Download Hormone Control of Calcium Metabolism

Aims
Hormone Control of
Calcium Metabolism
„
„
Calcium Homeostasis
Hormone Control Calcium Metabolism
„
Vitamin D
PTH
Calcitonin
„
Other hormones
„
„
Suwattanee Kooptiwut, MD., MSc., Ph.D.
„
Calcium and Phosphate function
1
Calcium homeostasis
2
Vitamin D synthesis
THE ONLY “IN”
BONE
SKIN
DIETARY HABITS,
SUPPLEMENTS
BLOOD CALCIUM
LIVER
7-DEHYDROCHOLESTEROL
INTESTINAL ABSORPTION
VITAMIN D3
KIDNEY
25(OH)VITAMIN D
25-HYDROXYLASE
1α-HYDROXYLASE
hν
KIDNEYS
VITAMIN D3
25(OH)VITAMIN D
(25-HCC)
URINE
THE PRINCIPLE “OUT”
3
1,25(OH)2 VITAMIN D
(1,25-DHCC)
(ACTIVE METABOLITE)
TISSUE-SPECIFIC VITAMIN D RESPONSES
4
Vitamin D action (enterocyte)
Vitamin D action
ƒ GUT
ƒ
Ca2+ and PO4 3-absorption from the gut
epithelium
Eletrochemical gradient
ƒ
Ca2+ binding protein (CaBP) or by affecting
Ca2+ transport directly
ƒ
Ca2+ ATPase pump Ca2+from enterocyte
to blood
ƒ BONE
ƒ
mineralization from blood Ca2+ to bone
5
IMCal: Intestinal membrane calcium binding protein
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Vitamin D action
Abnormal Vitamin D secretion
ƒ KIDNEY
„
ƒ
tubular calcium resorption, possibly by
the action of CaBP
ƒ PARATHYROID
„
ƒ Inhibit transcription of the PTH gene
(feedback regulation)
Vitamin D deficit
„ Uncalcified osteoid tissue Clinical
syndromes broadly categorized as Rickets
and Osteomalacia.
„ Decreased blood calcium.
Vitamin D excess
„Hypercalcemia (rare).
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Rickets / Osteomalacia
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Parathyroid hormone (PTH)
„
84-amino acids polypeptide hormone
„ PTH is released from the chief cells of
the parathyroid gland.
A decreased in plasma Ca2+mediates the
release of PTH through calcium receptor.
„
Increased cAMP in the chief cells is involved
in this process.
„
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10
PTH actions (Kidney)
Direct
„
„
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PTH increases resorption of Ca2+in the distal
tubules.
PTH increases PO43 - and HCO3- excretion in
the urine.
12
PTH actions (Kidney)
Indirect
PTH actions (Bone)
PTH
„
1-α hydroxylase
1,25 DHCC
25 HCC
Intestinal absorption of Ca2+
PTH acts on osteoblasts to inhibit the
synthesis of collagen (inhibition of bone
formation).
ƒ PTH acts on osteoblasts to stimulate
secretion of cytokines, which acts on the
osteoclasts to promote demineralization
and Ca2+release (osteoclastic bone
resorption)
13
PTH actions (Bone)
„
14
PTH actions (Bone)
PTH also activates Ca2+pumps within the
surface osteoblasts to move Ca2+out of bone
fluid and into the extracellular fluid (ECF).
PTH (basal level)
Osteoblasts
Bone formation
Osteoclasts
Bone resorption
Bone remodeling
15
PTH actions
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Calcium, PTH, and Vitamin D
feedback loop
PTH
BONE RESORPTION
Bone
Bone
resorption
Parathyroid glands
URINARY LOSS
SUPPRESS PTH
1,25(OH)2 D PRODUCTION
RISING BLOOD Ca2+
Calcium
retention
Blood calcium
NORMAL BLOOD Ca2+
FALLING BLOOD Ca2+
Vitamin D3
Kidney
BONE RESORPTION
Dietary
calcium
absorption
Intestine
URINARY LOSS
STIMULATE PTH
1,25(OH)2 D PRODUCTION
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Abnormal PTH secretion
„
PTH deficit
„
„
„
Calcitonin
32 amino acids peptide.
„
parathyroidectomy
Hypocalcemia signs and symptoms
Calcitonin is released from parafollicular
(C or clear cells) of the thyroid gland.
„
PTH excess
„
Increased plasma Ca2+can stimulate
calcitonin release.
„
Primary hyperparathyroidism
is the most common cause of hypercalcemia.
„The defect lies with the parathyroid tissue ex. adenoma
„
„
„
„
cAMP is the second messenger in the secretory
process.
„
Secondary hyperparathyroidism
The defect is from other tissue such as chronic renal disease.
Hypercalcemia signs and symptoms
19
Parafollicular cells
20
Calcitonin action
„
„
The exact physiologic role of calcitonin is
uncertain.
BONE
„
„
the osteclastic acitivity.
KIDNEY
„
Ca2+excretion in urine.
21
Calcium homeostasis
THE ONLY “IN”
Other Hormones
Calcitonin
Vit D
DIETARY HABITS,
SUPPLEMENTS
22
„
BONE
PTH
BLOOD CALCIUM
INTESTINAL ABSORPTION
Calcitonin
Active vitamin D
PTH
KIDNEYS
„
Vit D
PTH
GH, IGFs
„Activate chondrocytes
„
intestinal Ca2+absorption.
„
renal PO43 – reabsorption.
Thyroid hormone
„Physiological level: Increase bone formation.
„
URINE
THE PRINCIPLE “OUT”
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Excess: Increase bone resorption by
decrease1,25 DHCC and increase
renal Ca2+excretion.
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Sex hormones
Estrogen
PTH action on bone
Androgen
PTH action on kidney
Bone resorption
Ca2+ excretion
Sex hormones
Osteoporosis
Bone formation
25
Other Hormones
„
Glucocorticoids
„
GI Ca2+absorption.
„
Renal Ca2+excretion.
„
PTH.
Osteoporosis
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