Chapter outlines
| Basic Physiology |
| HYPOPHOSPHATEMIA |
| Etiology |
| Acute respiratory alkalosis |
| Sepsis |
| Increased insulin secretion |
| Diabetic ketoacidosis |
| Hungry bone syndrome |
| Postoperative |
| Clinical Features |
| Acute hypophosphatemia |
| Chronic hypophosphatemia |
| Diagnosis |
| History and physical examination |
| Basic investigations |
| Measurement of urinary phosphate excretion |
| Measure serum PTH and vitamin D levels |
| Other helpful tests |
| Management |
| Basic principles |
| Precautions |
| Correction of underlying causes |
SERUM PHOSPHATE AND HYPOPHOSPHATEMIA
Phosphorus is a vital component of all body tissues and plays an essential role in various body functions. The terms phosphate and phosphorus are commonly used interchangeably.
BASIC PHYSIOLOGY
- Phosphate is the most abundant intracellular anion, the second-largest mineral in the body after calcium, and comprises approximately 1% of the body weight.
- Distribution: Most (about 85%) of the body’s phosphorus is found within bone and teeth as hydroxyapatite, and the rest is distributed in tissues throughout the body. As only 1% of total body phosphorus is found in the extracellular fluid (ECF), the value of serum phosphorus may not necessarily reflect total body phosphorus content. In addition, even a change in pH leads to a shift of phosphate (acidosis shifts phosphate from intracellular fluid (ICF) to ECF) and affects the value of serum phosphorus.
- Normal value: Normal serum phosphorus levels in adults range from 2.5 to 4.5 mg/dL (0.75 to 1.45 mmol/L). It is best measured in the fasting state since there is as much as 50% diurnal variation (lower value in the morning and higher at night and after meals). Clinically, serum phosphorus level reflects nutritional status.
- Function: Phosphorus plays a major role in bone formation and is involved in cellular energy metabolism for almost all cellular functions (e.g., cell membranes, phospholipids, nucleic acids, acid buffering, enzyme systems, the energy carrier ATP-adenosine triphosphate, etc.).
REFERENCES
- Gaasbeek A, Meinders AE. Hypophosphatemia: an update on its etiology and treatment. Am J Med. 2005;118(10):1094–1101.
- Wang L, Xiao C, Chen L et al. Impact of hypophosphatemia on outcome of patients in intensive care unit: a retrospective cohort study. BMC Anesthesiol. 2019;19(1):86.
- Halevy J, Bulvik S. Severe hypophosphatemia in hospitalized patients. Arch Intern Med. 1988;148(1):153–155.
- O’Brien TM, Coberly L. Severe Hypophosphatemia in Respiratory Alkalosis. Adv Stud Med. 2003;3(6):345–348.
- Barak V, Schwartz A, Kalickman I, et al. Prevalence of hypophosphatemia in sepsis and infection: the role of cytokines. Am J Med. 1998;104(1):40–7.
- Khan AA, Mir AA, Vani ZA, et al. Significance of hypophosphatemia as an indicator of Gram negative sepsis. International Journal of Health and Clinical Research, 2021;4(10):63–66.
- Shor R, Halabe A, Rishver S, et al. Severe hypophosphatemia in sepsis as a mortality predictor. Ann Clin Lab Sci. 2006;36(1):67–72.
- Marinella MA. Refeeding syndrome and hypophosphatemia. J Intensive Care Med. 2005;20(3):155–9.
- Kebler R, McDonald FD, Cadnapaphornchai P. Dynamic changes in serum phosphorus levels in diabetic ketoacidosis. Am J Med 1985;79(5):571–6.
- Rasmussen A. Hypophosphatemia during postoperative glucose infusion. Acta Chir Scand. 1985;151(6):497–500.
- van der Vaart A, Waanders F, van Beek AP, et al. Incidence and determinants of hypophosphatemia in diabetic ketoacidosis: an observational study. BMJ Open Diab Res Care 2021;9(1):e002018.
- Wolfsdorf J, Craig ME, Daneman D, et al. Diabetic ketoacidosis in children and adolescents with diabetes. Pediatr Diabetes. 2009;10(12):118–33.
- Ditzel J, Lervang HH. Disturbance of inorganic phosphate metabolism in diabetes mellitus: clinical manifestations of phosphorus-depletion syndrome during recovery from diabetic ketoacidosis. Diabetes Metab Syndr Obes. 2010;3:319–324.
- Choi HS, Kwon A, Chae HW, et al. Respiratory failure in a diabetic ketoacidosis patient with severe hypophosphatemia. Ann Pediatr Endocrinol Metab. 2018;23(2):103–106.
- Witteveen JE, van Thiel S, Romijn JA, et al. Hungry bone syndrome: still a challenge in the post-operative management of primary hyperparathyroidism: a systematic review of the literature. Eur J Endocrinol. 2013;168(3):R45–53.
- Narayan A, Subramanian A. Severe hypophosphataemia: a rare cause of postoperative muscle weakness. BMJ Case Rep. 2018;2018:bcr2017221193.
- Knochel JP, Barcenas C, Cotton JR, et al. Hypophosphatemia and rhabdomyolysis. J Clin Invest. 1978;62(6):1240–1246.
- Zhao Y, Li Z, Shi Y, et al. Effect of hypophosphatemia on the withdrawal of mechanical ventilation in patients with acute exacerbations of chronic obstructive pulmonary disease. Biomed Rep 2016;4(4):413–416.
- Farkas J. Hypophosphatemia. Internet Book of Critical Care, May 9, 2019. Visit: https://emcrit.org/ibcc/hypophos/ Accessed 1 January 2022.
- Florenzano P, Cipriani C, Roszko KL, et al. Approach to patients with hypophosphataemia. Lancet Diabetes Endocrinol. 2020;8(2):163–174.
- Imel EA, Econs MJ. Approach to the hypophosphatemic patient. J Clin Endocrinol Metab. 2012;97(3):696–706.
- García Martín A, Varsavsky M, Cortés Berdonces M, et al. Phosphate disorders and clinical management of hypophosphatemia and hyperphosphatemia. Endocrinol Diabetes Nutr (Engl Ed). 2020;67(3):205–215.
- Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335–43.
- Wolfsdorf JI, Allgrove J, Craig ME, et al. ISPAD Clinical Practice Consensus Guidelines 2014. Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Diabetes. 2014;15 Suppl 20:154–79.
- Haffner D, Emma F, Eastwood DM, et al. Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia. Nat Rev Nephrol. 2019;15(7):435–455.
- Lyseng-Williamson KA. Burosumab in X-linked hypophosphatemia: a profile of its use in the USA. Drugs Ther Perspect 2018;34(11):497–506.