disorders of calcium and phosphate metabolism - pum.edu.pl · major mediators of calcium and...
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Disorders of Calcium and
Phosphate Metabolism
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Major Mediators of Calcium and
Phosphate Balance
Parathyroid hormone (PTH)
Calcitriol (active form of vitamin D3)
Calcitonin
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Parathyroid Hormone
In parathyroid cells – 115 amino acid pre-
pro-PTH – cleaved to 90 aa pro-PTH –
cleaved again:
1-84 aa full molecule = INTACT PTH – is
excreted – this is 4 to 35 % of total PTH.
BUT further cleavage in cells also gives
carboxyl fragments: 7-84 aa = inactive PTH-
C – also excreted with half-life 24-36 h !!
Amino terminal fragments presumably
have short half-life – also active
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Role of PTH
Stimulates renal reabsorption of calcium
Inhibits renal reabsorption of phosphate
Stimulates bone resorption
Inhibits bone formation and mineralization
Stimulates synthesis of calcitriol
Net effect of PTH ↑ serum calcium
↓ serum phosphate
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Regulation of PTH
Low serum [Ca+2] Increased PTH secretion
High serum [Ca+2] Decreased PTH secretion
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Stimulates GI absorption of both calcium
and phosphate
Stimulates renal reabsorption of both
calcium and phosphate – contrast PTH
Can stimulate bone mineralisation (as well
as resorption) – contrast PTH – only
resorption
Role of Calcitriol
Net effect of calcitriol
↑ serum calcium
↑ serum phosphate
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Regulation of Calcitriol
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Different Forms of Calcium
At any one time, most of the calcium in the body exists as the mineral hydroxyapatite, Ca10(PO4)6(OH)2.
Calcium in the plasma:
45% in ionized form (the physiologically active form)
45% bound to proteins (predominantly albumin)
10% complexed with anions (citrate, sulfate, phosphate)
To adjust the total calcium in states of hypoalbuminemia:
[Ca+2]Corrected= [Ca+2 mg/dl]Measured+[0.8 x (4– Albumin(g/dL)]
[Ca+2]Corrected=[Ca+2 mM]Measured+[0.02 x (47 – Albumin (g/L)]
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Etiologies of Hypercalcemia Increased GI Absorption
Milk-alkali syndrome
Elevated calcitriol
Vitamin D excess
Excessive dietary intake
Granulomatous diseases
Elevated PTH*
Hypophosphatemia
Increased Loss From Bone
Increased net bone resorption
Elevated PTH*
Hyperparathyroidism
Malignancy*
Osteolytic metastases
PTHrP secreting tumor
Increased bone turnover
Paget’s disease of bone
Hyperthyroidism
Decreased Bone
Mineralization
Elevated PTH*
Aluminum toxicity
Decreased Urinary
Excretion
Thiazide diuretics*
Elevated calcitriol
Elevated PTH*
Familial
Hypocalciuric hypercalcemia
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Possible causes of hypercalcemia
elevated PTH
malignancy
Vit. D
Granulomatous disease
Thyrotoxicosis
Diuretic therapy
Immobilization
Renal disease
Calcium therapy
Milk-alkali syndrome
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Secondary
Hyperpara
HYPOCALCEMIA
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Etiologies of Hypocalcemia
Decreased GI Absorption
Poor dietary intake of calcium
Impaired absorption of calcium
Vitamin D deficiency
Poor dietary intake of vitamin D
Malabsorption syndromes
Decreased conversion of vit. D to calcitriol
Liver failure
Renal failure
Low PTH eg. via low Mg.
Hyperphosphatemia
Decreased Bone Resorption/Increased
Mineralization
Low PTH (aka hypoparathyroidism) eg. via low Mg.
PTH resistance (aka pseudohypoparathyroidism)
Vitamin D deficiency / low calcitriol
Hungry bones syndrome
Osteoblastic metastases
Increased Urinary Excretion
Low PTH eg. via low Mg.
s/p thyroidectomy
s/p I131 treatment
Autoimmune hypoparathyroidism
PTH resistance
Vitamin D deficiency / low calcitriol
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>2.2
normal <2.2
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AND CALCITONIN !!
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Etiologies of Hyperphosphatemia
Increased GI Intake
Fleet’s Phospho-Soda
Decreased Urinary Excretion
Renal Failure
Low PTH (hypoparathyroidism)
s/p thyroidectomy
s/p I131 treatment for Graves disease or thyroid cancer
Autoimmune hypoparathyroidism
Cell Lysis
Rhabdomyolysis
Tumor lysis syndrome
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Etiologies of Hypophosphatemia Decreased GI Absorption
Decreased dietary intake (rare in isolation)
Diarrhea / Malabsorption
Phosphate binders (calcium acetate, Al & Mg containing antacids)
Decreased Bone Resorption / Increased Bone Mineralization
Vitamin D deficiency / low calcitriol
Hungry bones syndrome
Osteoblastic metastases
Increased Urinary Excretion
Elevated PTH (as in primary hyperparathyroidism)
Vitamin D deficiency / low calcitriol
Fanconi syndrome
Internal Redistribution (due to acute stimulation of glycolysis)
Refeeding syndrome (seen in starvation, anorexia, and alcoholism)
During treatment for DKA
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HPT
the symptoms of hyperparathyroidism can be remembered by the rhyme "moans, groans, stones, bones, and psychiatric overtones":
"moans" (complaints of not feeling well)
"groans" (abdominal pain, gastroesophageal reflux)
"stones" (kidney)
"bones" (bone pain)
"psychiatric overtones" (lethargy, fatigue, depression, memory problems).
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