ch # 79 CALCIUM AND PHOSPHATE METABOLISM ppt

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Chapter # 79 UNIT # 14 PARATHYROID HORMONE, CALCITONIN, CALCIUM AND PHOSPHATE METABOLISM,VITAMIN D, BONE AND TEETH.

CALCIUM AND PHOSPHATE METABOLISM:

Ch # 79 Parathyroid Gland 2 CALCIUM AND PHOSPHATE METABOLISM Over view of calcium and phosphate in the ECF and plasma Ca plays a key role in many physiologic processes including,contraction of skeletal,,cardiac,&smooth muscle,bld clotting and transmission of nerve impulses and bone formation. ECF conc. 9.4 mg/dl. Hypercalcemia. Hypocalcemia 0.1%in ECF and 1% in cells. 14% to 15% phosphate in cell and 1% in ECF. CALCIUM IN PLASMA AND INTERSTITIAL FLUID 40% of total Ca in bld is bound to plasma proteins. 10%of Ca combined with other substance (diffusible but non ionized) 50%of Ca in plasma is diffusible and ionized.

CALCIUM AND PHOSPHATE CONCENTRATION IN BODY FLUIDS:

Ch # 79 Parathyroid Gland 3 CALCIUM AND PHOSPHATE CONCENTRATION IN BODY FLUIDS Changing the level of phosphate in ECF does not cause major immediate effects on body. Conversely even slight inc;or dec; Ca level can cause immediate physiological effect. HYPOCALCEMIA(nervous excitement and Tetany) Dec Ca conc in ECF EFFECTS Cause over excitability in nervous sys which cause tetany. Carpopedal spasm it is a tetany of hand, occurs at conc 6mg/dl, but become lethal at 4mg/dl .

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Ch # 79 Parathyroid Gland 4 HYPERCALCEMIA Inc. Ca in ECF EFFECTS Depression of nervous sys. Sluggish reflex activities of CNS. Dec. QT interval in ECG. Constipation. Lake of appetite These effects begins to appear at 12 mg/dl, becomes marked at 15mg/dl, but at 17mg/dl Ca, PO4 crystals start to appear through out the body.

ABSORPTION AND EXCRETION OF CALCIUM AND PHOSPHATE:

Ch # 79 Parathyroid Gland 5 ABSORPTION AND EXCRETION OF CALCIUM AND PHOSPHATE Absorption of calcium Daily Ca intake is 1000mg/day . (350 mg/dl) 35%of Ca is absorb through intestine, remaining excreted in feces, 250mg/dl is added from the secretions of GI juices.90% of Ca intake is excreted. enhanced by vitamin D. Absorption of Phosphate Almost all dietary phosphate is absorbed in to the bld from the gut and later excreted in urine. Enhanced by vit D but dec by presence of excess Ca.

RENAL EXCRETION OF CALCIUM AND PHOSPHATE:

Ch # 79 Parathyroid Gland 6 RENAL EXCRETION OF CALCIUM AND PHOSPHATE 10% of ingested calcium is excreted in urine. 41%bound with plasma proteins therefore not filtered by glomerular capillaries. Rest is combined with anions(9%)+(50%) and filtered through renal tubules. 99%of the filtered Ca reabsorbed and about 100mg/day is excreted in urine. 90%reabsorbed in proximal tubules. Loops of Henle and early distal tubules remaining 10% is reabsorb in late distal tubules is very selective, depend on Ca ion conc. In the bld.

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Ch # 79 Parathyroid Gland 7 When the conc. is low in bld the reabsorption is great so almost no Ca is lost in urine Inc. in bld ion conc. Above normal increases Ca excretion markedly. Renal phosphate excretion is controlled by an overflow mechanism Critical value is1 mmmol/l. The kidney regulate the phosphate conc. In the ECF by altering the rate of phosphate excretion in accordance with the plasma phosphate conc. And the rate of phosphate filtration by the kidney.

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Ch # 79 Parathyroid Gland 8

Tensile and Compressional strength of Bone:

Ch # 79 Parathyroid Gland 9 Tensile and Compressional strength of Bone Each collagen fiber is composed of repeating periodic segments every 640 angstrom along its length. Hydroxyapatite crystals lie adjacent to each segment of the fiber, bound tightly to it. Collagen fibers of bone have great tensile strength, whereas the Ca salts have great compressional strength.

PPT and absorption of Ca and P in Bone-----equilibrium with the ECF.:

Ch # 79 Parathyroid Gland 10 PPT and absorption of Ca and P in Bone-----equilibrium with the ECF. Hydroxyapatite does not ppt in the ECF despite supersaturation of ca and P. Pyrophosphate , ppt inhibitor.

MECHANISM OF BONE CALCIFICATION:

Ch # 79 Parathyroid Gland 11 MECHANISM OF BONE CALCIFICATION Osteoblasts secret collagen molecule and ground substance in initial stage of bone production. Collagen monomers polymerized and forms collagen fiber the resultant tissue called osteoid, a cartilage like material differing from cartilage in that Ca salts readily ppt in it. Now Osteoblast become entrappted in osteoid are called osteocytes. With in few days Ca salts deposit on surface of collagen fiber product called hydroxyapatite crystal. Initially deposited substance is amorphous,over a period of weeks or month they become crystals. Arteriosclerosis is caused due to ppt of Ca in the arterial walls. Ca frequently deposit in degenerating tissues.

CALCIUM EXCHANGE BETWEEN BONE AND EXTRACELLULAR FLUID:

Ch # 79 Parathyroid Gland 12 CALCIUM EXCHANGE BETWEEN BONE AND EXTRACELLULAR FLUID Exchangeable Calcium Calcium that is always in equilibrium with Ca ions in ECF. It is also found in highly permeable types of cell e.g LIVER and GIT . Importance Buffering mechanism .

DEPOSITION AND ABSORPTION OF BONE-REMODLING OF BONE :

Ch # 79 Parathyroid Gland 13 DEPOSITION AND ABSORPTION OF BONE-REMODLING OF BONE DEPOSITION OF BONE BY OSTEOBLASTS (Bone forming cells) Bone is being deposited by osteoblasts,it is continually being absorbed where osteoclasts are active. Osteoblasts are present on outer surface of bone and bone cavity. Form new bones constantly . ABSORPTION OF BONE FUNCTION OF OSTEOCLASTS (Bone-resorbing cells) Large phagocytic,multinucleated cells formed in bone marow. Bone absorption occurs immediately adjacent to osteoclasts by following mech Osteoclast send villus like projection towards bone forming ruffled border.

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Ch # 79 Parathyroid Gland 14 Villi secrets two types of substance Proteolytic enzymes release by lysosomes Acids release by mitrochondria. Enzymes digest organic matrix of bone. Acids cause solution of bone salts.

BONE DEPOSITION AND ABSORPTION ARE NORMALY IN EQUILIBRIUM:

Ch # 79 Parathyroid Gland 15 BONE DEPOSITION AND ABSORPTION ARE NORMALY IN EQUILIBRIUM Rate of bone deposition and absorption are equal to each other. Osteoclast usually exist in small but concentrated masses. Once it begins to develop it creat a tunnel and new bones begin to develop. It laid down in successive layers of lamellae on inner surface until the tunnel filled. Each new area of bone deposited is called osteon.

REMODLING OF BONE:

Ch # 79 Parathyroid Gland 16 REMODLING OF BONE Bone is continually being absorbed by osteoclast and being deposite by osteoblast. Importanc Shape of bone. New organic matrix is deposite in old bones which have become weak because of degeneration of bone.

CONTROL OF RATE OF BONE DEPOSITION BY BONE “STRESS”:

Ch # 79 Parathyroid Gland 17 CONTROL OF RATE OF BONE DEPOSITION BY BONE “STRESS” Bone is deposited in proporation to compressional load that the bone must carry. The bones of athletes become considerably heavier than nonathletes. Continual physical stress stimulates osteoblastic deposition and calcification of bone.

REPAIR IF FRACTURE ACTIVATES OESTOBLASTS:

Ch # 79 Parathyroid Gland 18 REPAIR IF FRACTURE ACTIVATES OESTOBLASTS Fracture activates all the osteoblast involved in the break. Number of new osteoblast formed are so called osteoprogenitor. Large bulge of osteoblastic tissue and new organic bone matrix followed shortly by deposition of calcium salts develop between two broken ends of bone called callus.

Vitamin D:

Ch # 79 Parathyroid Gland 19 Vitamin D Vitamin D has a potent effect to increase calcium absorption from the intestinal tract it also has important effects on both bone deposition and bone absorption.vitamin D itself is not the active susbtance that actually causes these effects.vitamin D must first be converted through a succession of reactions in the liver and the kidney to the final active product,1,25-dihydroxycholecalciferol,also called 1,25(OH)2D3.

Cholecalciferol (Vitmin D3) Is formed in the skin:

Ch # 79 Parathyroid Gland 20 Cholecalciferol (Vitmin D3) Is formed in the skin Vitamin D3 is the most important compounds derived from sterols belong to the vitamin D family and is formed in the skin as a result of irradiation of 7 dehydrocholestrol,a substance normally in the skin, by ultravoilet rays from the sun.Consequently, appropriate exposure to the sun prevents vitamin D deficiency

Cholecaiciferol is converted to 25 Hydroxycholecalciferol in the liver :

Ch # 79 Parathyroid Gland 21 Cholecaiciferol is converted to 25 Hydroxycholecalciferol in the liver The 25-hydroxycholecalciferol has a feedback inhibitory effect is extremely important for two reasons First If the feedback mechanism precisely regulates the concentration of 25-hydroxycholecalciferol in the plasma.If the intake of vitamin D3 can increase many times,the concentration of 25-hydroxycholecalciferol remains nearly normal.This high degree of feedback control prevents excessive action of Vitamin D when it is present in too great quantity Second If this controlled conversion of vitamin D3 to 25-hydroxycholecalciferol converses the vitamin D stored in the liver for future use

Formation Of 1,25-dihydroxycholecalciferol In The Kidneys And Its Control By Parathyroid Hormone:

Ch # 79 Parathyroid Gland 22 Formation Of 1,25-dihydroxycholecalciferol In The Kidneys And Its Control By Parathyroid Hormone In the Proximal Tubles of the kidney of 25-hydroxycholecalciferol1,25- is converted into dihydroxycholecalciferol.This substance is most active form of Vitamin D.In the absence of kidneys,vitamin D loses almost all its effectiveness. The conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol requires PTH.In the absence of PTH,almost none of the 1,25-dihydroxycholecalciferol is formed.Therefore,PTH exerts a potent influence in determining the functional effects of vitamin D in the body.

CALCIUM IONS CONCENTRATION CONTROLS THE FORMATION OF 1,25-Dihydroxycholecalciferol :

Ch # 79 Parathyroid Gland 23 CALCIUM IONS CONCENTRATION CONTROLS THE FORMATION OF 1,25-Dihydroxycholecalciferol In plasma concentration of 1,25-dihydroxycholecalciferol is inversely affected by concentration of calcium in plasma. Reasons Calcium ion itself has a slight effect in preventing the conversation of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol. The rate of secretion of PTH greatly suppressed when the plasma calcium ion conc rises above 9 to 10mg/100ml. Calcium conc below this level PTH promotes the conversion of 25-hydroxycholecalciferol to 1,25- dihydroxycholecalciferol in the kidneys. Lack of this in turn dec the absorption of calcium from intestine, bones,renal tubules causing the calcium ion conc to fall back toward its normal level.

ACTIONS OF VITAMIN D:

Ch # 79 Parathyroid Gland 24 ACTIONS OF VITAMIN D Active form of vitamin D 1,25 dihydroxycholecalciferol has several effects on intestine ,kidneys and bones. Inc absorption of calcium and phosphate into ECF.

HORMONAL EFFECT OF VITAMIN D TO PROMOTE INTESTINAL CALCIUM ABSORPTION:

Ch # 79 Parathyroid Gland 25 HORMONAL EFFECT OF VITAMIN D TO PROMOTE INTESTINAL CALCIUM ABSORPTION Causes formation of calcium-binding protien in brush border of intestinal epithelial cells absorbs Ca. Causes formation of calcium-stimulated ATPase in brush border of intestinal epithelial cells. Formation of alkaline phosphate in intestinal epithelial cell. Enhances absorption of phosphate from intestine. Promotes bone calcification by causing Ca transport from ECF thru osteocytic mem into bone fluid.

VITAMIN D PROMOTES PHOSPHATE ABSORPTION BY THE INTESTINE:

Ch # 79 Parathyroid Gland 26 VITAMIN D PROMOTES PHOSPHATE ABSORPTION BY THE INTESTINE Phosphate is absorbed easily ,flux through GI epithelium is enhanced by vit D. It results from 1,25-dihydroxycholecalciferol . VITAMIN D DEC RENAL CALCIUM AND PHOSPHATE EXCRETION Vit D inc calcium ,phosphate absorption by epithelial cells of renal tubule ,by tending to dec excretion of these substances in urine.

EFFECT OF VITAMIN D ON BONE AND ITS RELATION TO PTH ACTIVITY:

Ch # 79 Parathyroid Gland 27 EFFECT OF VITAMIN D ON BONE AND ITS RELATION TO PTH ACTIVITY Extreme quantities of vit D causes absorption of bone. In absence of vit D,the effect of PTH in causing bone absorption is greatly reduced. In smaller quantities promotes bone calcification one of the ways in which it does this is to inc calcium and phosphate absorption from intestine. On absence of such inc it enhances the mineralization of bone.

PARATHYROID GLANDS:

Ch # 79 Parathyroid Gland 28 PARATHYROID GLANDS Number : 4 in human beings. Location : each parathyroid gland is located behind each of upper and lower poles of thyroid gland. COLOUR : Dark- brown fat like, appearance. SIZE : 6 mm long, 3mm wide, 2mm thick . TYPES OF CELLS : Chief cells: Secrete parathyroid hormone. Oxyphill cells: secrete little parathyroid hormone . NATURE OF PARATHYROID HORMONE : Protein in nature .

ACTION OF PARATHYROID HORMONE:

Ch # 79 Parathyroid Gland 29 ACTION OF PARATHYROID HORMONE Mechanism of action : cyclic AMP mechanism. On blood Ca and PO4 Conc .: Inc blood Ca conc. Due to ; Inc Ca absorption from bone and Dec Ca excretion by kidney. Dec blood PO4 conc. Due to; IncPO4 excretion by kidney; this effect overrides. Inc PO4 absorption from bones. On bone : Increase absorption of Ca and PO4 from bone in two steps: Rapid absorption of Ca and PO4 Slow absorption of Ca and PO4

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Ch # 79 Parathyroid Gland 30 C. On kidneys: a)inc.Ca absorption in distal tubules and collecting duct b)inc PO4 excretion by decreasing PO4 reabsorption in proximal tubule . ON GIT :Parathyroid hormone converts 25 –hydroxycholecalciferol into 1,25-dihydroxycholeciferol which cause: (1) inc. Ca absorption from intestine (2) inc. PO4 absorption from intestine . ON LACTING MAMMARY GLAND : Reduces Ca secretion in milk.

REGULATION OF PARATHYROID HORMONE:

Ch # 79 Parathyroid Gland 31 REGULATION OF PARATHYROID HORMONE STIMULATING FACTORS Dec calcium conc.ECF Rickets Pregnancy Lactation INHIBITING FACTORS Inc.Ca ion conc.in ECF Excess Ca in diet Excess vit D3 in diet

Calcitonin:

Ch # 79 Parathyroid Gland 32 Calcitonin The hormone produced by the parafollicular cells of the thyroid gland is calcitonin or CT, It is involved in the homeostasis of blood calcium level.Calcitonin is a 32-amino acid peptide with a molecular weight of about 3400. Ct lowers the amount of calcium level.CT lowers the amount of calcium and phospate in the blood by inhibiting bone breakdown and accelerating the absorption of calcium by the bones. It appears to exert its effect in lowering calcium and phosphate blood levels by inhibiting osteoclastic action and the parathyroid hormone (PTH).

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Ch # 79 Parathyroid Gland 33 1.If CT is administered to a person with a normal level of blood calcium it causes hypocalcemia( low bld Ca level). 2.If CT is given to a person with hypercalcemia (high blood calcium level), the level returns to normal The blood calcium level directly controls the secretion of CT according to a negative feedback system that does not involve the pituitary gland .

Actions of Calcitonin :

Ch # 79 Parathyroid Gland 34 Actions of Calcitonin On Blood Ca++ Conc Decreases blood Ca++ Conc . On Bones Dec activity of calcium in osteocytic mem. Inc osteoblastic activity. Dec formation of osteoclasts. Dec rate of bones remodeling . On GIT Dec calcium absorption from intestine ----->Ca++ lost in feces. On Kidney Dec calcium absorption from distal tubule and collecting duct---->Ca++ lost in urine.

PATHOPHYSIOLOGY OF PTH, VIT D, BONE DISEASES:

Ch # 79 Parathyroid Gland 35 PATHOPHYSIOLOGY OF PTH, VIT D, BONE DISEASES HYPOPARATHYROIDISM When the parathyroid glands do not secrete sufficient PTH, the osteocytic reabsorption of exchangeable calcium decreases and the osteoclasts become almost totally inactive . Symptoms Hypocalcemia------>Tetany. Hyperphosphatemia. Obstruction of respiration due to spasm of laryngeal muscles Treatment Parathyroid hormone Vit. D3 with calcium

Hyperparathyroidism :

Ch # 79 Parathyroid Gland 36 Hyperparathyroidism Increase secretion of parathyroid hormone. Types : Are of Two A)Primary Hyperparathyroidism Due to primary defect in parathyroid gland Caused By Tumor of one of parathyroid glands. Hyperparathyroidism causes extreme osteoclastic activity in the bone.

SYMPTOMS:

Ch # 79 Parathyroid Gland 37 SYMPTOMS 1) HYPERCALCEMIA Causes Depression of central and peripheral nervous systems. Muscular weakness. Constipation. Abdominal pain. Peptic ulcer. Lack of appetite. Depressed relaxtion of heart during systole

2) Osteitis Fibrosa Cystica :

Ch # 79 Parathyroid Gland 38 2) Osteitis Fibrosa Cystica It is a disease of bone in hyperparathyroidism, characterized CAUSES Increase osteoblastic activity. Punched-out cystic areas of bone filled with osteoclasts. Extensive decalcification of bone. Easy Fracture. Increase osteoblastic activity in an attempt to form new bone. Increase plasma alkaline phosphatase .

3) Parathyroid Poisoning And Metastatic Calcification:

Ch # 79 Parathyroid Gland 39 3) Parathyroid Poisoning And Metastatic Calcification When parathyroid hormone rises too,calcium phosphate precipitates and begins to deposit in Alveoli Of lungs. Renal Tubules. Thyroid gland. Gastric glands. Arterial walls This extensive metastatic deposition of calcium phosphate can develop within a few days

4) Formation Of Kidney Stones In Hyperparathyroidism :

Ch # 79 Parathyroid Gland 40 4) Formation Of Kidney Stones In Hyperparathyroidism Most patients with mild hyperparathyroidism have an extreme tendency to form kidney stones. TYPES Calcium phosphate stones. Calcium Oxalate stones. The solubility of most renal stones is slight in alkaline media, the tendency for formation of renal calculi is considerably greater in alkaline urine than in acid urine.For this reason, acidotic diets and acidic drugs are frequently used for treating renal calculi .

Secondary Hyperparathyroidism :

Ch # 79 Parathyroid Gland 41 Secondary Hyperparathyroidism It is sec to defects outside the parathyroid gland. Cause vitamin D deficiency or chronic renal disease in which the damaged kidneys are unable to produce sufficient amounts of the active form of vitamin D, 1,25-dihydroxycholecalciferol.

Rickets :

Ch # 79 Parathyroid Gland 42 Rickets It is a disease in children due to vitamin D3 deficiency. Causes 1)Vitamin D3 deficiency. 2)Diminished exposure to sunlight. 3)Ca and PO4 deficiency in diet. Symptoms Slight fall of plasma Ca++ level (because parathyroid hormone prevents fall in plasma Ca++ level by Ca-absorption from bone) Excess fall of plasma P04 level.

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Ch # 79 Parathyroid Gland 43 Bones become weak due to excess Ca absorption from bone. Tibia bows forward (bow leg). Sternum protrudes forward (pigeon breast). tetany develop when bones exhausted of Ca.

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Ch # 79 Parathyroid Gland 44 Treatment Administration of Ca, PO4 and vitamin D3 in diet. Osteomalacia(Adult Rickets ) It is a disease in adults due to vitamin D3 deficiency. Steatorrhea (failure to absorb fat) because vitamin D is fat-soluble and calcium tends to form insoluble soaps with fat;in steatorrhea, both vitamin D and calcium tends to pass into the feces.An adult has poor calcium and phospate absorption that adult rickets can occur.

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Ch # 79 Parathyroid Gland 45 Symptoms 1)Demineralization of bones. 2)Bowing of long bones. 3)Vertical shortening of vertebrae. 4)Flattening of pelvic bones---->Narrowing of pelvic outlet---->Difficulty in childbirth. 5)Spontaneous fracture. 6)Collapse of vertebrae

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Ch # 79 Parathyroid Gland 46 Vitamin D-Resistant Rickets When symptoms of rickets or osteomalacia appear due to decrease absorption of phosphates by kidneys, it is called Vitamin D-resistant rickets;because it must be treated by phosphate compounds. Renal Rickets When symptoms of rickets or osteomalacia appear due to failure of damaged kidneys to form 1,25-dihydroxycholecalciferol.

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Ch # 79 Parathyroid Gland 47 Osteoporosis It is a disease of old age due to diminished organic matrix in bone . Causes 1)Lack of physical stress on bones due to inactivity. 2)Malnutrition. 3)Lack of vitamin C. 4)Postmenopausal lack of estrogen secretion. 5)Cushing Disease

PHYSIOLOGY OF TEETH:

Ch # 79 Parathyroid Gland 48 PHYSIOLOGY OF TEETH The teeth cut grind and mixed the food eaten. To perform these functions the jaws have power full muscles. An occlusive force between the front teeth of 50-100 pounds and for the jaw teeth 150-200 pounds. the upper and lower teeth are provided with projection and facets that interdigitate so that the upper set of teeth fits with the lower this fitting called occlusion.

PARTS OF TOOTH:

Ch # 79 Parathyroid Gland 49 PARTS OF TOOTH There are two division . ANATOMICAL DIVISION CROWN: Part of tooth that protrude out of gum into mouth . ROOT : Part of tooth that is present in bony socket of jaw . NECK : Part of tooth b/w crown and root, and in surrounded by gum . PHYSIOLOGICAL DIVISION DENTINE : Forms main body of tooth . Composed of dense hydroxyapatites and collagen fibers. It is deposited and nourished by odontoblast. Function: Resists compressional and tensional forces .

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Ch # 79 Parathyroid Gland 50 ENAMEL : Covers visible outer surface of tooth. Composed of dense hydroxyapatites embedded in a meshwork of protein similar to keratin. Formed by ameloblast before eruption of tooth . Function Resist acid, enzyme and other corrosive agents. CEMENTUM : Covers other surface of tooth present in bony socket. Formed by periodontal membrane that lines tooth socket. PULP : Present in pulp chamber of tooth, composed of connective tissue nerve fiber, blood vessel and lymphatic. Function Provide nutrition. KINDS OF TEETH There are two kinds of teeth DECIDUOUS TEETH: 20 in human being. Erupt b/w 7 th month and 2 nd year of life Permanent teeth: 28 to 32 in number depending upon whether 4 wisdom teeth appear or not.

ERUPTION OF TEETH:

Ch # 79 Parathyroid Gland 51 ERUPTION OF TEETH Protrusion of teeth from jaw bone through oral epithelium into mouth, is called eruption of teeth. CAUSE OF ERUPTION : Root of tooth and underlying bone progressively push the tooth upward . FACTOR THAT INCREASE TOOTH DEVELOPMENT GH Thyroid Hormones Calcium Vitamin D3 DENTAL CARIES Decay or erosion of teeth is called dental caries. Dental caries is promoted by increase no. of carbohydrate in diets. Because bacteria live on carbohydrate. CAUSED BY. Action of acids and proteolytic enzyme of bacteria, esp. streptococcus mutans.

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Ch # 79 Parathyroid Gland 52 PREVENTION OF CARIES BY F2 : Flourine displaces OH ions from hydroxyapatite crystals; this makes enamel less soluble by acids. F2 is toxic to bacteria. When small pits develop F2, promote calcium phosphate deposition to heal enamel surface. MALOCCLUSION It means failure of projections of upper and lower teeth to interdigitate properly. Caused by : Hereditary abnormality that causes teeth of one jaw to grow in abnormal position . Corrected by : Appling prolonged gentle pressure against teeth with appropriate braces. GINGIVITIS: gum Inflammation of gum.

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