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Calcium Homeostasis and Hormonal Regulation
Serum calcium maintained at a constant level
Cellular & tissue effects of calcium depend on blood calcium maintenance within a specific range.
Adult human body contains 1,000 g of calcium
99% as hydroxyapatite salt
1% in extra-cellular fluids
Diet is only source of calcium
Urine is only significant “way out”
Hormonal Control of Calcium Metabolism
A hormone, not actually a vitamin
Shares striking similarities in origin with steroid hormones: it is a metabolic product of cholesterol synthetic pathway
Tissues involved in synthesis: skin, liver, kidneys
Tissues it affects: gut, bone, parathyroids
Can also be obtained from dietary sources: fortified milk, multivitamins, cod liver oil
Parathyroid Hormone (PTH)
Secreted from 4 parathyroid glands in region of thyroid gland
Parathyroid glands have calcium-sensing receptors that respond to calcium levels by increasing or decreasing PTH secretion.
Stimulates bone resorption and release of calcium into blood
Acts on kidney to increase fractional reabsorption of renal tubular calcium & drive production of active metabolite
Promotes intestinal absorption of calcium
All functions raise blood calcium & are mediated via a specific PTH receptor.
Organ Physiology and Calcium Metabolism
Factors required for calcium absorption
Normal intestinal function (short bowel syndrome & genetic or physiologic defects may have negative effect)
Adequate dietary calcium intake
Normal vitamin D availability & metabolism
Role of Kidneys
Diseased kidney impairs calcium metabolism.
PHPT, calcium kidney stones
Bone turnover (remodeling): coupled process of simultaneous bone formation & breakdown occurring throughout life
Bone formation is mediated by osteoblasts.Bone breakdown (resorption) is mediated by osteoclasts.
When resorption exceeds formation, bone mass decreases (increased risk of fracture).
Two main types of bone in skeleton
Cortical: primary type in long bones (femur); strong, rigid
Trabecular: axial skeleton (vertebrae); has many cross-hair type connections (trabeculae), providing strength & elasticity
Blood calcium levels above expected normal range
Binding of calcium to other substances must be taken into account when considering total calcium levels.
PHPT most common cause of hypercalcemia in outpatient setting.
Causes of hypercalcemia(other than PHPT)
Secondary and tertiary hyperparathyroidism
CSR (calcium sensing receptor) abnormalities
Endocrine Causes of Hypercalcemia
Cancers (PTHrP), tumors
Signs and Symptoms
CNS: lethargy, decreased alertness, depression, confusion, forgetfulness, obtundation, coma
GI: anorexia, constipation, nausea & vomiting
Renal: impairs kidney’s ability to concentrate urine, leading to dehydration, increased risk of kidney stones
Skeletal: increased bone resorption, increased bone demineralization & risk of fracture
Cardiovascular: causes or exacerbates hypertension
Familial Hypocalciuric Hypercalcemia
Stable, mild hypercalcemia from birth
Hyperthyroidism and Addison’s disease, Addisonian crisis can also cause hypercalcemia
Medications That Can Cause Hypercalcemia
State of blood calcium levels below expected range; best measured by ionized calcium
Signs and symptoms
Neuromuscular: tetany in hands, feet, legs, back; Chvostek’s sign; numbness & tingling in face, hands, & feet
CNS: irritability, seizures, personality changes, impaired intellectual functioning
Cardiovascular: QT prolongation, electromechanical dissociation
Parathyroid glands, when functioning properly, will not only correct falling blood calcium but also prevent it by increasing PTH secretion.
Compensatory rise in PTH secretion is known as secondary hyperparathyroidism.
Intestinal disorders resulting in inadequate calcium or vitamin D absorption
Genetic defects resulting in impaired ability to recover filtered calcium from tubular fluid
Endocrine Causes of Hypocalcemia
Neck surgery (removal of or damage to parathyroid glands)
Autoimmune destruction of parathyroid tissue
Mutations in PTH gene
Pseudohypoparathyroidism (lack of responsiveness to PTH)
Medications That Affect Calcium Metabolism
Medications that stimulate bone resorption
Metabolic Bone Diseases
Occurs in growing bone (in children)
Bony deformities from bending of long bones due to gravity
Occurs in bone in adults (after closure of epiphyseal plates)
No bony deformities
Most prevalent metabolic bone disease in adults
Based on clinical characteristics and/or a DEXA scan
Fragility fracture: fracture occurring at an inappropriate degree of trauma
Directed at primary consequence of disease: fracture
Modification of preventable risk factors, such as smoking & alcohol consumption
Prevention for those with family history: minimize bone loss, increase bone density, & prevent fracture
Adequate dietary calcium & vitamin D