Hormonal Control of Calcium & Phosphate Metabolismppt

The calcium in the plasma is present in three forms:
• 40 % of the calcium is combined with the plasma proteins .
• 10 % of the calcium is combined with anionic substances (citrate and phosphate.
• The remaining 50 % of the calcium in the plasma is ionized. This ionic calcium is the form that is important for most functions of calcium in the body.

Factors affecting calcium concentration
1) Changes in plasma protein concentration- Increased [protein] – increased total [Ca2+]
2) Changes in anion concentration- Increased [anion] – increased fraction of Ca2+ that is complexed – decrease ionized [Ca2+]
3)Acid base abnormality . Acidosis (Increased [H] )– more H attacd to albumin lead to increased ionized [Ca2+]

Approximately 85 % of the body s phosphate is stored in bones,14 to 15% is in the cells, and less than 1 % is in the extracellular fluid. Although extracellular fluid phosphate concentration is not nearly as well regulated as calcium concentration, phosphate serves several important functions and is controlled by many of the same factors that regulate calcium.


Calcium Homeostasis
Blood calcium is tightly regulated by:
1) Principle organ systems:
• The small intestine is the site where dietary calcium is absorbed.
• Bone serves as a vast reservoir of calcium. Bone is composed of organic matrix that is greatly strengthened by deposits of calcium salts ; known as hydroxyapatite
• The kidney :calcium is reabsorbed from the tubular system back into blood

2) Hormones:Parathyroid hormone (PTH) , Vitamin D , Calcitonin

Parathyroid hormone (PTH)
Parathyroid hormone is protein hormone secreted from cells of the parathyroid glands and finds its major target cells in bone and kidney. Normally there are four parathyroid glands in humans; they are located immediately behind the thyroid gland. It contains mainly chief cells (secrete PTH) and a small number of oxyphil cells( not certain, but they are believed to be modified or depleted chief cells that no longer secrete hormone).
Physiologic Effects of Parathyroid Hormone
The main function of parathyroid hormone is bring calcium ion concentrations in extracellular fluid back within the normal range if it fall below normal. Parathyroid hormone accomplishes its job by stimulating three processes (figure 1):
• Mobilization of calcium from bone: PTH stimulates osteoclast activity and bone resorption, but this occurs through an indirect mechanism. PTH binds to receptors on the adjacent osteoblasts, causing them to release cytokines, which activates receptors on preosteoclast cells, causing them to differentiate into mature osteoclasts. The mature osteoclasts then release enzymes and acids that promote bone resorption.
• Enhancing absorption of calcium from the small intestine: PTH stimulates this process, but indirectly by stimulating production of the active form of vitamin D in the kidney. Vitamin D induces synthesis of a calcium-binding protein in intestinal epithelial cells that facilitates efficient absorption of calcium into blood.
• Suppression of calcium loss in urine: PTH stimulates tubular reabsorption of calcium. Another effect of PTH on the kidney is to stimulate loss of phosphate ions in urine.
Control of Parathyroid Hormone Secretion
PTH is released in response to low extracellular concentrations of free calcium .The parathyroid cell monitors extracellular free calcium concentration via an integral membrane protein that functions as a calcium-sensing receptor. When calcium concentrations fall below the normal range, there is a steep increase in secretion of parathyroid hormone. Low levels of the hormone are secreted even when blood calcium levels are high.

Disease States
Excessive secretion of parathyroid hormone is seen in two forms:
• Primary hyperparathyroidism is the result of parathyroid gland disease, most commonly due to a parathyroid tumor .
• Secondary hyperparathyroidism is the situation where disease outside of the parathyroid gland leads to excessive secretion of parathyroid hormone. A common cause of this disorder is kidney disease - if the kidneys are unable to reabsorb calcium, blood calcium levels will fall, stimulating continual secretion of parathyroid hormone to maintain normal calcium levels in blood. Secondary hyperparathyroidism can also result from inadequate nutrition.
• Inadequate production of parathyroid hormone - hypoparathyroidism - typically results in decreased concentrations of calcium and increased concentrations of phosphorus in blood. Common causes of this disorder include surgical removal of the parathyroid glands and disease processes that lead to destruction of parathyroid glands.