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51 Cards in this Set
- Front
- Back
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what are the roles of calcium ions? |
- Bone and teeth formation (storage of 99% of calcium in bone)
- Normal skeletal and smooth muscle function - Blood coagulation - Normal activity of intracellular enzymes - Maintenance of activity of excitable tissues - Neuromuscular transmission - Cellular hormone release - Normal functioning of the heart |
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How can plasma calcium exist? |
- Free ionised (50%) 1-1.4 mmol/L metabolically and physiologically active
- Protein bound (45%) mainly to albumin and globulins - Complex with several anions (5%) - e.g. bicarbonate, citrate, phosphate and sulphate. |
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what is the level of calcium regulated? |
The calcium level of the body is influenced by dietary intake (~1 g/day) and by the regulatoryactivity of three principal hormones, acting on bone, kidney and the intestinal tract:
1- Parathyroid Hormone - secreted by the parathyroid glands 2- Calcitonin - secreted by thyroid parafollicular 'C' cells 3- 1",25-Dihydroxycholecalciferol- a metabolite of vitamin D |
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How is calcium stored? |
Most (99%) of the body calcium is stored in bone: - a fraction of this may be rapidly mobilizedwhen necessary. Metabolism of phosphate is closely linked with that of calcium |
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how is phosphate related to calcium? |
Phosphate isnecessary for the synthesis of many important molecules in the body e.g. nucleic acids (DNA,RNA), ATP, cAMP, membrane phospholipids, and is also an essential component of bone (ascalcium phosphate and other complex salts). |
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explain the anatomy of parathyroid glands |
The parathyroid glands, consist of 4 ovoid-shaped bodies, each the size of a pea, embeddedposteriorly in the four poles of the thyroid gland, within the thyroid capsule. The parathyroidchief cells secrete parathyroid hormone, which regulates calcium and phosphate metabolism
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how is PTH controlled? |
its secretion from parathyroid chief cells is determined by the circulating blood level of ionizedCa2+. A low plasma Ca2+ concentration directly stimulates PTH release by the parathyroid glands,and a high level suppresses it (negative feedback); the latter effect is believed to involve aGprotein coupled cell-surface receptor for Ca2+.Plasma phosphate levels have no direct effect on parathyroid PTH secretion.
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where are the main sites of PTH action? |
1. kidney 2. bone 3. GI |
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what is the action of PTH at kidney? |
PTH causes a rapid increase in distal tubular reabsorption of Ca2+ from theglomerular filtrate, and increases the excretion of phosphate in the urine. Plasma Ca2+concentration is therefore increased, while the plasma phosphate level falls. PTH also promotesthe formation of the active vitamin D metabolite 1",25-dihydroxy-cholecalciferol (1,25-(OH)2D3) within the kidney tubular cells, which in turn, facilitates the release of Ca2+ frombone and enhances the rate of absorption of Ca2+ from the small intestine and the kidney |
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what is the action of PTH on bones ? |
PTH has a dual action: it stimulates the rapid efflux of Ca2+ from the labile calciumpool, into the extracellular fluid (facilitated by 1,25-(OH)2D3); it also stimulates bone cells(indirectly) to release calcium (and phosphate) by a slower process of bone dissolution orresorption. |
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what is the action of PTH on GI tract? |
PTH stimulates intestinal absorption of Ca2+ and phosphateindirectly. This effect (slow) is mediated by the vitamin D metabolite 1,25-(OH)2D3. PTHstimulates the activity of the enzyme 1-hydroxylase involved in the production of 1,25-(OH)2D3in the kidney.
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what are the types of bone cells affected by parathyroid hormone |
osteoblasts; only affected by PTH oesteoclasts; the effects of PTH on osteoclast bone resorption arethought to be mediated indirectly through the release of cytokine stimulating factors, responsiblefor activation and differentiation of osteoclasts from precursor cell |
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what is osteoblast? |
Osteoblasts are specialized cells responsible for new bone formation. |
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what is osteoclast? |
Osteoclasts are larger multinucleated cells lining the bone-forming surface of bone tissue, thatdigest previously formed bone matrix to release calcium and phosphate into the extracellularbone fluid (bone resorption). The slow process of resorption (lasting 2-4 weeks) is followed bynew matrix deposition and mineralization (bone formation; lasting 3-7 months), so that totalbone mass remains constant; this is known as bone remodeling and is important for maintainingnormal bone strength, and for preserving calcium homeostasis |
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what is the intracellular mechanism of action of PTH? |
Mechanism of action of parathyroid hormoneThe effect of PTH on renal tubular and bone cell activity is believed to be mediated mainly viastimulation of specific plasma membrane receptors coupled to a rise in intracellular cAMP. |
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what are the symptoms of hypoparathyroidism? |
1- Hyper-excitability of nerve and neuromuscular tissue, with 'pins and needles' in the face orfingers, muscle cramps and spasms leading to tetany, possible spasms of the larynx and evenepileptic seizures/convulsions. 2- Chvostek's sign - twitching of the facial muscles following light tapping over the facial nerve,and Trousseau's sign - tetanic spasm of the wrist and fingers following overinflation of asphygmomanometer cuff placed over the upper arm for more than 3 mins. 3- Dental abnormalities, dry scaly skin and hair, brittle nails and cataracts may also be presentin more chronic persistent cases. 4- Low blood PTH level causes hypocalcaemia and hyperphosphataemia. |
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what are the possible causes of hypoparathyroidism? |
-accidental damage from thyroid surgery - autoimmune disease (rare) such individuals may possess specific serum antibodies directedagainst their parathyroid tissue |
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what is pseudohypoparathyroidism? |
parathyroid function is normal, but the primary target tissues(bone and kidney) are insensitive to the actions of PTH.
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what are the treatments available? |
vitamin D supplements to enhance calcium absorption and utilization - calciferol tablets (vitamin D2) - the vitamin D derivative dihydrotacysterol (AT 10) |
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what do you need to monitor during vitamin D supplement therapy? |
frequent serum and urinary calcium measurements are made to ensure thatovertreatment and consequent hypercalcaemia does not occur. |
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what is hypocalcaemic tetany? what are the treatments? |
muscle tremor due to the low plasma calcium level this is acute hypoparathyroidism - IV infusion of 10% calcium gluconate - Subcutaneous injection of a PTH analogue: Teriparatide - Human recombinant PTH itself (100 μg daily by subcutaneous injection) can also beused in cases of severe postmenopausal osteoporosis |
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what is phosphaturia? |
(excess loss of phosphate in the urine) |
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what are the possible causes of hyperparathyroidism? |
- single chief cell tumor (adenoma) - enlargement of parathyroid gland(s) by parathyroid carcinoma - enlargement of parathyroid gland(S) by chronic hypocalcaemia due to intestinal Ca/vitamin D malabsorption, chronic renal failure |
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what are the symptoms of hyperparathyroidism? |
1- Confusion, cognitive impairment, depresssion. 2- Tiredness, lethargy, anorexia, nausea, vomiting, dehydration (due to excessive loss of urine),cardiac arrhythmias and possible heart block. 3- Renal stones made from insoluble calcium phosphate (or oxalate), due to increasedurinary excretion of Ca2+ and phosphate; this may cause renal colic and haematuria (appearanceof blood in the urine), eventually leading to renal failure. Gallstones may also occur. 4- Gastrointestinal complaints: abdominal pain, constipation, dyspepsia, peptic and duodenalulceration. 5- Bone lesions: -due to resorption of calcium from bone. In severe cases, osteitis fibrosa (bonecysts) accompanied by bone pain and possible fractures can occur. 6- High blood PTH level causes hypercalcaemia and hypophosphataemia. Hyperparathyroidismhas been described as a disease of "bones, stones and abdominal groans" |
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what are the treatments of hyperparathyroidism? |
Treatment is by surgical removal of overactive parathyroid tissue, although some tumours maybe difficult to locate. Postoperative persistence of hyperparathyroid symptoms or developmentof permanent hypoparathyroidism (with hypocalcaemia) are common. Inadvertent damage to therecurrent laryngeal nerves may also occur (rarely) |
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what is calcitonin? |
Calcitonin (CT) is a 32 amino acid peptide secreted by the parafollicular 'C' cells of the thyroidgland. |
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how is calcitonin controlled? |
The main factor involved in regulating calcitonin release from 'C' cells is the free ionized Ca2+concentration in the blood. A rise in plasma Ca2+ stimulates calcitonin release, and vice versa.[note the opposite effect of Ca2+ on PTH secretion].
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what are the actions of calcitonin? |
In contrast to PTH, calcitonin is a Ca2+ -lowering factor; it decreases plasma calcium (andphosphate) levels principally by: 1- Decreasing the efflux of Ca2+ from bone, and also by inhibiting bone resorption through adirect suppression of osteoclast activity. 2- Inhibiting renal tubular reabsorption of calcium and phosphate; calcitonin has little effect onintestinal Ca2+ fluxes. Although these effects are generally opposite to those of PTH, calcitonin is not considered to beas important as PTH and vitamin D in the normal regulation of calcium or skeletal homeostasisin humans. |
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what are the clinical uses of calcitonin? |
1. paget's disease 2. hypercalcaemic state |
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what is paget's disease? |
Paget's disease is a chronic disorder characterized by an abnormally high level of boneresorption. The affected bones (usually the skull, spine, pelvis and long bones) become deformedwith abnormal density under X-ray. The condition is initially largely asymptomatic; plasma Ca2+and phosphate levels are normal: joint and bone pain, fractures, and skull enlargement mayhowever develop |
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what are the treatments of paget's disease available? |
- Synthetic salmon calcitonin (salcatonin: Miacalcic) may be given by injection to reduce boneresorption. - Bisphosphonate drugs reduce osteoclastic bone resorption by a direct mechanism. e.g. - Disodium etidronate (Didronel). - Oral disodium etidronate (Didronel PMO), or sodium alendronate (Fosamax), are also usedto prevent excessive bone loss in established postmenopausal vertebral osteoporosis: (see below). |
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what is hypercalcaemic state cured? |
Hypercalcaemic states. Porcine calcitonin or salcatonin (subcutaneous or intramuscular) canbe used to reduce plasma Ca2+ concentration in hypercalcaemic patients (particularly wheninduced by malignant disease). In severe cases, a slow intravenous infusion of salcatonin maybe given. Slow intravenous infusion of bisphosphonate drugs e.g. disodium pamidronate (Aredia) orsodium clodronate (Loron) are also used in the control of tumour-induced hypercalcaemia ofmalignancy. |
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what is vitamin D? |
Vitamin D is a fat soluble sterol, which can influence calcium and phosphate metabolism. It isregarded as a hormone, since it can be produced endogenously in small amounts within oneorgan then travels via the blood to affect cells at distant sites.Vitamin D (ingested or synthesized in the skin after sunlight exposure) is transformed in the liverand kidneys to an active form 1",25-dihydroxy-cholecalciferol (1,25-(OH)2D3) before beingreleased into the bloodstream to affect the small intestine, bone and kidney. |
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what are the forms of vitamin D exist? |
- Vitamin D2 (calciferol; ergocalciferol), a plant-derived vitamin, produced by solar UVirradiation of a plant sterol (ergosterol) and contained in most clinically available preparations.
- Vitamin D3 (cholecalciferol), the natural animal vitamin D, synthesized within the skin of manand higher mammals from an inactive precursor 7-dehydrocholesterol by the UV effect ofsunlight. To become active, it is first hydroxylated in the liver to 25-hydroxycholecalciferol (25-(OH)D 3) and then to the active form 1",25-dihydroxycholecalciferol (1,25-(OH)2D 3 ; calcitriol)in the kidneys, under the influence of parathyroid hormone. Note: vitamin D2 (calciferol), following ingestion is metabolised to 1",25-dihydroxycalciferol(1,25-(OH)2D2), which is equivalent in activity to 1,25-(OH)2D3. |
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what are the actions of vitamin D? |
1,25-(OH)2D3 promotes calcium absorption from the upper small intestine (main action) andfrom bone and kidney (weak action), with a secondary increase in phosphate absorption. Thisaction is mediated by a specific cytosolic vitamin D receptor protein (VDR) which then interactswith nuclear DNA to activate specific genes. In the intestine and kidney, this results in the enhanced synthesis of cytosolic calcium bindingproteins as well a transporter pump protein (Ca-Mg-ATPase) involved in calcium absorption.Consequently, the effect of 1,25-(OH)2D3 may show a lag period of 1-3 days before the plasmacalcium level rises. The action of 1,25-(OH)2D3 on bone resorption may be indirectly mediated by release ofparacrine factors from stimulated osteoblast cells. |
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explain deficiency of vitamin D |
Deficiency of vitamin D causes rickets in young children and osteomalacia (soft bones) in adults(particularly heavily-veiled women and housebound elderly); this is characterized by aninadequate calcification of the bone matrix and a softening of the skeleton.In children:- the growing ends of bone are swollen, and the bone becomes bent and deformed,giving a characteristic 'bowed legs' appearance.In adults:- the main feature is bone pain, partial bone fractures and muscle weakness. |
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what are the possible causes of vitamin D deficiency? |
Vitamin D deficiency may be due to a metabolic abnormality (e.g. inherited absence or reducedrenal 1α-hydroxylase activity), intestinal fat malabsorption, chronic liver disease, insufficientexposure to sunlight or simple dietary lack. |
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what are the vitamin D rich food? |
fish, liver, eggs, cod liver oil and fortified milk, cerealsand margarine |
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what is the treatment of vitamin D deficiency? |
Treatment involves giving small oral doses of vitamin D (up to 10 g daily) to enhance calciumabsorption, together with a calcium supplement if necessary. |
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what are currently available vitamin D supplement preparations? |
- Adcal-D3 (Ca Carbonate with 10 μg vitamin D3)- Calcichew D3 tablets (Ca carbonate with 5 μg vitamin D3) - Calcium and Ergocalciferol (vitamin D2) tablets (Ca lactate and phosphate with10 μg vitamin D2) - Calciferol (ergocalciferol, vitamin D2) or cholecalciferol (vitamin D3) (in 250 μg tablets,or by intramuscular injection in vegetable oil) |
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what is vitamin D resistant ricket? |
Vitamin D-resistant rickets is caused by a defect in the vitamin D receptor; such individualsdevelop rickets but are resistant to physiological doses of vitamin D. Higher doses of vitamin Dor vitamin D metabolites are therefore required for treatment.
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what is vitamin D excess |
Vitamin D excess (hypervitaminosis D) usually results from overtreatment with a vitamin Dpreparation. It may also occur spontaneously in some patients with sarcoidosis (a chronicgranulomatous skin disorder), where an enhanced synthesis of vitamin D3 occurs in the skin aftersun exposure.
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what are synthetic vitamin D analogues? clinical use? |
calcipotriol and tacalcitol inhibit the overproduction ofkeratinocytes, and are used to treat psoriasis 乾癬
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what are the hormones affecting calcium homeostatis? |
- Gonadal steroids. Oestrogens maintain the bone mass in women, by preventing boneresorption. After the menopause the lack of oestrogen may lead to osteoporosis (decalcificationand reduction in bone density) with possible bone fragility and potentially fatal hip and vertebralcompression fractures; [testosterone has a similar protective function in men].
- Glucocorticoids. Glucocorticoids in high doses or chronically present in Cushing's syndromecan affect bone metabolism and calcium turnover, leading to 'glucocorticoid-inducedosteoporosis' |
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what is osteroporosis? |
Osteoporosis is characterized by a decreased bone mass. The bone becomes abnormally thinand porous, due to an uncompensated loss of bone mineral and matrix; there is also a microarchitecturaldeterioration of bone tissue, contributing further to the ease with which fracturesoccu
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why is women more prone to osteoporosis? |
Women are more prone to develop the condition after the menopause. A generally lowerincidence in males would be expected, partly due to their larger initial bone mass, and partlybecause of the protective anabolic effects of secreted androgens |
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what are the two types of osteoporosis? |
Primary osteoporosis may be postmenopausal (type I) or age-related (type II). The former is seenin women between 55-75 years, due to the lack of ovarian oestrogens, whereas the latter iscommonly found in both men and women between 70-75 years, and attributed to a progressiveinefficiency of the bone remodeling process and decrease in gastrointestinal Ca2+ absorption withage. |
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what are the symptoms of osteoporosis? |
1- Bone pain due to a fracture (occurring spontaneously or following minimal trauma), or severeback pain due to vertebral collapse.
2- Loss of height and curvature of the spine. 3- Fractures: typically of the hip, vertebrae, ribs, distal radius (Colles' fracture),humerus and proximal femur |
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what are the prevention and treatment of osteoporosis? |
- Adequate dietary intake of calcium, exercice
- No smoking, no alcohol - Oral calcium supplements - HRT - Oral bisphosphonates - Vitamin D + calcium supplement for elderly |
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how can HRT treat osteoporosis? |
In postmenopausal women, oestrogen replacement as part of HRT is the most effective methodof decreasing the rapid bone loss and reducing fracture risk. Therapy should be started withinthe first 5 years following menopause and continued for at least 5-10 years.In women with an intact uterus, combined oestrogen/progestogen HRT is necessary to reducethe risk of developing endometrial cancer. |
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what types of biophosphonates available? |
a cyclical basis (disodium etidronate;Didronel PMO) or continuously (sodium alendronate; Fosamax) |
