Renal handling of water and solute

Vivian Imbriotis | April 30, 2026

If you try to upset my homeostasis, urine big trouble.

Renal handling of water should be answered with sensor/controller/effector.

Renal handling of Na or K should be answered by breaking the nephron down into segments.

Renal handling of glucose should describe glucose, then describe its handling in the PCT, then describe the consequences of glucosuria.

Renal handling of water

ECF volume is largely regulated by sodium balance, so H2O balance typically $\approx$ serum osmolality.

ECF osmolality tightly maintained ~280mOsm

H2O balance regulated by ADH, polypeptide hormone

Synthesized in hypothalamus
Stored in posterior pituitary until released
$T_{\frac{1}{2}}=20$mins; degraded by vasopressinase in liver + kidney

Sensors

Osmoreceptors in vascular organ of lamina terminalis in hypothalamus; exposed to ECF. These cells have copious aquaporins and stretch-activated Na channels $\to$ depolarize when water moves into cells $\to$ sense changes in ECF osmolality.
Central vein stretch receptors and carotid body/aortic arch baroreceptors $\to$ hypothalamus when $\downarrow$preload or $\downarrow$MAP.
Decreased renal perfusion $\to$ renin $\to$ ATII $\to$ hypothalamus

(2) and (3) are more potent stimulus $\to$ water retention $\to$ $\uparrow$ECF volume $\downarrow$tonicity in shocked states

Controller

Hypothalamus integrates signals

Signals posterior pituitary to release ADH

Effector; ADH $\to$

Brain: increased thirst
Renal vasculature (V1 receptor): constrict efferent arterioles $\to$ decreased pressure and flow in peritubular vessels $\to$ pressure gradient favors water reabsorption; reduced medullary concentration gradient washout
Cortical collecting duct (V2 receptor) - aquaporin vesicles translocated to surface $\to$ increased water permeability; also increases urea permeability in distal collecting duct $\to$ magnified H2O reabsorption by countercurrent mechanism

Renal handling of sodium

Na is main ECF cation and determines ECF volume.

$140\text{mM} \cdot 0.130\text{L/min} \cdot 60\text{min/hr} \cdot 24\text{hr/day} = 26,000\text{mmol/day}$ but only ~140mmol excreted (so 99.5% reabsorbed).

Regulation mainly by SNS, RAAS and ANP

Freely filtered. Catecholamines or ATII $\to \ \downarrow GFR \to \downarrow$Na filtered $\to$ Na retention.

PCT - 65% reabsorbed

Apical symport with AAs and glucose (e.g. via SGLT1). Responsible for tubuloglomerular balance ($\uparrow GFR \to \uparrow \text{tubular Glucose/AA mass} \to \uparrow Na\text{ reabsoption}$)
Apical antiport with $H^+$. CO2 diffuses into cell $\xrightarrow{\text{carbonic anhydrase}} HCO_3^-+H^+$, then bicarb symported 3:1 with sodium basolaterally.

Both are secondary active powered by basolateral Na/K ATPase which is upregulated by ATII.

Descending LOH impermeable to Na

Ascending LOH - 10% absorbed (90% cumulative)

Apical symport w/ 2Cl + K via NKCC2; K cycled back to tubule. Secondary active powered by basolateral Na/K ATPase; $\propto$ medullary concentration gradient, $\therefore$ determined by ADH. More Cl anion reabsorbed then cation, which generates...
Positive transtubular voltage $\to$ paracellular Na reabsorption

DCT - 6% absorbed (96% cumulative)

Symport w/ chloride with via NCC channel (thiazide-sensitive channel); secondary active with basolateral Na/K ATPase.

Collecting duct - variable absorption

Exchange with potassium. Na apically absorbed by ENAC $\to$ K excreted by ROMK. Maintained by basolateral Na/K ATPase. Upregulated by aldosterone.

Renal handling of potassium

K is main ICF cation. $[K]_{ECF}$ important for resting membrane potential $\to$ tightly regulated.

Normal $[K]_{ECF} \in [3.5-5]$

Regulation of excretion is by aldosterone; $\downarrow [K]_{ECF} \to$Aldosterone release from adrenal cortex.

Freely filtered.

PCT - 60% reabsorbed

Entirely paracellular via solvent drag

Descending LOH is impermiable to K

Ascending LOH - 20% reabsorbed (80% cumulative)

Apical symport with Na + 2Cl via NKCC2; secondary active with basolateral Na/K ATPase, which also creates positive transtubular voltage $\to$ paracellular K reabsorption

DCT / Collecting ducts - secreted or reabsorbed

Principle cells: secretion in exchange with sodium. Na apically absorbed by ENAC $\to$ K excreted by ROMK. Maintained by basolateral Na/K ATPase. Upregulated by aldosterone. Increased by $\uparrow$ sodium delivery or flow rate to distal nephron. Inhibited by low pH.
$\alpha$-intercalated cells: Apical active antiport of K (in) and H (out) by K/H ATPase

Renal handling of glucose

Glucose, an essential monosaccharide, is freely filtered

$$Glu_{\text{filtered}} = GFR \cdot BGL = 0.135 \cdot 5 \approx 0.7\text{mmol/min}$$ (note BGL analysers actually display the plasma glucose concentration)

Normally kidney reabsorbs 100% of filtered load $\to$ no glucose in urine

All reabsorption is in PCT, by symport with sodium, secondary active powered by basolateral Na/K ATPase. Glucose then exits basolaterally by GLUT1/2.

SGLT2 is high-capacity, low affinity (reabsorbs first 90% of glucose)
SGLT1 is low-capacity, high affinity (mops up remaining 10%)

SGLT has a maximal reabsorption rate. When filtered glucose load >Tmax of 2mmol/minute (typically BGL > 16mM), additional glucose is lost to urine.

Renal consequences of glycosuria

Water loss by osmotic diuresis
Wasting of glucose $\xrightarrow{may}$ ketogenesis
Loss of K due to increased flow rate in distal tubule
Predisposition to UTI