Acid-Base Regulation • Arterial pH: 7.35-7.45 • ICF pH: 7.0  this is because metabolic processes produce H + o Protein breakdown  phosphoric acid o Anaerobic respiration  lactic acid o Fat metabolism  organic acids and ketone bodies o Transporting CO2 as HCO3-  ↑H+ release Proteins: intracellular and plasma buffers 𝐻+ + 𝐻𝑏 ⇔ 𝐻𝐻𝑏 Phosphate: renal tubular buffer 𝐻𝑃𝑂4− + 𝐻+ ⇔ 𝐻2𝑃𝑂4 Ammonia: renal tubular buffer 𝑁𝐻3 + 𝐻+ ⇔ 𝑁𝐻4+ Bicarbonate: extracellular and tubular buffer 𝐻2𝑂 + 𝐶𝑂2 ⇔ 𝐻2𝐶𝑂3 ⇔ 𝐻+ + 𝐻𝐶𝑂3− Three most important buffering systems 1. Respiratory system: bicarbonate 2. Blood: bicarbonate, phosphate and protein 3. Renal, bicarbonate, phosphate and ammonia • 52% of buffering is intracellular • 5% in RBCs • 43% in ECF o 40% bicarbonate o 1% protein o 1% phosphate Non-Volatile Acid Load • Sulphuric, phosphoric and organic acids (~70mmol/day) • Kidneys divide the load by o Excreting ~70mmol/day of H+ into urine o Generating ~70mmol/day of new HCO3-  Hence the net H+ excretion is: H+ bound to PO34−, creatinine, uric acid + H+ bound to NH3 − excretion of filtered HCO−3 Acid and Base Handling in Tubules • PCT: o Reabsorb 80% of filtered HCO3-  Na/H exchanger (NHE), NHE3 is the most important o Produces and secretes NH4+  TAL: o Reabsorbs 10-15% of filtered HCO3-  DCT/CD: o Reabsorbs all remaining HCO3- plus secreted HCO3- by α-intercalated cells o Produce titratable acids (α-intercalated cells) o Produces new HCO3(β-intercalated cells) α-Intercalated Cells • Apically: o Secretes H+ via:  H+ ATPase  H+/K+ ATPase exchanger o Also has Cl channels • Basolaterally o HCO3-/Cl- exchanger β-Intercalated Cells are the inverse