(High capacity, low gradient system)
For every hydrogen ion secreted
--> 1 bicarbonate ion is generated
--> bicarbonate diffuses into peritubular capillaries
By luminal Na-H antiporter
In the lumen, H+ combines with filtered HCO3 to form water and CO2
--> CO2 diffuses into the cell
NB:
By basolateral Na-HCO3 symporter
NB:
(Low capacity, high gradient system)
All H+ secreting cells have primary active H-ATPase pump in the luminal membrane
Has
Neither filtered H+ or excretion of free H+ makes significant contribution to H+ secretion
At minimum urinary pH (4.4)
--> [H+] = 0.06mmol/day
--> Much less than the 50-100mmol ingested or produced everyday
* KB: 70+ mmol/day
Also,
H+ combining with HCO3 in lumen
--> Formation of CO2 and water in the tubule
--> Diffusion of CO2 back
Thus,
Effective for resorption of HCO3 but not for net excretion of H+
Therefore,
Excretion of H+ must involve non-bicarbonate urinary buffer
pKa = 6.8
Filtered phosphate is normally the most important non-bicarbonate urinary buffer
At normal pH 7.4,
Plasma level of phosphate = About 1mmol/L
90% free (not bound to protein)
--> about 160mmol/day filtered
Resorption about 75-90%
--> Kidney can use phosphate to excrete about 40mmol of H+ per day.
Beta-hydroxybutyrate and acetoacetate
--> pKa of the bases are low (4.5)
--> Only about half of the respective filtered bases can be used as buffers
Thus,
Not effective buffers
Processing of the carboxyl group of the amino acid produces HCO3
Processing of the amino group produces ammonium
Ammonium is further processed by liver to urea or glutamine
* The process consumes a HCO3
* No net production of HCO3
2 amino acids + O2
--> 2NH4+ + 2HCO3-
--> Urea or glutamine (+CO2 and some H2O)
Glutamine released from the liver is taken up by proximal tubule cells
* Both from lumen (20%) and from interstitium (80%)
--> Glutamine converted to bicarbonate and NH4+
* Basically reverse of what liver does
--> NH4+ is secreted into lumen by Na-H antiporter and HCO3 diffuses into peritubular capillaries
Thus,
The amount of NaOH (i.e. base) needed to be added to increase urine pH to 7.4
--> Presumably equivalent to amount of H+ added to the tubular fluid that combined with phosphate and organic buffers.
NB:
Phosphate (pKa~6.8) is the most imporant and significant of the titratable acids
* Limited by the amount of phosphate filtered
Creatinine (pKa ~ 5.0) may also contribute when urinary pH is low
In severe diabetic ketoacidosis, beta-hydroxybutyrate (pKa 4.8) is the major component of TA
* [KB: online text acid and base]
Total acid excretion
= [Titratable acid] + [NH4+] - [HCO3]
In response to acidosis, increased production and excretion of NH4+ is quantitatively much more important than increased formaton of titratable acid
PaCO2 and arterial pH act directly on kidney to increase acid excretion
PaCO2 acts by
--> Diffusion into tubular cells
--> Increasing pCO2 intracellularly
--> Decreasing intracelluar pH
Extracellular pH action is unrelated to PaCO2.
[KB: online text on acid and base]
Decreased extracellular pH
--> Liver preferentially converts ammonium to glutamine (instead of to urea)
--> More glutamine available
Also,
Decreased extracellular pH
--> Increased renal glutamine oxidation by proximal tubule
--> Increased excretion of NH4+
NB:
[KB: online text] There is a lag period between an acid load and NH4+ excretion reaching a maximum level
Normally all HCO3 are reabsorbed
[KB online text on acid and base]
The 4 major factors which control bicarbonate reabsorption are
An increase in any of these four factors causes an increase in bicarbonate reabsorption.
NB:
Over-excretion of H+ can be due to
--> All three causes metabolic alkalosis
Decreased ECF volume
--> Elevated angiotensin
--> Elevated aldosterone
--> Increased sodium resorption in exchange for acid
* i.e. Na-H antiporter
--> Increased HCO3 resorption
--> Increase urinary acid excretion
Thus,
Urinary acidity is high despite metabolic alkalosis
[AV6:p176] Chloride depletion stimulate hydrogen ion secretion
--> Reasons not explained.
???? I wonder if it is related to the Cl-HCO3 antiporter in the basolateral membrane of type A intercalated cells
Aldosterone stimulates hydrogen ion secretion
Potassium depletion also weakly stimulate tubular hydrogen ion secretion and NH4+ production
Combination of both stimulates tubular H+ secretion significantly
Thus,
Excessive use of diuretics
--> Hypovolemia and hypokalemia
--> Increase H+ excretion
--> Metabolic acidosis
Chloride depletion may also be involved and may compound the problem