ANP): from cardiac atria when blood volume/pressure too HIGH. Causes: vasodilation of afferent arteriole, Na+ excretion (natriuresis), inhibits renin and aldosterone. Opposes RAAS. PTH (Parathyroid hormone): promotes Ca2+ reabsorption in DCT, phosphate excretion. Vitamin D (activated in kidney): promotes Ca2+ reabsorption. Erythropoietin (EPO): produced by kidney in hypoxia → stimulates RBC production in bone marrow.

GFR is the volume of filtrate formed per minute by both kidneys. Normal GFR: 125 mL/min (180 L/day). GFR depends on: net filtration pressure (glomerular hydrostatic pressure - Bowman capsule pressure - oncotic pressure), surface area of filtration, permeability of filtration membrane. Autoregulation maintains GFR relatively constant despite blood pressure changes: Myogenic mechanism: afferent arteriole smooth muscle responds to stretch. High BP → constriction → reduces flow. Low BP → dilation → increases flow. Tubuloglomerular feedback: macula densa detects high NaCl delivery → ATP and adenosine release → afferent arteriole constriction → reduces GFR. GFR measurement: inulin clearance (gold standard — freely filtered, not reabsorbed or secreted). Clinical: creatinine clearance (easier to measure, slightly overestimates true GFR). eGFR (estimated GFR): calculated from serum creatinine, age, sex. Normal kidney function: eGFR > 90 mL/min/1.73m2. Kidney failure: eGFR < 15.

RAAS is a major target for antihypertensive and cardiac drugs. ACE inhibitors (angiotensin-converting enzyme inhibitors): e.g., enalapril, lisinopril, ramipril. Block conversion of angiotensin I → II. Effects: vasodilation, reduced aldosterone, lower blood pressure, protection of kidneys in diabetic nephropathy. Side effect: dry cough (ACE also breaks down bradykinin — its accumulation causes cough). ARBs (angiotensin receptor blockers): e.g., losartan, valsartan, candesartan. Block angiotensin II receptors (AT1 receptor). Similar effects to ACE inhibitors but without cough (bradykinin still broken down). Direct renin inhibitors: aliskiren — blocks renin directly (first step). Aldosterone antagonists (spironolactone, eplerenone): block aldosterone receptor → natriuresis, used in heart failure and primary hyperaldosteronism (Conn syndrome). Loop diuretics (furosemide): block Na+/K+/2Cl- transporter in thick ascending limb.

Nephron is the functional unit of kidney. ~1 million nephrons per kidney. Parts: Malpighian body (renal corpuscle): glomerulus (capillary tuft) + Bowman capsule. Filtration occurs here. Proximal convoluted tubule (PCT): major reabsorption. ~65-70% of filtered Na+, water, all glucose, amino acids, urea (some), uric acid (some). Brush border (microvilli) for increased surface area. Loop of Henle: descending limb (water permeable, solute impermeable) → ascending limb (solute permeable, water impermeable). Creates hyperosmotic medullary interstitium for concentrated urine. Thin ascending limb: passive NaCl reabsorption. Thick ascending limb (TAL): active NaCl reabsorption (NKCC2 transporter). Distal convoluted tubule (DCT): hormone-regulated Na+ reabsorption (aldosterone), Ca2+ reabsorption (PTH). Collecting duct: water reabsorption (ADH), Na+/K+ exchange (aldosterone). Final urine concentration determined here.

Glomerular filtration: blood pressure forces water and small solutes from glomerular capillaries into Bowman space. Forms primary filtrate (ultrafiltrate) at 125 mL/min. Large molecules (proteins, blood cells) retained in blood. Tubular reabsorption: useful substances (glucose, amino acids, salts, water) taken back from filtrate into blood. PCT: bulk reabsorption. Loop: concentrating mechanism. DCT and collecting duct: fine-tuning. Tubular secretion: additional unwanted substances actively secreted from blood into filtrate. K+, H+, NH4+, creatinine, uric acid, drugs (penicillin, aspirin). Allows excretion beyond what was filtered. Final urine: 1-1.5 L/day (of 180 L filtered). Contains: water, urea (major nitrogenous waste in ureotelic humans), creatinine, uric acid, K+, Na+, Cl-, H+, various metabolites. Normal urine characteristics: clear, pale yellow (urochrome from bilirubin breakdown), specific gravity 1.003-1.030, pH 4.6-8.0.

Glomerulonephritis: inflammation of glomeruli. Immune complex deposition. Proteinuria, haematuria. Can progress to kidney failure. Nephrotic syndrome: massive proteinuria (>3.5g/day), hypoalbuminaemia, oedema, hyperlipidaemia. Causes: minimal change disease (most common in children), membranous nephropathy, focal segmental glomerulosclerosis. Diabetic nephropathy: leading cause of end-stage renal disease (ESRD). High blood glucose → glomerular damage → proteinuria → progressive loss of GFR. RAAS blockade (ACE inhibitors/ARBs) slows progression. Acute kidney injury (AKI): sudden loss of kidney function. Pre-renal (low blood flow), intrinsic (ischaemia, nephrotoxins), post-renal (obstruction). Usually reversible. Chronic kidney disease (CKD): progressive irreversible loss of kidney function. eGFR < 60 for >3 months. Stage 5 (ESRD, eGFR<15): requires dialysis or transplantation. Haemodialysis: blood filtered through artificial membrane twice/three times weekly. Peritoneal dialysis: peritoneum acts as membrane, dialysate in peritoneal cavity.