Distal Tubule H⁺ Pump & Renal Tubular Acidosis

Distal Nephron Controls

H⁺-ATPase pump activity 90%

Ammoniagenesis / NH₃ buffer supply 70%

Tight-junction H⁺ backleak 10%

Live Readouts

Steady state

Urine pH7.40

Net acid excretion50 mEq/day

Blood pH (systemic)7.40

How it works

α-intercalated cells of the collecting duct pump protons across their apical membrane with an ATP-driven H⁺-ATPase (and H⁺/K⁺-ATPase), while a basolateral Cl⁻/HCO₃⁻ exchanger (AE1) returns newly generated bicarbonate to blood:

CO2 + H2O --CA-II--> H2CO3 --> H+ + HCO3-
H+ (cell) --ATPase--> H+ (lumen)     [apical]
HCO3- (cell) <--AE1--> Cl- (blood)   [basolateral]
NH3 + H+ (lumen) --> NH4+  (trapped, pKa ~9.25)

Secreted H⁺ that stays free drives the lumen pH down; H⁺ captured as ammonium (NH₄⁺) is excreted without lowering pH further, so ammonia availability sets how much acid can leave without over-acidifying the tubule. The pump can sustain roughly a 1000-fold (≈3 pH unit) gradient against blood before backleak — abnormal H⁺ permeability through the tight junctions — dissipates it back into the cell:

target pH ≈ blood_pH − 3.0 × (pump activity)
actual pH ≈ target + 0.5 × backleak × (blood_pH − target)

In distal (Type 1) renal tubular acidosis, a defective or absent H⁺-ATPase (or a leaky gradient) caps urine pH above ~5.5–6.5 no matter how acidotic the blood becomes — the classic diagnostic mismatch of an inappropriately alkaline urine during systemic acidemia. Net acid excretion (titratable acid + NH₄⁺ − HCO₃⁻ lost) then falls below the ~1 mEq/kg/day of endogenous acid production, and blood pH drifts down over time.

Pump activity — fraction of functional apical H⁺-ATPase; low values are the primary distal RTA defect.
Ammonia buffer supply — NH₃ delivered to the lumen to trap H⁺ as NH₄⁺; raises net acid excretion without dropping pH further.
Backleak — apical/tight-junction H⁺ permeability; a "gradient defect" that lets secreted acid leak back into the cell.

Free H⁺ (acidifies lumen) NH₄⁺ (buffered, excreted) α-intercalated cell pump

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