Calcium metabolism Flashcards
Calcium: list the physiological functions of calcium; list the principle causes of hypocalcaemia and hypercalcaemia. Endocrine control of calcium; recall the principle hormones which regulate serum calcium concentration, their physiological effects, their mechanism of action and their regulation. Phosphate: recall the regulation of phosphate reabsorption Hyperparathyroidism: recall the differences between primary, secondary and tertiary hyperparathyroidism
Where are the parathyroid glands relative to the thyroid?
Humans usually have four parathyroid glands. Found behind the thyroid – indicated by the green dots.
What are the roles of calcium in the body? (x7)
NEUROMUSCULAR EXCITABILITY – in the synapse. Muscular contraction – from the SER. Strength in bones – made primarily of complex calcium salts. Intracellular second messenger Intracellular co-enzyme Hormone/neurotransmitter stimulus-secretion coupling – important in neuroendocrine physiology. Blood coagulation (factor IV)
How is calcium found in the bone?
As complex hydrated calcium salt (hydroxyapatite crystals).
How is calcium found in the blood? (x3) Which is active?
Some present as ionised Ca2+. Some bound to protein. Some left as a soluble salt. ONLY the free unbound Ca2+ is active.
What is the percentage of bound and unbound calcium in the blood? What is the total concentration?
2.5mM 50% unbound. 45% protein bound.
What are the four biological outputs of calcium in the body? In order.
Faeces Urine Bones Invisible loss – dead cells, hair nails.
What hormones increase Ca2+ in the blood? (x2)
Parathyroid hormone (PTH OR Parathormone) 1,25(OH)2 Vitamin D3 (Dihydroxy-cholecalciferol OR CALCITRIOL).
What hormone decreases Ca2+ in the blood?
Calcitonin.
Where are each of the hormones responsible for [Ca2+] regulation synthesised?
PTH synthesised in the parathyroid hormones. Calcitonin is synthesised in the thyroid – by parafollicular cells which surround the follicular cells and colloid (that synthesise thyroid hormones) As seen in the photo. Calcitriol produced in the kidneys.
Where are calcium sensing receptors found? (x3)
Mainly on the parathyroid glands. Also in the kidneys and GI tract.
What type of receptor is the calcium sensing receptor?
G-protein coupling receptor.
How does the calcium sensing receptor work? (x3 areas)
High calcium levels. Calcium binds to the receptor and activates it. In the parathyroid, it suppresses PTH release. In the kidneys, Calcitriol is suppressed, and more is excreted in the urine. In the GI tract, less Calcium is absorbed back into the blood.
What happens when calcium levels drop?
Receptors are deactivated, so parathyroid glands produce more PTH to increase blood concentration.
How is the parathormone synthesised?
Initially synthesised as pre-proPTH.
Describe the relationship of PTH on bone, kidneys and the small intestine.
Direct, direct and indirect effect. Respectively.
What are the actions of PTH on your kidneys? (x3) Why does it affect phosphate?
It increases Ca2+ reabsorption (back into the blood). Stimulates 1alpha hydroxylase (a receptor). This is important in synthesising 1,25(OH)2 Vitamin D3. So, 1,25(OH)2 D3 synthesis increases.
In the kidneys, it increases excretion of PO43- in the urine. One of the key calcium salts in bone is Calcium Phosphate (Ca3(PO4)2). PTH breaks down this salt in bones, which means that phosphate levels rise in the blood. Calcium and phosphate homeostasis is therefore coregulated. PTH also decreases phosphate levels as a result.
What are the actions of PTH on bones?
Bone turnover is controlled by osteoclasts (bone break down) and osteoblasts (building bone up). PTH stimulates osteoclasts and inhibits osteoblasts. This increases bone resorption – freeing the calcium trapped in the bone, into your blood.
What are the indirect actions of PTH on the small intestine?
PTH increases synthesis of Calcitriol in the kidneys. This calcitriol acts on the small intestines and increases calcium AND phosphate absorption from the small intestines (this is despite PTH decreasing levels of phosphate in the kidneys). It tries to get more calcium out of your diet and into your blood.
How – physiologically – does PTH interact with the bone to increase calcium mobilisation?
PTH binds to PTH receptor on osteoblasts. Osteoblasts regulate the other cells in the bone. When receptor activated, Osteoclast activating factor (OAFS) are produced by the osteoblasts. This stimulates the osteoblast = bone resorption. Give an example of an OAF. RANKL – receptor activator of nuclear factor kappa-B ligand.
How is PTH synthesis and release regulated?
- PTH increases [Ca2+]. This has a negative feedback on the parathyroid gland which activates calcium sensing receptors, thus inhibiting parathyroid and PTH production and release. 2. Increased Vitamin D3 (Calcitriol) also negatively feedbacks on PTH (by decreasing [Ca2+] and inhibiting the parathyroid). 3. Catecholamines stimulate parathyroid via beta receptors. Catecholamines are neurotransmitters. This is an example of nervous control of PTH levels. 4. AND obviously, decreased [Ca2+] stimulates the parathyroid.
How is dihydroxy-cholecalciferol synthesised?: what is the preceding chemical of dihydroxy-cholecalciferol and what are it’s sources? (x2)
Cholecalciferol is obtained from diet, and 7-dehydroCHOLESTEROL in the skin which is manufactured to cholecalciferol by UV light.
How is dihydroxy-cholecalciferol synthesised?: from cholecalciferol. (x2 stages)
Cholecalciferol is also called Vitamin D3. Converted to and stored as 25 hydroxy-cholecalciferol in the liver. Also called 25(OH) D3. When 1alpha-hydroxylase is stimulated by PTH, 25 hydroxy-cholecalciferol is converted into 1,25 dihydroxy-cholecalciferol (OR 1,25(OH)2 D3 OR Calcitriol) in the kidneys.
What are the additional actions of Calcitriol? (x2)
(As well as increased Calcium and phosphate absorption from the small intestines – this is its main action!) Calcitriol increases osteoblast activity which increases bone synthesis and actually decreases calcium levels in the blood. This is because, the effects of Calcitriol are more long-term and chronic: it doesn’t just restore calcium levels, it restores bones too. In the kidneys, it increases Calcium and phosphate in the KIDNEYS – both will couple to form bone.
What does fibroblast growth factor 23 do?
FGF-23 regulates phosphate metabolism. If phosphate goes too high, FGF-23 is stimulated which mostly affects the kidney to decrease phosphate.
How does FGF-23 decrease phosphate levels in the blood? What hormone also has the same physiological affect?
It inhibits phosphate reabsorption in the kidney by affecting the Na+/PO43- co-transporter which reabsorbs phosphate back into the blood. FGF-23 (and PTH [we mentioned that PTH does this earlier]) inhibits the cotransporter which therefore inhibits phosphate reabsorption. Means that more sodium and phosphate is released in the urine instead.
What feedback system regulated FGF23?
FGF-23 is stimulated by increased levels of calcitriol (calcitriol increases phosphate). Increased FGF-23 also inhibits calcitriol. This is a negative feedback system that controls your phosphate levels in the blood.
What are the actions of calcitonin?
Decrease Calcium levels in the blood. ACTS ON BONE – inhibits osteoclast activity (which breakdown bone). ACTS ON KIDNEY – increases urinary excretion of calcium (sodium and phosphate).
What is calcitonin production in the parafollicular cells stimulated by?
Increased calcium concentration in the blood. Gastrin – hormone secreted by the stomach and pancreas.
Why does calcitonin have limited effect compared to the hormones that increase calcium levels?
Because low calcium is more common, and the biological effects are more severe than hypercalcemia. This also explains why there are two hormones responsible for increasing blood calcium.
What are the causes of hypocalcaemia? (x3)
Hypoparathyroidism. Pseudohypoparathyroidism – body does not respond to the parathyroid hormone. Vitamin D deficiency.
What are the causes of hypoparathyroidism? (x3)
IDIOPATHIC – meaning unknown cause. This is the main cause. Hypomagnesaemia – needed for parathyroid function and PTH release. Surgery – removing thyroid may remove parathyroid accidently.
What does vitamin D deficiency also cause?
Rickets in children. Osteomalacia in adults. Main clinical feature is decreased calcification of bone matrix resulting in softening of bone or bowing of bones in children, and fractures in adults.
How may hypoparathyroidism, pseudohypoparathyroidism and vitamin D deficiency be differentially diagnosed?
Not in specification. Just quite a cool thing to know. And actually quite simple.
What are the causes of hypercalcaemia?
Primary hyperparathyroidism. Tertiary hyperparathyroidism. NOT SECONDARY HYPERPARATHYROIDISM (this is actually associated with hypocalcaemia). Vitamin D toxicosis.
What is the difference between primary, secondary and tertiary hyperparathyroidism?
PRIMARY: Adenoma growing in the parathyroid, so PTH increases, and increased Ca2+. Because of this adenoma, the negative feedback mechanism is broken, and you keep on releasing PTH even though your calcium is high.
SECONDARY: Where your calcium levels are low, but your body does not respond to increased PTH. So PTH continues to be secreted, but it cannot fully restore calcium levels. Caused by kidney disease – means Calcitriol is not produced and you cannot increase reabsorption back into the blood. An additional cause if malnutrition – there is no extra calcium in the body for the PTH to affect so Ca2+ stays low.
TERTIARY: People previously have secondary hyperparathyroidism. In secondary, the parathyroid grows and more PTH produced. Occurs when the cause of your secondary hyperparathyroidism (e.g. kidney disease) is cured. Because the parathyroid has been hyperactive for so long, it no longer responds effectively to negative feedback systems. PTH continues to be released even though calcium levels are high. This is similar to primary hyperparathyroidism.
