Equis ISSN 2398-2977

Hyperphosphatemia

Contributor(s): Graham Munroe, Vetstream Ltd

Introduction

  • Definition: serum inorganic phosphate >4.5 mg/dl (>1.45 mmol/l). 
  • Phosphate is the major intracellular anion. Has structural role in cell membranes, hydroxyapatite of bone, nucleic acids and phosphoproteins including adenosine triphosphate (ATP). Important in oxygen transports (2,3-diphosphoglycerate), second messenger systems (cyclic adenosine monophosphate), coenzyme systems (nicotinamide adenine dinucleotide phosphate). Important in the regulation of protein, fat and carbohydrate metabolism. Involved in the activation of vitamin D and calcium homeostasis. 
  • Phosphorus exists as organic (phospholipids, phosphate esters) and inorganic (orthophosphoric acid, pyrophosphoric acid) forms. 80-90% of total body phosphate is inorganic in bone as hydroxyapatite. 15% is organic and in soft tissues. Most serum phosphorus is inorganic orthophosphoric acid. 10-20% of inorganic is protein bound. 80-90% is free or bound to magnesium, sodium and calcium.  
  • <1% of total body phosphate found as extracellular active forms with only 33% of this being ionized. 
  • Total body phosphate levels closely regulated in conjunction with calcium.

Pathogenesis

Etiology

  • Decreased excretion: post-renal failure (urinary tract obstruction or rupture), acute renal failure, chronic renal failure (rare: usually associated with hypophosphatemia Link: Hypophosphatemia (NEW)). 
  • Although the mechanisms are unclear, early chronic renal failure    Kidney: renal failure  leads to increased levels of parathyroid hormone (PTH). This causes enhanced excretion of phosphate by the kidneys. However, by late chronic renal failure this mechanism is inadequate leading to hyperphosphatemia. The increased level of PTH   Endocrine: hyperparathyroidism  continues to stimulate calcium and phosphate release from the bone. Hyperphosphatemia also inhibits production of calcitriol and therefore reduces intestinal calcium absorption.
  • Decreased glomerular filtration rate in acute renal failure   Kidney: renal failure  , prerenal/renal/postrenal azotemia may lead to reduced phosphate excretion. 
  • Increased intake: 
    • Vitamin D toxicosis   Vitamin D3  calcipotriol/calcipotriene-containing skin preparations, cholecalciferol-containing rodenticides, plant ingestion (rare), eg wild jasmines,Cestrum diurnum,Solanumspp. 
    • Iatrogenic due to over-administration of phosphate supplements or bran.
  • Strangulating intestinal lesions.
  • Severe colitis   Colitis X  .
  • Acute tumor-lysis syndrome/reperfusion injury: 
    • Rapid cell destruction releases large amounts of phosphate (and potassium) into circulation. Seen most commonly with high stage lymphomas.
    • Similar release can be seen with any condition causing lysis of large numbers of cells (rhabdomyolysis   Muscle: myopathy - exertional rhabdomyolysis  , soft tissue trauma, hemolysis).
  • Hypoparathyroidism   Endocrine: hypoparathyroidism    associated with hypocalcemia. 
  • Hyperthyroidism   Endocrine: hyperthyroidism    due to increased bone metabolism and enhanced renal reabsorption. 
  • Osteolysis. 
  • Acromegaly.
  • Spurious - hyperlipidemia, hyperproteinemia, thrombocytosis, monoclonal gammopathy.
  • Endurance exercise may lead to transient hyperphosphatemia.

Predisposing factors

General
  • Factors causing hypocalcemia generally lead to secondary hyperparathyroidism. PTH and Vitamin D (and analogues) both act to increase plasma calcium and phosphate levels.
  • Concurrent hypercalcemia   Hypercalcemia  increases the risk of soft tissue mineralization.

Pathophysiology

  • 60-70% of ingested phosphate is hydrolyzed to an inorganic form that is absorbed actively and passively. Active transport is increased by the presence of calcitriol primarily in the presence of hypophosphatemia.
  • Passive absorption is largely dependent on the phosphorus content of the diet as well as the type of protein. Phosphorus is excreted in the urine and primarily reabsorbed in the proximal tubules as a result of the effects of PTH. Increases in PTH decreases reabsorption in the proximal tubules. 
  • Other hormones that can increase reabsorption of phosphorus in the proximal tubules include growth hormone, insulin and thyroxine. ACTH, glucocorticoids and calcitonin decrease proximal tubular reabsorption of phosphorus.
  • Calcium is mobilized in response to secondary hypocalcemia, leading to abnormal or inadequate bone formation, bone demineralization and skeletal vulnerability to injury.

Diagnosis

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Treatment

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource
  • Schropp D M & Kovacic J (2007) Phosphorus and phosphate metabolism in veterinary patients. J Vet Emerg Crit Care 17, 127-134 VetMedResource.

Other sources of information

  • Marino P (2007) Renal and Electrolyte Disorders: Calcium and Phosphorus. In: The ICU Book. 3rd ein. Lippincott, Williams & Wilkins. pp 639-655. 
  • Schryver H F & Hintz H E (1987) Minerals. In: Current Therapy in Equine Medicine. Ed: Robinson N E. 2nd edn. W B Saunders, USA. pp 393-405.


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