8.2 Body Fluids and Renal Physiology

Body-fluid compartments and osmolarity

Kidney and urinary-tract anatomy is in 4.2 Urogenital System. Physiology starts with how water is partitioned. In a typical adult man, total body water (TBW) is about 60% of body weight (closer to 50% in a typical woman, lower still with obesity because adipose is dry). The 60-40-20 rule is the exam shorthand: TBW 60%, intracellular fluid (ICF) 40%, extracellular fluid (ECF) 20% of body weight. Of ECF, about three-fourths is interstitial and one-fourth is plasma (plus a small transcellular slice: CSF, aqueous humor, GI lumen, synovial fluid). A 70 kg man: TBW ~42 L, ICF ~28 L, ECF ~14 L, plasma ~3.5 L.

Osmolarity of ICF and ECF is equal at steady state (~290 mOsm/L) because most cell membranes are water-permeable via aquaporins. Na+ and accompanying anions hold ECF volume; K+ and organic phosphates hold ICF volume. Isosmotic volume expansion (infusion of isotonic NaCl) raises ECF only. Hyperosmotic volume expansion (high NaCl intake, hypertonic saline) raises ECF osmolarity, pulls water from ICF, and expands ECF more than the infused volume. Hypo-osmotic volume expansion (SIADH) adds water to both compartments. Diarrhea is roughly isotonic ECF loss; adrenal insufficiency loses ECF Na+ and may swell cells; sweat is hypotonic so remaining ECF shrinks and becomes hyperosmotic.

Starling forces at the capillary: net filtration = Kf [(Pc − Pi) − σ(πc − πi)]. Low plasma oncotic pressure (nephrotic syndrome, liver failure) and high venous pressure both produce interstitial edema. The kidney is both a capillary bed (glomerulus) and the organ that sets the Na+ inventory that determines ECF volume and therefore venous pressure.

Micturition

The bladder is a compliant reservoir until a threshold volume fires stretch afferents in the pelvic nerves. Sympathetic fibers (L1–L2, hypogastric) relax the detrusor (β3) and contract the internal urethral sphincter (α1) for storage. Parasympathetic fibers (S2–S4, pelvic splanchnics) contract the detrusor (M3) and help open the internal sphincter for voiding. The external urethral sphincter is skeletal muscle (pudendal nerve) under voluntary and pontine control. The pontine micturition center coordinates sphincter relaxation with detrusor contraction; cortical areas permit delay. A suprapontine lesion can cause urge and loss of social control with a coordinated sphincter; a spinal lesion between pons and sacral cord produces an initial spinal shock (atonic bladder) then a hyperreflexic bladder with detrusor–sphincter dyssynergia. A sacral lesion (cauda equina) yields a flaccid, overflow bladder. Residual volume after a coordinated void should be small; high residual volume is a failure of emptying, not of the 60-40-20 rule.

GFR and its determinants

Glomerular filtration rate (GFR) in a young adult is about 125 mL/min (180 L/day). Renal plasma flow (RPF) is about 600 mL/min; renal blood flow is about 20% of cardiac output. Filtration fraction (FF) = GFR/RPF ≈ 0.20. Only the plasma that is not filtered continues into the peritubular capillary, so a high FF concentrates post-glomerular protein and raises peritubular oncotic pressure—favoring proximal reabsorption.

The glomerular capillary is a high-pressure filter:

Net ultrafiltration pressure = (PGC − PBS) − (πGC − πBS)

πBS is normally ~0 (little protein in Bowman space). Kf is the product of hydraulic conductivity and surface area; mesangial contraction lowers Kf. PGC is set by arterial pressure and by the resistance ratio of afferent versus efferent arterioles.

Angiotensin II constricts both arterioles but prefers the efferent, defending GFR when RPF falls (volume depletion). Afferent prostaglandins (PGE2, PGI2) dilate the afferent arteriole; NSAIDs can precipitate acute drops in GFR in a volume-depleted patient. Autoregulation of RBF and GFR between roughly 80–180 mmHg mean pressure uses a myogenic afferent response and tubuloglomerular feedback: high NaCl at the macula densa (NKCC2) releases adenosine/ATP that constricts the afferent arteriole of that same nephron. Low distal NaCl does the opposite and also triggers renin from granular cells.

Clearance C = U × V / P. Inulin clearance equals GFR (filtered, neither reabsorbed nor secreted). Creatinine clearance slightly overestimates GFR because of a little tubular secretion. PAH at low concentration is filtered plus nearly completely secreted, so PAH clearance estimates effective RPF. Free-water clearance CH2O = V − Cosm; positive in water diuresis (dilute urine), negative when ADH is concentrating urine. Do not confuse these laboratory GFR estimates with the size of a practice-question bank.

Quick Answer: Moderate efferent constriction raises PGC, GFR, and filtration fraction. Afferent constriction lowers PGC and GFR together. Ang II is the efferent defender; NSAIDs remove the afferent defender.

Tubular reabsorption and secretion along the nephron

Proximal tubule reabsorbs about 65–67% of filtered Na+ and water isosmotically, essentially all filtered glucose and amino acids, about 80–90% of bicarbonate, and a large share of K+, phosphate, and urea. The engine is basolateral Na/K-ATPase. Apical NHE3 secretes H+; luminal carbonic anhydrase IV and intracellular CA II reclaim HCO3− (acetazolamide blocks this and causes bicarbonate diuresis and a hyperchloremic acidosis). Early PT uses SGLT2 (low affinity, high capacity) for glucose; late PT uses SGLT1. Threshold and transport maximum (Tm) explain glucosuria when filtered load exceeds Tm (plasma glucose roughly >180–200 mg/dL). Organic anions (including PAH) and cations are secreted. Isosmotic reabsorption means luminal fluid remains ~290 mOsm; the TF/P inulin ratio rises because water left with Na+ while inulin stayed behind.

Thin descending limb is highly water-permeable (AQP1) and relatively salt-impermeable: tubular fluid equilibrates with the hyperosmotic medulla and concentrates. Thin ascending limb passively loses salt and is water-impermeable. Thick ascending limb (TAL) is the diluting segment: NKCC2 reabsorbs Na+, K+, and 2 Cl−; ROMK recycles K+ to the lumen and creates a lumen-positive potential that drives paracellular Mg2+ and Ca2+. The TAL is impermeable to water, so urine is diluted here. Loop diuretics (furosemide, bumetanide) block NKCC2: salt wasting, hypokalemia, metabolic alkalosis, and increased urinary Ca2+ (opposite of thiazides). Bartter syndrome is a genetic TAL lesion with a similar picture.

Early distal convoluted tubule uses NCC (Na–Cl cotransporter), still water-impermeable. Thiazides block NCC, increase Ca2+ reabsorption (useful in calcium stone formers), and can cause hyponatremia. Gitelman syndrome mimics chronic thiazides. The connecting tubule and collecting duct split into principal cells and intercalated cells.

Principal cells: apical ENaC (Na+ in) and ROMK (K+ out); basolateral Na/K-ATPase. Aldosterone (mineralocorticoid receptor) increases ENaC, the pump, and K+ conductance—volume repletion at the cost of K+ and H+ loss. ADH (vasopressin) binds V2 receptors, raises cAMP, and inserts AQP2 so water follows the medullary gradient; V1 receptors vasoconstrict. Amiloride blocks ENaC; spironolactone / eplerenone block the aldosterone receptor. ANP/BNP increase GFR and inhibit collecting-duct Na+ reabsorption.

α-intercalated cells secrete H+ via H+-ATPase and H/K-ATPase and generate new HCO3− for the blood—the kidney's response to acidosis. β-intercalated cells secrete HCO3− via pendrin in alkalosis. Inner medullary collecting duct also inserts UT-A1 under ADH so urea can add to medullary osmoles (urea recycling). The countercurrent multiplier (loops of Henle) builds the gradient; vasa recta are the exchanger that remove reabsorbed water without washing the gradient out.

Acid–base: Henderson–Hasselbalch, gap, and compensation

Henderson–Hasselbalch for plasma:

pH = 6.1 + log([HCO3−] / (0.03 × PCO2))

Normal pH 7.40, HCO3− ~24 mEq/L, PCO2 ~40 mmHg. The ratio, not the absolute HCO3−, sets pH. Respiratory disorders change PCO2 first; metabolic disorders change HCO3− first. The kidneys adjust HCO3− over hours to days (reclaim all filtered HCO3− in the PT, then generate new HCO3− via intercalated H+ secretion and titratable acid / ammonium). The lungs adjust PCO2 in minutes.

Anion gap = Na+ − (Cl− + HCO3−), normally about 8–12 mEq/L (lab-dependent; some tables include K+). A high-gap metabolic acidosis means unmeasured anions: lactate, ketoacids, sulfate/phosphate in renal failure, methanol formate, ethylene-glycol glycolate/oxalate, salicylate. A normal-gap (hyperchloremic) metabolic acidosis means HCO3− was lost and Cl− rose: diarrhea, pancreatic fistula, carbonic anhydrase inhibitors, RTA. Urine anion gap (Na + K − Cl) is a crude NH4+ marker: negative in GI HCO3− loss (kidney still excreting NH4+ with Cl−), positive when the kidney cannot excrete acid (RTA).

RTA I (distal): cannot secrete H+, urine pH >5.5 despite acidosis, hypokalemia, calcium phosphate stones. RTA II (proximal): cannot reabsorb HCO3−; once plasma HCO3− falls, distal acidification can still drop urine pH. RTA IV (hypoaldosteronism / resistance): hyperkalemic, mild acidosis, impaired NH4+ production. Vomiting loses gastric HCl → metabolic alkalosis; volume depletion plus aldosterone then maintains the alkalosis and can produce paradoxically acid urine. Diarrhea loses stool HCO3− → normal-gap acidosis and hypokalemia. Hyperaldosteronism causes hypertension, hypokalemia, and metabolic alkalosis with not volume depletion.