Calcium Flashcards
What does parathyroid hormone do in terms of calcium?
Regulates extracellular fluid ca2+, which negatively regulates parathyroid hormone
Tightly regulated.
Vitamin D is also regulated by parathyroid hormone
What form is Ca2+ in in the extracellular fluid?
50% free (ionized) form. This is the bioactive form. It regulates PTH.
40% is protein bound, mostly to albumin.
10% complexed with anions, sch as bicarbonate
Where is Ca2+ and phosphate stored and what causes it’s excretion from the body?
The bone and kidneys
Both absorbed in the intestines too.
What produces PTH and how?
Chief cells in the parathyroid glands produce PTH.
Ionized calcium bind to a G-protein coupled receptor (CaR) in chief cells causing negative regulation of PTH production and secretion.
Released in response to reduction in serum calcium.
What does PTH do?
It modulates the levels of serum calcium and phosphate to restore normal.
It stimulates osteoclast bone reabsorption.
Increasing phosphate and Ca levels
It acts on the renal tubule to stimulate reabsorption of Ca2+
Increases Ca reabsorption and decreasing phosphate reabsorption
Long loop (indirect): Stimulates the generation of bioactive Vitamin D (1,25 dihydroxyvitamin D) - stimulates intestinal calcium and phosphate absorption.
WHat regulates PTH production?
Serum ionized calcium (negative regulation)
Serum phosphate (positive regultor)
Serum 1,25 dihydroxyvitamin D (negative)
How is Ca levels in the renal tubule regulated?
The CaR is on the basolateral side of the tubule and is bound by Ca2+.
If not bound by Ca2+ then it stops inhibiting the activation of the Na/2Cl/K+ channel, the Ca2+ channels, and the K+ channel (opposite flow direction) on the lumen side of the nephron. This increase Ca2+ reabsorption.
How is the active form of vitamin D created?
In the kideny, 25 hydroxyvitiminD -> 1,25 hydroxyvitimin D
PTH promotes the conversion of the second reaction by stimulating the enzyme 1 alpha hydroxalase. Phosphae reduces the activation of this enzyme.
Does calcitonin regulate Ca2+?
no
What does parathyroid hormone-related peptide (PTHrP) do?
Has paracrine function and regulates breast, skin and bone development.
Not a physiological regulator of Ca.
Produced in excess by some cancers. Can mimic the actions of PTH when produced in very high levels, such as by a tumour, causing hypercalcaemia. In these cases it does regulate Ca2+
What are the causes of hypercalcaemia?
1) PTH dependent (increase in serum Ca2+ and high levels of PTH).
Common PTH-dependent causes are primary hyperparathyroidism - almost always caused by an adenoma of one of the PTH glands. Occasionally caused by hyperplasia of the parathyroid hormone.
Familial benign hypercalcaremia: Mutation of the CaR in the chief cells - causes chief cells to always think the receptor is not being stimulated by Ca2+ -> PTH production and secretion.
2) PTH - independent (increased serum calcium but no elevation in PTH).
2a) main cause is cancer, most common is a parathyroid hormone-related peptide secreting tumour but can also be caused by a cancer in the skeleton causing reabsortion of bone Ca, with impaired excretion (such as kidney failure). Multiple myeloma is a common version of this.
Tumour.
2b) vitamin D dependent PTH independent
- A tumour expressing the 1-alpha hydroxylase enzyme that converts 25-hydroxyvitimin D into 1,25 hydroxyvitimin D resulting in more intestinal Ca2+ reabsorption from the diet.
- sarcoidosis - increase in 1-alpha hydroxylase enzyme -> more 1,25 dihydroxyvitamin D -> more absorption of Ca from the intestines
- Vitamin D intoxication
What are the causes of hypocalcaemia?
Hypoparathyrodisim is the main cause:
Thyroid surgery causing damage to the parathyroid glands.
X-ray therapy to head and neck -> damage parathyroid function.
Autosomal dominant hypocalcaemia (ADHH) Hyper function mutations in the Ca sensing receptors -> decreased PTH production
Low levels of Mg impairs the ability of the parathyroid gland to respond normal to Ca signalling.
Autoimmunity can cause hypoparathyroidism.
Ion accumulation: Wilson’s disease (copper) and beta thalassaemia (iron).
Parathyroid hormone resistance - can produce but the cells won’t respond to PTH. Lots of PTH produced but low Ca2+ levels.
Abnormalities in Vitamin D metabolism.
Vitamin D deficiency - sunlight deprived. Impaired absorption form the intestine (coeliac disease)
Advanced renal failure - can’t produce the 1 alpha hydroxalase enzyme form of vitamin D production. (check renal function in those with Ca deficiency)
What regulates phosphate levels in the extrcellular fluid?
Intestinal absorption - regulated by 1,25 hydroxyvitamin D.
Bone reabsorption induced by PTH and vitamin D
Kindney excretion - increased excretion of phosphate by PTH and phosphatonins (fibroblast growth factor 23 (FGF23)
Increased excretion of phosphate causes impaired bone mineralization.
Where does phosphate come from and go?
Diet - vitamin D important
The flux between intracellular and extracellular fluid - Respiratory alkalosis can cause phosphate to go intracellular
Kidney regulates phosphate - responsible many causes of hypo/hyperphosphatemia
What are the causes of hyperphosphatemia?
Increased input - IV phosphate, cell death (wide tissue necrosis)
Decreased output - renal failure, PTH deficiency or resistance
