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Hormone Control of Calcium Metabolism - PHYSIOLOGY, PHYSIOLOGY

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Microsoft PowerPoint - Calciummet08.ppt...
Calcium and Phosphate function
THE ONLY “IN”
THE PRINCIPLE “OUT”
Bone release Ca++Bone release Ca++ Bone incorporates Ca++Bone incorporates Ca++
Intestine absorbs Ca++Intestine absorbs Ca++Kidney conserve Ca++Kidney conserve Ca++
Ca++ is excreted in urineCa++ is excreted in urine Ca++ is excreted from dietCa++ is excreted from diet
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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 sensing receptor (CaSR).
PTH binds to PTH/PTHrP receptor.
2nd messenger of PTH is cAMP (PKA pathway).
Parathyroid glandsParathyroid glands
in the urine.
PTH increases Ca2+ reabsorption at the distal
convoluted tubules (transcellular).
NCX: sodium/calcium exchanger
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PTH
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PTH acts on osteoblasts to inhibit the synthesis of collagen (inhibition of bone formation).
PTH actions (Bone)
PTH acts on osteoblasts to stimulate secretion of RANKL , which acts on the osteoclasts to promote demineralization and Ca2+release (osteoclastic bone resorption)
RANKL: receptor activator of NF-kB ligand
PTH also activates Ca2+pumps within the surface osteoblasts to move Ca2+out of bone fluid and into the extracellular fluid (ECF).
PTH actions (Bone)
[Ca2+] [PO4 3 - ]
[Ca2+] [PO4 3 - ]
Osteoblasts
Parathyroid glandsParathyroid glands
Increase blood Ca++Increase blood Ca++
Bone releases Ca++Bone releases Ca++ Kidney conserve Ca++Kidney conserve Ca++ Increase active Increase active VitVit D D Intestine absorbs Intestine absorbs
Ca++Ca++
PTH excess Primary hyperparathyroidism
is the most common cause of hypercalcemia. The defect lies with the parathyroid tissue ex. adenoma
Secondary hyperparathyroidism The defect is from other tissue such as chronic renal disease.
Hypercalcemia signs and symptoms
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Vitamin D mechanism of action The action of Vit. D is mediated by altered gene
transcription resulting in the synthesis of specific proteins.
5’ UNTRANSLATED REGION VITAMIN D RESPONSIVE GENE
TRANSCRIPTION START SITE
VIT D / VDR
epithelium
Ca2+ binding protein (CaBP) or by affecting Ca2+ transport directly
plasma membrane Ca2+ ATPase pump Ca2+
(PMCA) from enterocyte to blood
BONE mineralization from blood Ca2+ to bone
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Eletrochemical gradient
Ca2+
Ca2+
PARATHYROID
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Uncalcified osteoid tissue Clinical syndromes broadly categorized as Rickets and Osteomalacia. Decreased blood calcium.
Vitamin D excess Hypercalcemia (rare).
Rickets / Osteomalacia
NORMAL BLOOD Ca2+
RISING BLOOD Ca2+
FALLING BLOOD Ca2+
Calcitonin 32 amino acids peptide.
Calcitonin is released from parafollicular (C or clear cells) of the thyroid gland.
Increased plasma Ca2+can stimulate calcitonin release. cAMP is the second messenger in the secretory
process.
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BONE the osteclastic activity.
3 – reabsorption.
Physiological level: Increase bone formation.
Excess: Increase bone resorption by decrease1,25 DHCC and increase renal Ca2+excretion.
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Bone resorption Ca2+ excretion
PTH.
Hormone secretion and hormone action
Neurotransmission
A covalent modifier of the activity of numerous enzymes.
A component of many intermediates in glucose metabolism eg G-6-P.
A component of all high energy transfer compounds eg ATP, NADP.
Blood Calcium
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NEUROMUSCULAR: INVOLUNTARY MUSCLE CONTRACTION (TETANY), 7TH CRANIAL NERVE EXCITABILITY (CHVOSTEK’S SIGN), NUMBNESS AND TINGLING IN FACE, HANDS, AND FEET, TROUSSEAU’S SIGN
CNS: IRRITABILITY, SEIZURES
Hypercalcemia: sign and symptoms
CNS: lethargy, depression, decreased alertness, confusion, and coma GI: anorexia, constipation, nausea, and vomiting RENAL: diuresis, impaired concentrating ability, dehydration. Hypercalciuria is a risk for kidney stones. SKELETAL: most causes of hypercalcemia are associated with increased bone resorption, and thus, fracture risk CARDIOVASCULAR: shortened QT interval
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Plasma calcium
PTH secretion
Plasma Phosphate
Renal Phosphate
1,25 DHCC
INTESTINAL ABSORPTION
BONE RESORPTION
Plasma phosphate
Urine phosphate
Urine calcium
Plasma calcium
Calcitonin secretion

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