What is bone formed from?
What are the cells present in the bone?
Osteoblasts and osteoclasts
What is the function of the osteoblasts?
Synthesise osteoid and participate in mineralisation/calcification of osteoid (bone deposition)
What is the function of osteoclasts?
Release lysosomal enzymes which break down bone (bone resorption)
How does bone remodelling occur?
How do you differentiate between osteoclasts?
RANKL is expressed on osteoblast surface which binds to RANK-R to stimulate osteoclast formation and activity
What is Osteoprotegerin?
Decoy receptor for RANKL -> inhibits osteoclast differentiation
How is bone remodelling regulated?
Osteoblasts synthesise new bone, expressing receptors for PTH and calcitriol which regulate bone remodelling and Ca balance
How does Ca homeostasis work?
How do changes in EC Ca affect nerve and skeletal muscle excitability?
Hypercalcaemia = Ca blacks Na influx so less membrane excitability. Hypocalcaemia = enables greater Na influx so MORE membrane excitability
What is the normal range of serum Ca?
What are the signs and symptoms of hypocalcaemia? [CATs go numb]
Sensitises excitable tissues leading to muscle cramps/tetany, tingling; parasthesia (hands/mouth/feet/lips), convulsions, arrhythmias, tetany
What is Chvostek's sign?
Tap facial nerve just below zygomatic arch -> twitching of facial muscles indicates neuromuscular irritability due to hypocalcaemia
What is Trousseau's sign?
Inflation of BP cuff for several minutes induces carpopedal spasm indicating NM irritability due to hypocalcaemia
What are the causes of hypocalcaemia?
What are the signs and symptoms of hypercalcaemia? [ Stones, abdominal moans and psychic groan]
Stones (renal effects) -> polyuria/thirst, nephrocalcinosis, renal colic, chronic renal failure; Abdominal moans (GI effects) -> anorexia, nausea, dyspepsia, constipation, pancreatitis; psychic groans (CNS effects) -> fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)
What are the causes of hypercalcaemia?
How do you approach diagnostically hypercalcaemia - 1ry hyperparathyroidism?
Raised Ca and Raised (unsuppressed) PTH
How do you approach diagnostically hypercalcaemia - hypercalcaemia of malignancy?
What is a vitamin D metabolite?
Calcitriol (bioactive form)
What is the principal effect of calcitriol?
Stimulates intestinal absorption of Ca and PO4^3-, providing necessary ions for normal bone mineralisation
What are the other effects of calcitriol?
Regulates osteoblast differentiation; renal effects -> increased Ca reabsorption, decreased PO4 reabsorption via FGF23 (hormone produced by bone whihc increases urine PO4 excretion)
What is a Vit D deficiency state?
Lack of mineralisation in bone -> results in softening of bone, bone deformities, bone pin, severe proximal myopathy
What is the name of Vit D deficiency in adults and children?
Children = Rickets, Adults = osteomalacia
How are Vit D metabolites and calcium metabolism related?
What are the causes of Vit D deficiency?
Diet, lack of sunlight, GI malabsorption (coeliac, IBD), renal/liver failure, Vit D receptor defects
What is primary hyperparathyroidism?
Problem with parathyroid gland causing the increase in PTH
What is secondary hyperparathyroidism?
PTH goes up SECONDARY to increase of Ca
How do you diagnose Vit D deficiency?
How does impaired renal function (renal failure) lead to bone disease?
PO4 rises, accentuating hypocalcaemia, stimulating PTH due to low Ca levels; increase in PO4 leads to calcification/calcium deposition in vessels (coronary)