Hypercalcaemia and metabolic alkalosis with betel nut chewing: Emphasis on its integrative pathophysiology

Background. Events in the gastrointestinal tract that might contribute to a high absorption of calcium were simulated in vitro to evaluate why only a small proportion of individuals who ingest alkaline calcium salts develop hypercalcaemia, hypokalaemia and metabolic alkalosis. Methods. A patient who chewed and swallowed around 40 betel nuts daily developed hypercalcaemia, metabolic alkalosis, hypokalaemia with renal potassium wasting, and renal insufficiency. The quantities of calcium and alkali per betel nut preparation were measured. Factors that might increase intestinal absorption of calcium were evaluated. Results. Hypercalcaemia in the index case was accompanied by a high daily calcium excretion (248 mg, 6.2 mmol). Circulating levels of 1,25-dihydroxyvitamin D₃ and parathyroid hormone were low. Hypokalaemia with a high transtubular K⁺ concentration gradient, metabolic alkalosis, a low excretion of phosphate and a very low glomerular filtration rate were prominent features. Conclusions. Possible explanations for the pathophysiology of metabolic alkalosis and hypokalaemia are provided. We speculate that a relatively greater availability of ionized calcium than inorganic phosphate in the lumen of the intestinal tract could have enhanced dietary calcium absorption.