Changes

Calcium is essential for many intracellular and extracellular functions. These include:

Calcium is essential for many intracellular and extracellular functions. These include:

1. Enzymatic reactions and membrane stability;

1. Enzymatic reactions and membrane stability

2. Second messenger signalling systems;

2. Second messenger signalling systems

3. Nerve conduction and neuromuscular transmission;

3. Nerve conduction and neuromuscular transmission

4. The release of hormones by exocytosis;

4. The release of hormones by exocytosis

5. Muscle contraction (smooth and skeletal);

5. Muscle contraction (smooth and skeletal)

6. Blood coagulation;

6. Blood coagulation

7. Milk Production;

7. Milk Production

8. Structural integrity of bone and teeth.

8. Structural integrity of bone and teeth

Calcium is distributed throughout the body, primarily extracellularly but also intracellularly. Intracellular calcium is maintained at very low levels (10,000 fold less than in serum); 99% of calcium is found in bone as Extracellular Matrix, in the form of hydroxyapatite.

Calcium is distributed throughout the body, primarily extracellularly but also intracellularly. Intracellular calcium is maintained at very low levels (10,000 fold less than in serum); 99% of calcium is found in bone as Extracellular Matrix, in the form of hydroxyapatite.

Within the serum, 55% of the Calcium is ionised - this is the biologically active form, and 10% of the calcium is in complexes such as citrate and phosphate. Together with the ionised form, this constitutes '''ultrafilterable calcium'''. 35% of the calcium is also bound to plasma proteins.

Within the serum, 55% of the calcium is ionised - this is the biologically active form, and 10% of the calcium is in complexes such as citrate and phosphate. Together with the ionised form, this constitutes '''ultrafilterable calcium'''. 35% of the calcium is also bound to plasma proteins.

Extracellular calcium can be measured in two ways:

Extracellular calcium can be measured in two ways:

==Serum Calcium Abnormalities==

==Serum Calcium Abnormalities==

'''Elevated''' blood calcium levels (hypercalcaemia) can be attributed to increased PTH concentration and increased active vitamin D3. '''Reduced''' blood calcium levels (hypocalcaemia) can occur with decreased PTH, reduced Vitamin D activation and calcitonin inhibition of calcium mobilisation from bone.

'''Elevated''' blood calcium levels (hypercalcaemia) can be attributed to increased parathyroid hormone (PTH) concentration and increased active vitamin D3. '''Reduced''' blood calcium levels (hypocalcaemia) can occur with decreased PTH, reduced Vitamin D activation and calcitonin inhibition of calcium mobilisation from bone.

==Calcium Homeostasis==

==Calcium Homeostasis==

===Parathyroid Hormone (PTH)===

===Parathyroid Hormone (PTH)===

Synthesis of PTH is from a preprohormone of 115 amino acids into a  [[Prohormones - Anatomy & Physiology|prohormone]] of 90 amino acids. This prohormone is then packaged into vesicles, as the 84 amino acid PTH molecule. It is secreted by the chief cells of the parathyroid gland continuously with a basal secretory rate of around 25% of the maximum possible rate. Secretion rate increases with a '''decrease in serum ionised calcium''' (hypocalcemia). Regulation of PTH is highly sensitive due to membrane receptors on Chief cells coupled to G-Proteins. Receptor stimulation decreases secretion; this is therefore a direct [[Negative Feedback - Anatomy & Physiology|negative feedback]] mechanism. The half-life of PTH in circulation is short - less than 10 minutes which also allows tight regulation of calcium levels. PTH is metabolised in the liver and kidneys.

Synthesis of PTH is from a preprohormone of 115 amino acids into a  [[Prohormones - Anatomy & Physiology|prohormone]] of 90 amino acids. This prohormone is then packaged into vesicles, as the 84 amino acid PTH molecule. It is secreted by the chief cells of the parathyroid gland continuously with a basal secretory rate of around 25% of the maximum possible rate. Secretion rate increases with a '''decrease in serum ionised calcium''' (hypocalcemia). Regulation of PTH is highly sensitive due to membrane receptors on chief cells coupled to G-proteins. Receptor stimulation decreases secretion; this is therefore a direct [[Negative Feedback - Anatomy & Physiology|negative feedback]] mechanism. The half-life of PTH in circulation is short - less than 10 minutes which also allows tight regulation of calcium levels. PTH is metabolised in the liver and kidneys.

PTH leads to increased calcium levels in the blood by actions on bone. There are two phases;  

PTH leads to increased calcium levels in the blood by actions on bone. There are two phases;  

2. '''Slow Phase''' - This phase involves the activation of osteoclasts and the creation of new osteoclasts, and takes ~48 hours to activate. There are no receptors for PTH on osteoclasts, so the signal comes from existing osteoblasts and osteocytes. This results in a progressive depletion of bone mineral.

2. '''Slow Phase''' - This phase involves the activation of osteoclasts and the creation of new osteoclasts, and takes ~48 hours to activate. There are no receptors for PTH on osteoclasts, so the signal comes from existing osteoblasts and osteocytes. This results in a progressive depletion of bone mineral.

PTH also leads to increased calcium levels in the blood by actions on the kidneys. PTH increases the calcium reabsorption at the level of the late distal tubules and collecting ducts. It also increases [[Magnesium|magnesium]] reabsorption. This occurs at the expense of [[Phosphorus|phosphorus]] in the proximal tubule. Thus Mg and Ca are reabsorbed and Potassium is excreted in the urine.  

PTH also leads to increased calcium levels in the blood by actions on the kidneys. PTH increases the calcium reabsorption at the level of the late distal tubules and collecting ducts. It also increases [[Magnesium|magnesium]] reabsorption. This occurs at the expense of [[Phosphorus|phosphorus]] in the proximal tubule. Thus Mg and Ca are reabsorbed and K is excreted in the urine.  

PTH also leads to increased calcium levels in the blood by actions on the GI tract. Indirect effects occur via the activation of Vitamin D3.

PTH also leads to increased calcium levels in the blood by actions on the GI tract. Indirect effects occur via the activation of Vitamin D3.

There are four biological actions of Calcitriol (active Vitamin D3):

There are four biological actions of Calcitriol (active Vitamin D3):

1. '''Increase calcium absorption from the intestine''' via active transport mechanisms. Calcitriol increases the synthesis of '''Calbindin''' (Calcium binding protein) which transports calcium from the intestinal lumen to the Vitamin D activated Calcium ATPase pumps on the basolateral membrane of the enterocytes (via secondary active transport). This process takes approximatley 48 hours.

1. '''Increase calcium absorption from the intestine''' via active transport mechanisms. Calcitriol increases the synthesis of '''calbindin''' (Calcium binding protein) which transports calcium from the intestinal lumen to the vitamin D activated calcium ATPase pumps on the basolateral membrane of the enterocytes (via secondary active transport). This process takes approximately 48 hours.

2. '''Increase phosphorous absorption from the intestine''' - Phosphorous is found in grains, and is absorbed in the small intestine via active transport mechanisms which are responsive to calcitriol.

2. '''Increase phosphorous absorption from the intestine''' - Phosphorous is found in grains, and is absorbed in the small intestine via active transport mechanisms which are responsive to calcitriol.

3. '''Decrease Calcium and Phosphorous excretion via the kidney''' - Calcitriol acts on the renal tubular epithelial cells to increase calcium and phosphorous reabsorption from the nephron. This action is WEAK compared to the action of PTH, which acts to reabsorb calcium but lose phosphorous from the nephron.

3. '''Decrease Calcium and Phosphorous excretion via the kidney''' - Calcitriol acts on the renal tubular epithelial cells to increase calcium and phosphorous reabsorption from the nephron. This action is WEAK compared to the action of PTH, which acts to reabsorb calcium but lose phosphorous from the nephron.

4. '''Normal bone functioning (osteoclast and osteoblast functions)''' - Calcitriol is needed for normal bone absorption and deposition. Without Vitamin D3, bone is not resorbed in response to PTH.

4. '''Normal bone functioning ([[Bones and Cartilage - Anatomy & Physiology|osteoclast and osteoblast functions]])''' - Calcitriol is needed for normal bone absorption and deposition. Without Vitamin D3, bone is not resorbed in response to PTH.

===Calcitonin===

===Calcitonin===

Calcitonin acts to decrease calcium levels in the plasma. It is overall a weaker regulatory mechanism than PTH. Secreted by the parafollicular cells of the thyroid gland, calcitonin is stimulated by hypercalcemia, and has the opposite effects of PTH on the bone:

Calcitonin acts to decrease calcium levels in the plasma. It is overall a weaker regulatory mechanism than PTH. Secreted by the parafollicular cells of the thyroid gland, calcitonin is stimulated by hypercalcemia, and has the opposite effects of PTH on the bone:

1. Fast Phase - puts calcium into bone fluid by inhibiting osteoclasts' absorptive abilities.

1. Fast Phase - puts calcium into bone fluid by inhibiting osteoclasts' absorptive abilities.

2. Slow Phase - puts calcium into bone by reducing the formation of new osteoclasts.

2. Slow Phase - puts calcium into bone by reducing the formation of new osteoclasts.

There are also slight (insignificant) effects on the kidney and [[Alimentary System Overview - Anatomy & Physiology|GIT]].

There are also slight (insignificant) effects on the kidney and [[Alimentary System Overview - Anatomy & Physiology|gastrointestinal tract]].

==Links==

==Links==

[[Category:Electrolytes]]

[[Category:Electrolytes]]

[[Category:Endocrine System - Anatomy & Physiology]]

[[Category:Endocrine System - Anatomy & Physiology]]

[[Category:To Do - AimeeHicks]][[Category:To Do - Review]]

[[Category:A&P Done]]