Calcium Homeostasis Flashcards
What processes involve Ca2+?
Bone mineral formation as hydroxyapatite.
Blood clotting.
Muscle contraction - activate or inhibit enzymes.
Excitability of the NMJ.
What should the normal Ca++ intake be?
1g per day. Less if female and more if lactating.
When is the absorption of calcium highest?
Childhood, pregnancy and lactation.
What are 3 promoters of calcium absorption?
Lactose
basic AA
Vit D
Name an inhibitor of Ca++ absorption
Phytic acid (IP6)
What is plasma concentration of Ca++ (and breakdown values).
2.5mM.
1.2mM = free, 1mM = plasma proteins 0.3mM = in complexes (eg with citrate).
Hypocalcaemia and it’s effects - what is lethal?
Hyperexcitability of NS, tetany, <1.5mM lethal.
Because at low [Ca] Na+ channels work best.
Hypercalcaemia and it’s effects - what is lethal?
Sluggish NS responses, ectopic calcification
>3.75mM lethal.
Explain parathyroid hormone release.
Released when blood Ca++ is low.
2 pathways - 1 inhibited and one activated.
1) PLC - IP3 - inhibition of secretion
2) AD-Cyc - cAMP = PTH secretion.
Low Ca++ - PLC pathway inhibited and AC pathway activated - PTH secretion
Explain how secreted PTH has its effects on bone…
PTH binds to osteoblast receptor…activates AC…increase cAMP…collagen synthesis is inhibited and osteoblasts release cytokines which bind to receptors in osteoclasts…release Ca++ and PO4-…release H+ and collagenase…resorbs bone…blood Ca++ increased. As is Pi…but effect on kidney….
Explain PTH effect on kidney
Increase Ca reabsorption.
Decrease Pi reabsorption. Increase excretion.
activate 1alphahydroxylase - which activates vitamin D.
Hyperparathyroidism?
Due to gland hyperfunction/hyperplasia
Hypercalcification due to excessive bone resorption. And ectopic calcification.
Hypoparathyroidism?
surgical removal of parathyroid glands.
Pseudoidiopathic - mutant PTH
Pseudohypoparathyroidism - post receptor defect
Hypocalcaemia.
Explain the action of calcitonin.
Decrease blood Ca++ and decrease blood Pi.
Formed in C/parafollicular cells of thyroid.
Released in response to high Ca++.
Act on osteoclasts via cAMP - suppress activity - no bone resorption.
In pregnancy - protect maternal skeleton.
Neonate (milk diet) - protect against sudden ca influx.
Explain how RANKL is produced and acts.
if low blood Ca++…osteoblasts produce RANKL which binds to RANK and causes osteocytes to activate and resorb bone…increasing Ca++.
What happens if oestrogen is present?
Increase in osteoprotegrin…binds RANKL so it can’t bind RANK and it can’t resorb bone.
What does RANK stand for?
Receptor activator of nuclear factor kappa-B.
Explain how vitamin D has its effects.
VItamin is either obtained via UV to the skin or in the diet. It is then converted by 25 hydroxylase in the liver to 25-OH-D. It is then converted in the kidney by 1 alpha hydroxylase to 1-25 (OH)2-D or if Ca++ excess and Pi excess to 24,25-(OH)2-D…
1,25-(OH)2-D inhibits growth and increase Ca and Pi.
How does vitamin D act on bones?
Vit D binds to receptors on osteoblasts….production of cytokines which bind to osteoclasts - bone resoprtion!
Also cause the differentiation of precursors to osteoblasts and osteoclasts.
What are the actions of Vit D on the kidney.
Genomic - steroid hormone - intracellular receptor…DNA…promote synthesis of proteins (including calbindins).
Non-genomic - direct effect on cell membrane to activate VOCC and increase Ca entry.
What is a Vit D deficiency in childhood?
Treatment?
Rickets - protruding forehead, pigeon chest, kyphosis and bending of long legs.
Treatment - fish oils and sun exposure.
Vit D deficiency in adulthood?
Osteomalacia.
Primary - dietary deficiency - low synthesis in skin.
Secondary - vit D resistant…bile duct obstruction, coeliac disease, liver disease and renal disease.
Who are at risk of vitamin D deficency?
Infant born in north negland or scotland in the winter and are breast fed by vit D resistant mothers.
Too much suncream.
Asian women and children.
Elderly and house bound - 10mg/day supplementation.
What other hormones affect Ca++ homeostasis?
Oestrogen deficiency (menopause) = osteoporosis.
Testosterone deficiency.
GCS - decrease Ca absorption and increase excretion.
Thyroid hormones - increase bone resorption.
Compare and contrast osteomalacia and osteporosis.
Osteomalacia - normal amount of bone, low mineral:matrix ration.
Osteoporosis: less bone but normal mineral:matrix ratio.
What are the risk factors for osteoporosis?
Menopause
Race - affects bone density (black>white>asain)
Family history
Physical activity
Nutrition (calcium is good. sodium, high protein and caffeine are bad).
Corticosteroids (inhibit osteoblasts).
What is the treatment for osteoporosis?
1200mg/day Ca++
Oestrogen replacement therapy.
Oestrogen receptor modulators.
Bisphosphonates (inhibit osteoclasts).
