Term
| What is the physiological importance of Calcium? |
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Definition
Calcium salts in bone provide structural integrity of the skeleton. Calcium ion in extracellular and cellular fluids is essential to normal function of a host of biochemical processes such as: Neuromuscular excitability, blood coagulation, hormonal secretion, enzymatic regulation |
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Term
| How specific is should the concentration of calcium in the body be? |
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Definition
| Both extracellulary and intracellulary, it must be maintained within a very narrow range. This is achieved by an elaborate system of controls. |
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Term
| What happens when extracellular calcium levels fall below normal? |
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Definition
The nervous system becomes progressively more excitable because of increased permeability of neuronal membrans to sodium. Hyperexcitability causes tetanic contractions |
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Term
| What is calcium associated with for regulation, and what else is this used for? |
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Definition
Calcium is tightly regulated with phosphorous in the body. Phosphorous is an essential mineral necessary for ATP, cAMP second messenger systems, and other roles. |
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Term
| How much calcium should be in our diet, bones, fecal excretions, urinary excretions, and exchangeable pool? |
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Definition
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Term
| Where should there be increased levels of phosphate? |
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Definition
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Term
| 99% of calcium is found where, and in what form? |
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Definition
| 99% of calcium is found in the bone, in hydroxyapatite crystals. However, although it is a major reservoir of Ca+, very little can be released from the bone. |
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Term
| What makes up 80% of our bones? |
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Definition
| Cortical bone, such as dense concentric layers of appendicular skeleton (long bones) |
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Term
| What makes up 20% of our bone mass? |
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Definition
| Trabecular bone, bridges off bone spicules of the axial skeleton (skull, ribs, vertebrae, pelvis) |
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Term
| How much of adult bone mass turns over each year? |
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Definition
| 10% of bone mass turns over each year during the remodeling process |
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Term
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Definition
| The differentiated bone forming cells and secrete bone matrix on which Ca++ and PO precipitate |
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Term
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Definition
| The mature bone cells that are enclosed in bone matrix |
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Term
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Definition
| Large, multinucleated cells derived from monocytes whose function is to resorb bone. |
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Term
| What factors are needed for mineralization? |
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Definition
Requires adequate Calcium and phosphate Dependent on Vitamin D Alkaline phosphatase and osteocalcin play roles in bone formation Their plasma levels are indicators of osteoblast activity |
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Term
| What processes control bone formation and resorption? |
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Definition
Bone resorption of Ca++ by two mechanisms Osteocytic osteolysis is a rapid and transient effect and osteoclastic resorption which is slow and sustained. Both are stimulated by PTH (Para-thyroid hormone) |
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Term
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Definition
Does not merely extract calcium, it destroys entire matrix of bone and diminishes bone mass. Cell responsible for resorption is the osteoclast |
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Term
| What is Osteoporosis and how can it be prevented? |
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Definition
Reduced bone density and mass Susceptibility to fracture Earlier in life for women than men but eventually both genders succumb You can reduce your risk with: Calcium in diet, habitual exercise, avoidance of smoking and alcohol intake, avoid drinking carbonated soft drinks |
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Term
| What is bone formation stimulated by? |
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Definition
Growth-hormone Insulin-like growth factors Insulin Estrogen Androgen Vitamin D (mineralization) Transforming growth factor-Beta Skeletal Growth factor Bone-derived growth factor Platelet-derived growth factor Calcitonin Parathyroid Hormone |
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Term
| Bone formation is inhibited by what? |
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Definition
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Term
| What stimulates bone resorption? |
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Definition
Parathyroid Hormone (Constant) Vitamin D Cortisol Thryoid Hormone Prostaglandins Interleukin-1 Interleukin-6 Tumor Necrosis Factor alpha Tumor Necrosis Factor beta |
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Term
| What inhibits bone resorption? |
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Definition
Estrogen Androgen Calcitonin Transforming Growth Factor-beta gamma-Interferon Nitric Oxide |
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Term
| What three hormones control Ca+, and how? |
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Definition
| Parathyroid hormone (PTH), 1,25-dihydroxy Vitamin D3 (Vitamin D3), and Calcitonin. These regulate Ca+ resorption, reabsorption, absorption and excretion from the bone, kidney and intestine. In addition, many other hormones effect bone formation and resorption. |
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Term
| What role does Vitamin D play? |
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Definition
Vitamin D, after its activation to the hormone 1,25-dihydroxy Vitamin D3 is a principal regulator of Ca+. Vitamin D increases Ca+ absorption from the intestine and Ca+ resorption from the bone. |
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Term
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Definition
Humans acquire Vitamin D from two sources Vitamin D is produced in the skin by ultraviolet radiation and ingested in the diet. Vitamin D is not a classic hormone because it is not produced and secreted by an endocrine "gland." Nor is it a true "vitamin" since it can be synthesized de novo (as needed?). Vitamin D is a true hormone that acts on distant target cells to evoke responses after binding to high affinity receptors. |
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Term
| How is Vitamin D synthesized? |
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Definition
Vitamin D3 synthesis occurs in keratinocytes in the skin. 7-dehydrocholesterol is photoconverted to previtamin D3, then spontaneously convers to Vitamin D3 Previtamin D3 will become degraded by over exposure to UV light and thus is not overproduced. Also 1,25-dihydroxy-D (the end product of Vitamin D synthesis) feeds back to inhibit its production. |
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Term
| What stimulates Vitamin D synthesis, and how is Vitamin D activated? |
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Definition
PTH stimulates Vitamin D synthesis. In the winter or if exposure to sunlight is limited (indoor jobs!), then dietary Vitamin D is essential. Vitamin D itself is inactive, it requires modification to the active metabolite, 1,25 dihydroxy-D. The first hydroxylation reaction takes place in the liver yielding 25-hydroxy D Then 25-Hydroxy D is transported to the kidney where the second hydroxylation reaction takes place. |
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Term
| Synthesis of Vitamin D (continued) |
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Definition
25-hydroxy D is converted to 1,25-dihydroxy-D, the most potent metabolite of Vitamin D, by use of the mitochondrial P450 enzyme 1alpha-hydroxylase. The 1alpha-hydroxylase enzyme is the point of regulation of D synthesis. Feedback regulation by 1,25-dihydroxy D inhibits this enzyme. PTH stimulates 1alpha-hydroxylase and increases 1,25-dihydroxy D. |
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Term
| Synthesis of Vitamin D (continued) |
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Definition
25-OH-D3 is also hydroxylated in the 24 position which inactivates it. If excess 1,25-(OH)2-D is produced, it can also be to remove it. Phosphatet inhibits 1alpha-hydroxylase and decreased levels of PO4 stimulate 1alpha hydroxylase activity |
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Term
| Is Vitamin D water soluble or lipid soluble? |
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Definition
Vitamin D is a lipid soluble hormone that binds to a typical nuclear receptor, analogous to steroid hormones Because it is lipid soluble, it travels in the blood bound to hydroxylated alpha-globulin. There are many target genes for Vitamin D |
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Term
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Definition
The main action of 1,25-(OH)2-D is to stimulate absorption of Ca+ from the intestine This vitamin induces the production of calcium binding proteins which sequester Ca+, buffer high Ca+ concentrations that arise during initial absorption. |
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Term
| What are some Vitamin D disorders? |
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Definition
Vitamin D-dependent rickets Type II Mutation in 1,25-(OH)2-D receptor Disorder characterized by impaired intestinal calcium absorption |
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Term
| How does Vitamin D affect bone formation? |
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Definition
Proper bone formation is stimulated by 1,25-(OH)2-D. In its absence, excess osteoid accumulates from lack of 1,25-(OH)2-D repression of osteoblastic collagen synthesis. Inadequate supply of Vitamin D results in rickets, a disease of bone deformation. |
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Term
| What is PTH and where does it come from? |
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Definition
PTH is synthesized and secreted by the parathyroid gland which lies posterior to the thyroid glands. The blood supply to the parathyroid glands is from the thyroid arteries. The Chief Cells in the parathyroid gland are the principal site of PTH synthesis |
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Term
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Definition
PTH is translated as a pre-prohormone Cleavage of leader and pro-sequences yield a biologically active peptide of 84 amino acids. Cleavage of C-terminal end yields a biologically inactive peptide. |
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Term
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Definition
The dominant regulator of PTH is plasma Ca+ Secretion of PTH is inversely related to [Ca+] |
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Term
| How does PTH respond to changes in Ca+? |
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Definition
PTH secretion responds to small alterations in plasma Ca+ within seconds. This is because a unique calcium receptor within the parathyroid cell plasma membrane senses changes in the extracellular fluid concentration of Ca+. |
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Term
| What is PTH's primary action? |
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Definition
The overall action of PTH is to increase plasma Ca levels and decrease plasma phosphate levels PTH acts directly on the bones to stimulate Ca resorption, and on the kidney to stimulated Ca reabsorption in the distal tubule of the kidney and to inhibit reabsorption of phosphate (thereby stimulating its excretion). PTH also acts indirectly on intestine by stimulating 1,25-(OH)2-D synthesis |
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Term
| What is Primary Hyperthyroidism and how is it caused? |
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Definition
Calcium homeostatic loss due to excessive PTH secretion Due to excess PTH secreted from adenomatous or hyperplastic parathyroid tissue Hypercalcemia results from combined effects of PTH-induced bone resorption, intestinal calcium absorption and renal tubular reabsorption. Pathophysiology related to both PTH excess and concomitant excessive production of 1,25-(OH)2-D. |
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Term
| What is hypothyroidism and how is it caused? |
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Definition
Hypocalcemia occurs when there is inadequate response of the Vitamin D - PTH axis to hypocalcemic stimuli. Hypocalcemia is often multifactorial Hypocalcemia is invariably associated with hypoparathyroidism Bihormonal - concomitant decrease in 1,25-(OH)2-D |
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Term
| What is PTH-deficient hypothyroidism and how is it caused? |
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Definition
Reduced or absent synthesis of PTH Often due to inadvertent removal of excessive parathyroid tissue during thyroid or parathyroid surgery. |
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Term
| What is the cause of PTH-ineffective hypothyroidism? |
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Definition
| Synthesis of biologically inactive PTH |
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Term
| What is Pseudohypoparathyroidism? |
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Definition
PTH-resistant hypothyroidism; this is due to defect in PTH receptor-adenylate cyclase complex Mutation in G alpha S subunit. |
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Term
| What is Calcitonin's main action? |
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Definition
Calcitonin acts to decrease plasma Ca+ levels. While PTH and Vitamin D act to increase plasma Ca+ -- only Calcitonin causes a decrease in plasma Ca+. Calcitonin is synthesized and secreted by the parafollicular cells of the thyroid gland. |
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Term
| What changes the level of Calcitonin? |
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Definition
The major stimulus of calcitonin secretion is a rise in plasma Ca+ levels Calcitonin is a physiolgocial antagonist to PTH with regard to Ca++ homeostasis. |
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Term
| How is Calcitonin activated? |
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Definition
- Calcitonin acts via increased cAMP concentrations to inhibit osteoclast motilty and cell shape and inactivates them The major effect of calcitonin administration is a rapid fall in Ca+ caused by inhibition of bone resorption. |
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