Endocrine Control of Calcium Metabolism (12) Flashcards
what form is calcium usually found as in the body
calcium salts.
what are the multiple roles of calcium
Neuromuscular excitability. Muscle contraction. Strength in bones. Intracellular second messenger. Intracellular co-enzyme.
Hormone/ neurotransmitter stimulus-secretion coupling. Blood coagulation (factor IV)
where is calcium mainly found
mainly found in bone (99%, approx. 1kg) as complex hydrated calcium salt (hydroxyapatite crystals).
how is calcium present in the blood
as unbound ionised calcium (which is the biologically active component), bound to plasma proteins, or a tiny bit is left as soluble salts. It is present in the blood in dynamic equilibrium
what calcium is bioactive
the free unbound Ca2+
what is the total blood [Ca2+]
~2.5mM. 1.25mM is unbound, 1.13mM is bound and 0.13mM is a soluble salt
what percentage of calcium is bound, unbound or a soluble salt
50% unbound (ionised), 45% bound to plasma proteins and 5% as diffusible salts
how is calcium handled by the body
intake via diet (~1000mg/24hr). then absorbed via GI tract into the blood. Some is excreted as faeces (~850mg/24hr). Once in the blood calcium can pass into the kidneys and regulate the content or the blood. A lot of calcium entering into kidney returns into the blood. Some is lost in urine (~150mg/24hr). The hydroxyapatite crystals in the bone can be broken down to increase blood calcium levels. There is invisible loss of calcium via dead cells, hair, nails etc.
what two hormones increase [Ca2+] in the blood
parathyroid hormone (PTH) and 1,25 - dihydroxycholecalciferol (calcitriol)
what hormone decreases [Ca2+] in the blood
calcitonin
how many parathyroid glands are there
four
where is parathyroid hormone PTH released
the parathyroid gland
where is calcitonin produced
in the parafollicular cells
describe the structure of the parathyroid glands
made up of follicles with parafollicular cells
describe the structure of parathyroid hormone / parathormone/ PTH
initially synthesised as protein pre-pro-PTH. its 84 aa polypeptide. binds to transmembrane G-protein linked receptors. when it binds to the G-protein linked receptor it leads to activation adenylate cyclase, with phospholipase C acting as a 2nd messenger
what are the actions of PTH on the kidneys
Increased Ca2+ reabsorption from tubular fluid in the proximal and distal tubules. Increased PO43- excretion in urine. Stimulates 1a hydroxylase activity which hydroxylases 25 OH Vit D3 to calcitriol (1,25(OH)2D3). The calcitriol then acts on the small intestine
what are the actions of PTH on the small intestine
The 1,25 (OH)2D3 acts to increase Ca2+ absorption into the blood and increase absorption of PO43-. these both lead to an influence in the blood calcium conc.
what are the actions of PTH on bones
stimulates osteoclasts (breakdown). inhibits osteoblasts (rebuilding). this leads to increased bone reabsorption.
what effect does PTH have on blood
PTH causes increased Ca2+ reabsorption and increased PO43- excretion from the kidneys. Increased Ca2+ and PO43- absorption from the small intestine. Increased Ca2+ mobilisation due to increased osteoclast activity. These all lead to increased Ca2+ conc in blood
what is the action of PTH in bone (in detail)
PTH leads to inhibition of new bone formation. It binds to PTH receptor on osteoblasts, which stimulates osteoclast activating factors (OAFs e.g RANKL). The OAFS stimulate osteoclasts to increase bone matrix breakdown and release Ca2+ and PO43+ which leads to increased bone reabsorption.
why doesn’t PTH have a direct effect on osteoclasts
there are no receptors present
how is PTH regulated
decreased plasma [Ca2+] causes increased PTH production in parathyroid glands. This leads to increased plasma [Ca2+]. The increased Ca2+ has a negative feedback on parathyroid glands.
what does increased PTH lead to (with regards to PTH regulaton)
synthesis of calcitriol which leads to increased plasma [Ca2+]. Calcitriol also has a -ve feedback effect on the parathyroid glands to reduce PTH production which then reduces [Ca2+]. Catecholamines stimulate the beta receptors on the cells producing PTH so they secrete more PTH.
How is calcitriol/ 1,25 (OH)2D3 synthesised
its precursor is cholecalciferol (Vitamin D3). Vitamin D3 is a steroid that circulates around the body and is taken up by the liver. enzyme 25-hydroxylase converts it to 25-hydroxy-cholecalciferol which is then stored in the liver. It then circulates from the liver to the kidney. enzyme 1alpha hydroxylase (stimulated by PTH) converts 25-hydroxy-cholecalciferol to calcitriol.
