1. Inadequate dietary intake
While the kidney can excrete urine that is virtually free of sodium, there continues to be a small amount of potassium excretion even in the setting of diets completely devoid of potassium. With extreme potassium free diets, such as anorexia nervosa and alcoholism, the hypokalemia is worsened by concurrent magnesium depletion.
The most important determinants of intracellular potassium shifts are postprandial insulin and catecholamine release. These physiologic conditions can be exacerbated by beta-adrenergic–agonist administration, as well as high adrenergic states, which can be seen in situations such as alcohol withdrawal and myocardial infarctions. Rare causes include insulinomas and hypokalemic periodic paralysis.
3. Gastrointestinal losses
The most common cause of nonrenal potassium wasting is gastrointestinal loss, both diarrhea and vomiting. Diarrhea may have a high potassium and bicarbonate content resulting in hypokalemia with a concurrent nongap (hyperchloremic) metabolic acidosis. Vomiting leads to hypokalemia with a metabolic alkalosis with most of the potassium loss due to renal wasting (secondary to hypovolemia-induced hyperaldosteronism).
Renal potassium wasting occurs in states where increased distal sodium delivery is coupled to increased aldosterone activity. This most commonly occurs with diuretic use. Rarely, renal tubulopathies (Bartter syndrome or Gitelman syndrome) or renal tubular acidosis may present with hypokalemia.
Primary hyperaldosteronism (Conn syndrome) is due to excess aldosterone production by the adrenal glands, which causes extracellular volume expansion resulting in hypertension associated with hypokalemia and a metabolic alkalosis. Other rare forms of increased mineralocorticoid activity may be identified by measuring plasma renin activity and serum aldosterone levels.