5. Calcium metabolism & bone physiology.pptx

Calcium Metabolism

:

• _{1.5% of body weight is Calcium, about 1100 gm; 99% is in the} skeleton. The normal plasma level is

9.4 mg/dL

• _{So it is important to know the plasma}

protein level when evaluating the total plasma Calcium concentration which can be corrected for the albumin level

• _{The ionized Calcium is necessary for:}

– Blood coagulation.

– Muscle contraction.

– Nerve function

– Hormone release & regulation of

many enzymes

.

• _Ca++ _{binds to negatively charged proteins so binding is pH dependent,}

more binding occurring in alkaline pH.

• _{So the pH affect the ionized Ca}++ _{level e.g. in symptoms of tetany which}

is produced as a result of hypocalcemia, alkalosis lower the threshold and acidosis raise the threshold for tetany, because plasma protein are more ionized when the PH is high, providing more protein anions to

• _{The average dietary Calcium intake for adult is 600-800 mg/day. In}

pregnancy & lactation extra Calcium is needed about 1200 mg/day.

• _{Most of the Calcium is absorbed in proximal small intestine}

regulated by Vitamin D. (Through an active transport system in a manner that Ca++ _{absorption is high when the Calcium intake is low & Calcium absorption is}

decreased when Calcium intake is high).

• _{A large amount of Ca is filtered in the kidney but 98-99% of this}

reabsorbed:

– _{mainly in the proximal tubule(60%)} – _{25% in the loop of Henle}

– _{small amount in the distal tubule which is regulated by PTH.}

Calcium Metabolism

Control of Calcium Metabolism

:

• _{Three major hormones are primarily concerned with the}

regulation of Calcium metabolism:

1. 1, 25 dihydroxycholecalciferol

hormone formed from Vitamin D.

2. Parathyroid hormone:

3. Calcitonin:

Phosphorus Metabolism

• _{Phosphorus is found in ATP, cyclic AMP (cAMP), 2,}

3-diphosphoglycerate (2,3 DPG) & other vitally important

compounds in the body.

• _{Total body phosphorus is 500-800 gm; 85-90% is in the skeleton.} • _{Two-third of phosphorus is in organic compound & the remaining}

third is inorganic phosphorus (Pi).

• _{The inorganic phosphorus in the plasma is filtered in the glomeruli}

& 85-90% of the filtered is reabsorbed mostly in proximal tubule

& this is inhibited by PTH.

• _{Inorganic phosphorus is absorbed in the duodenum & small}

In the liver, vitamin D3 is converted to

25-hydroxycholecalciferol (Calcidiol) which is

converted in the

proximal tubule of the kidney to the more active metabolite which is 1, 25 dihydrocholecalciferol

through the action of 1-α hydroxylase located in the cells of the

proximal tubule.

• _{PTH promotes the conversion of} 25-hydroxycholecalciferol to 1, 25

dihydrocholecalciferol in the kidney

• _{The formation of 1, 25 (OH)2 D3 in} the kidneys is regulated in a

feedback fashion by plasma Ca+2 _&

PO4-3

• _{When the plasma Ca}+2 _{level is high,}

little 1, 25 dihydro cholecalciferol is produced & its production is

increased by low & inhibited by high plasma PO4-3 _{on 1-α hydroxylase.}

Action of Vitamin D:

1. In the intestine the net effect of 1,25 (OH)2 cholecalciferol is to stimulate Calcium /phosphate transport from the small intestine lumen into the circulation

2. Facilitation of Ca reabsorption in the kidney.

3. 1,25 (OH)2 D3 acts on the bone where it mobilizes Ca++/ _PO4-3 _by

increasing the active transport of Ca+2 _{out of osteoblasts in to ECF.}

 _{The poor intestinal absorption of Ca}+2 _{in Vitamin D deficiency often leads to}

Endocrine Physiology

Mechanism of action of Vitamin D

• _{It increase Ca absorption in}

GIT through formation of calcium binding protein (Ca-BP)

• often it binds to a cytoplasm receptor

• the receptor complex is then trans-located to the nucleus

• where it increase the formation of mRNA which dictate the formation of Ca-BP

Bone Physiology:

•

Bone is a living tissue with a collagenous matrix

impregnated with mineral salts especially

phosphate of

Calcium

and mostly in the form of Hydroxyapatites.

– _{It supports the body}

– _{maintains mineral homeostasis such as Calcium}

– _{helps the lung and kidney in the maintenance of acid base}

•

Throughout life the mineral in the

skeleton actively turned over and bone

is constantly

resorbed

and

reformed

The cells in bone that are primarily concerned with bone formation and resorption are osteoblasts,

The Parathyroid Glands

:

• _{Normally these are four parathyroid} glands, located immediately behind the thyroid gland.

• _{The parathyroid of the adult human} being contains mainly chief cells and oxyphil cells.

Endocrine Physiology

Parathyroid

Hormone (PTH)

The Parathyroid Glands: actions

1. It acts directly on

bone

to increase bone resorption

and mobilizes Ca

By 2 separate effects:

– _{Rapid phase in minutes by activation of the already}

existing bone cells to promote Calcium & phosphate absorption (Osteolysis).

– _{Much slower phase requiring several days or even weeks,}

2. PTH increases tubular absorption of Ca which occurs in distal tubules and the collecting ducts, while it decreases proximal tubular reabsorption of phosphate ions so cause immediate and rapid loss of phosphate in the urine.

3. PTH increase the formation of 1, 25 dihydroxycholecalciferol so it increases Ca absorption from the intestine.

 _{So the net result is increased in Calcium ion & decreased}

Mechanism of action of PTH

• _{The action of PTH on the bones and the kidneys involves}

activation of adenylate cyclase and increase formation of cAMP in the affected cells.

• _{The hormone increases the permeability of osteoclasts and} osteoblasts to the Ca+2 _{into the ECF.}

Secretion & regulation

•

When the plasma

Ca

level is high

secretion of

PTH is

inhibited

and the

Ca

is deposited in the bones

.

is low, secretion is increased and Ca+2 _{are mobilized from the}

bones.

•

In conditions such as

chronic renal disease

and

rickets

where the plasma Ca

level is chronically low, so there is

parathyroid hypertrophy and secondary

hyperparathyroidism.

*

Calcitonin

:

• _{Secreted by parafollicular cells in thyroid which are known as}

clear cells or C-cells. Salmon calcitonin is more than 20 times active in humans than human calcitonin.

• _{The hormone is more active in young individual and may} play a role in skeletal development also it may protect the bones of the mother from excess Calcium loss during

Calcitonin actions

• _{Calcitonin receptors are found in bones and the kidneys. It is}

function is decreasing the circulatory calcium and phosphate level by inhibiting bone resorption directly due to inhibition of the Ca+2 _{permeability of osteoclasts as well as osteoblasts. It}

also increases Ca+2 _{excretions in the urine.}

• _{Calcitonin secretion is increased in the presence of high Ca}+2

concentrations especially above 9.5 mg/dL.

Osteomalacia/Osteoporosis

:

•

Osteomalacia:

It is rickets in adults in which the amount of Calcium

accretion per unit bone matrix is deficient.

•

Osteoporosis: