Keef: Renal handling of bicarbonate Flashcards
What do the kidneys do to help mitigate changes in acid load?
1) The kidneys conserve filtered bicarbonate
2) The kidneys can make “new” bicarbonate to replace the bicarbonate lost during buffering.
3) The kidneys can excrete excess bicarbonate (alkalosis)
4) The kidneys can excrete fixed acid
H2CO3 HCO3-(New) + H+(excrete
In the proximal tubule, how low can the pH go?
6
In the distal tubule, how low can the pH go?
4.4
In the distal tubule, is there carbonic anhydrase in the membrane between the cell and the tubular lumen?
No!
What else is different about bicarbonate absorption in the distal nephron?
The H+ cannot move freely into the tubular lumen via the exchange of Na+. Instead it must use an H+ATP-ase.
What kind of cells are found in the distal nephron, which secrete H+?
alpha intercalated cells
During alkalosis, what happens to excretion of bicarb?
It increases! If the pH goes up, less H+ secretion, so more bicarb will show up in the urine, because it is not being reabsorbed, and urine pH will become more basic.
What is the main point of carbonic anhydrase inhibitors?
Increase bicarb excretion by blocking carbonic anhydrase. This returns pH toward 7.4
2 methods in which the kidney can eliminate fixed acid?
- Formation of NH4+ (NH4+ can be secreted in proximal tubule from glutamine–>NH4+ + HCO3-; in the distal nephron, it is secreted as NH3+ and combines with H+ to form NH4Cl)
- Formation of titratable acid
What is the predominate titratable acid in the tubular fluid?
Phosphate
At low pH, what form is phosphate in?
At high pH?
H2PO4-
HPO42-
Predominate form of phosphate in the body. What does it get converted to in the lumen, for secretion and excretion?
NaHPO4-
H2PO4-
Glutamine can enter the proximal tubule and form NH4+ and HCO3-. Then, NH4+ can leave into the tubule lumen via exchange with Na+ and can form (blank) and be excreted.
NH4Cl
What is the biggest “job” the kidneys perform?
Reabsorption of filtered bicarb.
When calculating reabsorption rate of bicarb, what should be considered?
Reabsorption rate = filtered load - excretion rate
BUT excretion rate is negligible
Net acid excretion equation
NAE = TA + NH4+ - HCO3 in the urine = new HCO3- generation
Net acid excretion is equal to (blank)
The amount of new HCO3- generated. Acid is secreted at the same rate of formation of new bicarb.
Amount of new HCO3 in mmol added to body per day under normal conditions.
59mmol/day
In acidosis, amount of new HCO3 in mmol added to body per day.
200mmol/day
In alkalosis, amount of new HCO3 in mmol lost from body per day.
-80mmol/day
Which is greater: reabsorbed or new bicarbonate?
Reabsorbed bicarbonate FAR EXCEEDS new bicarbonate.
Is more H+ secreted or excreted?
The amount of H+ secreted FAR EXCEEDS the amount of H+ excreted.
How to measure fixed acid in the urine?
Titratible acid is determined by titrating urine back to pH 7.4. The amount of OH required to get pH back up to 7.4 will give you the amount of titratible acid.
About how much H+ combined with NH3 is excreted in diabetic acidosis? How about H+ as titratible acid?
LOTS (tenfold!)
Kind of a lot!
About how much H+ combined with NH3 is excreted in chronic renal disease? How about H+ as T.A.?
Hardly any - a low amount :(
Normal amount
When using loop diuretics (K+ losing), will you experience hypo or hyperkalemia? Alkalosis or acidosis?
Hypokalemia; alkalosis
When using K+ sparing diuretics (amiloride), will you experience hypo or hyperkalemia? Alkalosis or acidosis?
Hyperkalemia; acidosis
What determines the lowest possible urine pH in the distal nephron?
Gradient for H+ ions in distal nephron
Does the extent of HCO3- reabsorption determine the lowest possible tubular pH?
NO! Although H+ secretion and tubular pH fuel bicarbonate (HCO3-) reabsorption this process is
virtually complete at tubular pH values greater than 4.4
An increase in luminal carbonic anhydrase activity would enhance the production of (blank)
and hence the reabsorption of (blank)
CO2
HCO3-
Normal range for anion gap?
8-16 mEq/L
The anion gap is useful for the differential diagnosis of (blank). Thus, conditions which lead to (blank) can be divided into those which change the anion gap and those which do not.
Metabolic acidosis; metabolic acidosis
A change in the anion gap is produced by conditions in which an unmeasured (blank) is introduced into the
body.
anion
If HCO3- or Cl- DECREASE what happens to the anion gap?
It becomes larger! More cation than anion!
As lactic acidosis develops, (blank) buffers the excess H+ and is lost, while lactate (A-) concentration in the body increases to replace the lost (blank)
HCO3-; HCO3-
Ingesting NH4Cl results in HCl formation. The excess acid is buffered by (blank) resulting in loss of (blank) and a proportionate gain of Cl-. Since the increase in Cl- counterbalances the loss in (blank) in the anion gap equation, will there be a net change in anion gap?
HCO3-; HCO3-; HCO3-; NO
Things that might occur with chronic K+ deficiency (HYPOKALEMIA)
Low K+ will cause K+ to leave cells, and H+ to enter.
a. high plasma pH
b. neutral or acidic urinary pH
c. elevated plasma bicarbonate levels
d. low intracellular pH
When bicarb rises, Cl- will likely do what?
DECREASE. Reciprocal relationship.
With hypokalemia, will plasma bicarbonate increase or decrease.
INCREASE. Think about it. K+ will spill OUT of cells, so H+ will ENTER cells and be “trapped” there. So, cannot exchange for Bicarb.
Hypokalemia results in a shift of K+ out of cells, and a shift of H+ into cells. This loss of H+ from the extracellular compartment will lead to what?
Metabolic alkalosis
Unless some other complicating factor is involved (e.g., introduction of a foreign anion) the plasma concentrations of HCO3- and chloride (Cl-) vary in opposite directions to one another (i.e., as one goes up the other goes down). Thus during hypochloremia a (blank) in plasma HCO3-
concentration is expected.
increase
What condition can result in a decreased plasma bicarbonate?
diabetic ketoacidosis
Is phosphate secreted in the proximal tubule?
NO
Does diabetic ketoacidosis cause hypo or hyperkalemia?
Hyperkalemia!
Would diarrhea cause hyperkalemia?
No! Loss of bicarb, so build up of H+. This will cause K+ stores to be depleted.
If you throw up lots, what will happen to pCO2?
You will have alkaline plasma pH, so breathing rate will decrease and pCO2 will rise a bit to compensate.
One characteristic of renal failure is the inability to excrete sufficient (blank).
Acid. This leads to a decrease in pH, and will increase respiratory rate to eliminate some CO2.
