7.3 Fluid Balance, Glomerular Filtration & Tubular Reabsorption/Secretion
Key Takeaways
- Total body water is ~60% of body weight in men and ~50% in women; intracellular fluid is two-thirds and extracellular fluid one-third, with plasma comprising one-quarter of ECF.
- Glomerular filtration rate is governed by the Starling forces across the glomerular capillary; normal GFR is ~125 mL/min (~180 L/day), driven by a net filtration pressure of about 10 mmHg.
- The filtration barrier has three layers (fenestrated endothelium, basement membrane, podocyte slit diaphragms) and excludes molecules above ~70 kDa or those with strong negative charge.
- The proximal tubule reabsorbs ~65% of filtered Na+, water, and glucose isosmotically; the thick ascending limb reabsorbs Na+-K+-2Cl- without water; the distal tubule and collecting duct fine-tune Na+, K+, and water under hormonal control.
- Renal clearance (C = U·V/P) relates excretion to plasma concentration; inulin clearance equals GFR, while PAH clearance approximates renal plasma flow.
Body Fluid Compartments
Total body water (TBW) averages 60% of body weight in men and 50% in women (who carry proportionally more adipose tissue, which is hydrophobic). TBW distributes as:
- Intracellular fluid (ICF): two-thirds of TBW (~28 L in a 70-kg man).
- Extracellular fluid (ECF): one-third of TBW (~14 L), subdivided into interstitial fluid (three-quarters of ECF, ~10.5 L) and plasma (one-quarter of ECF, ~3.5 L).
A useful 60-40-20 rule for a 70-kg man: TBW 60% (~42 L), ICF 40% (~28 L), ECF 20% (~14 L). Fluid moves freely between plasma and interstitium across capillary walls according to Starling forces, whereas movement between ECF and ICF depends on osmolality; the Na+/K+-ATPase keeps Na+ largely extracellular and K+ intracellular, so Na+ is the dominant ECF osmole and K+ the dominant ICF osmole. Plasma osmolality is tightly regulated near 285-295 mOsm/kg by thirst and ADH.
Renal Blood Flow and Glomerular Filtration
The kidneys receive ~20-25% of cardiac output (~1.1 L/min in a 70-kg adult). Renal plasma flow (RPF) equals renal blood flow × (1 - hematocrit), so with a hematocrit of 0.45, RPF is about 625 mL/min. Renal clearance of para-aminohippuric acid (PAH) approximates RPF (~625 mL/min) because PAH is both filtered and secreted, with ~90% extraction in one pass. Inulin clearance equals GFR because inulin is freely filtered but neither reabsorbed nor secreted; clinically, creatinine clearance is used as a convenient estimate (slightly overestimates GFR because creatinine is also secreted).
Normal GFR is about 125 mL/min (~180 L/day, ~99% reabsorbed). GFR is determined by the Starling forces across the glomerular capillary:
Net filtration pressure (NFP) = (P_GC − P_BS) − (π_GC − π_BS)
where P_GC is glomerular capillary hydrostatic pressure (~55 mmHg), P_BS is Bowman's space hydrostatic pressure (~15 mmHg), π_GC is glomerular capillary oncotic pressure (~30 mmHg), and π_BS is essentially 0. Thus NFP ≈ (55 − 15) − (30 − 0) = 10 mmHg, and GFR = K_f × NFP, where K_f is the ultrafiltration coefficient (~12.5 mL/min/mmHg).
Autoregulation
GFR and RBF are held constant between mean arterial pressures of 80-180 mmHg by two mechanisms: the myogenic response (afferent arteriole constricts when stretched) and tubuloglomerular feedback (the macula densa senses increased NaCl delivery and releases ATP/adenosine that constricts the afferent arteriole). During volume depletion, angiotensin II preferentially constricts the efferent arteriole, raising P_GC and preserving GFR; during volume overload, afferent vasodilation increases RBF and GFR.
The Filtration Barrier
The filtration barrier has three layers, each selecting by size and charge:
- Fenestrated capillary endothelium: restricts cells and large particles.
- Glomerular basement membrane: a fused basal lamina with type IV collagen, laminin, and negatively charged heparan sulfate proteoglycans; the principal size- and charge-selective layer.
- Podocyte slit diaphragms: epithelial foot processes connected by nephrin complexes; final size barrier.
Molecules smaller than ~70 kDa and neutral or cationic pass freely; albumin (69 kDa, strongly anionic) is mostly repelled. Damage to the slit diaphragm (e.g., nephrin mutation in congenital nephrotic syndrome) or loss of negative charge (minimal change disease) causes proteinuria.
Tubular Reabsorption and Secretion
Filtered load = GFR × plasma concentration. The nephron reabsorbs ~99% of filtered water and Na+; segment-specific transport is the key to renal physiology.
Proximal Tubule (~65% reabsorption)
The proximal tubule reabsorbs ~65% of filtered Na+, K+, water, and glucose, isosmotically. Key transporters:
- Na+/H+ exchanger (NHE3) on the apical membrane: reabsorbs Na+ and secretes H+ (linked to bicarbonate reabsorption via carbonic anhydrase).
- Na+-glucose cotransporters (SGLT2 then SGLT1): reabsorbs 100% of glucose under normal conditions; glycosuria appears when plasma glucose exceeds the transport maximum (~375 mg/dL, ~180 mg/dL threshold for filtered load).
- Na+-amino acid cotransport.
- Basolateral Na+/K+-ATPase establishes the Na+ gradient that powers apical cotransport.
- Water follows solute paracellularly and through aquaporin-1.
The proximal tubule also secretes organic anions (PAH, urate) and cations (creatinine, oxalate) via OAT and OCT transporters.
Thick Ascending Limb (~25% NaCl reabsorption, no water)
The thick ascending limb (TAL) of the loop of Henle is impermeable to water. The apical Na+-K+-2Cl- cotransporter (NKCC2) reabsorbs Na+, K+, and Cl-, with K+ recycling back through ROMK to generate a lumen-positive potential that drives paracellular Ca2+ and Mg2+ reabsorption. Loop diuretics (furosemide) inhibit NKCC2. The TAL is the diluting segment and powers the countercurrent multiplier by establishing the corticomedullary osmotic gradient.
Distal Tubule and Collecting Duct (Fine-Tuning)
- Distal convoluted tubule (DCT): apical Na+-Cl- cotransporter (NCC) reabsorbs ~5% of NaCl; thiazide diuretics block NCC. The DCT also reabsorbs Ca2+ under parathyroid hormone (PTH) via apical TRPV5 channels.
- Collecting duct principal cells: apical ENaC (epithelial Na+ channel) reabsorbs Na+ under aldosterone; K+ is secreted through ROMK; aquaporin-2 (AQP2) inserts under ADH (vasopressin) to allow water reabsorption down the medullary gradient.
- Collecting duct intercalated cells: type A secrete H+ and reabsorb K+ in acidosis; type B secrete HCO3- in alkalosis.
Clearance Concept
Renal clearance C_X = (U_X × V) / P_X, where U is urine concentration, V is urine flow rate, and P is plasma concentration. Substances with C < GFR are reabsorbed (e.g., glucose, urea); C = GFR are freely filtered, neither reabsorbed nor secreted (inulin); C > GFR are secreted (PAH, creatinine to a small degree). Free water clearance C_H2O = V − C_osm distinguishes dilute (positive) from concentrated (negative) urine.
Per the PA-CAT Bulletin of Information, rev. 20240815, the Renal Physiology group lists fluid balance, GFR, glomerular filtration, renal blood flow, filtration barrier, and tubular reabsorption and secretion; questions frequently test Starling forces, segment transporters, and clearance relationships.
In a 70-kg man, which of the following best approximates the volume of extracellular fluid?
Which mechanism best preserves GFR during mild systemic hypotension from volume depletion?
Which transporter in the thick ascending limb is inhibited by furosemide, and what is the resulting effect on the corticomedullary gradient?