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Neurons are sensitive to changes in calcium levels. What are the effects of hypercalcaemia and hypocalcaemia on excitation?
- - Hypercalcaemia depresses the nervous system
- Also increased QT interval and constipation.
- - Hypocalcaemia causes excitement and tetany; as the ECF calcium falls <50% of normal, peripheral nerve fibres discharge spontaneously.
- Hypocalcaemic tetany occurs due to increased neuronal permeability to sodium ions, allowing easy initiation of action potentials.
What is the normal daily intake for calcium and phosphorus?
How much of this calcium is actually absorbed?
- - 1000mg/d or 1g/d
- - ~35% of dietary calcium is absorbed by the intestines
Normally, renal tubules reabsorb 99% filtered calcium.
90% of this filtrate is reabsorbed. The remaining 10% is dependent on serum calcium concentration. How does this filtration of calcium occur with reference to tubule locations?
- - 90% of calcium is reabsorbed in the PCT, LoH, early DCT.
- - 10% is reabsorbed in late DCT and CD; this is very selective dependent on serum Ca2+ concentration.
Bone is composed of 30% organic matrix and 70% salts.
What are the components of each of these?
- - Organic Matrix:
- Is 90-95% collagen fibres , remainder is gelatine known as ground substance. Ground substance is composed of ECF plus proteoglycans, esp condroitin sulphate and hyaluronic acid.
- - Bone Salts
- Crystalline salts, namely calcium and phosphate. The major crystalline salt is hydroxyapatite.
- Mg, Na+, K+, CO23- (carbonate) also present in bone salts.
Describe the basic stages of inactive to active formation of vitamin D
- 1. Cholecalciferol (from sunlight or diet)
- 2. 25-hydroxylase enzymes in liver convert cholecalciferol to 25-hydroxycholecalciferol (25-OH-D).
- 3. 1-alpha-hydroxylase enzymes in kidney covert 25-OH-D to 1,25-dihydroxycholecalciferol (1,25-OH2-D)
- NB: This 1,25-dihydroxycholecalciferol is the active form of vitamin D3.
Which 3 tissues does active vitamin D, 1,25-dihydroxycholecalciferol, exert its effects?
- - Intestines
- - Kidney
- - Bone
Active vitamin D promotes intestinal calcium absorption. How does it do this?
- - Increases formation of calcium-binding protein in intestinal epthelial cells. This protein functions in the brush border of these cells to transport calcium into the cell cytoplasm; calcium then moves through basolateral membrane by facilitated diffusion.
- Rate is calcium absorption is directly proportional to quantity of calcium-binding protein.
- - Also involved in formation of Ca2+ ATPase in brush border of epithelial cells.
What type of cell secretes parathyroid hormone?
- Chief cells located within the parathyroid gland.
The kidneys remove much of the full 84 amino acid PTH within minutes of secretion... what are the implications of this?
- That the physiological activity is mainly exerted by the PTH fragments which remain in the blood for hours, not PTH itself.
What effect does PTH have on renal phosphate excretion?
- It increases phosphate excretion
PTH-mediated rise in blood calcium is caused principally by what 2 effects?
- 1. PTH increases calcium and phosphate absorption from bone
- 2. PTH decreases excretion of Ca2+ by kidneys
PTH causes removal of bone salts from two areas of the bone. Which are they?
- 1. Bone matrix in vicinity of osteocytes lying within bone itself
- 2. Vicinity of osteoblasts lying along bone surface
How does PTH cause removal of bone salts?
- 1. Cell membranes of both osteoblasts and osteocytes have receptors for PTH.
- 2. PTH activates calcium-pump, causing removal of calcium-phosphate salts.
How does PTH exert its effects with respect to cellular signalling/messenger systems?
- - Largely mediated by cAMP second messenger system
- - Within minutes of administration, concentration of cAMP in osteocytes, osteoclasts and other target cells increases.
- - This cAMP, in-turn, is probably responsible for osteoclastic secretion of enzymes and acids to cause bone reabsorption and formation of 1,25-dihydroxycholecalciferol in the kidneys.
Where is calcitonin released from?
- C-cells of the thyroid gland
Which is a far more potent controlling hormone of calcium homeostasis, calcitonin or PTH?
- PTH by far
Why is ALP (alkaline phosphatase) raised in hyperparathyroid patients?
- 1. Osteoblast activity increases greatly in attempt to compensate for the old bone being reabsorbed by oesteoclasts.
- 2. When osteoblasts become active, they secrete large quantities of ALP.
Where is vitamin D stored?
- In the liver. Can take months for deficiency to manifest; before stores from the liver are used up.