L28 - Kidneys: Urine pH and Drug Removal

• What are the key functions of the nephron?

  Glomerular filtrationTubular SecretionTubular Reabsorption
• What are possible routes for substances entering the nephron?

  substances are partially, fully or not excreted.

  
• What's the eqn for 'amount excreted' from the kidney?

  Amount Excreted = amount filtered + amount secreted - amount reabsorbed

  
• What factors modify amount excreted from the kidney?

  - GFR modifies amount filtered- constriction/dilation of afferent/efferent arterioles (modifies GFR)- Aldosterone/vasopressin presence modifies reabsorption of salt/water
• Dilation vs Dilatation

  dilation = an enlargement (eg pupils)dilatation = stretching eg blood vessels
• Can proteins be excreted by the kidney?

  No - too large to pass through podocyte sieveUnless diminished kidney function!
• Proteinuria- what is it?- what does it indicate?- what happens if pt is taking a protein-based drug?

  = protein in the urine - indicates kidney issues: decreased filtering ability- dose of protein based drugs may need to be adjusted, as some drug will be eliminated by kidney
• How does the kidney help regulate body pH?- what key eqn is involved?- key enzyme?

  - by +/- carbonate (HCO3-)- kidney regulates HCO3-, hence pHcarbonic anhydraseCO2 + H2O <-> H2CO3 <-> HCO3- + H+

  
• What happens to pH if you remove carbonate?Where does equilibrium shift?

  pH decreases - equilibrium shifts right, increasing [H+]
• What happens to pH if you increase carbonate?Where does equilibrium shift?

  pH increases - equilbrium shifts left, decreasing [H+] conc
• How is carbonate (HCO3-) reabsorbed in the kidney?- process?- net result?

  1) H2CO3 (carbonic acid) formed in tubule cells2) H2CO3 broken down into H+ and HCO3-3) HCO3- transported into blood stream4) H+ transported into tubules and combines with filtered HCO3- to make carbonic acid (H2CO3)- carbonic acid then breaks down to CO2/H2O, which are reabsorbed into tubule cell - cycle!5) filtered HCO3- disappears, but HCO3- generated in tubule cell has entered bloodstream, so= NO NET LOSS of HCO3-

  
• How is carbonate (HCO3-) generated by H+ secretion?- process?- net result?- what happens to pH?


  1) carbonic acid generated in tubule cells (CO2 + H2O -> H2CO3)2) carbonic acid breaks down to H+ and HCO3- 3) H+ combines with filtered phosphate (HPO42-) in tubule cell, which is excreted4) HCO3- transported into body= NET GAIN of HCO3- so pH increases

  
• How is carbonate generated by glutamine metabolism?- what is glutamine?- process?- net result?- what happens to pH?

  glutamine = small amino acid (so can be filtered)1) glutamine enters tubule cell as filtrate or from blood plasma2) glutamine breaks down into NH4+ and HCO3-3) NH4+ secreted into tubules and excreted4) HCO3- transported into body= NET GAIN of HCO3- so pH increases

  
• What is alkalosis?

  body loses [H+] and pH increases above 7.45body = more alkali
• What is acidosis?

  body gains [H+] and pH decreases below 7.35body = more acidic
• What happens in the kidney in response to acidosis?

  - kidney wants to increase pH - generates more HCO3- via increased glutamine metabolism and H+ secretion into tubulesmore carbonate = higher pH- all HCO3- reabsorbed, AND more generated

  
• What happens in the kidney in response to alkalosis?

  - kidney wants to decrease pH- generates less HCO3- by decreased glutamine metabolism and H+ secretionless carbonate = lower pH- H+ secretion into tubules can't keep up with filtered HCO3-- Excess HCO3- excreted

  
• How does urine pH affect drug excretion?

  - most drugs are weak acids/bases- they're more soluble in their ionised form= ionised drugs are more soluble which increases excretion
• At what pHs are acidic/alkaline drugs most likely to be ionised/excreted?

  acidic drugs ionise at high pH (so are more excreted in alkaline urine)basic drugs ionise at low pH (so are more excreted in acidic urine)

  
• How can we treat aspirin poisoning?

  aspirin = weak acid so ionises at high pH- we need to make it more soluble so it can be excreted- so increase pH (eg by IV infusion of sodium biscarbonate)- urine pH increases, salicylic acid becomes ionised (more water soluble)- so aspirin excreted quicker