CALCIUM HOMEOSTASIS

New insight : BIVEK SINGH

OBJECTIVE OF SESSION• Calcium• Body distribution of calcium• Function of calcium• Absorption and excretion of calcium• Calcium homeostasis -hormonal regulation 1. Parathyroid hormone (PTH) 2. Vitamin D (Calcitriol) 3. Calcitonin

Calcium

Alkaline earth metal Atomic weight 20

Most abundant mineral in the human body

Body distribution•Total content inadult body is 25000mmol (approx. 1kg)•99% of calcium is found in bone•extracellular fluid is 22.5 mmol

Plasma calcium

1.protein bound fraction- 4-5mg/dl

2.complex with citrate and phosphate- 1mg/dl

3.ionised form- 4-5mg/dl

Major functions

•Calcification of bone and teeth•Muscle contraction•Role in neuromuscular transmission•Role in blood coagulation

•Calcium as second messenger

Absorption of calcium

• Calcium is taken in diet principally as calcium-phosphate,carbonate or tartarate

• About 40% of the average daily dietary intake of calcium is absorbed in gut.

• Absorption of calcium by gut mucosa occur by energy dependent active transport process.

Excretion of calcium

• Partly through kidney and mostly through intestine

• Renal threshold for serum calcium is 10mg/dl

• Excretion is increased in vitamin D deficiency

CALCIUM HOMEOSTATSIS

• Calcium homeostasis refers to the regulation of concentration of calcium ions in extracellular matrix

• Calcium homostasis is regulated by:

1. vitamin D (calcitriol)

2. parathyroid hormone (PTH)

3. calcitonin

Vitamin D (Calcitriol)

• Vitamin D has two sources i.e. skin and diet

• 25-hydroxy cholecalciferol is the storage form of vitamin D in liver

• 1,25-hydroxy cholecalcitriol is the active form of vitamin D

• Activated by PTH and hypophosphptemia through 1-alpha hydroxylase enzyme in kidney

VITAMIN D SYNTHESIS

SKIN LIVER KIDNEY

7-DEHYDROCHOLESTEROL

VITAMIN D3

VITAMIN D3

25(OH)VITAMIN D

hν25-HYDROXYLASE

25(OH)VITAMIN D

1,25(OH)2 VITAMIN D

(ACTIVE METABOLITE)

1α-HYDROXYLASE

TISSUE-SPECIFIC VITAMIN D RESPONSES

Action of Calcitriol on intestine

• Calcitriol stimulates the absorption of dietary calcium and phosphate .

• Calcitriol induces the synthesis of calcium binding proteins(Calbindin D) in the enterocytes. Thus increases the uptake of calcium by intestine.

Action of calcitriol on bone

• Calcitriol along with parathyroid hormone stimulates the osteoclastic bone resorption

• thus,mobilization of calcium and phosphate from bone.

Action of Calcitriol on the Kidney

• Calcitriol reduces the excretion of calcium and phosphate through the kidney.

• Increase reabsorption.

Parathyroid hormne• 4 parathyroid glands

• Release PTH in response to drop in serum calcium

• Magnesium needed to activate PTH release

• Effects on bone, kidney and indirectly on intestines

Action of PTH on bone• PTH causes resorption of bone by osteoclastic activity

• Due to increased stimulation of pyrophosphatase and collagenase

• This causes the mobilization of calcium from bone

• Increase blood calcium level

Action of PTH on kidney

• Increased reabsorption of calcium from kidney tubule

• Reduce the excretion of calcium

• Helps in synthesis of calcitriol by 1-alpha

hydroxlase enzyme

Action of PTH on intestine

• Indirectly• By promoting

synthesis of calcitriol

CALCIUM, PTH, AND VITAMIN D FEEDBACK LOOPS

NORMAL BLOOD Ca

RISING BLOOD Ca

FALLING BLOOD Ca

SUPPRESS PTH

STIMULATE PTH

BONE RESORPTION

URINARY LOSS

1,25(OH)2 D PRODUCTION

BONE RESORPTION

URINARY LOSS

1,25(OH)2 D PRODUCTION

Calcitonin

• Secreted by parafollicular cells of thyroid gland

• Metabolism is antagonistic to PTH hormone

• Normal concentration in plasma is 10-20 pg/ml

Action of calcitonin on bone & kidney

• Mainly acts on osteoclasts

• Reduces osteoclastic activities by reducing number and size of osteoclasts.Thus, inhibits bone resorption

• On kidney, it decreases calcium reabsorption from kidney

• Causes calciuria

CALCIUM HOMEOSTASIS

DIETARY CALCIUM

INTESTINAL ABSORPTIONORGAN PHYSIOLOGY

ENDOCRINE PHYSIOLOGY

DIETARY HABITS,

SUPPLEMENTSBLOOD CALCIUM

BONE

KIDNEYS

URINE

THE ONLY “IN”

THE PRINCIPLE “OUT”

ORGAN PHYS.

ENDOCRINE PHYS.

ORGAN, ENDOCRINE

Questions !!!!!!!!!Questions !!!!!!!!! oror suggestions ??????suggestions ??????biveksingh@hotmail.combiveksingh@hotmail.com

BIVEK SINGHBIVEK SINGHKIST MEDICAL COLLEGEKIST MEDICAL COLLEGELALITPUR,NEPALLALITPUR,NEPAL