Calcium Homeostasis Flashcards
Summarise diverse roles of calcium, demonstrating the importance of the regulation of calcium concentration.
- Signalling - Ca2+ important signalling molecules: exocytosis of synaptic vesicles e.g. neurotransmitters/hormones etc., contraction of muscle fibres, alters enzyme function.
- Blood clotting - essential component of clotting cascade.
- Apoptosis - programmed cell death
- Skeletal strength - 99% of calcium in the body is wrapped up in bone where it gives strength to the skeleton.
- Membrane excitability – Ca2+ decreases Na+ permeability. (Most critical in short term homeostasis.)
Explain the overall effect of PTH on plasma Ca2+ and phosphate concentrations.
a
Describe effects of PTH on renal formation of 1a, 25 – dihydroxycholecalciferol.
a
Describe the effect of 1a, 25 - dihydroxycholecalciferol on Calcium absorption from the gut.
a
Outline the effect of 1a, 25 - dihydroxycholecalciferol on parathyroid gland function.
a
Describe the nature and function of calcitonin.
a
Describe the effect of hypocalcaemia on Ca2+ and membrane excitability.
Hypocalcaemia increases neuronal Na+ permeability leading to hyperexcitation of neurons. In extreme cases, it causes tetany. If it spreads to larynx and respiratory muscles - asphyxiation.
Describe the effect of hypercalcaemia on Ca2+ and membrane excitability.
Hypercalcaemia decreases neuronal Na+ permeability, which will reduce excitability and depress neuromuscular activity and in extreme cases, trigger cardiac arrhythmias.
Describe the distribution of calcium in the body.
99% - bones!
~1Kg calcium is stored in the calcified extracellular matrix of bone, mostly in the form of hydroxyapatite (Ca10(PO4)6(OH)2) so phosphate homeostasis is also important in determining calcium balance.
- 9% - intracellular
- Mostly stored inside mitochondria and sarcoplasmic reticulum
- Free [Ca2+ ]ic very low
- Tightly regulated - 1% - extracellular
- 2.2-2.6mM in plasma
- Nearly half ECF Ca2+ is bound to protein
- So only 0.05% of the calcium in the body is free in solution and physiologically active
- Tightly regulated
Describe the extracellular calcium stores.
Calcium has a very high affinity for proteins (small positive charge attracted to large negative charge) and in plasma around 40% is bound to plasma proteins
So while [Ca2+ ]plasma is ~2.4mM, free ionised, and therefore physiologically active [Ca2+ ], it’s only about 1.2mM and accounts for ~50% of plasma calcium.
The remaining 10% of plasma calcium ions that are neither bound to plasma protein, nor free in solution, bind to plasma anions.
Describe the relationship between pH and Ca2+ binding.
Binding capacity is increased under alkalotic conditions.
e.g. if one hyperventilates, then plasma pH rises (remember the relationship between CO2 and H+):
CO2 + H2O H2CO3 H+ + HCO3-
and plasma proteins bind more Ca2+, causing plasma concentration to fall, which may precipitate hypocalcaemic tetany.
Opposite occurs with acidosis where binding capacity reduces and free [Ca2+]plasma rises.
Describe Ca2+ storage in bone.
Bone functions to provide mechanical support for the body but its role in maintaining Ca2+ balance takes precedence over this.
Define osteoblast.
Osteoblasts are the bone-building cells. They are highly active cells which lay down a collagen extracellular matrix which they then calcify.
They differentiate to form osteocytes in established bone. Osteocytes are much less active than osteoblasts but appear to regulate the activity of osteoblasts and osteoclasts.
Define osteoclast.
Osteoclasts are the cells that are responsible for mobilizing bone. They secrete H+ ions (pH 4) to dissolve the calcium salts and also provide proteolytic enzymes to digest the extracellular matrix.
Describe the endocrine control of calcium homeostasis.
Two key hormones act to increase [Ca2+]plasma;
- Parathyroid hormone (PTH): polypeptide hormone produced by the parathyroid glands.
- Calcitriol (active form of Vit D3): steroid hormone produced from Vitamin D by the liver and kidneys.
