Severe hypophosphatemia. Pathophysiologic implications, clinical presentations, and treatment

We conducted this review to heighten the awareness and describe pathologic manifestations of hypophosphatemia. We present 3 cases of varied manifestations of hypophosphatemia where recognition was delayed. In certain settings, severe hypophosphatemia has significant morbidity and potential mortality. Appreciation of the pathophysiologic basis for organ dysfunction in severe hypophosphatemia should result in early recognition and treatment. We reviewed the English-language literature for reported cases and research studies dealing with pathophysiologic mechanisms subserving clinical manifestations. We observed that depletion of adenosine triphosphate (ATP) would explain most of the derangement noted in cellular functions. Phosphate plays a key role in the delivery of oxygen to the tissue. Lack of phosphate, therefore, leads to tissue hypoxia and hence disruption of cellular function. Severe hypophosphatemia becomes clinically significant when there is underlying phosphate depletion. Otherwise, short-term acute hypophosphatemia is not usually associated with any specific disorder. Chronic hypophosphatemia, on the other hand, results in hematologic, neuromuscular, and cardiovascular dysfunction, and unless corrected, the consequences can be grave. Most of the time hypophosphatemia results from renal loss of phosphate, diagnosed by a fractional secretion of phosphate > 5%. It is hard to provide precise estimates of how many patients are seen with hypophosphatemia annually at academic medical centers. This is complicated by use of chemistry panels that do not measure inorganic phosphate unless specifically ordered. This often leads to delay in correct diagnosis, and, therefore, additional delay in providing appropriate management. A high index of suspicion alone avoids the unnecessary withholding of treatment that can be life saving.