Regulation of Calcium and Phosphate Levels in the Body

Calcium ion concentration in the extra cellular fluid is regulated precisely and even small changes of about 10% are quite unusual. The normal value of calcium ion concentration is 9.2 mg/dl or 2.4 mmol/l.

The importance of normal calcium ion concentration cannot be over emphasized as calcium ions are important for:

1. Membranes ( Excitability of neuromuscular junction and excitation contraction coupling)
2. Maintenance of tight junctions between the cells
3. Intracellular activities such as the second messenger system
4. Contraction of muscle cells
5. Nerve fibers
6. Blood clotting

Storage of Calcium:

In the adults, one to two kilograms of calcium ions are stored in the body (average being 1100 gm). 99% of this store is in the bones which serve as a large reservoir. Only 1% is present in the plasma and about 0.1% in the extra cellular fluid.

Calcium in Plasma:

The calcium occurring in the plasma exists in one of the three forms:

Non-ionized form:

1. 41% (about 1 mmol/l) bound to proteins, and is non diffusible through the capillaries
2. 9% (about 0.2 mmol/l) bound to anions, such as citrate and phosphate ions. It is diffusible through the capillaries.

3. Ionized Calcium:

50% (about 1.2 mmol/l or 2.4 meq/l) and is diffusible as well as ionized occurring in the heart, central nervous system and bones, etc.

Regulation of Calcium Ions:

The Calcium ion concentration in the body depends on the activities of three organs:

1. Bones
2. Intestines
3. Kidneys

Calcium ion concentration in the body fluids is maintained by the two mechanisms:

1. Buffer function of exchangeable calcium in bones (First line of defense)
2. Hormonal control of Calcium ion concentration

Buffer function of exchangeable calcium:

The exchangeable calcium salts (such as amorphous calcium phosphate, calcium hydrogen phosphate) are present in reversible equilibrium with calcium and phosphate ions in the extra cellular fluid.

Two homeostatic systems affect the calcium levels in the bones:

1. 500 mmol/day of Calcium ions move into and out of the readily exchangeable reservoir of bone.
2. Interplay between bone resorption and deposition (bone remodeling) i.e. from stable pool.

The interchange between plasma and stable pool is 7.5 mmol/day.

Hormonal control of Calcium ion concentration

The hormonal control is maintained by the negative feedback system by the opposing effects of parathyroid hormones and calcitonin. It acts through coordinating the storage, absorption and excretion of Calcium ions.

The target organs are:

1. Bones (through storage)

2. Intestines (through absorption)

3. Kidneys (through excretion)

Both parathyroid hormone and calcitonin begin to act in 3-5 minutes.

The exchangeable calcium ion mechanism in the bones is the process of buffering the calcium levels in the extra cellular fluid.

In children, the calcitonin causes rapid deposition of calcium in the bones and some other tissues.

In adults, parathyroid hormone plays more significant role in the maintenance of normal calcium concentration in the body.

In kidneys 98 to 99% of the filtered calcium is reabsorbed, out of which 60% occurs in the proximal convoluted tubule and 39% in the ascending loop of Henle and descending convoluted tubule ( under the action of parathyroid hormone).

In GIT, it is actively absorbed by calcium dependent ATPase (under the action of vitamin D3.

Hypercalcemia:

If calcium ion concentration increases by 30% above normal i.e. greater than 12 mg/dl, the neurons and the muscle cells become unresponsive, a condition known as hypercalcemia.

Following features are visible:

1. Depression of the central nervous system/peripheral nervous system

2. Muscle weakness

3. Constipation, abdominal pain, peptic ulcer, anorexia.

4. Depressed relaxation of the heart (in diastole)

Hypocalcemia:

If calcium ion concentration decreases to less than 35% of normal i.e. less than 7.2 mg/dl, excitation of nervous system occurs, known as hypocalcemia. Tetany is also seen and is evident as carpopedal spasm, laryngismus stridulus. It may lead to death if calcium ion concentration decreases to 4 mg/dl.

Regulation of Phosphate:

Extra cellular phosphate ion concentration is not regulated as precisely as that of calcium ions. Total phosphate ion concentration in the body is 500-800 gm out of which 85-90% occurs in the bones, 10-15% in the cells and less than 1% in the extra cellular fluid.

Phosphate ions play very important roles in the body as

1. Phosphate ions are found in the ATP, AMP, 2,3 DPG and proteins.
2. Phosphorylation and dephosphorylation of proteins regulate cell functions.

Plasma phosphate levels are 12 mg/dl. 80-90% of the phosphate in glomerular filtrate is reabsorbed actively (mostly in proximal convoluted tubule). Phosphate is also absorbed in the duodenum and intestines by the active/ passive process.

Bone Remodelling:

The human skeleton is completely remodeled in every ten years, the main objectives being:

1. To keep the skeleton ‘engineered’ for its maximum effectiveness in mechanical use.
2. To help maintain plasma calcium levels.

There are three types of cells in the bones:

1. Osteoblasts:

Osteoblasts are the modified fibroblasts which secrete extra cellular organic matrix (e.g. type 1 collagen) in which the calcium phosphate crystals precipitate.

2. Osteocytes:

Osteocytes are the retired osteoblasts which are imprisoned within the bony walls.

3. Osteoclasts:

Osteoclasts are the members of the monocyte family. They resorb bone in their vicinity by releasing acids and enzymes.

The osteoblasts secrete osteoprotegrin and osteoprotegrin ligand.

Osteoprotegrin ligand activated the osteoclasts, while osteoprotegrin binds osteoprotegrin ligand to inhibit osteoclasts. A definite balance exists between osteoprotegrin and osteoprotegrin ligand.

Estrogens stimulates osteoprotegrin gene to preserve bone mass. The bone renewal process is primarily under the hormonal control.