Kidney Lecture 3:Urine pH and Drug Removal

Substance X Partially Filtered Mostly Secreted Fully Excreted Substance Y Partially Filtered Partially Reabsorbed Partially Excreted Substance Z Partially Filtered Fully Reabsorbed Not Excreted Renal processing of a substance based on several factors To what degree the substance is filtered? How much is reabsorbed? How much is secreted? What factors alter the amount filtered, reabsorbed, or secreted? amount excreted= amount filtered+ amount secreted - amount reabsorbed

Whole proteins and protein-based drugs are not excreted by kidneys Exception in cases of diminished kidney function Proteinuria : high levels of protein in urine

Balance of filtration, secretion, and reabsorption

Acidosis and alkalosis Regulation of carbonate Reabsorption of filtered carbonate Generation of new carbonate via loss of H+ bound to phosphate Generation of new carbonate via glutamine metabolism

Acidic vs Alkaline urine and drug ionisation

Carbonic Anhydrase - Key enzyme in acid-base homeostasis Adding or subtracting carbonate (HCO3-) lowers or raises H+ by influencing this equation Kidney regulates HCO3- and thereby pH

Carbonic acid created in tubular cells breaks down into H+ and HCO3- H+ transported into tubules, combines with filtered HCO3- HCO3- transported into body While filtered HCO3- disappears, HCO3- generated inside cell enters the body Net result : no loss of HCO3-

Carbonic acid generated in tubular cells H+ combines with filtered phosphate (HPO42-) and is excreted HCO3- transported into body Net result: Gain of HCO3-

The amino acid glutamine enters tubule cells either from the filtrate or blood plasma Glutamine is metabolised inside the cell to ammonia (NH4+) and HCO3- Ammonia secreted into the tubules and excreted HCO3- transported into the body Net result: Gain of HCO3-

When the body loses hydrogen ions (H+), pH increases becoming more alkali – Akalosis Response to alkalosis H+ secretion into tubules cannot keep up with filtered HCO3- Excess HCO3- excreted Glutamine metabolism decreased reducing HCO3- generation When the body gains hydrogen ions (H+), pH decreases becoming more acidic – Acidosis Response to acidosis Lots of H+ is secreted into tubules All filtered HCO3- is reabsorbed Additional HCO3- is absorbed as H+ excreted bound to phosphate Glutamine metabolism enhanced generating more HCO3-

Most drugs are either weak acids or bases In alkaline urine, acidic drugs are ionised In acidic urine, alkaline drugs are ionised Ionised drugs are more water soluble, which increases their excretion