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acid_base

acid-base physiology

introduction

  • intracellular (IC) pH at 6-6.8 is lower than extracellular (EC) pH which is normally at 7.35-7.45, but is sensitive to changes in EC pH, and as cell processes are regulated by IC pH, the maintenance of EC pH is important.

some chemistry

  • Acid: substance that can donate a proton;
  • Base: substance that can accept a proton;
  • Buffer: substance that reduces the change in pH upon the addition of acid or base by production of poorly dissocaited acid or base;
  • Aprotes: ions that cannot donate nor accept protons (eg. Na+, Cl-);

respiratory and metabolic control of pH

  • transport of CO2 in the blood has a profound effect on the acid-base status of the blood and the body as a whole

Henderson-Hasselbalch equation

blood pH = 6.1 + log [bicarb/(0.03 x PCO2)]

  • arterial bicarb is usually 24mmol/L
  • PCO2 is usually 40mmHg
  • thus normal arterial pH = 7.4
  • see also wikipedia

acid production

amino acids

  • gluconeogenesis from amino acids ⇒ NH4+ & HCO3- from their amino & carboxy groups, the NH4 is incorporated into urea and the proton formed is buffered IC by bicarb., so little NH4+ & HCO3- escape into ECF;
  • metab. of sulphur containing amino acids ⇒ sulphuric acid;
  • metab. of phosphorylated amino acids ⇒ H3PO4-
  • both are strong acids which enter ECF and are major load to the buffers in ECF usually about 50 mEq/d of H+;

carbon dioxide

  • CO2 formed by metabolism in tissues is mainly hydrated to carbonic acid ⇒ total H+ load of > 12,500 mEq/d;

abnormal acid production

  • XS acid production in: hypoxia/exercise (lactic acid);
  • diabetic ketosis (acetoacetic acid / B-OH butyric acid);
  • starvation (decreased insulin ⇒ ketoacids);

acid excretion/losses

renal excretion

  • bicarb. reabsorp. in prox. tubules depends on:
  • filtered load (GFR x plasma [ ]);
  • rate of H+ secretion (as bicarb. exchanged for H+);
  • usually almost complete reabs. occurs (500mEq/d);
  • once [bicarb] plasma >28meq/L ⇒ bicarb appears in urine;
  • generation of new bicard. in distal parts nephron results in net secretion of H+ needed to maintain H+ balance in most cases;
  • H+ secretion prop. to arterial pCO2 (as more carbonic acid);
  • limiting urinary pH of 4.5 would significantly limit ability to excrete significant amounts of acid if it wasn't for the presence of urinary buffers:
    • bicarb ⇒ reabsorption of CO2 + water;
    • HPO4– ⇒ H2PO4-;
    • ammonia ⇒ ammonium ion;
  • K depletion ⇒ intracellular acidosis ⇒ increased renal H+ secretion ⇒ EC alkalosis;
  • K excess ⇒ increased K secretion (exchanged for Na and thus this competition for tubular Na due to H secretion also being exchanged for tubular Na ⇒ decreased H secretion);
    • ⇒ EC acidosis;

impaired renal excretion of acid

  • type I renal tubular acidosis is due to reduced ability to excrete acid from distal tubules;
    • primary (AD or sporadic);
    • obstructive uropathy;
    • nephrocalcinosis;
    • drugs (amphotericin B, lithium, toluene);
    • other rare: HbS, systemic lupus erythematosus (SLE), Sjogrens, thyroiditis, Marfan's;
  • type II renal tubular acidosis due to XS losses of bicarb. from proximal tubules:
    • primary defect (rare);
    • carbonic anhydrase inhibitors/deficiency
    • Fanconi synd. (decreased reabsorption bicarbonate, glucose, amino acids, phosphate, etc.)
  • primary;
  • hyporeninaemic - usually if chronic nephritis;
  • “chloride shunt” with hypertension, decreased renin;
  • decreased sensitivity to aldosterone;
  • renal immaturity;
  • obstructive uropathy;
  • K sparing diuretics;

abnormal acid losses

  • vomiting gastric acid ⇒ loss of HC1 ⇒ metab. alkalosis;

derangements of acid-base status

    • decreased bicarbonate and pH
    • increased bicarbonate and pH
  • respiratory acidosis:
    • hypoventilation retains carbon dioxide resulting in high pCO2 and bicarbonate, and lower pH
  • respiratory alkalosis:
    • hyperventilation blows off carbon dioxide resulting in low pCO2 and bicarbonate, and higher pH, often associated with symptoms of hypocalcaemia such as paraesthesia, or if severe, tetanic spasm of hands and feet.

compensatory mechanisms

  • the EC pH range compatible with life covers a 5-fold range: 7.0 - 7.7 (0.00002-0.0001 mEq/L).
  • the body uses compensatory mechanisms to try to maintain EC pH, but these are slower than buffers, although more effective in returning pH to normal:
    • renal (onset hrs, complete 2-5 days) if a primary respiratory problem;
    • respiratory (onset minutes, complete 12-24 hours) if a primary metabolic problem;
  • neither completely return pH to normal except if primary event is a respiratory alkalosis

renal compensation to maintain homeostasis in the following primary events:

  • metab. acidosis:
    • H+ and organic anions are secreted in exchange for cations (esp. Na) and bicarb., it is only when acid load is very large that cations are lost with the anions ⇒ diuresis, depletion of cation stores;
    • chronic acidosis ⇒ incr. glutamine synthesis in liver using some of the ammonium that is usually converted to urea ⇒ provides kidneys with additional source of:
    • ammonium ⇒ incr. secretion of ammonia ⇒ further improving renal compensation for acidosis;
    • bicarb. (decarboxylation of prop.to-ketoglutarate) ⇒ incr. bicarb.
    • plasma ⇒ incr. buffer;
  • metab. alkalosis:
    • bicarb. excreted if [bicarb] plasma >28;
    • the compensatory resp. acidosis raises pCO2 and inhibits renal compensation by ⇒ incr. acid secretion, but effect slight only;
  • resp. acidosis:
    • ⇒ incr. H+ secretion ⇒ incr. bicarb. reabs. even though plasma bicarb. already elevated ⇒ further incr. plasma bicarb.!;
    • ⇒ incr. Cl- excretion ⇒ decr. [Cl-] plasma;
    • ⇒ incr. pH;
  • resp. alkalosis:
    • ⇒ decr. H+ secretion ⇒ decr. bicarb. reabs. even though plasma bicarb. already low ⇒ further decr. plasma bicarb.!;
    • ⇒ decr. pH;

respiratory compensation

  • even though the lungs can modify pH by changing pCO2 and altering the ratio of carbonic acid to bicarb., this process cannot cause loss or gain of H+. as they cannot regenerate bicarb. to replace that lost when H+ was buffered. The generation and excretion of bicarb. are responsibilities of the kidneys;
  • metab. acidosis:
    • e.g. if sufficient strong acid is added to lower plasma bicarb. by half:
      • if CO2 was not formed and thus not excreted, pH would fall to 6.0 and death would occur;
      • If the bicarb. is regulated so it remains constant, the pH would fall to only 7.1 - uncompensated metab. acidosis;
      • Actually, the rise in pH stimulates respiration so that the pCO2 falls rather than rises or stays constant thus raising pH further - resp. compensation. The renal compensatory mechanisms then bring about excretion of the extra H+ and return buffer system to normal;
acid_base.txt · Last modified: 2013/12/20 16:21 (external edit)