Disorders of Calcium Homeostasis Flashcards
What occurs in calcium metabolism?
Vitamin D3 is hydroxylated in the liver to calcidiol, which is turned into calcitriol in the kidneys
Where is calcitriol transported to?
Small intestines = increases absorption of dietary calcium
Bone = releases calcium and phosphates
What do the responses of the small intestine and bone to calcitriol do?
Increases serum calcium
What is the role of the parathyroid glands in calcium metabolism?
Sense low serum calcium and increase PTH secretion
What is the role of PTH in calcium metabolism?
Acts on kidneys to increase calcitriol formation and decrease calcium excretion, also increases activity of bone
What senses serum calcium levels in the parathyroid gland?
Calcium-sensing receptor (C ASR) = G-protein coupled receptor involved in regulation of extracellular calcium homeostasis
What are the general symptoms of hypercalcaemia?
Bone pain, gallstones, abdominal pain, psychiatric complaints
What are the symptoms of acute hypercalcaemia?
Thirst, dehydration, confusion, polyuria
What are the symptoms of chronic hypercalcaemia
Myopathy, fractures, osteoporosis, depression, hypertension, pancreatitis, DU, renal calculi
What are some causes of hypercalcaemia?
Primary hyperparathyroidism, malignancy, vitamin D and thiazides, TB, sarcoidosis, familial hypocalciuric hypercalcaemia, high turnover, bedridden, thyrotoxic, Paget’s
How is primary hyperparathyroidism diagnosed?
Raised serum calcium
Raised serum PTH (or inappropriately normal)
Increased urine calcium excretion
How does hypercalcaemia arise from malignancy?
Metastatic bone destruction, PTHrp from solid tumours, osteoclast activating factors
How is hypercalcaemia from malignancy diagnosed?
Raised calcium and alkaline phosphatase, x-ray, CT, MRI, isotope bone scan
How should acute hypercalcaemia be treated?
Rehydrate with 0.9% saline (4-6L in 24hrs)
Consider loop diuretics once rehydrated
Rarely salmon calcitonin
Chemotherapy may reduce calcium in malignancy
How are bisphosphonates used to treat acute hypercalcaemia?
Single dose will lower calcium over 2-3 days, maximal effect at 1 week
When are steroids used to treat acute hypercalcaemia?
In sarcoidosis = 40-60mg prednisolone per day
How is primary hyperparathyroidism managed?
Surgery
Cinacalcet = calcium mimetic, useful if unfit for surgery
What are the indications for a parathyroidectomy?
End organ damage
Very high calcium (>2.85mmol/L)
Age <50
eGFR <60mL/min
What are some examples of end organ damage that would qualify a patient for a parathyroidectomy?
Bone disease = osteitis fibrosa et cystica, brown tumours
Gastric ulcers, renal stones, osteoporosis
What is primary hyperparathyroidism?
Primary overactivity of parathyroid gland, high calcium and PTH
What is secondary hyperparathyroidism?
Physiological response to low calcium or vitamin D, low calcium, high PTH
What is tertiary hyperparathyroidism?
Parathyroid becomes autonomous after many years of overactivity, high calcium and PTH
What are some genetic syndromes associated with hypercalcaemia?
MEN1/2 and familial isolated hyperparathyroidism
What are some features of MEN1/2?
Will almost always have developed a parathyroid adenoma with hypercalcaemia at a young age
What are some features of familial isolated hyperparathyroidism?
Adenoma occurs as in primary hyperparathyroidism
What are some features of familial hypocalciuric hypercalcaemia?
Autosomal dominant, deactivating mutation in calcium sensing receptor, usually benign or asymptomatic
How is hypocalciuric hypercalcaemia diagnosed?
Mild hypercalcaemia, reduced urine calcium excretion, PTH may by marginally elevated, genetic screening
What are some MSK symptoms of hypocalcaemia?
Paraesthesia (fingers, toes, perioral), muscle cramps, tetany, muscle weakness, fatigue, fits, broncho/laryngospasm
What are some signs of hypocalcaemia?
Chovstek’s sign (tapping over facial nerve), Trousseau sign (carpopedal spasm), QT prolongation on ECG
How is acute hypocalcaemia treated?
IV calcium gluconate 10ml, 10% over 10mins (in 50ml saline/dextrose)
Infusion = 10ml 10% in 100ml infusate, at 5ml/h
What are some causes of hypoparathyroidism?
Congenital absence = DiGeorge syndrome
Destruction = surgery, radiotherapy, malignancy
Autoimmune, hypomagnesaemia, idiopathic
What is the long term management of hypocalcaemia?
Calcium supplement = >1-2g per day
Vitamin D tablets = 1 alphacalcidol 0.5-1mcg
Depot injection = cholecalciferol 300000 units every 6 months
Why is PTH release inhibited in hypomagnesaemia?
Calcium release from cells is dependent on magnesium
What are some features of hypomagnesaemia?
Intracellular calcium is high, skeletal and muscle receptors are less sensitive to PTH
What are some causes of hypomagnesaemia?
Alcohol, thiazides, PPI, GI illness, pancreatitis, malabsorption
What causes pseudohypoparathyroidism?
Genetic defect = dysfunction of G-protein (Gs alpha subunit), mutation in GNAS gene
What are some features of pseudohypoparathyroidism?
Low calcium, high PTH (due to PTH resistance)
What can occur due to pseudohypoparathyroidism?
Bone abnormalities (McCune Albright), obesity, subcutaneous calcification, learning disability, brachdactyly (4th metacarpal)
What is pseudo-pseudohypoparathyroidism?
Albright’s hereditary osteodystrophy but no alteration in PTH action so normal calcium levels
What can cause vitamin D deficiency?
Dietary deficiency, chronic renal failure, lack of sunlight, drugs (e.g anticonvulsants)
Malabsorption = gastric surgery, coeliac, liver disease, pancreatic failure
What are some features of osteomalacia?
Low calcium, muscle wasting (proximal myopathy), dental defects (caries, enamel), bone tenderness, fractures, rib and leg deformity
What can chronic renal disease cause?
Vitamin D deficiency and secondary hyperparathyroidism
What are some features of chronic renal disease?
May have high 25-OH vit D, need to check 1-25 OH vit D, titrate treatment to PTH levels, don’t forget phosphate binders
What are the long term consequences of vitamin D deficiency?
Demineralisation of bone, fractures, rickets, osetomalacia, malignancy (especially colon), heart disease, diabetes
What is the treatment of chronic vitamin D deficiency?
Vitamin D3 tablets (400-800lU per day after loading with 3200iU per day for 12 weeks), Calcitrol, Alfacalcidol
Combined calcium and vitamin D (Adcal D3)
What causes vitamin D-resistant rickets?
X-linked hypophosphataemia = variable penetration, PHEX or FGF23 gene mutation
What is the role of FGF23?
Regulates phosphate levels in plasma and is secreted by osteocytes in response to calcitriol
What are some features of vitamin D-resistant rickets?
Low phosphate, high vitamin D = treat with phosphate and vitamin D supplements +/- surgery
What is the most important test to do for calcium disorders?
PTH
