3. Physiology
        3.12. Renal
3.12.9. Renal handling of acid-base balance

Renal handling of acid-base balance

By segments

Proximal tubule

Thick ascending limb of loop of Henle

Distal convoluted tubues and collecting duct system

Proximal tubule

(High capacity, low gradient system)

For every hydrogen ion secreted

--> 1 bicarbonate ion is generated

--> bicarbonate diffuses into peritubular capillaries

Secretion of hydrogen

By luminal Na-H antiporter

In the lumen, H+ combines with filtered HCO3 to form water and CO2

--> CO2 diffuses into the cell


Overall effect

Transport of bicarbonate

By basolateral Na-HCO3 symporter


DCT and CD

(Low capacity, high gradient system)

All H+ secreting cells have primary active H-ATPase pump in the luminal membrane

Type A intercalated cells


Type B intercalated cells

Buffering and H+ excretion

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


H+ combining with HCO3 in lumen

--> Formation of CO2 and water in the tubule

--> Diffusion of CO2 back


Effective for resorption of HCO3 but not for net excretion of H+


Excretion of H+ must involve non-bicarbonate urinary buffer


pKa of phosphate

pKa = 6.8

Filtered phosphate is normally the most important non-bicarbonate urinary buffer

At normal pH 7.4,


Phosphate handling

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


Not effective buffers


Amino acids

Processing of amino acids

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

Ammonium and glutamine

2 amino acids + O2
--> 2NH4+ + 2HCO3-
--> Urea or glutamine (+CO2 and some H2O)

Step 1

Glutamine released from the liver is taken up by proximal tubule cells
* Both from lumen (20%) and from interstitium (80%)

Step 2

--> Glutamine converted to bicarbonate and NH4+
* Basically reverse of what liver does

Step 3

--> NH4+ is secreted into lumen by Na-H antiporter and HCO3 diffuses into peritubular capillaries


Other notes on ammonium


Quantitative measurement of acid secretion

Titratable acid

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.



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

Total acid excretion
= [Titratable acid] + [NH4+] - [HCO3]

In acidosis

In response to acidosis, increased production and excretion of NH4+ is quantitatively much more important than increased formaton of titratable acid


Regulation of renal acid excretion

Stimulation for acid excretion

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.

Other factors

[KB: online text on acid and base]

Regulation of NH4+ excretion

Decreased extracellular pH

--> Liver preferentially converts ammonium to glutamine (instead of to urea)

--> More glutamine available


Decreased extracellular pH

--> Increased renal glutamine oxidation by proximal tubule

--> Increased excretion of NH4+


[KB: online text] There is a lag period between an acid load and NH4+ excretion reaching a maximum level


Regulation of HCO3 resorption in proximal tubule

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.


Factors causing kidneys to maintain or generate metabolic alkalosis

Over-excretion of H+ can be due to

  1. Volume contraction
  2. Chloride depletion
  3. Combination of aldosterone excess and K+ depletion

--> All three causes metabolic alkalosis

Volume contraction

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


Urinary acidity is high despite metabolic alkalosis

Chloride depletion

[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

Combination of aldosterone excess and K+ depletion

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


Excessive use of diuretics

--> Hypovolemia and hypokalemia

--> Increase H+ excretion

--> Metabolic acidosis

Chloride depletion may also be involved and may compound the problem


Other notes





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