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Commonest cause of hypocalcaemia is HYPOPARATHYROIDISM -Common ↓ calcium , ↑ phosphate and ↓ or inappropriately N levels of PTH.Surgical Idiopathic Neonatal Familial Autoimmune. Metal deposition ( Iron , copper , aluminium ) Post radiation Infiltrative Functional ( in low magnesium ) Congenital
Vitamin D related –↓ ed absorption ( dietary , malabsorption ) ↓ed synthesis ( lack of sun , liver failure , renal failure , 1 alpha hydroxylase deficiency ) Impaired Vit D metabolism ( usually drug related ) Genetic syndromes.Vid D deficiency should be considered in a patient with cl features of rickets , osteomalacia , hypophosphataemia , ↑ AlkPo4 or ↑ PTH levels
In relation to phosphate –Hypomagnesemia Acute pancreatitis Any critical illness as burns or sepsis Osteomalacia Overhydration.CKD (common cause of low Ca ) Phosphate therapy hypoparathyroidism rhabdomyolyis
In relation to magnesium –Inhibits PTH secretion and also resistance to PTH action ↓ Magnesium can be due to GI loss Renal cause Medications related (Diuretics , Alcohol) Cisplastin (chemotherapy). Inhibitors of bone resorption (calcitonin and Bisphosphonates ) Loop diuretics Glucocorticoids Interference with Vit-D metabolism ( anti-convulsants ) PPIs- can lead to low magnesium leading to hypocalcaemia
Resistance to para thyroid action –Mutations in PTH signalling pathway- PTH resistance Pseudohypoparathyroidism Low calcium and phosphate patient are short with round face and short 4th metacarpal Renal insufficiency Medications ( block osteoclastic bone resorption) include Bisphosphonates
Extravascular calciun deposition –Hungry bone syndrome Pancreatitis Rhabdomyolysis Tumour lysis syndrome Widespread osteoblastic metastasis
Neuromuscular excitability –Tingling (fingers , toes , tips) Numbness Cramps Spasms (carpopedal ) layngopspam-stridor Tetany (repetitive discharge of peripheral nerve after a single stimulus) Seizure threshold reduced
Clinical signs –Chvostek’s sign-twitching and/ or contracture of the facial muscles – tapping on the facial N at a specific point on face Trousseaus signs- carpopedal spasm occurring after a few minutes of inflation of a sphygnomanometer cuff above systolic blood pressure ( both specific and sensitive for hypocalcaemic tetany )
Symptoms – Vit d related Bone pain Fracture Proximal myopathy
Hypoparathyroidism related –Mental retardation Personality disturbance Extrapyramidal signs Cataracts Papilloedema.
Other manifestations –ECG Delayed repolarisation- prolonged QT int Refractory CCF ( if underlying cardiac dis ) Subcapsular cataract Dry flaky skin Brittle dystrophic nails Alopecia Movement disorder ( basal ganglia calcification ) rickets in children (low Ca + low phosphate as in Vit D deficiency )
Investigations –Vit D level Parathyroid hormone Renal function LFTs including Amylase ECG ( prolongation of QT interval 500 ms ) Phosphate Magnesium ABG in acute presentation ( alkalosis ) Urine calcium/creatinine ratio
Secodary hyperparathyroidism –Vit D Deficiency ○ elderly ○ lack of sunlight ○ nutritional ○ malabsorption syndrome ○ liver disease or CKD Parathyroid hormone resistance ○ hypomagnesaemia ○ pseudohypoparathyroidism Drugs ○ inhibitors of bone resorption as bisphosphonates calcitonin denusomab ○ inhibitors of calcium and magnesium resorption as PPIs ○ altered vit D metabolism eg Phenytoin Chelation of circulating calcium ○ acute pancreatitis ○ early rhabdomyolysis ○ massive tumour lysis ○ large blood transfusions Low ionised calcium concentrations ○ hyperventilation ○ acute severe illness
PTH-low –Reduced parathyroid function ○ hypomagnesaemia ○ drugs as cinacalcet ○ neonatal hypocalcaemia Parathyroid loss ○ surgery ○ autoimmune disease ○ agenesis
Parathyroid hormone ( PTH ) Stimuates osteoclasts –> bone resorption leading to ↑ Calcium and Phosphorus conc Stimulates 1 alpha hydroxylase activity in kidney –> inc in 1,23 dihydroxyvitamin D production Inhibits renal excretion of calcium Indirectly increases intestinal Ca and Ph absorption Calcium has negative feedback effect on PTH
Chronic Kidney disease ( CKD ) PTH ↑ Phosphate ↑ Magnesium normal or elevated Calcitriol ↓ 1,25 (OH)2 Vit D ↓ Creatinine ↑
Phosphate –Hypoparathyroid disorders associated with hyperphosphataemia Low serum Phosphate conc are associated with ↑↑ PTH conc as in ○ secondary hyperparathyroid states as Vit D deficiency and osteomalacia Fasting levels can be
Magnesium –Hypomagnesaemia is associated with PTH impairment Conc < 0.5 mmol/L can lead to ↓ Ca Consider in acute or chronic diarrhoea , malabsorption syndromes , alcoholism , drugs – PPI or thiazide diuretics
Ostemalacia and rickets –Normal boney matrix which is undercalcified Rickets if calcium deficiency occurs during bone growth , Osteomalacia after epiphyseal closure Bone pain , fractures and proximal myopathy Blood tests if Vit D related ○ hypocalcemia and 2ary hyperparathyroidism –> ↑ renal Ph excretion and ↓ urinary calcium –> hypophosphataemia and ↑ AlkPo4
References
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Hypocalcaemia Reviewed by Dr Adrian Bonsall | Last edited https://patient.info/doctor/hypocalcaemia
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Secondary Hyperparathyroidism: Pathophysiology and Treatment
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Biochemical Investigations in Laboratory Medicine via http://www.pathology.leedsth.nhs.uk/dnn_bilm/Metabolic/Metabolicbonedisease/Osteomalacia.aspx
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- Management of hypocalcemia ABC of Intravenous Fluids , Electrolyte Disorders and AKI Management in Adults via http://www.wasd.org.uk/wp-content/uploads/2017/03/C07-Hypocalcaemia.pdf
- Schafer AL, Shoback DM. Hypocalcemia: Diagnosis and Treatment. [Updated 2016 Jan 3]. 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/NBK279022/ ( Abstract )