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Hypophosphataemia in Anorexia Nervosa Postgrad Med J: First Published As 10.1136/Pmj.77.907.305 on 1 May 2001

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Hypophosphataemia in Anorexia Nervosa Postgrad Med J: First Published As 10.1136/Pmj.77.907.305 on 1 May 2001 Postgrad Med J 2001;77:305–311 305 Hypophosphataemia in anorexia nervosa Postgrad Med J: first published as 10.1136/pmj.77.907.305 on 1 May 2001. Downloaded from L Håglin The prevalence, causes, and consequences of can cause hypophosphataemia related paralysis hypophosphataemia in the clinical treatment of and respiratory insuYciency.19 various diseases are described in the literature, Hypophosphataemia with symptoms of but are not so seriously regarded as a severe phosphate depletion was first described in con- electrolytical disturbance.1–3 The clinical condi- nection with starvation during wartime and in tions when hypophosphataemia should be sus- prisoners when refeeding was initiated after a pected are listed in fig 1. There is a triad of dis- period of phosphate loss.20 21 Milk (rich in turbances: hypokalaemia, hypomagnesaemia, phosphate) was a life saver.21 22 Protein energy and hypophosphataemia which often follows undernutrition predisposes to hypophospha- trauma, and glucose overload.4 In anorexia taemia.423When a gradual breakdown of tissue nervosa patients, hypokalaemia, hypochlorae- takes place during starvation, total depletion of mia, and metabolic alkalosis are commonly the body’s phosphate stores may develop, even seen.5–7 though the serum phosphate level most often 1 A high prevalence of hypophosphataemia is remains normal. Anorexia in adolescent girls seen among post-traumatic and/or critically ill occurs at a serum phosphate level of 0.8–1.0 24 patients undergoing intensive care.8 Infectious mmol/l. Reference values vary with age. diseases are also associated with the risk of It has been stated that anorexia nervosa is a developing hypophosphataemia.9 Immunologi- condition characterised by protein energy cal disturbances can result from a deficiency of undernutrition, which may also explain other 10 deficiencies said to exist in anorexia nervosa several nutrients, such as zinc. Hypophospha- 25 taemia was found in anorexia nervosa patients patients. Most deficiencies have a protein with respiratory distress and signs of source, for example zinc, selenium, potassium, 11–13 phosphate and calcium, in addition to vitamin pneumonia. Recently, it was reported that 26 the main causes of death of patients with ano- D deficiency, due to low fat intake. These deficiencies may also contribute to loss of rexia nervosa was electrolytic disturbance and appetite. Department of Social infection.11 14 Medicine, University The incidence of hypophosphataemia in a Anorexia, well described symptom in phos- Hospital, SE-901 85 hospital population is usually associated with phate depletion and/or hypophosphataemia, Umeå, Sweden undernutrition followed by refeeding.15–18 Re- has frequently been documented before other disturbances in both experimental and clinical Correspondence to: cent reports of hospital undernutrition should conditions.4 Eight out of 10 case reports on the http://pmj.bmj.com/ Lena Håglin alert health and medical staV to the signifi- [email protected] sequelae of hypophosphataemia in anorexia cance of low serum phosphate concentrations. nervosa have described female patients. In one Submitted 30 December For example, overambitious treatment of un- study, only two of 65 adolescents with anorexia 1999 dernourished patients with high energy intake Accepted 22 August 2000 nervosa were boys.7 Causes and consequences are both related to gender, the consequences of Hypophosphataemia in addition to: phosphate depletion diVering because of the smaller muscle mass of women than of men.27 on September 23, 2021 by guest. Protected copyright. Progressive hypercalciuria and negative cal- cium balance developed in women but not • Malnutrition/undernutrition (semistarvation) men.27 A smaller total phosphate pool in female • Refeeding (syndrome) rats has been found in experiments.28 Fatigue • Alcoholism (withdrawal) High risk in connection and muscle weakness, often reported in with: anorexia nervosa patients, may be an early • Diabetic ketoacidosis • Anorexia nervosa hypophosphataemic sign of phosphate deple- 6724 • Infectious disease tion, as is loss of appetite. • Chronic infections The dangerous consequences of phosphate • Stress condition (surgery, burns, etc) depletion emphasise the urgency of this • Antacids and diuretics • Diabetic ketoacidosis discussion (box 1). The fatal condition is con- • Accelerated growth (puberty) • PEM in children nected with disturbed oxidative phosphoryla- tion and adenosine triphosphate (ATP) deple- • Catch-up growth in preterm infants • Crohn's disease tion in almost all vital functions. Loss of • Intensive care patients: parenteral • Malignancies etc appetite can predispose to major complica- nutrition tions, such as growth disturbances, neurologi- • Haemofiltration/dialysis cal sequelae, and demineralisation of the • Renal failure skeleton. Hypophosphataemia has been re- ported in anorexia nervosa patients in connec- • Post-renal transplantation tion with neurological complications and both • Hyperparathyroidism respiratory and congestive heart failure. Sev- Figure 1 Clinical conditions when hypophosphataemia should be suspected (PEM = protein eral case reports of hypophosphataemia in energy malnutrition). anorexia nervosa, in addition to the most www.postgradmedj.com 306 Håglin involved in almost all cellular processes, the Postgrad Med J: first published as 10.1136/pmj.77.907.305 on 1 May 2001. Downloaded from Box 1: Consequences of phosphate specific disturbances in diVerent conditions are depletion and/or hypophosphataemia even more diYcult to identify. V for di erent functions in anorexia Low levels of ATP in red blood cells cause nervosa hypoxia and haemolysis while contractility is x Loss of appetite (anorexia). reduced in the myocardium and respiratory x Neuromuscular. muscles.432Experimentally induced phosphate x Cardiopulmonary. depletion aVects left ventricular energy genera- tion, impairing myocardial contractile x Haematological. force.32 33 Red blood cells are dependent on a x Gastrointestinal. certain level of extracellular phosphate, as the x Renal. means of membrane transport is passive diVu- x Endocrinological. sion. Low levels of both ATP and 2,3 diphosphoglycerate have been reported in x Skeletal. hypophosphataemia in a patient with anorexia And nervosa.34 Low levels of ATP in leukocytes Life threatening due to ATP depletion and impaired immunofunction.4 An intracellular deranged composition of phospholipids in depletion of inorganic phosphate, which has membranes of the nervous system, heart, been shown in experimental studies to be cor- red corpuscles. related to serum levels (concentrations are And about 100:1), first aVects the phosphorylation Sudden death. of creatine to creatinine phosphate, which is the primary donor of phosphate to adenosine diphosphate.1432Secondly, resynthesis of ATP frequently cited reports from experimental is diminished. Electrolytic imbalance across studies, are referred to in the present paper. cellular membranes, caused by a diminished The purpose of this review is to expand our adenosine triphosphatase activity, results in an knowledge of the role of phosphate, especially intracellular accumulation of calcium, sodium, its depletion, a neglected condition in the clini- chloride, and water. This is probably the cal situation. mechanism of oedema described in patients with anorexia nervosa and also in protein Underlying pathophysiology/ energy undernutrition.23 35 biochemistry Disturbances of the acid-base balance and Reduced protein synthesis has been described electrolyte status have been reported in cases of in experimental studies as being associated anorexia nervosa and in phosphate deple- with restricted eating.29 It was concluded that tion.511303637 Lactic acidosis and rhabdomy- an increased amount of phosphate is needed olysis can be caused by deranged phosphate for ATP production which in turn is a prereq- metabolism.30 A comparable condition has http://pmj.bmj.com/ uisite for protein synthesis (maintenance of the been described in an anorexia nervosa patient nitrogen balance) and appetite. This shows who had metabolic alkalosis and respiratory that phosphate depletion leads to anorexia by acidosis.6 Starvation, with severe nutrient defi- contributing to low protein synthesis. ciencies, may accelerate phosphate loss via the Normal serum phosphate concentrations do urine.24 38 Such loss is associated with increased not preclude pre-existing total body depletion acid excretion.37 of phosphate, with a low intracellular pool vis- The ketone bodies produced by starvation, à-vis nitrogen (lower phosphate/nitrogen ra- on September 23, 2021 by guest. Protected copyright. 30 and/or the lactic acids produced by physical tio). Starvation with weight loss results in a training, lead to an excess of hydrogen ions. negative nitrogen balance a ecting the skel- V The phosphate buVer, whose main source is eton, muscles and hormones, with changes in bone, eliminates these ions. Bone, a dynamic the protein nutritional status (low albumin store for calcium and phosphate, helps to regu- concentrations). Low serum albumin is a late late the composition of the extracellular fluid. and severe manifestation of protein energy undernutrition, if there is a superimposed An early sign of phosphate depletion in women is calcium loss via the urine, and increased risk infection. 27 When anabolism is induced by high energy of hypercalcaemia. Significantly higher serum intake—and particularly carbohydrates—as the concentrations of calcium and lower serum main source
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