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
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);
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;
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.
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;