Session 11: Calcium Metabolism Flashcards
How much calcium does an adult human contain? Where can it be found?
Around 1000g of calcium. 99% of it is found in bone in the form of hydroxyapatite crystals. Around 1% is found in ECF (plasma calcium levels)
Serum calcium levels.
Around 2.2-2.6 mM or mmol/L
Free calcium ([Ca2+]) levels in blood.
Around 1.0-1.3 mM or mmol/L
How is calcium transported in the body?
~45% bound to protein (albumin) ~45% free calcium (Ca2+) ~10% complexed with low-molecular-weight organic ions like Pi and citrate.
Give roles of calcium.
Intracellular signalling pathways Nerve transmission Builds and maintains bone and teeth Regulate heart rhythm Eases insomnia Helps regulate passage of nutrients in and other of cell walls Assists in normal blood clotting Helps maintain proper nerve and muscle function Lowers BP Important to normal kidney function Needed for activity of some enzymes and some hormone receptor binding. Reduces blood cholesterol levels Reduces incidence of colon cancer.
Why is additional calcium given in major blood transfusions?
Because citrate is put into blood bags so the calcium doesn’t coagulate the blood. Citrate chelates calcium ions in the blood bags. So if you give a lot of blood all that blood will have the calcium bound to citrate and they will be prone to bleeding and other problems resulting in hypocalcaemia if you don’t give calcium at the same time.
Hormones important in regulation of calcium and phosphate.
Parathyroid hormone (PTH) Calcitriol aka active form of vitamin D. Calcitonin
Anatomy of parathyroid gland.
Small glands embedded in the thyroid gland. Usually 4, in rare cases can be 6. In very rare cases the mediastinum can be filled with parathyroid glands (Up to 100).
Label.
PTH synthesis briefly.
Pro-pre hormone activated by proteolytic cleavage.
Synthesised by chief cells in the parathyroid glands.
Regulation of synthesis of PTH.
Transcriptional and post transcriptional levels by serum calcium levels.
Low serum calcium up-regulates gene transcription
High serum calcium down-regulates gene transcription
Low serum calcium also prolongs survival of mRNA
How is PTH stored?
It is barely stored. It is just continuously synthesised.
What degrades PTH?
Chief cells both synthesise and degrade PTH.
Explain calcium homeostasis.
Which organs are involved etc.
Through diet we get areound 1000mg each day. 825 mg is excreted daily so there is a net gain of 175 mg.
Out of the 1000mg in the GI 500mg is absorbed and 325 is secreted. These numbers add up to the 825 excreted and 175 taken up in net. The amount absorbed is going to the ECF.
There is also turnover of calcium in the bone where around 280mg of ECF calcium is used to form bone daily and the same amount 280mg is broken down into ECF by resorption.
Lastly kidneys will filter a lot of calcium around 10000mg a day. 9825 mg is reabsorbed daily. Giving a net of 175 calcium excreted via urine each day.
Which organs does PTH target in calcium homeostasis?
Bone
Intestine (indirectly)
Kidneys
Explain how an increase in PTH levels affect bone.
Increase resorption of bone by stimulating osteolysis. This is by binding to osteoblasts which secrete cytokines to stimulate differentiation and increase activity of osteoclasts.
This breaks down bone to release calcium and phosphate (Pi) from the hydroxyapatite crystals into ECF.
Explain how an increase in PTH levels has an effect in kidneys.
Increases calcium reabsorption so less calcium is excreted in urine.
Additionally
Also promotes activation of vitamin D to the activated form calcitriol.
Explain how an increase in PTH levels has an effect on the GI tract.
It indirectly affects the intestines by promoting activation (increasing renal C-1 hydroxylase activity) of vitamin D to Calcitriol in the kidneys.
Calcitriol then increases transcellular uptake of calcium in the GI tract.
How is PTH transported in the blood?
Without any protein bound to it aka freely.