pH affects… | • Protein folding | • Ligand binding to enzymes | • Phospholipid charge
Effect of decreased pH on… | • Excitation-contraction coupling | • Myocyte sensitivity to catecholamines | • Arrhythmogenesis
• Reduced (Ca2+ displaced from troponin/tropomyosin) | • Decreased → reduction in inotropy → CO, BP | • Increased
Effect of increased pH on… | • Arterioles (coronary/cerebral) | • Energy production | • Respiratory drive | • O2 delivery to tissues
• Constriction | • Increased anaerobic glycolysis, lactate production | • Decreased | • Decreased (increased affinity of O2 for Hb)
3 most common metabolically generated acids
• H2CO3 | • H2SO4 | • H3PO4
How does the body handle H2CO3 in the immediate term (seconds)?
Chemical buffering (titrate acid with HCO3-)
How does the body handle increased H2CO3 over minutes to hours?
Respiratory buffering (reduce PCO2 via ventilation)
How is the respiratory drive modulated to accommodate changes in PCO2?
Carotid and central chemoreceptors
How are changes in [bicarb] titrated over hours to days?
Renal reclamation or regeneration of bicarb (requires upregulation of transporters)
In which nephron segment do these processes occur? | • Bicarb reclamation | • Bicarb generation
• PCT | • Collecting duct
How are changes in acid-base status buffered in the long-term?
Bone resorption (takes days)
2 organic anions recycled by the liver back to HCO3- (which can be used to titrate acids)
Lactate | β-OH butyrate
Nephron segment that contains the Na/H exchanger
In the PCT, [amino acid] is broken down into [products] → [product] is excreted into the lumen via the Na/H exchanger while [product] is reabsorbed back into the bloodstream
Glutamine | Ammonium + bicarb | Ammonium | Bicarb
In the TALH, ammonium enters the cell via the [transporter] → ammonium is broken down into [products] → [product] titrates any residual bicarb in the lumen while [product] diffuses out the basolateral membrane (diffuses into CD lumen)
Na/K/2Cl (on the K site) | Ammonia + H+ | H+ | Ammonia
In the collecting duct, [gas] diffuses into the [cell type] and reacts to form [products] → [product] is transported out the basolateral membrane and [product] is transported out the apical membrane → form lumenal [cation]