Calcium homeostasis Flashcards
Symptoms of hyocalcaemia
Neuromuscular irritability
Muscle cramps/tetany
Seizures
Acute neuromuscular symptoms treated with IV calcium gluconate. Chronic hypocalcaemia treated with oral calcium+vit D
How does hypocalcaemia affect the ECG
In severe hypocalcaemia, there is a prolonged QT interval
Symptoms of hypercalcaemia
Kidney stones Ectopic calcification
Loss of bone
Muscle weakness
Nausea, vomiting, tiredness, muscle weakness, confusion
Treated with fluids, loop diuretics. Can also give calcitonin, bisphosphonates
Which cells in the parathyroid gland make PTH
chief cells.
How are free Ca2+ levels affected by pH
Most Ca2+ in the blood is bound to albumin and other plasma proteins.
Free ionised [Ca2+] is regulated by hormones, and is involved in physiological reactions. The ratio of free:bound Ca2+ is determined by pH. Increased [H+] reduces Ca2+ binding, low levels increase binding. [Ca2+] is raised in acidosis.
What are the actions of PTH
Acts via GPCRs coupled to cAMP. This activates PKA and alters gene expression. All effects increase [Ca2+]
Bone: PTH activates OBs which stimulate OC and therefore increase bone resorption.
Kidney: Activates synthesis of vitamin D3 from vitamin D. This is the precursor for calcitriol (active vitD). Increases absorption of Ca2+ from teh distal nephron (90% of Ca2+ reabsorption occurs in the PCT). Reduces PO2 reabsorption.
GIT: Increases absorption of Ca2+ and PO4 by stimulating the transcription of 1a-hydroxylase in the kidney. This catalyses the synthesis of calcitriol.
Symptoms of hypoparathyroidsim
Paraesthesia in the lips, fingers and toes
Tetany
Lack of PTH leads to low blood Ca2+ and high PO4. Low Calcium increases neuromuscular excitability. Reduced excitability of cardiac muscle can precipitate first degree heart block.
Primary and secondary hyperparathyroidism
Excess PTH activity causes increase blood [Ca2+] and reduced PO4.
Primary hyperparathyroidism is caused by excess PTH secretion e.g. adenomas
Secondary hyperparathyroidism results from vitD deficiency or renal failure (cannot make vit D)
What are the actions of calcitonin
Calcitonin lowers blood Ca2+ and PO4 by inhibiting the activity of OCs. Prevents excessive resorption of bone. Important for short term regulation of Ca2+
How does kidney disease cause hyperparathyroidism?
Paitents with impaired renal function cannot make vitamin D3. Deficiency in vitamin D causes hypocalcaemia, which activated the parathyroid glands to release PTH.
Increase in PTH doesn’t increase vitamin D production, so there is no increase in Ca2+ absorption. No negative feedback on the parathyroid, and hormone release is increased.
Because PTH effects on the kidney is lost, PTH effects on the bone are increased. Causes increase Ca2+ loss from bone
What is tertiary hyperparathyroidism?
Long term problem associated with renal failure.
Parathyroid glands become desensitised to Ca2+ and vitamin D through loss of receptors and therefore there is loss of negative feedback. This means even if Ca2+ and vitamin D levels are corrected, PTH is produced.
What are the actions of calcitriol on Ca2+ homeostasis
Increases Ca2+ and PO4 in the ECF by acting on the intestine, bone and kidney.
Intestine: Increases the active transport of Ca2+ and phosphate across epithelial cells of the small intestine by stimulating the tran
Bone: Increases the activity of OCs to promote bone reabsorption which mobilises Ca2+ and PO4 for mineralisation. Deficiency results in inadequate mineralisation of bone.
Effects of PTHrP
Parathyroid hormone related peptide
Made by many tissues. Involved in mobilising Ca2+ for the foetus during pregnancy. Secreted by cancers.
Cause hypocalcaemia
Describe the absorption of Ca2+ from the gut
Calcium (and phosphate) are absorbed primarily by the small intestine by active transport and diffusion. Active transport is regulated by vitamin D.
- 1,25OHD3 (calcitriol) increases Ca2+ uptake by enterocytes (TRPV6),
- increases Ca-ATPase on enterocytes on the basolateral memebrane. It als
- increases the number of CaBP in intestinal mucosal cells, enhancing the capacity of cells to transport Ca2+.
Describe the synthesis of vitamin D
The active form of vitamin D (calcitriol) is 1,25OHD3
Vitamin D can be provided by the diet (D2), or formed in the skin by the action of sunlight on 7-dehydrocholesterol (D3)
Vitamin D3 and D2 are inactive. They travel to the liver where they are transformed to 25-OHD3. This is released into the blood and is hydroxylated by 1alpha- OHase in the kidney to produce active vitamin D.
The activity of 25-hydroxylase in the liver is unregulated, and determined by substrate concentrations. Activity of 1a-OHase is stimulated by PTH.
