1519546
Description
Flashcards by Hannah Tribe, updated more than 1 year ago
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Created by Hannah Tribe
over 9 years ago
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| Question | Answer |
| What are the main functions of calcium in the body? (6) | 1. Bone growth/remodelling (mineralisation) 2. Muscle contraction 3. Stabilisation of membrane potentials 4. Secretion of hormones etc. 5. Enzyme co-factor (e.g. in blood clotting) 6. Second messenger |
| In which forms does phosphate exist in the body? | HPO4(2-) and H2PO4- |
| What are the functions of Pi? (5) | 1. Formation of high energy compounds that can be used to provide energy (ATP and creatine phosphate) 2. Formation of signalling molecules (cAMP) 3. Intracellular anion 4. Component of DNA, RNA and phospholipid membranes 5. Bone mineralisation |
| How is calcium distributed in the body? | 99% is in the skeleton 0.1% is within cells 0.99% is extracellular (45% as Ca++, 45% bound to plasma proteins, 10% bound with ions to form salts) |
| What is the distribution of phosphate in the body? | 90% in the skeleton 9.97% is within cells 0.03% is extracellular (50% is free, 50% bound) |
| Which processes determine the net balance of calcium and phosphate in the body? (4) | 1. Their absorption from the gut 2. Their excretion as faeces 3. Their retention or excretion through the kidneys 4. The rate of bone metabolism |
| What is 'corrected calcium' on a blood test? | This is the level of Ca++, adjusted as if albumin levels were normal (in case the high or low levels of calcium is simply due to albumin problems rather than calcium problems) |
| The bones act as a __________ of calcium | Buffer |
| What causes the storage of calcium/phosphate in bones and what causes its removal from bone? | Osteoblasts lay down and mineralise the bone, and osteoclasts resorb it. |
| What causes osteoclasts to be differentiated from stem cells? | Osteoblasts produce RANK ligand, which binds to RANK receptors on the osteoclast precursors and activates nuclear kappa beta, which alters gene transcription to stimulate differentiation into osteoclasts. |
| What are the general actions of PTH? (2) | 1. Raise blood calcium levels by stimulating increased calcium reabsorption from the kidneys, increasing bone resorption and increasing calcium absorption in the gut by stimulating synthesis of active vit D in the kidney. 2. Decrease serum Pi levels by increasing its excretion from the kidneys (directly, by internalisation of the sodium/phosphate transporters in the PCT, and indirectly by stimulating bone to secrete FGF23, which also acts on the kidney) |
| How does PTH work to increase calcium release from bone? | PTH stimulates osteoblasts to produce and release RANK ligand, which binds to stem cells to stimulate nuclear factor kappa beta and cause gene transcription that leads to the differentiation of osteoclasts, which resorb the bone and release calcium |
| How is secretion of PTH contolled? (2) | 1. Calcium sensing receptors in the parathyroid gland detect circulating levels of calcium, and when this rises too high, a GPCR system inhibits the secretion of PTH 2. High levels of active vitamin D also inhibit the synthesis of PTH. |
| Where else can calcium sensing receptors (CaSRs) be found and what is their action? (2) | 1. In the kidney, activation of CaSRs (by raised levels of calcium) caused increased secretion of calcium into the urine. 2. In the thyroid gland, raised serum calcium activates the CaSRs and stimulates the release of calcitonin, which lowers calcium levels. |
| What is the main function of vitamin D? | increase serum calcium levels |
| How does vitamin D achieve this? | Vitamin D binds to vitamin D receptors (VDRs) on the nucelar membranes of cells (can travel through cell membranes as they are steroid hormones) and stimulates a cascade that leads to gene transcription. In the intestinal mucosa, it causes expression of the Ca++ transporter TRPV (on apical side) and Ca++ATPase (basolateral side) to increase reabsorption. |
| In bone, there are VDRs on _______________, which stimulate the _____________ of calcium to the bone for ________________. | osteoblasts, delivery, mineralisation |
| What other 2 actions does vitamin D have? | 1. Inhibits the synthesis of PTH via negative feedback if serum calcium levels are too high. 2. Stimulates the synthesis of FGF-23 |
| What does FGF-23 do? | Fibroblast-like growth factor is a hormone released mainly from osteoblasts, which acts on the kidney (on tyrosine kinase receptors) to down-regulate the expression of sodium/phosphate transporters, causing increased phosphate excretion when serum Pi levels are high. It also inhibits the synthesis of vitamin D via negative feedback. |
| What is the name of the endogenous, inactive form of vitamin D and where is it found? | Cholecalciferol, in the skin |
| How is it made? | The precursor to cholecalciferol is converted to it by the action of UVB rays from the sun |
| What happens to the cholecalciferol next? | It is taken in the bloodstream to the liver (bound by protein), where it is hydroxylated using P450 enzymes to 25-hydroxyvitamin D3. |
| What happens to 25-hydroxyvitamin D3? | It is transported from the liver to the kidneys, where it undergoes a further hydroxylation under the action of 1-alpha hydroxylase (primarily found in the PCT cells) to give the active form of vitamin D, calcitriol (1,25 dihydroxyvitamin D) |
| What controls the synthesis of vitamin D? (3) | 1. PTH stimulates its synthesis 2. FGF-23 inhibits its synthesis 3. It regulates its own activity via negative feedback |
| What are the consequences of vitamin D deficiency? (3) | 1. Increased PTH production (secondary hyperparathyroidism) 2. Increased bone resorption (to try and raise serum calcium) 3. Decreased mineralisation of bone = osteomalacia (due to excess PTH causing increased Pi excretion and therefore lack of calcium phosphate to form hydroxyapatite crystals) |
| What is calcitonin? | A peptide hormone produced in the thyroid gland (parafollicular C cells) in response to hypercalcaemia. It decreases bone resorption. |
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