Renal Handling of Bicarbonate (B2: W8) Flashcards
What is the first line of defense against an acid load?
Chemical buffering (Henderson Hasselbalch)
- 2nd: Regulation of CO2 levels by the lungs
- 3rd: The kidneys!!
- Regulation of fixed (metabolic) acid and bicarbonate by the kidneys
What do the kidneys do to regulate bicarbonate?
- Conserve bicarbonate - almost all of it is reabsorbed
- Can make “new” bicarbonate to replace the bicarbonate lost during buffering
- Can excrete excess bicarbonate in the event of alkalosis
- Can excrete fixed (metabolic) acid
- Done at the same time as making new bicarbonate
- H2CO3 → HCO3-(new) + H+
- H+ excreted
How do the kidneys handle bicarbonate when urine pH is less than 6?
Approximately all bicarbonate is reabsorbed and none is excreted
- Freely filtered
How much of the filtered bicarbonate is reabsorbed in the proximal tubule?
80%
How is bicarbonate reabsorbed in the proximal tubule?
- H+ ions moved up concentration via Na exchanger into the lumen
- Secondary active transport
- Cycling of acidity
- For the purpose of bicarbonate reabsorption
- Filtered bicarbonate binds to H+ → H2CO3
- Carbonic anhydrase: H2CO3 → CO2 + H2O
- CO2 goes across apical membrane
- Carbonic anhydrase used again
- Filtered bicarbonate is reabsorbed into the body
- Indirect bicarbonate reabsorption
Which are the acid secretion epithelial cells of the distal nephron?
Alpha intercalated cells
What is the lowest possible pH of the urine in the distal nephron?
4.4
How is bicarbonate reabsorbed in the distal nephron?
- ATP drives acid (H+) into lumen
- Direct energy
- Low permeability of hydrogen ions across membrane
- Stuck in lumen
-
NO carbonic anhydrase in distal nephron
- H2CO3 → H2O + CO2
- CO2 crosses apical membrane
- Reabsorbed into blood
What happens to renal handling of bicarbonate in an alkalotic (metabolic alkalosis) patient?
The kidneys excrete excess bicarbonate during alkalosis
- Alkalosis is metabolic (not respiratory) - due to bicarbonate
- Intracellular pH is high
- Does not favor the secretion of hydrogen ions
- Bicarbonate does not have the H+ to bind to
- Stuck in lumen
- Increase in bicarbonate excretion
- Urine is alkalotic
What happens to renal handling of bicarbonate when a patient is alkalotic (respiratory)?
Increased bicarbonate excretion
- Alkalosis is respiratory
- Low CO2
- Increase in pH
What are the clinical uses of carbonic anhydrase inhibitors (e.g. Diamox)?
Drugs that block carbonic anhydrase
- Antiglaucoma agents
- Diuretics
- Antiepileptics
- Management of mountain sickness
- Gastric and duodenal ulcers
- Neurological disorders
- Osteoporosis
Why would a person take a carbonic anhydrase inhibitor drug?
In the situation of respiratory alkalosis
- Blocks carbonic anhydrase
- Bicarbonate is not reabsorbed as much
- More is excreted
- Body returns to optimal pH of 7.4
Why do people use carbonic anhydrase inhibitors for mountain sickness?
- O2 is low
- Increase in respiration
- Blow off CO2
- Respiratory alkalosis
- Blocked by carbonic anhydrase inhibitors
What is a negative side effect associated with Diamox, a carbonic anhydrase inhibitor?
Dehydration
- Less bicarbonate is reabsorbed
- ALso loose Na, K, CL
- Osmotic diuresis: dehydration
How do the kidneys eliminate fixed acid?
Two methods
- Formation of titratable acid
- Formation of ammonium (NH4+)
Must eliminate mM quantities of fixed acid while H+ free in solution is nM (6 orders of magnitude greater!)
What is the predominate titratable acid in tubular fluid?
Phosphate
- Hydrogen binds to HPO42-
How is titratable acid formed?
- Free in solution
- H+ is pumped into tubular lumen
- Binds to HPO42-
- This can be excreted
- Since we are excreting hydrogen ions, the bicarbonate inside the cell becomes “new”
- New because it was paired with an H molecule that left in the urine
How is ammonium ion formed in the proximal tubule?
- Glutamine enters cell
- Produces NH4+ and HCO3-
- Bicarbonate goes back to body
- Ammonium secreted into proximal tubule lumen
- Uses Na electrochemical gradient
- Binds to Cl-
- Excreted as NH4Cl
How is ammonium ion used in the collecting duct to eliminate fixed acid?
- NH3 is secreted into collecting duct
- H+ being pumped into lumen with ATP
- NH3 + H+ → NH4+
- Binds to Cl-
- NH4Cl eliminated in urine
What is the role of aldosterone in renal handling of acid?
Aldosterone directly stimulates H ATPase
- In alpha intercalated cells
- Distal tubule
- Enhances H secretion and excretion
How is reabsorption rate of filtered bicarbonate calculated?
Reabsorption Rate = Filtered Load - Urinary Excretion
= (GFR • Px) - (Ux • V)
- Biggest job of kidneys is to reabsorb filtered bicarbonate
- All that goes into the nephron from the body has to go back to the body
- Urinary excretion is negligible
How is the net acid excretion (NAE) calulated?
Net acid excretion = TA + NH4+ - HCO3 in urine
- Consider the titratable acid that got out, the ammonium, and the bicarbonate
- Kidneys simultaneously make new bicarbonate and excrete acid
How does net acid excretion (NAE) relate to HCO3-?
Net acid excretion is equal to the amount of new HCO3- generated
Which is more abundant; reabsorbed bicarbonate or new bicarbonate?
Reabsorbed bicarbonate far exceeds new bicarbonate
- Reabsorption activity is far greater than the part involved in generating new bicarbonate
Is more acid secreted into the tubule or excreted?
The amount of H+ secreted far exceeds the amount of acid that is excreted
- Making new bicarbonate and bicarbonate reabsorption requires hydrogen secretion
- H secreted mostly influences bicarbonate reabsorption
How do we measure fixed acid in the urine?
- Titratable acid is determined by titrating urine back to pH 7.4
- NH4+ excretion is determined by measuring NH4+ content
What happens to the body in response to potassium losing diuretics, such as thiazide or furosamide?
- Principle cell membrane is depolarized
- Increased K secretion
- Some of this K stimulates H secretion
- Body is alkalotic and hypoclemic due to loss of H and K
What happens to the body in response to potassium-sparing diuretics, like amiloride?
- Na conductance is blocked in principal cells
- Less K is secreted into the lumen
- Less H is secreted due to less K
- Can result in acidosis and hyperkalemia in the body
