Ca2+ homeostasis Flashcards
What hormone regulates Ca2+
Parathyroid hormone from parathyroid gland
What is the function of Ca2+
Structural integrity of skeleton and tooth enamel
Neurotransmitter release.
Blood coagulation
What is hypocalcaemic tetany?
Extracellular Ca2+ falls below normal, nervous system becomes progressively more excitable due to increased permeability of Na+ - this causes tetanic contraction
What are the 3 ways in which calcium exists?
Ionised (free Ca2+), anion complex (CaCO3), bound to albumin or globulins
What happens to calcium absorbed into the gut through the diet?
80% excreted in the faeces. 35% absorbed by the extracellular fluid, 15% secreted back into the gut from the extracellular fluid
What happens to ca2+ absorbed into the extracellular fluid?
Some secreted back into gut, the rest is excreted in the urine
What is the rapidly exchangeable pool?
Ca2+ on the surface of the skeleton, they are always being exchanged
What occurs to Ca2+ in the rapidly exchangeable pool?
Bone formation - from pool to bone.
Bone resorption - from bone to pool
What are the 3 major target organs of Ca2+?
Intestine
Kidney
Bone
How is calcium absorbed from the intestine passively?
Across layer of epithelium, down the concentration gradient, between cells = paracellular pathway. This occurs in the ileum
What is the transcellular pathway of absorption in the intestine?
Calcium ions taken up into the cell by diffusion and bind to calcium binding proteins to maintain concentration gradient, at the other end calcium gets released and is pumped out of the cell against the concentration gradient using ATP. This occurs in the duodenum and jejunum
How is Ca2+ reabsorbed in the proximal tube in the kidneys?
Transcellular pathway
How is Ca2+ reabsorbed int he loop of Henle in the kidneys?
Paracellular pathway
How is Ca2+ absorbed in the distal tubule of the kidneys?
Transcellular pathway
Why is the transcellualr pathway in the distal tubular important?
Ca2+ uptake can be regulated by parathyroid hormone
What is bone remodelling?
The constant formation and resorption of bone
In which area of bone does bone remodelling occur?
Trabecular bone
What are the areas of bone?
Trabecular and compact
Why does calcium exchange occur on the trabecular bone?
Greater SA as it is spongy
What is the function of osteoblasts?
Bone forming cells that secrete organic bone matrix (osteoid) on which mineralisation occurs
What is the function of osteocytes?
Mature bone cells enclosed in bone matrix. They are connected to other cells via cannaliculi to allow for nutrient and ion exchange
What is the function of osteoclasts?
Large multinucleate cells that resorb bone
From what cell type are osteoclasts derived?
Monocytes
What 3 hormones function in Ca2+ homeostasis?
Parathyroid hormone (PTH)
1,25 DHCC
Calcitonin
Where is PTH synthesised and secreted?
Parathyroid gland (behind thyroid gland)
What cells int he parathyroid Galen are the site of PTH synthesis?
Chief cells
How does pTH become active?
It is first formed as a pre-prohormone which is cleaves to form PTH
What is the main effect of PTH on Ca2+ concentration?
Increases plasma Ca2+
When is PTH stimulated for release?
low levels of Ca2+ in blood
What is the mechanism of action of PTH on bone?
Increases the number of osteoclasts and increases osteoclast activity to increase bone resorption. Decreases bone formation by decreasing collagen synthesis by osteoblasts
What is the mechanism of action of PTH on the kidneys?
Acts to increase Ca2+ resorption in the distal tubule by increasing ca2+ uptake into cells.
Stimulates 1-alpha-hydroxylase which catalyses the formation of 1,25DHCC
What is the mechanism of action of PTH on the intestine?
indirect action by stimulating 1,25DHCC
How is 1,25DHCC formed?
From vitamin D to the liver where is is converted to 25 HCC, to kidney where PTH stimulates 1-alpha-hydroxylase which converted 25HCC to 1,25DHCC
What is the mechanism of action of 1,25 DHCC?
Main affect on the intestine to increase Ca2+ absorption from the intestine by increasing number of calcium binding proteins.
What is the mechanism of action of 1,25 DHCC on the kidney?
Increases tubular reabrotpion of CA2+ = minor affect
What is the mechanism of action fo 1,25 DHCC on bone?
Promotes the actions of PTH = bone resorption
PTH promotes the synthesis of 1,25DHCC and 1,25 DHCC promotes the effects of PTH. How is this controlled?
1,25 DHCC inhibits the production of PTH
What is the effect of calcitonin?
Decrease plasma Ca2+ levels
Where is calcitonin synthesised and secreted?
Parafollicular cells of the thyroid gland
What is the main target cell of calcitonin?
Osteoclasts
What is the affect of calcitonin on bone?
Inhibit osteoclast motility and cell shape to inactivate them so bone respotion can’t occur
What is the effect of calcitonin on kidneys?
Decrease tubular reabsorption oF CA2+ but this is a weak affect
Why does excess calcitonin not produce hypocalcaemia?
PTH and 1,25 DHCC dominate
What is osteoporosis?
Reduced bone mass and density
What causes osteoporosis?
Uncoupling of the equilibrium of bone formation dn resorption
In osteoporosis does bone formation exceed bone resorption?
No, other way around
Is bone present in osteoporosis biochemically normal?
Yes
What causes rickets?
Inadequate mineralisation of bone matrix
What causes hypercalcaemia?
Excess PTH or 1,25DHCC
