Introduction to Bone: physiology and disease A mini-course designed for summer students; Sponsored by the Center for Skeletal Research June 27, 2018 Calcium and phosphate homeostasis Henry Kronenberg, MD Extracellular Intracellular Calcium ions Phosphate ions Extracellular Intracellular Concentration 10 -7 M 1-2 x 10 -3 M Functions signal for • structural: DNA, RNA • neuronal activation • high energy bonds • hormone secretion • signaling by phospho- • muscle contraction proteins/lipids Calcium ions Phosphate ions
Transcript
Introduction to Bone: physiology and diseaseA mini-course designed for summer students; Sponsored by the Center for Skeletal Research
June 27, 2018
Calcium and phosphate homeostasis
Henry Kronenberg, MD
Extracellular
Intracellular
Calcium ions Phosphate ions
Extracellular
IntracellularConcentration 10-7 M 1-2 x 10-3 M
Functions signal for • structural: DNA, RNA• neuronal activation • high energy bonds• hormone secretion • signaling by phospho-• muscle contraction proteins/lipids
Calcium ions Phosphate ions
ExtracellularConcentration
total, in serum 2.5 x 10-3 M 1.00 x 10-3 Mfree 1.2 x 10-3 M 0.85 x 10-3 M
Functions bone mineral bone mineralblood coagulation source for intracellularcell adhesion (cadherin)source for intracellular
IntracellularConcentration 10-7 M 1-2 x 10-3 M
Functions signal for • structural: DNA, RNA• neuronal activation • high energy bonds• hormone secretion • signaling by phospho-• muscle contraction proteins/lipids
Calcium ions Phosphate ions
Regulators of mineral metabolism
• Parathyroid hormone
• Vitamin D
• Fibroblast growth factor (FGF) 23• Calcium
• Phosphate
Regulators of mineral metabolism
• Parathyroid hormone
• Vitamin D
• Fibroblast growth factor (FGF) 23• Calcium
• Phosphate
Level of calcium in blood was low. Level of calcium normalized.
1 34 fully active
Parathyroid hormone (PTH)
PTH1 13 34 84
PTH bioactivity
600aa
Parathyroid Bone
PTH
Ca++
Calcium regulates PTH secretion
Parathyroid adenomas:one cell goes bad
Primary hyperparathyroidism:• Too many cells• Cells respond less well to hypercalcemia
Patient 1The patient was in the merchant marine in WWI. Just after the war, at age 30, he noticed back pain and the beginning of loss of height. Over the next several years, he passed “gravel” in his urine.
Patient 1The patient was in the merchant marine in WWI. Just after the war, at age 30, he noticed back pain and the beginning of loss of height. Over the next several years, he passed “gravel” in his urine.
At age 33, he fractured his upper arm and later his lower arm. X-rays showed multiple fractures and osteopenia. The diagnosis of hyperparathyroidism was suggested, and he was found to have a high level of calcium in the blood and urine. Surgery was performed and two normal parathyroid glands removed.
Patient 1The patient was in the merchant marine in WWI. Just after the war, at age 30, he noticed back pain and the beginning of loss of height. Over the next several years, he passed “gravel” in his urine.
At age 33, he fractured his upper arm and later his lower arm. X-rays showed multiple fractures and osteopenia. The diagnosis of hyperparathyroidism was suggested, and he was found to have a high level of calcium in the blood and urine. Surgery was performed and two normal parathyroid glands removed.
At age 39, after more vertebral crush fractures and kidney stones, he underwent 4 more operations (the last 3 at MGH). At the last one, a parathyroid tumor was removed from his mediastinum. He died a few days later of sepsis in association with a renal stone.
Patient 2This patient is an 72 year old woman who had some routine blood tests performed at the time of her annual exam.
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