Glomerulus & Tubule

Master answer

Non-volatile acid

” An acid produced from sources other than carbon dioxide, which cannot be excreted in the lungs. “

• e.g. lactate, sulphate, phosphate and ketone bodies
• 70-100mmol non-volatile acid produced per day
• 4000-5000mmol HCO₃^– filtered by glomerulus per day
• Renal acid-base is largely determined by handling of bicarbonate ions
  • 80% of filtered bicarbonate resorbed in proximal tubule
  • 20% resorbed in distal tubule and collecting duct
  • Urinary Buffers (Dibasic Phosphate and ammonia) play a role

Bicarbonate Resorption

Proximal tubule

In the tubular cell:

• H⁺ leaves the tubular cell through the apical membrane via
  • H⁺/Na⁺ antiporter (secondary active transport via Na⁺/K⁺ ATPase on basolateral membrane)
• The HCO₃^– re-enters the circulation via the Na/HCO₃^– symporter
• H⁺ combines with HCO₃^– in tubule to form H₂CO₃
• H₂CO₃ switches back to CO₂ and H₂O, CO₂ is resorbed to turn back into the tubular cell to generate more HCO₃ for resorption

More bicarbonate resorbed when:

• Higher filtered HCO₃^–
• Higher PaCO₂
• Lower luminal flow rate
• Angiotensin 2

Distal convoluted tubule and collecting duct

• Similar mechanism with regards to resorption of HCO₃^– via secretion of H⁺
• Difference is that H⁺ is transported across the apical membrane via an H⁺ ATPase (active transport)

Role of Buffers

• The maximum urinary pH is 4.5
• To eliminate more protons, they must be buffered in the tubular fluid
• H⁺ is bound preferentially to buffers only in the presence of low tubular HCO₃^–
• Buffering, and so elimination of H⁺ without its conjugate HCO₃^–, requires resorption of HCO₃^– in the proximal convoluted tubule

Phosphate (HPO₄^2-):

• Becomes concentrated in tubules
• pKa = 6.8, so operates effectively as a buffer at tubular pH

Ammonia

• Glutamine broken down in tubular epithelia cells to two NH₄⁺ and two HCO₃^–
  • Comes from hepatic amino acid metabolism
• The new HCO₃^– is transported back to the circulation via the Na/HCO₃^– symporter to re-enter the circulation
• NH₄⁺ becomes ion trapped in the tubular fluid
• Proximal tubular fluid is not acidic enough to keep NH₄⁺ in the tubule
• It is resorbed in the ascending limb, moves through the medulla to re-enter the collecting duct
• Here urine has a low pH, and so NH₄⁺ can be eliminated with its proton attached

Mooney 2016

Answer by Mooney