Calcium Homeostasis & Disorders Flashcards
how is calcium homeostasis achieved & maintained?
diet
gut absorption
PTH
Vit. D
what affects gut absorption of calcium?
age
hormones
bowel pathology
what affects PTH levels?
hyper/hypoparthryroidism
malignant hypercalcaemia
what affects vit. D levels?
diet absorption renal liver UVB exposure drugs
what kind of feedback controls calcium?
negative
what kind of receptors are present on the parathyroid gland for calcium?
G-protein coupled recepetor
what happens to PTH levels when calcium’s GPCR is activated?
PTH is suppressed
what does Vit. D do?
encourages calcium deposition in bones & suppresses PTH
what does PTH do?
increases calcium uptake, makes you store calcium in bones & prevents loss through kidneys
what are the acute symptoms of hypercalcaemia?
thirst, dehydration, confusion, polyuria
what are the chronic symptoms of hypercalcaemia?
myopathy, osteopaenia, fractures, depression, hypertension,
abdominal pain- pancreatitis, ulcers, renal stones
what are the 2 main causes of hypercalcaemia?
primary hyperparathyroidism
malignancy
what are some other causes of hypercalcaemia?
drugs
granulomatous disease
familial hypocalciuric hypercalcaemia
tertiary hyperparathyroidism
what drugs can cause hypercalcaemia?
vit D
thiazides
what biochemical picture do you need to diagnose hyperparathyroidism?
raised serum caclium
raised serum PTH
increased urine calcium excretion
what are the malignant mechanisms that can cause hypercalcaemia?
- metastatic bone destruction
- PTHrp from solid tumours
- osteoclast activating factors
what is hypocalciuric hypercalcaemia?
autosomal dominant station that deactivates the calcium sensing receptor
how is hypocalciuric hypercalcaemia diagnosed?
Mild Hypercalaemia
Reduced urine calcium excretion
PTH may be (marginally) elevated
Genetic Screening
what is osteoporosis?
Progressive systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture
what are the common fracture sites in osteoporosis?
neck of femur
vertebral body
distal radius
humeral neck
what predicts fracture risk independently of other risk factors?
bone mineral density
osteopenia
low bone mass
name some endocrine secondary causes of osteoporosis
hyperthyroidism
hyperparathyroidism
Cushing’s disease
name some gastrointestinal secondary causes of osteoporosis
coeliac disease
IBD
chronic liver disease
chronic pancreatitis
name some respiratory secondary causes of osteoporosis
CF
COPD
what are bisphosphonates?
anti-resorptive agents
what do bisphophonates do?
prevent bone loss at all sites vulnerable to osteoporosis
what are the long term concerns of bisphosphonate therapy?
osteonecrosis of the jaw
oesophageal Ca
atypical fractures
what is denosumab?
fully human monoclonal antibody that targets and binds with high affinity and specificity to RANKL
RANKL
receptor activator of nuclear factor-kB ligand
what are the adverse effects of denosumab?
hypocalcaemia
eczema
cellulitis
what are the direct effects of corticosteroids on bone?
reduction of osteoblast activity & lifespan
suppression of replication of osteoblast precursors
reduction in calcium absorption
wha are the indirect effects of corticosteroids on bone?
inhibition of gonadal & adrenal steroid production
what is page’s disease?
abnormal osteoclastic activity followed by increased osteoblastic activity
what occurs in page’s disease?
abnormal bone structure with reduced strength & increased fracture risk
what is osteogenesis imperfecta?
rare group of genetic disorders mainly affecting bone
what are the 3 main causes of hypocalcaemia?
hypoparathyroidism
Vit. D deficiency
chronic renal failure
what is the emergency treatment of acute hypocalcaemia?
IV calcium gluconate 10 ml, 10% over 10 mins (in 50ml saline or dextrose)
name some causes of hypoparathyroidism
Congenital absence (DiGeorge syndrome) Destruction (surgery, radiotherapy, malign) Autoimmune - most common Hypomagnesaemia Idiopathic
why is magnesium important in calcium homeostasis?
calcium release from cells is dependent on magnesium
what happens in magnesium deficiency
intracellular calcium is high & PTH release is inhibited
what is pseudohypoparathyoridism?
genetic defect causing PTH resistance & resulting in low calcium but high PTH
which gene is affected in pseudohypoparathyroidism?
GNAS 1
what clinical signs occur in pseudohypoparathyroidism?
bone abnormalities obesity subcutaneous calcification learning disability brachdactyly
brachdactyly
shortening of 4th metacarpal
what is pseudo-pseudohypoparathyroidism?
same as psuedohypoparathyroidism with normal calcium levels
