Renal Acid Base Regulation Notes

Renal acid base regulation

pH= -log₁₀ (H+), normal arterial pH is 7.4, (H+)= 40nm

Very important to maintain constant pH in both the intracellular and extracellular compartments of the body , otherwise denature proteins, prevent enzymatic reactions from taking place

There are three lines of defence against acidosis/alkalosis

-Buffers, ventilator mechanisms, renal mechanisms

Buffer: The primary buffer in the body is HC03- and its main function is to minimise the magnitidue of Ph changes via the reversible reaction

a) Ventilator mechanisms

-the pH resulting from solution of C02 in the blood and consequent dissociation of carbonic acid is given by Henderson-Hasselbalch equation

H2C03 H+ + HC03- normal HC03- concentration extracellular is 24nm, Pc02 is 40Kpa, so substituting the values gives pH = 7.4

-Ratio of bicarbonate : Pc02 x 0.03 remains equal to 20, the pH remains at 7.4. The bicarbonate concentration is determined by the kidney and the pC02 by the lung

-If excess HC03-, base excess, alkalinity, base deficit leads to acidity

Production of acids

a) Volatile acids: produced through the metabolism of carbohydrates and fats, leads to production of C02, carried in the body as H2C03 and excreted by lungs, this prevents C02 from forming H+

b) Non volatile acids: produced through metabolism of sulphur containing amino acids-cysteine- produces H2S04), Cationic amino acids (lysine-produces HCL), metabolism of phosphate leads to H2P04-

-Acid production is offset by HC03- production by HCO3- from anionic amino acid metabolism (aspartate), organic ions such as citrate

-Net acid production is 70mEq/day- Uses up 70mEq/day of HC03-

Function of the kidney to maintain acid-base balance

i) Reabsorb the filtered load of HC03-, buffer- each day the glomeruli filter 180 L of blood plasma, each containing 24mmol of HC03-, so the daily filtered load of HC03- is 4320 mmol- if this filtered load of HCO3- were left behind in urine-metabolic acidosis

Mechanism of reabsorption: H+ transported into the lumen by tubule cell titrates filtered HC03- to C02 to water- catalysed by apical carbonic anhydrase

C02 and H20 diffuses into the tubule cell- regenerates intracellular H+ and HC03- in aid of intracellular carbonic anhydrase

-The cell secretes the H+ out of the apical membrane into the tubule lumen – in the proximal tubule is viathe Na+/H+ exchange, as there is a large Na+ gradient (NH3) but in distal collecting tubule mediated by H+ ATPase

-The HC03- out across the basolateral membrane into blood- in the proximal tubule, HC03- exits the tubular cells via the HC03-/Na+ symporter coupling 3 HC03- with Na+ movement, but in the distal tubules HC03- leaves via the HC03-/CL- exchanger

-The HC03- reabsorption does not represent net H+ excretion into the urine

Site of reabsorption

-80% of HC03- is reabsorbed along the proximal tubule, by the end of the proximal tubule luminal pH falls to 6.8

-Thick ascending limb reabsorbs additional 10% of filtered HC03

-distal collecting tubule to the inner medullary collecting duct reabsorbs the remaining 10%

Carbonic anhdyrase: inhibits bicarbonate reabsorption, increased excretion of HC03-, increase excretion of K+, Na+, water-alkaline urine, metabolic acidosis-depletes extracellular bicarbonate

ii) Replensishing the lost HC03-

-70 mmol/day of H+ produced from non volatile acids generated is neutralised by

a) Extracellular HC03- in a reaction H⁺ + HC03^- H20 + C02, so HC03- decreases by the amount of H+ i consumes

Non-HC03- bufferes in blood neutralise the remaining load, so B- also decreases by amount equal to H+ it consumes

Tiny fraction of H+ remaining in blood, leads to a small drop in Extracellular pH

Role of the kidney: Regenerate the HC03-, B- in the...

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