Dept. of Oral Pathology & Microbiology Disturbances in mineral metabolism:

These are essential for body functions which includes:

 Bone formation

 Activation of endocrine functions

 Maintenance of cardiovascular functions…etc

 They also act as co-factors in various enzymatic functions Calcium:

 Adult human body:-1-2kg.

 98% in skeleton & rest in plasma.

 In plasma Ca is present in 3 forms:

- 50% of is in free or ionic form

- 40% is bound to protein

-Rest 10% occurs as citrate, phosphates or bicarbonates Effects of decreased Calcium levels in plasma:

 Increased neuromuscular irritability.

 Tetany- characterized by perioral muscular spasm & carpopedal spasm

 Convulsions & laryngospasms

 Defective blood coagulation

 Disturbance in normal heart rhythm

 Irregularity in normal membrane permeability.

 Defective formation of bones & teeth.

 Bone resorptions & increased osteoporosis. Effects of increased calcium levels in plasma:

 Anorexia, nausea, vomiting, constipation, depression & lethargy etc.

 Depressed nerve conductivity & muscle rigor

 Coma.

 Deposition of solid calcium & phosphorus stones, within the blood vessels, mucous membrane , skin and kidney etc . Pathologic Calcification is the abnormal deposition of calcium in various tumors & & organs of the body. Types - Dytrophic Calcification - Metastatic Calcification . - Calcinosis.  Dystrophic Calcification: It is a type of pathologic calcification in which calcium salts are deposited in the dead or degenerating tissue of the body. It is is not associated with increased levels of serum calcium but related to the change in the local environment. Eg .increased local tissue alkalinity,etc. Egs: Pulp stones Calcification of gingival tissue, tongue & buccal mucosa. CEOT, ossifying fibroma CEOC Calcification of the tuberculous lymph nodes Blood vessel arteriosclerosis. Area of faulty degenerative tissue. Metastatic Calcification:

 Abnormal deposition of calcium in the tissue due to increase in the amount of serum calcium .  It occurs in hyperparathyroidism or in hypervitaminosis D. Calcification usually involves tissues, lung, kidney, GI Tract , blood vessels & oral mucosa & jawbones. Calcinosis:  Abnormal deposition of calcium below or within the skin or epithelium .  Seen in cases of scleroderma and dermatomyositis etc. Phosphorus:

 Essential mineral in bone metabolism  Related to calcium ions in the formation of bones & teeth.  Helps in metabolism of carbohydrates & fat by the process of phosphorylation..  Forms phosphoproteins ,nucleoproteins & nerve phosphatides etc  Adenosine triphosphate(ATP) is the energy resource for various biologic functions of the body & phosphorus plays an important role in the formation of ATP.  Normal plasma conc of phosphorus -2-4 mg/dl.  Hyperphosphatemia may result in abnormal calcification .  Hypophosphatemia may result in anorexia, bone pain, muscular weakness , waddling gait, defective growth in children & hemolytic anemia etc Hypophosphatasia

 Hereditary disorder  Characterized by the deficiency of alkaline phosphatase in the blood & in the tissues. Clinical features:

 Premature loss of primary teeth.  Enlarged pulp chambers of the primary teeth .  Lack of cementum formation on the root surface.  Hypoplasia of enamel.  Inadequate mineralization of the long bones with rickets like change.  Premature exfoliation of permanent teeth. Iron

 Iron deficiency seen in protein energy malnutrition Causes: -Chronic blood loss due to worm infestations. -Decreased absorption of iron . -Increased hepatic sequestration of iron.  Absorption : Absorbed in ferrous or ferric salts from the upper part of duodenum. Clinical features:  Esophageal web in plummer-Vinsons syndrome.  Spooning of nails.  Oral ulceration & sore tongue. Myeloperoxidase is an iron containing enzyme involved in antibacterial activation of neutrophilis (PMN) Iron def anemia causes a decrease in the myeloperoxidase activity resulting in decreased antibacterial activity of PMN. Hemochromotosis : condition resulting from increased iron absorption in the body & it causes pigmentation of skin & mucosa due to excessive iron deposition. Magnesium:

 Helps in phosphorylation process.  Acts as a cofactor in certain enzymatic activity especially for phosphatase & co- carboxylase enzyme etc Deficiency seen in protein energy malnutrition & may also occur due to severe loss of this mineral in case of vomiting & diarrhea etc. Deficiency of magnesium causes the following:  CNS depression  Anorexia.  Nausea  Vomiting  Carpopedal spasm No specific oral lesion. Zinc:

Zinc deficiency results in Delayed wound healing Retarded bone growth Defective keratinization etc Causes :Chronic intake of poor quality protein especially the vegetable proteins.  Increased iron conc & decreased zinc con c in the body increases the possibility of Cancer or precancer development. Disturbance in vitamin metabolism: Vitamin D: • Chemically behaves like a hormone. • Fat soluble • Absorbed in the intestines as dietary vitamin D3. • Active form of Vitamin D is 1,25dihydroxycholecalciferol. Functions of Vitamin D:  Helps in the absorption of calcium & phosphorus from the intestine & its metabolism.  It increases the renal reabsorption of calcium  Promotes the calcification of bone , cartilage & teeth.  Antagonistically acts against the action of parathyroid hormone.

The deficiency of vitamin D produces rickets in growing children & osteomalacia in adults. C/f of Rickets:  Failure of calcification of cartilage, bone & teeth.  Disturbed growth of the jaws , especially mandible.  Delayed eruption of teeth.  Malpositioning of teeth.  Development of Class II malocclusion. Osteoporosis:

 Disease characterized by gradual loss of mineral content in the bone. Etiology:  Low intake of calcium & minerals.  Lack of intestinal absorption of minerals.  Decreased Estrogen levels in blood leading to demineralization of bone.  Increased Urinary loss of calcium.  Hyperparathyroidism  Stress.  Long term steroid therapy.  Tetracycline & anticonvulsant therapy. C/f:  Frequently seen in post menopausal women.  Increased incidences of spontaneous fracture of bone esp. femoral neck fracture. R/f:  Loss of lamina dura of alveolar bone with increased tooth mobility & tooth exfoliation.  Increased incidences of jawbone fracture  Xray reveals bone rarefaction & thinning of the cortex. Familial Hypophosphatasia. (Vitamin D resistant rickets)

 Hereditary disorder transmitted as X linked dominant trait  Characterized by - decreased level of phosphorus in the body - decreased renal reabsorption & - increased renal excretion of the mineral. C/f:  Decrease in the body length.  Bowing of legs .  Increase incidence of bone fracture.  Muscular weakness. Oral manifestations: Examination of tooth reveals the following:  Formation of globular hypocalcified dentin.  Large pulp horns, which may be extending up to the dentinoenamel junction.  Periapical lesions in multiple teeth.  Abnormal cementum formation.  Loss of lamina dura. Vitamin A

 Fat soluble vitamin  derived from carotenes (plant pigments)  Commonly found in the fish oils, butter & eggs etc  Carotene transforms into vitamin A  Absorption takes place in the small intestine. Functions:  Helps in the maintainence of the structure & function of specialized epithelium  Produces photosensitive pigments in the eye.  Prevents the growth of epithelial malignant tumors  Maintains normal skeletal growth.  Maintainance of lysosomal stability & synthesis of glycoprotein . Effects of Vitamin A deficiency:  Night blindness  Bitots spot- a gray, triangular , elevated spot in the conjunctiva.  Xerophthalmia (dry conjunctiva )  Corneal ulceration  Follicular keratosis of the skin  Squamous metaplasia of the epithelium  Decreased salivary secretions  Hyperkeratosis of the oral mucosa. Effects of Hypervitaminosis A (excess Vit A in the body)  Among children cortical thickening of bone, retarded bone growth, hemorrhage & bulging of the fontanells.  Among adults , fatigue, anorexia, bone pain, skin pigmentations & alopecia. Etc.. Vitamin B complex

Thiamine(B1): Plays an important role in carbohydrate metabolism. Deficiency causes beriberi Oral manifestations: edema of tongue, loss of its papillae & glossodynia. Niacin (nicotinic acid)

 Plays an important role in the intracellular oxidation process  Deficiency causes pellagra.  Summarized by 3 D’s- dementia ,dermatitis ,diarhea There can be also disturbed gastrointestinal & neurological functions. Oral manifestations: • Burning sensation, swelling , redness, pain & ulceration. • Tongue becomes red , enlarged & depapillated with a bald surface. • Painful lips & angular chelitis often develop. • Dermatitis involving the exposed parts of the body, especially around the neck above the cloths margin ( Casals necklace) Riboflavin(B2)

 Riboflavin deficiency causes reddening, inflammation & depapillation of the tongue.  Tongue also sometimes becomes ulcerated & cyanotic( magenta glossitis)  Lip show fissures, painful cracks , scaling & maceration (angular cheilosis).  Lip lesions may extend into the oral mucosa & give rise to white patchy lesions. Folic Acid

 Deficiency of folic acid causes: -Loss of filliform & fungiform papilla of tongue producing a smooth, shiny appearance of the tongue -Defective keratinization & increased susceptibility to infection in the oral mucosa . -Gingivitis & oral ulceration. Vitamin C ( Ascorbic acid)

 Plays an important role in the synthesis of collagen , the substance , which forms the ground substance of the connective tissue.  Available in fresh foods , however heating or drying of fruits cause loss of considerable amount of vitamin.  Def of vit c leads to scurvy Oral manifestations: • Petechiae & ecchymosis in the oral mucous membrane. • Hyperemia , edema & enlargement of the gingiva with an increased bleeding tendency. • Mild to marked loosening of teeth & sometimes exfoliation of teeth. • Retardation of wound healing. • Defective function of odontoblast & osteoblasts cells. Vitamin K

 Essential for synthesis of prothrombin (clotting factor-II)  Also helps in synthesis of other clotting factors eg factor VIII, IX & X.  Synthesized by intestinal microflora in humans & some amount of vitamin K can be available from natural fruits.  Deficiency : decreased prothombin levels with increased tendency for hemorrhage & bruising.  Also increased bleeding after tooth extraction & following minor surgical interventions, etc Disturbances in protein metabolissm:

Amyloidosis: Amyloids are abnormal fibrillar proteins ,which have a peculiar homogenous , translucent appearance & a characteristic staining property. Amyloidosis is a pathological condition characterized by the extracellular deposition of amyloids within the tissue Types: 2 types: Primary (idiopathic) type: Arising as a result of abnormal immunoglobin synthesis & consists of fragments of IgG molecules in the tissues. Secondary (reactive) type: Occurs as a complication of many diseases , esp the chronic destructive inflammatory lesions like rheumatoid arthritis and few malignant conditions. C/f:- Oral amyloidosis is commonly seen among patients suffering from multiple myeloma or monoclonal gammopathy , etc & the disease occurs due to overproduction of immunoglobin light chains. Localized A in the oral cavity commonly produces macroglossia & gingival swelling etc & the swelling is usually firm & indurated . There can be presence of hemorrhagic bullae on the surface of the lesion which ruptures to produce shallow ulcer. Tongue lesion may present a lobulated growth which sometimes may be so massive that it will prevent the closure of mouth  Surface of the lesion appears pale or purplish & the lateral border of the tongue often shows indentations of teeth.  Petechiae & ecchymosis can be present in other parts of the oral mucous membrane in amyloidosis.  Systemic A may cause jaw claudication.  Reactive amyloidosis occurs secondary to rheumatoid arthritis or chronic infections like tuberculosis or osteomyelitis etc  Amyloids can also be found in large amounts in Pindborgs tumor.  Amyloidosis of the salivary glands may produce xerotomia. Histopathology: Microscopically appears as weakly eosinophillic , homogenous , hyaline materials which often show a perivascular distribution.Congo red stain used Gives typical apple green birefringence with polarized light. Treatment: Surgical excision Porphyria

 An inborn error of porphyrin metabolism & is characterized by overproduction of uroporphyrin & other related substances.  Can also result from certain infections .  2 types: Erythropoietic porphyria Hepatic porphyria  Erythropoietic porphyria characterized by red urine, photophobia, hairy face & reddish or brownish coloured teeth.  Tooth discoloration is due to deposition of porphyrins in enamel, dentin & cementum etc..s/t causes vesiculobullous skin lesions .  Does not require any treatment only veneering of teeth is done to improve esthetics. Disturbances in carbohydrate metabolism. Hurlers syndrome.  Characterized by elevated mucopolysaccharide levels in urine  Fatal in nature .  Affects children. Clinical manifestations. • Mental retardation. • Dwarfism with large head & prominent foreheads. • Hypertelorism • Puffy eyelids & corneal clouding • Hepatosplenomegaly. • Deformed face with broad saddle nose. Oral manifestations:

• Short & broad mandible • Coarse & thick lips • Lack of tooth eruption or delayed eruption. • Large tongue, open mouth • Microdontia, diastema formation. • Gingival hyperplasia R/f: • Radiolucencies around the crowns of the unerupted teeth in the jaw due to muccopolysaccharide deposition. • Localized bone destruction in the jaw. H/p: • Abnormal deposition of intracellular mucopolysaccharides in different vital organs ,eg. Liver , spleen ,heart & nervous system, etc. • Presence of hunters cells in the tissue , these cells are large with crescent shaped nuclei & metachromatically staining cytoplasms. Treatment: • No treatment possible. • Death often occurs. • Cardiac or lung involvement. Disturbance in lipid metabolism:

Letterer- Siwe Disease: • Most fatal form of histiocytosis X. • Occurs before 2yrs of age. C/f:- • Primarily affects the visceras like spleen, liver, lung, lymphnodes, bone marrow & skin etc • Hepatosplenomegaly & Lymphadenopathy. • Fever , malaise & irritability • Petechiae or ecchymosis of skin & mucous membrane. • Anemia, mucosal ulcerations & gingival hyperplasia. • Loosening & premature exfoliation of teeth. • Radigraphs reveal diffuse areas of bone. Treatment: • No specific treatment. Gauchers Disease:

• Characterized by deposition of kerasin (a lipid) in the reticular cells of liver, spleen ,bone marrow & lymph nodes. • Occurs at any age. • Females >males. • Clinical manifestations :- Skin pigmentation , gingival bleeding , hepatospenomegaly & ecchymosis etc • Patients may also suffer from CNS disorders & increased incidences of pneumonia,,etc • Microscopically , large foam cells with crumpled silk cytoplasm ( Gauchers cells ) are found in the lesion . Disturbance in hormone metabolism: Hypopituitarism: • In infancy leads to dwarfism.

Causes : • Tumor of pituitary ,eg craniopharyngioma • Hypophyseal fibrosis. • Supracellar cyst. • Destruction of pituitary gland by trauma. C/f: • Sparse hair on the head & other hairy regions. • Atrophy of all organs of the body. • Wrinkled atrophic skin & childish face. • Hypogonadism , impotence & amenorrhoea • Extreme weight loss • Coma & death in several cases. O/m: • Delayed exfoliation of deciduous teeth. • Delayed eruption of permanent teeth. • Crowding of teeth. • Underdevelopment of maxilla & mandible. • Smaller crown size of the teeth & smaller root length Hyperpituitarism: • In infancy leads to gigantism • Among adults it produces acromegaly. Causes: • Hypersecretion of growth hormone due to benign pituitary adenoma. • Increased function of anterior pituitary. Gigantism: Clinically • Generalized symmetric overgrowth of the body. • Genital underdevelopment • Excessive perspiration. • Headache , lassitude , joint & muscle pain. • Defective vision. Oral manifestations: • Enlarged maxilla & mandible. • Marked increase in the vertical dimension of face. • Large size of teeth • Early eruption of teeth. • Root length is greater than normal • Macroglossia & hypercementosis, etc. Acromegaly:  Thick bones , large hands & feet.  Enlarged skull with increased intracranial pressure.  Headache ,photophobia & visual disturbances .  Hepatomegaly & Cardiomegaly.  Osteoporosis, arthralgia , excessive sweating & myalgia.  Bowing of legs & barrel shaped chest. O/m: • Large mandible with with class III malocclusion (prognathism). • Macroglossia with indentations of teeth on the lateral border of tongue. • Thick lips • Proclination of teeth with diastema formation • Hypercementosis • Periodontitis • Poor fitting of old prosthesis due to large size of the jaw. • Enlargement of maxillary air sinuses • Large nose ,ears & prominent eyebrows. Treatment : • Surgery or radiotherapy to pituitary tumor. Hypothyroidism

 Decreased metabolic rate of the body resulting in retardation of growth & function of the entire body systems.  During childhood produces a a disease called cretinism &produces myxedema among adults. Causes 1. Decreased secretion of ACTH by pituitary. 2. Atrophy or damage to the thyroid gland Cretinism:

Clinically  Neonatatal jaundice, horse cry , constipation& teething problems.  A short poorly developed & mentally retarded child.  Delayed development of speech & walking capability  Larger size of the skull & sparse briitle hair,brittleness of the fingernails.  Hypotension, protuberant abdomen with umbilical hernia.  Retraction of the bridge of the nose with flaring.  Atrophy of the sweat glands.  o/m:  Delayed eruption & exfoliation of deciduous teeth.  Macroglossia with protruding tongue thick lips.  Constant drooling of saliva from the mouth.  Malocclusion & underdevelopment of mandible.  Wide face with lack of longitudinal growth. Myxedema:

 Develops among middle aged males.  Weakness, fatigue ,lethargy, low blood pressure& mental retardation.  Dry coarse skin, swelling of the face & extremities.  Cold intolerance , husky voice, decreased sweating & anorexia.  Loss of memory, hearing impairment , arthralgia, muscle cramps& paresthesia  Lethargic stage may progress to coma. O/m:  Dull expressionless face with periorbital puffiness & loss of hair.  Tongue, lips & eyelids etc are edematous(non pitting) & swollen.  Large tongue often interferes with speech .  Underdevelopment of maxilla & mandible. Treatment : Administration of thyroid preparations Hyperthyroidism:

Causes:Hyperplasia of thyroid gland with increased function. Increased plasma secretion due to benign tumor in the gland . Clinically: Increased female prediliction. Hypertension & exhaustion. Excitability& irritability. Weight loss, palpitations & anorexia. Easy tearin g, photophobia, warm smooth skin. Nervouness, muscle weakness, tremors . Exophthalmus, hyperdefecations Osteoporosis, excessive sweating. O/m:  Early exfolation of deciduous teeth.  Premature eruption of perm teeth.  Alveolar bone atrophy.  Increased susceptibiliy to oral infections. Treatment:  Antithyroid drugs.  Surgery / radiotherapy to the thyroid gland tumor if any. Diabetic mellitus

 Metabolic disorder characterized by glucose intolerance , & is caused by an imbalance b/w insulin supply & insulin demand.  Insulin is a Hormone produced by the beta cells of the islets of langerhans of pancreas.maintains the balance b/w high & low glucose levels in blood.  2 types of diabetic mellitus  Insulin – dependent diabetic mellitus.  Non insulin dependent diabetic mellitus.  .Diabetes exhibits hyperglycemia due to lack of insulin or reduced effectiveness of insulin. Also affects metabolism of carbohydrates , proteins , fat , water & electrolytes.  C/m:  4 cardinal signs polyuria, polydipsia polyphagia weight loss.  Myopia, paresthesia of the limbs, pain in the limbs ,impotence etc  In some cases, asymptomatic .  O/m:  Severe periodontitis& periodontal abscess formation( diabetes increases the progression of periodontal disease by altering the tissue response to local irritants).  Pain & inflammation of gingiva, with frequent bleeding  Dry mouth & delayed wound healing.  Increased caries susceptibility.  Increased tendency for oral infections by hemolytic streptococci & staphylococci.  Oral candidiasis.  Burning mouth syndrome.  Increased prevalence of dry socket after tooth extraction.  Loss of taste sensation.  Increased incidence of enamel hypoplasia.  Atypical dental pain. Diagnosis: Blood sugar estimation-fasting ,postprandial & random. Glucose tolerance test(GTT) – if sugar conc in venous blood is above 130mg/dl,diabetes is confirmed. Urinary glucose estimations –if the level is above 10-20 mg/dl, diabetes should be suspected. Detection of ketone bodies in urine Treatment: Diet control( administration of sugar free diet) Administration of oral hypoglycemic drugs. Insulin therapy whenever necessary. Progeria

 Unknown etiology.  Characterized by dwarfism & premature senility.  Affected infants exhibit alopecia, skin pigmentation, atropic skin, high pitched voice,smaller mandible, muscular atrophy & joint deformity etc  Patients usually have an above normal IQ & they resemble a wizened little old person.  Delayed eruption of teeth & excessive secondary dentin formation