Renal Mechanisms of Acid-Base Balance Flashcards

1
Q

What are the kidneys two major roles in acid-base balance?

A
  1. Reabsorption of bicarbonate (HCO3-)
  2. Excretion of H+
    • as a titratable acid (i.e. buffered by urinary phosphate) OR
    • as NH4+
    • either method always causes synthesis and reabsorption of new HCO3- to replenish the HCO3- stores that were used to buffer the H+
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Reabsorption of HCO3-

A
  • 99.9% of filtered HCO3- is reabsorbed
  • Mostly occurs in the proximal tubule
    • luminal mb Na+ in/H+ out exchanger
    • H+ secreted into the lumen combines with filtered HCO3- to form H2CO3
    • Brush border carbonic anhydrase helps decompose H2CO3 to CO2 and H2O
    • CO2 and H20 readily cross the luminal mb and enter the proximal tubule cell
    • Inside the cell reactions occur in reverse catalyzed by intracellular carbonic anhydrase:
      • CO2 + H2O → H2CO3 → H+ + HCO3-
      • H+ is secreted by the Na+/H+ exchanger to reabsorb another HCO3-
      • HCO3- travels across the basolateral mb into the blood via:
        • Na+/HCO3- cotransport
        • Cl- out/HCO3- in exchanger
  • Special features of this process:
    • Na+ reabsorption is linked to HCO3- reabsorption
    • There is no net secretion of H+ via this mechanism, since it keeps getting reused to bring in more filtered HCO3-
    • Due to this, this mechanism produces little change in the tubular fluid pH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Effect of ECF Volume on HCO3- Reabsorption

A
  • ∆s in ECF volume alter isoosmotic reabsorption, of which HCO3- reabsorption is a part of
    • ECF volume expansion
      • inhibits isoosmotic reabsorption and ∴ inhibits HCO3- reabsorption
    • ECF volume contraction
      • stimulates isoosmotic reabsorption and ∴ stimulates HCO3- reabsorption
      • ⇣ECF volume also activate RAAS and ∴ AngII → stimulation of Na+/H+ exchanger in the proximal tubule → ⇡HCO3- reabsorption here
      • can lead to contraction alkalosis (e.g., from vomiting, loop, or thiazide diuretics)
        • treat by infusing isotonic NaCl to restore ECF volume
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Effect of PCO2 on HCO3- Reabsorption

A
  • ⇡PCO2 → ⇡HCO3- reabsorption
  • ⇣PCO2 → ⇣HCO3- reabsorption
  • Helps explain the phenomenon of renal compensation for chronic respiratory acid-base disorders
  • Mechanism not entirely clear but may due to ⇡supply of CO2 to renal cells in respiratory acidosis and ⇣supply of CO2 to renal cells in respiratory alkalosis
    • CO2 helps generate H+ for secretion via the Na+/H+ exchanger and HCO3- reabsorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Excretion of H+ as a titratable acid

A
  • Titratable acid = one excreted with urinary buffers
  • Occurs primarily in α-intercalated cells of the late distal tubule and collecting ducts
  • Luminal membrane:
    • H+ ATPase
      • stimulated by aldosterone
      • H+ secretion
    • H+-K+ ATPase
      • H+ secretion
      • K+ reabsorption
  • Lumen:
    • H+ combines with HPO4- → H2PO4
    • H2PO4- is then excreted in the urine (it is a titratable acid)
  • Tubular cell/basolateral membrane:
    • CO2 + H20 (from aerobic metabolism in the renal tubular cells) → H2CO3 → H+ + HCO3-
      • this is the H+ used in the H+ ATPase
      • the HCO3- is reabsorbed via an Cl-HCO3-exchanger in the α-intercalated cell
      • ∴, for each H+ excreted, one HCO3- is synthesized and reabsorbed to replenish extracellular HCO3- stores
        • HCO3- is continually replaced as it is used for the buffering of fixed acids
  • ***Note: the amount of H+ excreted as a titratable acid depends on the amount of available urinary buffer (e.g., HPO42-)
    • If you don’t have enough HPO42-, because you used it all up and only have H2PO4, then you won’t be able to excrete more H+ even if H+ is still in excess.
    • this is related to the concept of minimum urine pH; under a pH of 4.4 (tubular fluid ranges from 7.4 to 4.4), your urinary buffers have been completely used up, so they can’t find anymore H+ to remove as a titratable acid even if there’s is more H+ leftover.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Excretion of H+ and NH4+

A
  • Within the proximal tubular cell:
    • Glutaminase converts glutamine and glutamate to NH4+
      • this NH4+ breaks into H+ (for Na+/H+ exchanger) and NH3 diffuses freely across luminal membrane out of the cell
      • Glutamate is metabolized to α-ketoglutarate → CO2 + H2O → HCO3- (α-ketoglutarate enters TCA cycle and ETC), which gets reabsorbed across the basolateral mb
        • a source of newly synthezied HCO3-
  • Within the proximal tubule lumen: H+ combines with NH3 to form NH4+
  • Some NH4+in the lumen travels to the Loop of Henle (as NH3) and is then reabsorbed in the thick ascending limb of the loop of Henle (substitutes K+ in Na+/K+/2Cl- cotransporter) and deposited in the medullary interstitial fluid
  • H+ is secreted from α-intercalated cells of the collecting duct (from aerobic metabolism) into the lumen via H+ ATPases or H+-K+ ATPases; NH3 from the medullary interstitium diffuses down its concentration gradient into the tubular lumen
    • In the collecting duct lumen, H+ and NH3 combine to form NH4+ and get excreted.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Effect of Urinary pH on Excretion of NH4+

A
  • ⇣urinary pH → ⇡NH4+ excretion
  • ⇡urinary pH → ⇣NH4+ excretion
  • Makes sense logically because you need to get rid of the excess H+ and by having NH3 diffuse down its gradient into the lumen, you can excrete it as NH4+
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Effect of Acidosis on NH3 Synthesis

A
  • Chronic acidosis → ⇡NH3 synthesis from glutamine metabolism →⇡excretion of H+ as NH4+ and synthesis of more HCO3-
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Effect of plasma [K+] on NH3 synthesis

A
  • ⇡plasma [K+] (hyperkalemia) → ⇣NH3 synthesis
  • ⇣plasma [K+] (hypokalemia) → ⇡NH3 synthesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly