Calcium Homeostasis and Hormonal Regulation
impulse transmission and muscular contraction
calcium functions for optimal excitability of neural and muscular tissue
blood coagulation, hormone secretion, and intracellular adhesion
calcium functions for organ systems
skin, liver, small intestine, skeleton, parathyroid glands, kidneys
organs calcium maintains homeostasis for
mineral repository
calcium skeletal function
hydroxyapatite salt
makes up 99% of calcium in the human body
extracellular fluids
makes up 1% of calcium in the human body
ionized
form of 50% of calcium in the blood
protein bound
form of 40% of calcium in the blood
complexed to citrate and phosphate
form of 10% of calcium in the blood
pH
influences calcium binding
vitamin D, parathyroid hormone, and calcitonin
hormones responsible for regulating bone and mineral metabolism through calcium homeostasis
vitmain D
metabolic product of cholesterol synthesis; skin, liver and kidneys
7-dehydrocholesterol -> vitamin D3 (by UV light) + hepatic 25-hydroxylase = 25-hydroxy vitamin D
de novo vitamin D synthesis
hepatic 25-hydroxylase
metabolizes vitamin D3 to 25-hydroxy vitamin D
25-hydroxy vitamin D
measured to assess vitamin D stores
rickets and osteomalacia
two conditions which have low levels of vitamin D
renal 1alpha-hydroxylase
enzyme that converts 1,25-dihydroxy vitamin D to active form
PTH
regulates 1alpha-hydroxylase
increased vitamin D, increased calcium, increased intestinal absorption
relationship between vitamin D and calcium
PTH
preserves blood calcium and phosphate in the normal range
raise blood calcium, increase bone resorption to increase blood levels, increase kidney reabsorption of renal tubular calcium, stimulates 1alpha-hydroxylation of 25-hydroxyl vitamin D, indirectly stimulates intestinal absorption, and lowers phosphate levels through excretion
functions of parathyroid hormone (6)
calcium sensing receptors
contained within the parathyroid to regulate PTH secretion
suppresses PTH
high calcium affect on PTH
stimulates PTH
low calcium affect on PTH
1,25(OD)2D levels
control calcium absorption
phosphate
binds calcium in the lumen forming insoluble calcium phosphate precipitate
normal GI function
required for maintaining calcium absorption
renal failure
significantly impacts calcium and phosphate metabolism and secretion of phosphate; blocks hydroxylation leading to inactive forms of vitamin D being created; increased PTH then causes calcium phosphate complexes, hypercalcemia, and potential kidney stone development
bone
repository for calcium, phosphate, and magnesium
osteoblasts
mediate bone formation
osteoclasts
mediate bone breakdown and resorption
vitamin D and PTH
act on osteoblasts
osteoblasts
produce hormones to regulate osteoclasts
bone remodeling
imbalance leads to osteoporosis and fracture risk
cortical
shaft of long bones
trabecular
axial skeleton honeycomb bones
8.6-10.0 mg/dL
total calcium reference range
4.6-5.3 mg/dL
ionized calcium reference range
increased or decreased with ionized calcium levels
albumin's relationship to calcium levels
duration of elevation
factor that determines symptoms and damage of increased calcium levels
CNS, GI, renal, skeletal, and cardiovascular
systems affected by hypercalcemia
lethargy, decreased altertness, depression, confusion, coma (extreme cases)
CNS affects of hypercalcemia
anorexia, constipation, nausea, vomiting
GI affects of hypercalcemia
impaired concentration leading to hydration since calcium acts as a diuretic
renal affects of hypercalcemia
increased bone resorption and bone demineralization and increased fracture risk
skeletal affects of hypercalcemia
hypertension
cardiovascular affects of hypercalcemia
parathyroid gland and CSR disorders, cancer-mediated, granulomatous diseases (TBm Crohn's), medications (vitamin A and D toxicity), miscellaneous (William's syndrome or immobilization)
5 causes of hypercalcemia
PHPT-primary hyperparathyroidism
autonomous overproduction of PTH caused by adenoma, hyperplasia, carcinoma, familial syndromes
secondary and tertiary hyperparathyroidism
sustained PTH production caused by variety of factors-renal issues hypercalcemic and hyperphosphatemic lead to PT hyperplasia
familial hypocalciuric hypercalemia
inactivating mutation of CSR; calcium receptor antibodies; lithium carbonate
adrenal insufficiency, hyperthyroidism, pheochromocytoma
endocrine disorders that can cause secondary hyperparathyroidism
PTHrP production by tumors
parathyroid-related protein structurally similar to PTH produced in some tumor cells (breast and lung)
lymphomas
increase hydroxylation of vitamin D causing hypercalcemia
cytokine production by tumor cells
activates bone resorption
primary hyperparathyroidism
most common cause of hypercalcemia; autonomous production of PTH; often asymptomatic and identified through routine bloodwork; causes increased calcium, decreased phosphate, and normal to increased PTH
adenoma of one parathyroid gland
most common cause of hyperparathyroidism
familial hypocalciuric hypercalemia
benign condition caused by mutation affecting CSRs; PTH and calcium are increased but stable with a low urine calcium output
hypocalcemia
can be caused by organ system dysfunction, hormone issues, acid-base disturbances; leads to tetany, numbness, tingling, irritability, seizures, impaired mental function, and contractile dysfunction
hypoparathyroidism
can be caused by endocrine issues, vitamin D deficiency, hypomagnesemia, or secondary factors
post-operative, autoimmune, congenital mutations, and pseudohypoparathyroidism
four causes of hypoparathyroidism in which there is a lack of PTH
hypomagnesemia
leads to lack of PTH synthesis and release
secondary hypoparathyroidism
compensatory mechanism of parathyroid to address low calcium levels
pseudohypoparathyroidism
target tissues do not respond to PTH; intracellular signaling process does not work correctly
rickets
bone growth abnormality due to vitamin D deficiency; skeletal deformity and bending of long bones-usually legs
osteomalacia
abnormal bone mineralization after skeletal maturation; increased fracture risk
osteoporosis
most prevalent metabolic disease in adults; silent until fracture; risk factors include hypogonadism, post-menopause, age, family history, lean body, smoking, alcoholism, glucocorticosteroid excess, hyperparathyroidism, and vitamin D metabolism disorders
glucocorticosteroids
inhibit osteoblasts and induce apoptosis by stimulating osteoclasts leading to bone mass loss
tertiary hyperparathyroidism caused by chronic kidney disease
has a significant impact in bone and mineral metabolism; impacted kidneys do not excrete phosphate resulting in calcium-phosphate precipitation; increased PTH secretion to counteract decreased calcium results in hyperplasia which then causes increased calcium