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These figures may vary slightly between hospitals but < 0.8 mmol/ L is hypophosphataemia and < 0.3 mmol is considered to be severe
Role of phosphorus
Bone mineralisation ( needed for bone and teeth formation ) Cellular structural components ( various cellular metabolisms ) ◘ For formation of phospholipids , phosphoproteins , nucleic acids , nucleotides Storage and liberalization of metabolic energy Oxygen transport ( in RBC 2,3 DPG ) Intracellular signaling ( important mediator ) Enzyme activation Acid – base homeostasis Skeletal and smooth muscle contraction Osteopontin gene expression Chondrocyte apoptosis
80- 85 % in skeleton as hydroxyapatite
Metabolism -Normal daily intake is about 40-50 mmol Most of the phosphate is absorbed in the duodenum and upper jejunum Of the daily intake of phosphate about 90 % is excreted in the urine Majority of renal reabsorption of filtered phosphate happens in the proximal tubule and a small amount is absorbed in distal nephron Regulation of phosphate homeostasis is linked to ○ calcium metabolism * when Ca is ↓↓ then phosphorus levels are ↑↑ ie inverse ratio this inverse ratio is maintained by renal excretion ○ parathyroid hormone ( PTH ↓↓ the Po4 reabsorption from kidneys ) ○ renal excretion ○ intestinal absorption ○ vitamin D ( Vit D & PTH stimulate the absorption of phosphate from the intestine ) ○ FGF23 , 7- decrease phosphate reabsorption by Na-Ph cotransporters
Risk factors -Alcoholism Recovery from diabetic ketoacidosis Phosphate free total parenteral nutrition Chronic use of phosphate binding agents
Intracellular shifts- most common cause in critically ill patients Phosphate shifts into the cells Diabetic ketoacidosis Re-feeding syndrome Acute respiratory alkalosis Hungry bone syndrome
Reduced uptake from the GI tract Poor diet Chronic diarrhoea Use of medications as antacids containing Calcium , magnesium or aluminum ( Phosphate binders )
Increased renal excretion Diuresis or dialysis Dysfunction of proximal renal tubules ( most important reabsorption of phosphorus happens in the proximal tubule ) Hyperparathyroidism Vitamin D deficiency
Multi-factorial Alcoholism Critical illness ( for e.g sepsis , trauma , burns , major surgery particularly cardiothoracic , aortic or hepatic )
Drugs Antacids Acetazolamide Anticonvulsants Bisphosphonates
Rare genetic disorders as Dent disease ( affects Proxomal renal tubules ) Vitamin D resistant rickets ( type 1 , 2 ) Hereditary hypophosphatemic rickets with hypercalciuria
Presentation -Often an incidental finding in primary care Seen more commonly in hospitalized patients Acute hypophosphataemia -this results in significant morbidity and mortality Chronic hypophosphataemia can cause ○ abnormal growth & rickets in children ○ osteomalacia in adults ○ bone pain ○ reduced insulin sensitivity ○ glycosuria ○ ↑↑ magnesium This is often associated with genetic or acquired renal phosphate – wasting disorders This is usually asymptomatic – but symptoms are more common when it acute and severe ( for e.g < 0.3 mmol/ L ) If symptoms happen – they are due to ○ tissue hypxaemia ○ impaired cellular energy stores
Muscle -myopathy rhabdomyolysis weakness paraesthesia fatigue
Breathing –respiratory failure
Cardiac -arrhythmias cardiomyopathy ↓↓ cardiac contractility hypotension
Neurological -irritability paraesthesia dysarthria confusion hallucinations somnolence convulsions coma
Renal -hypercalciuria hypermagnesuria Bicarbonate-metabolic acidosis
Blood -Changes happen rarely but ATP depletion can lead to increased erythrocyte rigidity – prone to hemolysis reduced phagocytosis and granulocyte chemotaxis by WBCs thrombocytopenia
Management –When ever possible identify and correct the cause – the following tests may help in identifying the cause FBC Us & Es Phosphate Magnesium Calcium Parathyroid hormone Renal phosphate excretion
Be guided by the level of phosphate and the patients clinical condition , duration ( acute or chronic ) and if the patient is symptomatic –Consider the fact that the cause is often multifactorial but the 3 main mechanisms which lead to hypophosphatemia are transcellular redistribution decreased intestinal absorption increased renal / GI losses
Review medications-Where possible stop offending medications as antacids , phosphate binders
IV treatment may also be needed for symptomatic patients with moderate hypophosphatemia who cannot tolerate oral replacement for e.g malabsorption diarrhoea nil by mouth
Oral phosphate replacement -Phosphate sandoz® ( 16.1 mmol / tab ) effervescent Upto 6 tablets / day adjusted according to response for eg 1-2 tablets tds Advice to take with tumberful of water Each tablet also contains 20.4 mmol of Na and 3.1 mmol of K+ ( exercise caution in patients with CCF , hypertension ) Avoid taking with aluminium , calcium or magnesium salts as these will bind phosphate and reduce its absorption Diarrhoea is a common SE of oral phosphate therapy Exercise caution in patients with severe renal replacement and seek advice Concomitant hypocalcemia should also be corrected before treating hypophosphatemia before treatment ( to prevent further hypocalcemia ) Very few studies exist where efficacy and safety of oral replacement has been studied , E Engwerda et al ( 2018 ) have reported findngs from a small retrospective cohort study that individualised phosphate replacement was effective and safe for both moderate and severe hypophosphataemia , but was more accurate in moderate hypophosphataemia
It is difficult to find guidance on how frequently the phosphate level should be monitored. The author could only find one protocol from Maidstone and Tunbridge Wells NHS Trust which recommends to check levels daily and stop treatment when level is above 0.8 mmol / L
References
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Disorders of phosphate metabolism
- Sharma S, Hashmi MF, Castro D. Hypophosphatemia. [Updated 2020 Nov 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493172/
- Labpedia Phosphorus Phosphorus (P), Inorganic Phosphate (PO4), Inorganic Phosphorus – Labpedia.net
- Maidstone and Tunbridge Wells NHS Trust hypophosphataemia-quick-guide.pdf (formularywkccgmtw.co.uk)
- Worcestershire Acute Hospitals NHS Trust Acute treatment of Hypophosphataemia Guidelines
- GGC Medicines Adult Therapeutics handbook – Management of Hypophosphataemia Management of Hypophosphataemia (ggcmedicines.org.uk)
- The Essentials of Calcium, Magnesium and
Phosphate Metabolism: Part I. Physiology
S. B. BAKER, L. I. G. WORTHLEY
Department of Critical Care Medicine, Flinders University of South Australia, Adelaide, SOUTH AUSTRALIA Critical Care and Resuscitation 2002; 4: 301-306 Australasian (cicm.org.au) - Shaker JL, Deftos L. Calcium and Phosphate Homeostasis. [Updated 2018 Jan 19]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279023/
- Arnold J. Felsenfeld, Barton S. Levine,
Approach to Treatment of Hypophosphatemia,
American Journal of Kidney Diseases,
Volume 60, Issue 4, 2012, Pages 655-661, ISSN 0272-6386,
https://doi.org/10.1053/j.ajkd.2012.03.024. ( Abstract )
(http://www.sciencedirect.com/science/article/pii/S0272638612009456) - How is acute hypophosphataemia treated in adults?Published , updated · Leeds Medicines Information Centre
- Imel, Erik A, and Michael J Econs. “Approach to the hypophosphatemic patient.” The Journal of clinical endocrinology and metabolism vol. 97,3 (2012): 696-706. doi:10.1210/jc.2011-1319
- Hypophosphataemia – Josh Farkas the Internet Book of Critical Care hypophos.pdf (emcrit.org)
- Hypophosphatemia: an evidence-based approach
to its clinical consequences and management
Jamshid Amanzadeh* and Robert F Reilly, Jr www.nature.com/clinicalpractice
doi:10.1038/ncpneph0124 - Engwerda E, van den Berg M, Blans M, Bech A, de Boer H. Efficacy and safety of a phosphate replacement strategy for severe hypophosphatemia in the ICU. Neth J Med. 2018 Dec;76(10):437-441. PMID: 30569887. ( Abstract )
- Phosphate homeostasis and disorders
P Manghat1 , R Sodi2 and R Swaminathan Annals of Clinical Biochemistry
2014, Vol. 51(6) 631–656