7.3.1: Maintenance factors
Without a second mechanism acting to maintain it, the alkalosis would be only transitory.
Why?? This is because the kidney normally has a large capacity to excrete bicarbonate and return the plasma level to normal.
This rise in urinary bicarbonate loss occurs relatively promptly (ie onset within an hour) but excretion takes 24 hours to peak unless some abnormal condition is causing renal retention of bicarbonate. The factors involved in maintenance of the disorder are very important not only because they are necessary to develop a persisting (ie chronic) alkalosis but also because they can maintain the alkalosis even after the primary process generating it has resolved!
The alkalosis can persist after the initiating process has resolved ONLY IF there are additional factors maintaining it.
7.3.2: What are these abnormal 'maintenance factors'?
The four factors that cause maintenance of the alkalosis (by increasing bicarbonate reabsorption in the tubules or decreasing bicarbonate filtration at the glomerulus) are:
- Chloride depletion
- Reduced glomerular filtration rate (GFR)
- Potassium depletion
- ECF volume depletion
Chloride depletion is the most common factor
Volume depletion and potassium depletion may coexist in some disorders (eg vomiting). Severe potassium depletion alone can cause a metabolic alkalosis but this is typically only of mild to moderate degree. The mechanism seems to be related to an intracellular shift of H+ ('intracellular acidosis') in exchange for K+. The alkalosis is generated predominantly due to non-renal mechanisms. Renal mechanisms are frequently involved in causing the potassium depletion (eg in syndromes of mineralocorticoid excess).
Volume depletion has long been implicated in maintenance of an alkalosis. The idea is that hypovolaemia is associated with increased fluid and sodium reabsorption in the proximal tubule and bicarbonate is reabsorbed in preference to chloride; the alkalosis thus being maintained. The role of volume depletion has probably been over-emphasised: the co-existing chloride depletion is the most important factor responsible for persistence of the alkalosis. Correction of the volume deficit without correction of the chloride deficit will not result in correction of the alkalosis. These deficits are often corrected together with a saline infusion.
Diuretics can cause excess renal loss of fixed acid anions and result in alkalosis. Their use can also cause depletion of chloride, water (hypovolaemia) and potassium. These factors together maintain the alkalosis. For an alkalosis to develop in patients on diuretic therapy, there generally has to some decrease in chloride intake as well (eg if the patient is on a 'salt restricted' diet). A continued normal oral chloride intake (usually as NaCl) prevents patients on diuretics from getting an alkalosis.