calcium and bone Flashcards
calcium regulation: explain the hormonal regulation of blood calcium ion concentration; list the causes and clinical features of hypercalcaemia and hypocalcaemia
diagram of calcium homeostasis: interaction between PTH and vitamin D
diagram; PTH to increase serum Ca2+: increases Ca2+ reabsorption from bone, causes kidney to reabsorb Ca2+, regulates production of active vitamine D (calcitriol); inactive vitamin D (calcidiol) is from liver and undergoes 1a hydroxylation under control of PTA, increasing serum Ca2+ by increasing Ca2+ absorption from gut
phosphate absorption regulation
Na+/PO43- absorbed via cotransporter from urine in proximal convoluted tubule; PTH from blood inhibits this, as does fibroblast growth factor 23 (FGF23 - from osteocytes); this also inhibits calcitriol synthesis, reducing PO43- reabsorption from gut
where does phosphate reabsorption occur
via gut and kidneys
what does increase phosphate reabsorption cause to Na+
less Na+ excretion in urine (as co-transported in)
effect on serum PO43- in hyperparathyroidism
low as increased urine phosphate excretion (PTH inhibits Na+/PO43- transporters)
regulation of PTH secretion: high [Ca2+] ECF
Ca2+ binds to Ca2+ sensin receptor on parathyroid cell -> receptor activation leads to inhibition of PTH secretion
regulation of PTH secretion: low [Ca2+] ECF
Ca2+ not bound to Ca2+ sensin receptor -> no inhibition -> PTH secreted -> PTH action in body leads to increased [Ca2+] ECF
role of vitamin D in calcium homeostasis
diagram
where is vitamin D obtained from
vitamin D obtained from diet (ergocalciferol to inactive vitamin D calcidiol in liver) or sunshine (UVB light); in kidney, 1a-hydroxylase (stimulated by PTH) produces calcitriol (active vitamin D)
effect of cacitriol on PTH, and Ca2+
negative feedback on PTH; increases Ca2+ gut absorption, maintenance in bone, renal Ca2+ reabsorption
5 causes of vitamin D deficiency
malabsorption or dietary insufficiency, lack of sunlight (block UVB light), liver disease (can’t convert to calcidiol), renal disease (no stimulation of renal 1a-hydroxylase by PTH to convert to calcitriol), receptor defects in gut, bone, kidney and parathryoid gland
2 examples of diseases causing GI malabsorption of vitamin D
coeliac, inflammatory bowel
inheritance and prevalence of vitamin D receptor defects, and response to treatment
autosomal recessive, rare, resistant to vitamin D treatment
high EC Ca2+ (hypercalcaemia) effect on nerve and skeletal muscle excitability
Ca2+ blocks Na+ influx as more competition, so less membrane excitability
low EC Ca2+ (hypocalcaemia) effect on nerve and skeletal muscle excitability
enables greater Na+ influx as less competition, so more membrane excitability
4 signs and symptoms of hypocalcaemia (CATs go numb)
parasthesia (hands, mouth, feet, lips), convulsions, arrythmias, tetany
explain symptoms of hypocalcaemia
sensitises excitable tissues, to muscle cramps/tetany, tingling
what do Chvostek’s and Trousseau’s signs indicate
neuromuscular irritability due to hypocalcaemia
describe Chvostek’s sign
tap facial nerve just below zygomatic arch -> positive response is twitching of facial muscles
describe Trousseau’s sign
inflation of BP cuff for several minutes to induce carpopedal spasm
4 causes of hypocalcaemia
vitamin D deficiency, low PTH levels (hypoparathyroidism), PTH resistance (e.g. pseudohypoparathryoidism), renail failure
3 caues of low PTH levels (hypoparathyroidism)
surgical (neck injury), auto-immune, Mg2+ deficiency
how does renal failure cause hypocalcaemia
impaired 1a hydroxylation, decreasing production of 1,25(OH)2D3
signs and symptoms of hypercalcaemia
reduced neuronal excitability so atonal muscles; “stones” - renal effects, “abdominal moans” - GI effects and “psychic groans” - CNS effects”
renal effects of hypercalcaemia
polyuria and thirst, nephrocalcinosis, renal colic, chronic renal failure
GI effects of hypercalcaemia
gut slowed down so: anorexia, nausea, dyspepsia, constipation, pancreatitis
CNS effects of hypercalcaemia
fatigue, depression, impaired concentration, altered mentation, coma
4 causes of hypercalcaemia
primary hyperparathyroidism, malignancy (these 2 account for 90% of cases), conditions with high bone turnover, vitamin D excess (rare)
how might malignancy cause hypercalcaemia
tumours/metastases often secrete a PTH-like peptide; cancer cells in bone cause release of Ca2+
conditions with high bone turnover causing hypercalcaemia
hyperthyroidism, Paget’s disease of bone (immobilised patient)
diagnostic approach to hypercalcaemia: normal axis
parathyroid cells detect low Ca2+, so increase PTH which raises Ca2+ - negative feedback to switch PTH off when sufficiently raised
diagnostic approach to hypercalcaemia: primary hyperparathyroidism
raised Ca2+, low PO43- (PTH inhibits PO43- reabsorption in kidney), raised unsuppressed PTH (autonomous PTH secretion) as no negative feedback
diagnostic approach to hypercalcaemia: hypercalcaemia of malignancy
raised Ca2+, suppressed PTH (no issue in parathyroid glands, but cancer deposits in bone causing release of Ca2+ from bone)