2012A15 Describe the role of the kidneys in excretion of acid.

Acid flux

·  15,000mmol/day CO₂ (exhaled)

·  1,500mmol/day lactate (metabolised)

·  70-100mmol/day fixed acid (urinated ONLY) – typical Western diet

Kidney’s role

1.     Reabsorption of HCO₃^-

2.     Excretion of titratable acid, mostly buffered

3.     Excretion of ammonia

By location

·  Proximal tubule: high capacity (85% filtered HCO₃^-), low gradient (minimum pH 7)

·  Distal tubule: low capacity, high gradient (min pH 4.4)

Quantity

·  4000-5000mmol/day

Location

·  85% proximal tubule

·  10% thick ascending LOH

·  5% distal nephron intercalated cells (CNT/CCD/MCD)

Mechanism

·  ↑[HCO₃^-] -> right shift carbonic acid equilibrium (H⁺ + HCO₃^- <-> CO₂ + H₂O) -> ↓[H⁺]

Diagramme

Definition

·  Amount of base needing to be added to make urinary pH 7.4

·  Formed when HCO₃^- reabsorption almost exhausted

Source

·  Mostly phosphoric acid 30mmol/day (max ~60mmol/L)

·  Small amount sulfuric, acetoacetic

·  Tiny amount free H⁺ filtered (at pH 7.4 -> 40nmol/L -> 7.2μmol/day; minimal ↑ in acidosis)

Mechanism: e.g. phosphoric acid

·  HPO₄ is filtered by the glomerulus

·  H⁺ secreted by the PCT (Na⁺/H⁺ antiport)

·  H₂PO₄ <-> H⁺ + HPO₄^- (pKa 6.8)

·  Acidosis -> ↓urine pH -> ↑H₂PO₄ excretion

Source

·  60% from deamination of filtered glutamine in the PCT

o Glutamine -> 2NH₄⁺ + 2HCO₃^- + oxoglutarate

o HCO₃^- reabsorbed

o 35% filtered by glomerulus

5% from deamination of other filtered amino acids in the PCT

Mechanism

·  NH₄⁺ <-> NH₃ + H⁺ (pKa 9.2)

·  NH₄ secreted by Na⁺/NH₄ antiporter, trapped in urine

·  Small amount NH₃ diffuses into urine, -> NH₄⁺, trapped

·  70% NH₄⁺ reabsorbed in thick ascending LOH, recycled

·  ↑ up to 300mmol/day in acidosis (due to high pKa)

·  Note doesn’t contribute to titratable acidity since pKa 9.2 >> 7.4)