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Proximal tubule: Na+/H+ exchange and bicarbonate reclamation

Proximal tubule · 65-70% Na+ NHE3 Acetazolamide

The workhorse segment: bulk isosmotic reabsorption of ~65-70% of filtered sodium and water and ~80-90% of filtered bicarbonate through the NHE3-carbonic anhydrase system, all powered by the basolateral Na+/K+-ATPase.

Traced from the start

  1. Glomerular filtration barrier
  2. Proximal tubule: Na+/H+ exchange and bicarbonate reclamation

Detail

Reabsorbs
~65-70% of Na+, Cl-, K+ and water (isosmotic: fluid stays ~300 mOsm/kg); 80-90% of HCO3-; ~50% of urea passively
Transporter
Apical NHE3 (Na+ in, H+ out); luminal carbonic anhydrase IV converts H+ + HCO3- to CO2 + H2O; intracellular CA II regenerates HCO3-, exported by basolateral NBCe1; water via AQP1 and the paracellular path
Secretes
NH4+ (from glutamine ammoniagenesis, via NHE3) and H+; the main site of new bicarbonate generation
Hormone
Angiotensin II stimulates NHE3 and Na+/K+-ATPase; sympathetic alpha-1 tone also increases reabsorption; PTH and dopamine inhibit
Diuretic
Acetazolamide (carbonic anhydrase inhibitor): weak, self-limiting natriuresis with bicarbonaturia; used for glaucoma, acute mountain sickness, idiopathic intracranial hypertension and metabolic alkalosis; osmotic diuretics (mannitol) also act here

When it goes wrong

Acetazolamide

Hyperchloraemic (normal anion gap) metabolic acidosis with alkaline urine and hypokalaemia; avoid in cirrhosis (impaired NH4+ trapping precipitates encephalopathy) and severe CKD

Proximal (type 2) RTA from myeloma light chains, tenofovir, ifosfamide, cystinosis or Wilson disease

Normal anion gap acidosis with hypokalaemia; urine pH falls below 5.5 once serum HCO3- drops beneath the lowered threshold; bicarbonate loading alkalinises the urine with fractional HCO3- excretion >15%

Volume depletion with high angiotensin II (vomiting, diuretics)

Enhanced proximal Na+ and HCO3- reabsorption maintains a 'contraction' metabolic alkalosis that corrects only with saline

Practise this structure

2 questions in the bank tagged Acid Base.

A 76-year-old man is admitted after falling down four steps at home. He weighs 75 kg. He has fractures of the left fifth to eighth ribs and it hurts him to brea…

Foundations · middle twist

A 29-year-old woman has a plasma bicarbonate concentration of 15 mmol/L (reference 22–29 mmol/L) and a normal anion gap. Her urine pH is 6.2 during bicarbonate…

Mechanisms of disease · middle twist