L28 - kidney: urine pH & drug removal
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3 possible routes for substances entering nephron
• fully excreted • partially excreted • not excreted
explain route where substances would be fully excreted when entering nephron
• partially filtered • mostly secreted all substance leaves via urinary excretion
explain route where substances would be partially excreted when entering nephron
• partially filtered • partially reabsorbed • partially excreted
explain route where substances would not be excreted when entering nephron
• partially filtered • fully reabsorbed • not excreted
equation to find amount excreted?
amount excreted = amount filtered + amount secreted - amount reabsorbed
factors affecting the renal processing of substances
• degree substance is filtered • degree that is reabsorbed • degree that is secreted
what is proteinuria?
high levels of protein in urine
proteins in the kidney
• whole proteins and protein based drugs are not excreted by kidneys • exception in cases of bad kidney function
how do the kidneys regulate blood and urine pH?
• carbonic anhydrase enzyme converts CO2 + H2O into carbonic acid which dissociates to form HCO3- and H+ • kidney regulates carbonate so also pH
describe carbonate reabsorption
• carbonic acid created in tubule cells breaks down into HCO3- & H+ • H+ transported into tubules and combines with filtered HCO3- to form carbonic acid • HCO3- transported into blood to body • so net result: no loss of HCO3-
describe carbonate generation - H+ secretion
• carbonic acid generated in tubular cells • H+ combines with filtered HPO42- and is excreted • HCO3- transported into body • net result = gain of HCO3-
carbonate generation - glutamine metabolism
• a.a glutamine enters tubule cells from filtrate (tubule) or the blood plasma (interstitial space) • glutamine is metabolised inside the cell to NH4+ and HCO3- • ammonia secreted into tubules + excreted • HCO3- transported into body • net result: gain of HCO3-
regulation of body pH
• tightly balanced as processes dependent on pH • loss of H+, pH inc, alkalosis • gain H+, acidosis
response to acidosis
• lots of H+ secreted into tubules from tubule cells • all filtered HCO3- is reabsorbed • excess carbonate is absorbed as H+ excreted bound to phosphate • glutamine metabolism enhanced generating more HCO3-
response to alkalosis
• H+ secreted into tubules can’t keep up with filtered HCO3- • so excess HCO3- excreted • glutamine metabolism decreased reducing HCO3- generation
role of urine pH in drug excretion (acidic + alkaline urine)
• most drugs are weak acids/bases • in alkaline urine, acidic drugs are ionised • in acidic urine, alkaline drugs are ionised • ionised drugs are less likely to be reabsorbed, so increased secretion
what needs to happen in aspirin poisoning?
• aspirin needs to be quickly removed from body • IV infusion of sodium bicarbonate • carbonate enters urine, raises pH • aspirins active metabolite salicylic acid becomes ionised, reducing its reabsorption • so aspirin is excreted quicker, lowering plasma conc