Hypocalcemia-Low calcium

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

1. Hypocalcaemia Authored by Dr Colin Tidy, Reviewed by Dr Adrian Bonsall | Last edited 23 Dec 2015 https://patient.info/doctor/hypocalcaemia

2. Hypocalcemia Medscape July 2016 Manish Suneja et al
3. Cooper, Mark S, and Neil J L Gittoes. “Diagnosis and management of hypocalcaemia.” BMJ (Clinical research ed.) vol. 336,7656 (2008): 1298-302. doi:10.1136/bmj.39582.589433.BE
4. Fluids and electrolytes demystified Joyce Johnson et al Mc-Graw-Hill Professional
5. Harrison’s manual of medicine Dennis L Kasper McGraw-Hill Professional
6. Investigating hypocalcemia BMJ 2013 ; 346: f2213
7. Hypocalcemia Henry’s Clinical Diagnosis and Management by Laboratory Methods
8. Diagnosis and Management of hypocalcemia BMJ 2008 ;336 :1298
9. Hypocalcemia MSD Manuals by James L.Lewis et al

10. Secondary Hyperparathyroidism: Pathophysiology and Treatment Wissam Saliba and Boutros El-Haddad The Journal of the American Board of Family Medicine September 2009, 22 (5) 574-581; DOI: https://doi.org/10.3122/jabfm.2009.05.090026

11. Biochemical Investigations in Laboratory Medicine via http://www.pathology.leedsth.nhs.uk/dnn_bilm/Metabolic/Metabolicbonedisease/Osteomalacia.aspx

12. Fong, Jeremy, and Aliya Khan. “Hypocalcemia: updates in diagnosis and management for primary care.” Canadian family physician Medecin de famille canadien vol. 58,2 (2012): 158-62. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279267/
13. 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
14. 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 )