Regulation of Acid/Base Balance

Bicarbonate Excretion by the Kidney

• The kidney filters 4,000 to 5,000 mmols/day bicarbonate

(calculated via plasma bicarbonate x GFR = 24 x 180 = 4,230 mmol/day)

• Under normal conditions, filtered HCO₃^- is totally reabsorbed

• 90% reabsorbed in the proximal tubule, the rest in the distal tubule
• HCO₃^- reabsorption is crucial in acid-base balance as loss of bicarbonate has an acidifying effect
• Reabsorption of HCO₃^- occurs indirectly:

• H₂O and CO₂ in the tubular endothelium combine to produce H⁺ (which is exchanged for Na⁺ into the tubules and combines with tubular HCO₃^-) and HCO₃⁺ (which is transported back into the bloodstream)
• CO₂ formed in the tubule from HCO₃^- and H⁺ diffuses easily into the endothelium to continue the process of forming H⁺ and HCO₃^-

• If plasma HCO₃^- is >28mmol/L, renal threshold is exceeded and bicarbonate appears in the urine
• 4,000 - 5,000 mmol/day H⁺ ions are secreted each day, and without this accumulation and acidosis rapidly occurs

Metabolic Alkalosis

• Acute metabolic alkalosis - the renal threshold for bicarbonate is exceeded and bicarbonate is rapidly excreted in the urine

• This is rapidly corrected by the kidney which has a large capacity to excrete HCO₃^- by:
• Allowing some filtered bicarbonate to pass through to the urine
• Secreting bicarbonate via Type B intercalated cells.

• Chronic metabolic alkalosis - there MUST be a mechanism present interfering with the kidney's ability to excrete bicarbonate, eg.

• Reduced GFR, chloride depletion, potassium depletion and ECF volume depletion
• Recovery requires correction of the primary cause, as well as correction of the abnormal factor maintaining the disorder

Excretion of Non-Bicarbonate Buffers

• Every day 70–100mmol/day of fixed acids are excreted. This is the net excretion of H⁺ from the body, as secretion with bicarbonate doesn't actually remove H⁺ from the body
• Mainly phosphoric acid, ketoacids, sulfuric acid
• These arise from amino acid, carbohydrate metabolism and especially anaerobic metabolism

• Non-bicarbonate buffers are either:

• Filtered - most importantly phosphate

• Not regulated for the purposes of acid excretion
• Occurs in much the same way as bicarbonate is secreted
• 40mmol/day of fixed acid is excreted this way
• The ketones are important in buffering acidity in uncontrolled diabetes mellitus - they are filtered but because of their high concentration are only partially taken up, therefore are available in the distal nephron to buffer H⁺

• Synthesised - most importantly ammonia - is responsible for the balance of H⁺ excretion

• Free ammonia is toxic → in liver converted to glutamine
• The kidneys excrete acid by converting glutamine to bicarbonate and ammonium, excreting the ammonium, and returning the bicarbonate to the blood.
• Crucial in renal acid secretion, as production can be increased in the presence of large acid loads