Disorders of Calcium Homeostasis Flashcards
what substances are involved in calcium metabolism?
parathyroid hormone (PTH) vitamin D calcitonin 1 o-hydroxylase 25 hydroxylase
what stimulates most parathyroid hormone release?
low calcium
via calcium-sensing receptor (C ASR) in parathyroid
G protein coupled receptor
bone metabolism??.
…….
how does vitamin D resistant rickets develop?
inhibiting factors in the vitamin D pathway
- elderly immigrant
- pigmented sunscreen
- anticonvulsants
- renal disease
can inhibit the production and conversion of vitamin D into 1,25 OHD
general features of hypercalcaemia?
bones
stones
abdominal groans
psychic moans
acute hypercalcaemia features?
thirst
dehydration
confusion
polyuria
chroic hypercalaemia features?
myopathy fractures osteopaenia depression hypertension pancreatitis DU renal calculi
best test for hypercalcaemia?
PTH
- high = parathyroid issue
how can PTH be used to determine the underlying cause of hypercalcaemia?
if PTH is high - primary/tertiary hyperparathyroidism - FHH if PTH is low (high phosphate) - bone pathology
what are the 2 main causes of hypercalcaemia?
primary hyperparathyroidism
malignancy
other causes of hypercalcaemia?
drugs: vit D, thiazides
granulomatous disease
familial hypocalcuric hypercalcaemia
high turnover disease (e.g pagets, thyrotoxicosis)
what are the features of primary hyperparathyroidism?
raised serum calcium
raised serum PTH (or inappropriately normal)
increased urine calcium excretion (ensure vit D replete)
how can malignancy cause hypercalcaemia?
metastatic bone destruction
PTH from tumour
osteoclast activating factors
how is hypercalcaemia of malignancy diagnosed?
raised calcium and alk phos
X ray, CT, MRI
isotope bone scan
treatment of acute hypercalcaemia?
fluids loop diuretics bisphosphonates steroids (e.g for sarcoidosis) salmon calcitonin (rarely used) chemotherapy if due to malignancy
what test can show uptake by parathyroid scan and when is it used?
sestamibi scan
use if intention of removing glands
how is primary hyperparathyroidism managed?
definitive = surgery
cinacalet
- mimics calcium
- good if unfit for surgery
what are the indications for a parathyroidectomy?
end organ damage - bone disease - gastric ulcers - renal stones - osteoporosis very high calcium (>2.85mmol/L) under 50 eGFR <60mL/min
primary vs secondary vs secondary hyperparathyroidism biochemistry features?
primary = high calcium and PTH secondary = low calcium, high PTH tertiary = high calcium and PTH
name 2 genetic syndromes which can cause hyperparathyrodisim?
MEN1/2
- usually causes parathyroid adenoma with hypercalcaemia
Familial isolated hyperparathyroidism
- adenoma as in primary hyperparathyroidism
what is familial hypocalciuric hypercalcaemia?
autosomal dominant deactivating mutation in the calcium sensing receptor
usually benign/asymptomatic
how is familial hypocalciuric hypercalcaemia diagnosed?
mild hypercalcaemia
reduced calcium excretion
marginally elevated PTH
genetic screening
what are the symptoms and signs of hypocalcaemia?
paraethesia muscle cramps, tetany muscle weakness fatigue bronchospasm or laryngospasm fits chovsteks sign trousseau sign QT prolongation on ECG
how is acute hypocalcaemia managed?
emergency
- IV calcium gluconate 10ml, 10% over 10 mins (in 50ml dextrose or saline)
what can cause hypoparathyroidism?
congenital absence (di George) destruction autoimmune hypomagnesaemia idiopathic
what is the long term management for hypoparathyroidism?
calcium supplements
Vit D tablets
- 1 alphacalcidol
- depot injection (cholecaliferol)
what are the effects of hypomagnesia?
calcium release from cells is dependant on magnesium so intracellular calcium is high in hypomagnesaemia
PTH release is inhibited
skeletal and muscle receptors are less sensitive to PTH
replace with calcium and magnesium
what can cause hypomagnesia?
alcohol drugs thiazide PPI GI illness pancreatitis malabsorption
what is pseudohypoparathyroidism?
genetic defect of GNAS1 gene causing dysfunction of G protein
what is pseudo-pseudohypoparathyroidism?
Albright’s hereditary osteodystrophy
but no alteration in PTH action and thus normal calcium
what conditions are associated with vitamin D deficiency?
rickets
osteomalacia
what can cause vitamin D deficiency?
dietary deficiency/malabsorption - gastric surgery - coeliac disease - liver disease - pancreatic failure chronic renal failure lack of sunlight drugs (anticonovulstants)
what are the clinical features of osteomalacia?
low calcium muscle wasting (proximal myopathy) dental defects bone - tenderness, fractures, rib deformity, limb deformity
loosers zone?
transverse lucencies traversing partway through a bone, usually at right angles with the cortex
associated with osteomalacia and rickets
what can chronic renal disease cause?
vit D deficiency
- high 25-OH vit D
- can have low 1-25 OH vit D (useable)
secondary hyperparathyroidism
treatment of vit D deficiency due to chronic renal disease?
titrate treatment to PTH levels
name 2 long term consequences of vitamin D deficiency
bone disease - demineralisation/fractures - osteomalacia/rickets malignancy (esp colon) heart disease diabetes
how is chronic vitamin D deficiency managed?
vitamin D3 tablets
calcitriol
alfacalcidol
combined calcium + vitamin D (e.g adcal D3)
what are the features of pseudohypoparathyroidism?
low calcium but PTH is high due to PTH resistance bone abnormalities (McCune Albright) Obesity Subcutaneous calcification learning disability Brachdactyly (4th metacarpal)
what can cause vitamin D resistant rickets?
hypophosphataemia due to X linked PHEX or FGF23 gene mutation
what happens in vitamin D resistant rickets?
FGF 23 regulates phosphate levels in plasma and is secreted by osteocytes in response to calcitrol - can be dysfunctional in vit D resistant rickets
low phosphate
high vitamin D
how is vitamin D resistant rickets managed?
phosphate and Vit D supplements (1,25-OH vit D3)
with or without surgery
