Hormonal Control of Calcium Homeostasis
Intracellular calcium
- Majority of calcium in mitochondria and ER - Concentrations fluctuate greatly (100 nM to 1 uM) Integral to calcium's role in intracellular signaling, enzyme activation and muscle contractions
Primary hyperparathyroidism
- parathyroid gland disease - most commonly due to a parathyroid tumor (adenoma) which secretes PTH without proper regulation. - symptoms: chronic elevations of blood calcium concentration (hypercalcemia), kidney stones and decalcification of bone
Milk Fever - Predisposing Factors
1. Cold stress: subzero temperatures can induce hypocalcaemia 2. Body condition: milk fever is more prevalent in over-fat cows (fatty liver) than in thin cows à mobilization of fatty acids can affect blood calcium levels 3. Breed: some breeds of cows are more susceptible 4. Age: older cows have increased milk production and greater demands for calcium
Importance of Calcium
1. Structural component (with phosphate) of bones, teeth 2. Blood clotting 3. Maintain transmembrane potential of cells (along with Na+ and K+) 4. Muscle contraction 5. Second messenger in hormonal and neurocrine signal transduction
Histology of the Parathyroid Gland
1.) Chief cells: source of PTH; most numerous 2. oxyphil cells: unknown function, appear at puberty, increase in number with age.
Distribution of Calcium
1.) Intracellular Calcium 2.) Blood and Extracellular Fluid 3.) Bone
Hormones that Regulate Calcium Homeostasis
1.) Parathyroid 2.) Vitamin D 3.) Calcitonin
Calcitonin (CT)
A hypocalcemic hormone (↓ blood Ca2+) A 32 amino acid polypeptide hormone synthesized by parafollicular "C cells" of the thyroid gland Release is stimulated by elevated blood Ca2+ level
Parathyroid Hormone Secretion
Calcium concentrations fall below the normal range, there is a steep increase in secretion of parathyroid hormone Low levels of the hormone are secreted even when blood calcium levels are high
Blood and extracellular fluid
Concentration approximately 1 mM, or 10,000X the basal concentration of free calcium within cells.
Pathophysiology
Critical to maintain blood calcium concentrations within a tight normal range. Deviations above or below the normal range frequently lead to serious disease. Hyper and hypcalcemia.
Ca 2+ Physiology
Cytosolic and extracellular fluid physiology must be maintained within narrow limits despite wide fluctuations in Ca2+ intake. It is a key element in numerous physiological functions Derived from diet or as a structural component of bone
hormones regulate calcium homeostasis
PTH increases blood calcium and vitamin d synthesis. Vitamin D increases calcium absorption in the intestine. Calcitonin inhibits bone resorption.
Parathyroid Hormone (PTH)
PTH is a single-chain polypeptide hormone of 84 amino acids. PTH is a hypercalcemic hormone (↑ blood Ca2+) Control of PTH secretion = circulating Ca2+ levels Parathyroid cells (chief cells) have recognition sites for Ca2+ - calcium sensing receptors (CaSR) - seven-spanning membrane G-protein coupled receptor
Calcium Regulation
Regulation of calcium homeostasis occurs via transfer of calcium between the blood and 3 major target organs: bone, intestine, kidney.
Mechanism of PTH Release
Review Notes
Milk Fever: Prevention
The DCAD method • Feeding a calcium-deficient diet • Higher dietary magnesium If total absorbed diet calcium is substantially less than required by the cow, it is possible to stimulate the secretion of PTH before calving which can stimulate bone Ca resorption and intestinal Ca absorption mechanisms prior to calving to prevent milk fever
Function of Calcitonin
The main function of calcitonin is to inhibit bone resorption by inhibiting osteoclasts (breakdown of bone) 1. stimulates osteoblasts to form bone taking calcium out of the circulation 2. inhibits the mobilization of bone (and calcium) by osteoclasts 3. end result is a decrease in the level of calcium in the blood thus helping to maintain proper blood calcium levels
Bone
The majority of body calcium is in bone 99% of the calcium is tied up in the mineral phase The remaining 1% is in a pool that can rapidly exchange with extracellular calcium
Reabsorption
The process of re-absorbing (absorbing again)
Resorption
The processes of breaking down and assimilating (CA 2+ mobilization)
Calcium Regulation - Small Intestine
The site where dietary Ca2+ is actively transported across mucosa. Dependent on expression of a Ca2+ -binding protein in epithelial cells.
Calcium Regulation - Bone
The vast reservoir of Ca2+ (immediate source of Ca2+) Stimulates resorption of bone mineral releases Ca2+ and phosphate into blood
Calcium Regulation - Kidney
Under normal blood Ca2+ concentrations, almost all of the Ca2+ that enters glomerular filtrate is reabsorbed from the tubular system back into blood, which preserves blood Ca2+ concentration. If tubular reabsorption of Ca2+ decreases, Ca2+ is lost by excretion into urine.
Secondary hyperparathyroidism
disease outside of the parathyroid gland leads to excessive secretion of PTH - kidney disease - kidneys are unable to reabsorb Ca2+, blood calcium levels will fall, stimulating continual secretion of PTH to maintain Ca2+ levels in blood - inadequate nutrition - for example, diets that are deficient in Ca2+ or vitamin D - ↑decalcification of bone, leading to pathologic fractures or "rubber bones".
Milk Fever
economically important metabolic condition that occurs at the onset of lactation - can reduce the productive life of a dairy cow • clinical symptoms include: - reduced appetite and rumen motility - inhibition of urination and defecation - lateral recumbency - eventual coma and death • cows recovering from milk fever have greater incidence of: - ketosis, mastitis, dystocia, retained placenta, displaced placenta and uterine prolapse
Hypoparathyroidism
typically results in decreased Ca2+ blood (HYPOCALCEMIA) • causes include surgical removal of the parathyroid glands and disease processes that lead to destruction of parathyroid glands • leads to tetany and convulsions, and can be acutely lifethreatening • treatment focuses on restoring normal blood calcium concentrations by calcium infusions, oral calcium supplements and vitamin D therapy
Parathyroid Glands
• Generally two pairs, located behind the thyroid gland • About 2-5% of the human population has supernumerary parathyroids (usually 6 to 8 glands) • The parathyroid glands evolved from gills, which also regulate calcium and ionic balance in fishes • Parathyroid glands are not associated with thyroid in birds, reptiles, amphibians
Milk Fever: Treatment
• supplementing blood calcium levels until the bone and intestinal transport systems adapt to provide the necessary calcium • should be implemented as early as possible • most common à IV injection of calcium salts, usually calcium borogluconate • must be administered slowly as it can result in cardiac arrest • calcium and phosphorus supplements (oral gels) can also be given around parturition
Vitamin D
•Also known as cholecalciferol • acts to ↑ blood [Ca2+] • not actually a vitamin, instead a precursor of a steroid-like hormone • generated through the activity of PTH within the kidney • the most important effect of VitD is to facilitate absorption of Ca2+ from the small intestine • in concert with PTH, VitD also enhances fluxes of Ca2+ out of bone