METABOLIC RELATIONSHIP IN Ca/P REGULATION

METABOLIC RELATIONSHIP IN

Ca/P REGULATION

Ca and P are macroelements

• Ca and P in the organism were found as Apatite crystals in bones and teeth. Hydroxyapatite

crystals= Ca10(PO4)6(OH)2

• Calcium accounts for 1-2 % of body weight in humans (% 1.7).

• In Animals % 1,4-2,6

• Over 99 percent of total body calcium is found in teeth and bones

• Besides the role of calcium in the contribution to the structure of bones, also plays role in some significant cellular activities.

• Calcium has an indispensable role in many events such as nerve and muscle functions, hormonal mechanism of

action, blood clotting, cellular motility.

• Calcium is absorbed from the small intestine with the help of calcium-binding protein (calmodulin).

• Its excreted by the urine through the kidneys.

• In calcium deficiency, tetany and its related disorders in muscle and nerve are seen.

• In developing animals, in pregnant women, in laying hens, and nursing animals Ca should be sufficiently given in a daily basis in an adequate proportion

• In general, this ratio is between 2/1 and 1/1 in feedstuff.

• Ca / P ratio in the blood should be kept around 2/1

• Ca (mg/dl) x P (mg/dl) = ideally to be 36.

– ie: 9 x 4 = 36

• If this falls <30, Osteomalacia is seen in the elderly and rickets in the young animals.

Blood Ca/P Balance

• Various hormones, tissues and organs are in charge for providing Ca / P balance in blood.

• Hormones:

– PTH, Calcitonin, 1,25 (OH)2 Vit D3 (and others…)

• Tissue-Organs:

– Parathyroid gland, thyroid gland, skin

– Bone tissue, kidney, intestine, mammary gland, fetus

• In the parathyroid gland, the calcium-sensing

receptor controls calcium homeostasis by regulating the release of parathyroid hormone (PTH).

Blood Ca/P Balance

Is maintained by

•Intestinal absorption

•Uptake from kidneys

•Release and resorption by the bones

Ca uptake from the intestine

• 10-20% of the calcium in feed can be absorbed from the small intestine.

 Vit D

 PTH

 Calcitonin

 Sex steroids

 Ration low in Ca promotes uptake – Glucocorticoids

– Increase in Intestinal motility – Protein deficiency

– Insufficiency or absence of bile acids decreases absorption

Uptake from Kidneys

• Vit D

• PTH

• Metabolic acidosis

• Calcitonin

• Increase in extracellular volume

• Diuretics

• Prolonged starvation

• High level of phosphates

• Inactivity

12/19/21 Biyokimya AD Ders Notu 8

decreases increases

Kemiklerde salınım/depolanma

• Vit D – increases release

• PTH - increases release

• Sex hormones –induces bone metabolism

Prostaglandins – (especially Pg E) high doses induces resorption (storage).

 Plasma calcium homeostosis is mainly achieved by a hormonal system consisting of parathormone (PTH), calcitonin (CT), and the active metabolites of Vit D (1,25- (OH)₂-CC).

 This regulatory system regulates the exchange of Ca between plasma and three major organs (bone, intestine, kidney).

Blood calcium level

PTH

Blood Ca Ca Ca

Diet

PTH levels dtermined by Ca levels

When blood Ca level drops PTH levels increase

Increase in osteoclastic

activity

Absorption from intestines Ca uptake

from kidneys

Blood calcium levels

• Release/resorption Ca from bones

• Absorption from intestines

• Reuptake of calcium following the filtration in the kidneys

are kept within narrow limits

PTH

• Released from the parathyroid gland

• Hypercalcemic effect.

• It promotes the uptake of Ca from the distal

tubules in the kidneys. It inhibits the absorption of phosphate and bicarbonate.

• Increases the mobilization of Ca from the bones

• Increases the absorption of Ca by the aid of Vit D₃

Calcitonin

• It is released from thyroid gland parafolicular cells

• Calcitonin increases Ca, P elemination from kidneys

• Hypocalcaemic effect

• Inhibits most of the hormones secreted from GIS

• It prevents bone resorption by inhibiting osteoclasts in bones.

Vit D

• Active form : 1,25 (OH)²- CC

• Increases Ca mobilization from bones,

• Increases Ca absorption from intestine,

• Increases Ca uptake from the kidney tubules.

• PTH, increases the synthesis of1, 25 (OH)2

CC in kidneys

• Diet is an important source for cholecalciferol (Vit D3)

• It is converted to 25 hydroxycholecalciferol by the liver

• And finally to 1,25- dihydroxy cholecalciferol by kidney proximal tubules

• Production controlled by negatif feed-back mechanisms

• Hypocalcaemia induces PTH release

• Calcitonin was produced in response hypercalcemia to by thyroid gland C-cells

• Calcitonin is a potent Ca regulator. Causes Ca and P decrease in blood.

– Ca renal outcome: Normally, 98% of the filtered Ca is reabsorbed.

– Bone-Ca balance: Cell membrane contains Ca ++

sensitive receptors.

• Sex hormones, glucocorticoids (cortisol), thyroxine, GH, glucagon and other factors may also indirectly affect regulation.

• Cortisol and thyroid hormones (T3 and T4) inhibit Ca absorption from the intestines.

• Estrogens and STH stimulate renal hydroxylase to accelerate Ca absorption.

• Both PTH and CT secretion rate are related to calcemia