Renal Mechanisms of Acid-Base Balance Flashcards
1
Q
What are the kidneys two major roles in acid-base balance?
A
- Reabsorption of bicarbonate (HCO3-)
- 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+
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
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
- ECF volume expansion
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
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
- H+ ATPase
- 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
- CO2 + H20 (from aerobic metabolism in the renal tubular cells) → H2CO3 → H+ + HCO3-
-
***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.
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-
-
Glutaminase converts glutamine and glutamate to NH4+
- 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.
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+
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-
9
Q
Effect of plasma [K+] on NH3 synthesis
A
- ⇡plasma [K+] (hyperkalemia) → ⇣NH3 synthesis
- ⇣plasma [K+] (hypokalemia) → ⇡NH3 synthesis