Erik Romanelli Internal Medicine Clerkship Presentation - Hypophosphatemia Phosphate is an essential element in the human body, playing a critical

role in cellular metabolism (generation of ATP), regulation of cellular processes (phosphorylation of key enzymes), and maintenance of acid-base homeostasis (urinary buffering). Severe depletions of phosphorus can have multiorgan consequences related to decreases in ATP (which can result in metabolic encephalopathy, decreases in myocardial contractility, and respiratory failure due to diaghraghmatic weakness) and decreases in 2,3 DPG (which will increase the affinity of hemoglobin for oxygen, thereby reducing oxygen release at the tissue level). Hypophosphatemia affects approximately 2% of patients, and can be caused by numerous factors: shift of phosphorus from extracellular to intracellular compartments (as may be seen in refeeding syndrome, respiratory alkalosis, insulin infusion in DKA, and hungry bone syndrome), decreased gastrointestinal absorption (from malabsorptive syndromes such as Crohns or celiac sprue, chronic antacid usage, alcohol abuse, or due to Vitamin D deficiency), and increased urinary losses (as may be seen in hyperparathyroidism, Fanconi syndrome). Phosphate wasting can also be the result of several genetic or acquired renal disorders, which generally manifest in infancy. Research has elucidated that the overexpression of the FGF23 gene is common in many of these disorders (such as X-linked and autosomal dominant hypophosphatemic rickets, oncongenic osteomalacia) because of FGF23s role as a phosphaturic hormone that inhibits renal absorption of phosphorus in the kidneys. Hypophosphatemia has been implicated as a cause of rhabdomyolysis, respiratory failure, hemolysis and left ventricular dysfunction. Patients with severe hypophosphatemia (<1mg/dl) should be treated with intravenous repletion may be considered, especially for patients who have clinical sequelae of hypophosphatemia. Patients with moderate hypophosphatemia (1-2.5mg/dl), however are often asymptomatic and will not require therapy other than that aimed at the underlying cause, and possibly repleting the patient with oral phosphorus.
References: Amanzadeh J, Reilly RF (2006) Hypophosphatemia: an evidence-based approach to its clinical consequences and management. Nat Clin Pract Nephr 2: 136148. Geerse DA, Bindels AJ, Kuiper MA, et al (2010). Treatment of hypophosphatemia in the intensive care unit: a review. Crit Care 14:147-154. Subramanian R, Khardori R (2000). Severe hypophosphatemia. Pathophysiologic implications, clinical presentations, and treatment. Medicine (Baltimore) 2000; 79:1. Agus, Zalman S. Causes of hypophosphatemia (2011). UptoDate.