Lecture 9 Calcium Homeostasis Flashcards
What are the roles of calcium in the body
Important signalling molecules Essential component of clotting cascade Apoptosis Skeletal strength Membrane excitability
What does hypocalcaemia lead to within the cells
Increases Na+ permeability leading to hyper excitation and depolarisation leading to tetany and asphyxiation
What does hypercalcaemia lead to within the cells
Decreases Na+ permeability which reduced excitability and depress neuromuscular activity triggering cardiac arrhythmias
What proportion of calcium is in the bones
• Bones 99% (1Kg) in the form of hydroxyapatite (Ca10(PO4)6(OH)2
What proportion of calcium is intracellular
0.9% (24mM)
Mitochondria and Sarcoplamsic Reticulum
What proportion of calcium is in the extracellular fluid
0.1% (2.2.-2.6 mM)
Nearly half bound to protein
Define physiologically active plasma
Free ionised and not bound to protein
What effect does a high pH (alkaline) have on calcium binding to proteins
Increases it
What human function would increase pH and what effect would that have
Hyperventilation would increase pH and plasma concentration of calcium would fall leading to hypocalcaemic tetany
What human function would lead to decreased pH and what effect would that have
Hypoventialtion would decrease the pH and less protein would bind to calcium causing the plasma concentration to rise = hypercalcaemia
Total body calcium is determined by what
Calcium in (diet)- calcium out (kidney and faeces)
What is the function of osteoblasts
bone building cells. Highly active cells which lay down a collagen extracellular matrix which they then calcify
What do osteoblasts differentiate to
Osteocytes
What are osteocytes
less active than osteoblast but regulate the activity of osteoblasts and osteoclasts
What are osteoclasts
Responsible for mobilising bone. Secrete H+ ions to dissolved the calcium salts and also provide proteolytic enzymes to digest the extracellular matrix
Name 2 key hormones that act to increase calcium plasma concentration
PTH
Calcitriol
How does PTH increase calcium plasma concentration
Stimulate osteoclasts Inhibit osteoblasts Increasing reabsorption of Ca2+ from kidney tubules Increasing renal excretion of phosphate Stimulate kidneys to release calcitriol
How does calcitriol complement the action of PTH
• Binds to nuclear receptors in target tissues (intestines, bone and kidney) to:
Increase absorption of Ca2+ from the gut via ctaive transport
How is calcitriol derived
• A steroid hormone produced in two steps (1. liver, 2. kidneys) from dietary vitamin D or from precursors activated by sunlight on skin. Formation is also stimulated by hormone prolactin in lactating women in the kidney
In a healthy individual what percentage of calcium is absorbed
30%
In a vitamin D deficient individual how much calcium is absorbed
10-15%
In a pregnant individual how much calcium is absorbed
45-55%
Where is vitamin d predominantly stored
Fat
Vit D deficiency is more predominant in what group of people
- More prevalent in >65 years due to reduce gut absorption and reduced Ca2+ mobility, and Asian
- PTH works hard to maintain plasma calcium and in doing so continually removes calcium from bone = soft bones, growing bones become bent, easily fractured
- Rickets in children
What effect does calcitonin have on calcium levels
Produced in thyroid glands to decrease calcium in plasma. Binds to osteoclasts to inhibit bone resorption and increases renal excretion
In thyroid tumours what happens to the calcium levels
Calcitonin levels are high, plasma calcium is normal as effect of calcitonin is overridden by PTH
What effect does cortisol have on calcium
- Inhibits osteoblasts
- Increases renal excretion of calcium and phosphate
- Reduced intestinal absorption of calcium
- Increases PTH and bone resorption (osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood)
What effect does insulin have on calcium levels
- Increase bone formation
- Antagonises the action of cortisol
- Diabetics may have significant bone loss
What effect does oestrogen have on calcium
- Promotes bone formation via oestrogen receptors on osteoblasts
- Post-menopausal can cause osteoporosis
What effect does GH have on calcium levels
Stimulus for bone formation
What effect does prolactin have on calcium levels
• Promotes calcium absorption from the gut by stimulating synthesis of calcitriol
