This is THE most important physiology page in the renal section. Master this, and you'll understand diuretics, electrolyte disorders, acid-base, and tubular defects. Let me walk you through the nephron segment by segment. PROXIMAL CONVOLUTED TUBULE (PCT) The PCT is the workhorse—it does bulk reabsorption. Think of it as trying to reclaim as much of the valuable stuff as possible. Reabsorbs: - 65-80% of filtered Na+ and H2O (isotonic reabsorption—both move together) - ALL glucose and amino acids (via SGLT2 and amino acid transporters) - Most HCO3- (via carbonic anhydrase mechanism) - Most phosphate, K+, uric acid Key transporters: - Na+/H+ exchanger on apical membrane (blocked by carbonic anhydrase inhibitors indirectly) - Na+/K+-ATPase on basolateral membrane (powers everything) - SGLT2 (sodium-glucose cotransporter) Hormonal regulation: - Angiotensin II stimulates Na+/H+ exchanger → increases Na+, H2O, and HCO3- reabsorption - PTH inhibits Na+/phosphate cotransporter → increases phosphate excretion Secretes: - H+ (into lumen, combines with filtered HCO3- → CO2 + H2O → allows HCO3- reabsorption) - NH3 (important for acid excretion as NH4+) THIN DESCENDING LOOP OF HENLE Simple: permeable to WATER, impermeable to solutes. As filtrate descends into the hypertonic medulla, water gets sucked out osmotically. This CONCENTRATES the tubular fluid. This is the "concentrating segment." THIN ASCENDING LOOP OF HENLE Opposite: impermeable to water, permeable to solutes. NaCl passively diffuses out (down its concentration gradient). Tubular fluid becomes more dilute. THICK ASCENDING LOOP OF HENLE Still impermeable to water! But now actively transporting. Key transporter: Na+/K+/2Cl- cotransporter (NKCC2) - This is what LOOP DIURETICS block - Moves Na+, K+, and 2Cl- from lumen into cell - K+ backleak into lumen creates positive lumen potential - This positive potential drives PARACELLULAR reabsorption of Ca2+ and Mg2+ Important concept: When you block NKCC2 with loop diuretics: - You lose Na+, K+, Cl- in urine - You also lose Ca2+ and Mg2+ (no positive potential for paracellular reabsorption) This segment is the "diluting segment"—removes solutes without water, making tubular fluid hypotonic. DISTAL CONVOLUTED TUBULE (DCT) Still impermeable to water (early DCT). Fine-tuning begins. Key transporter: Na+/Cl- cotransporter (NCC) - This is what THIAZIDE DIURETICS block Ca2+ reabsorption here is TRANSCELLULAR: - Ca2+ enters cell through apical Ca2+ channel - Exits via basolateral Na+/Ca2+ exchanger - PTH STIMULATES this process → increases Ca2+ reabsorption Important concept: Thiazides SPARE calcium (hypocalciuria). Why? - Block NCC → less Na+ enters cell - Cell compensates by increasing Na+/Ca2+ exchange to bring in Na+ - This pulls MORE Ca2+ into blood - Result: less Ca2+ in urine (good for osteoporosis, hypercalciuria) This is OPPOSITE of loop diuretics (which waste calcium). COLLECTING TUBULE/DUCT This is where hormones rule. Principal cells: - Aldosterone → increases ENaC (Na+ channel) → more Na+ reabsorption - Aldosterone → increases K+ channel and Na+/K+-ATPase → more K+ secretion - ADH → inserts aquaporin-2 channels → water reabsorption α-intercalated cells: - Secrete H+ via H+-ATPase - Aldosterone increases their activity → more H+ secretion - This is how you regulate acid-base K+-sparing diuretics act here: - Spironolactone/eplerenone = aldosterone receptor antagonists - Amiloride/triamterene = block ENaC directly ADH (vasopressin): - Binds V2 receptors on principal cells - Triggers insertion of aquaporin-2 water channels - Without ADH: collecting duct is impermeable to water → dilute urine - With ADH: collecting duct becomes permeable → concentrated urine Urea reabsorption also occurs in the medullary collecting duct, stimulated by ADH, to maintain the medullary concentration gradient. anyway to remember this concept and transports easily