GOOD MORNING

ORAL ASPECTS OF METABOLIC DISEASES

Metabolism:- the sum of total of tissue activity as

considered in terms of physicochemical changes

associated with and regulated by the availability,
utilization and disposal of protein, fat, carbohydrate,
vitamins, minerals, water and the influences with the
endocrines exert on these processes.
Disturbances in mineral metabolism:
Hormones
Primary regulators
Ineffective
29 Minerals - 4 % of body weight

Minerals
Classification:
1.Macrominerals-high amounts
nutritionally imp
daily requirement- >100mg
Calcium, phosphorus, sodium, potassium, chloride, magnesium.
2.Microminerals/ trace elements:
low amounts <0.005% of body wt
essential
daily req <100mg
Chromium, zinc, copper, cobalt, iodine, etc

Inorganic and organic components Basic structure of bone and teeth

Help maintain osmotic relations of the body
fluids
Regulate acid base equilibrium of tissues
Form part of the hormones
Integral part of the enzymes
Activators of enzymatic reactions
Essential part of oxygen carrying pigments
Essential when a deficient intake consistently
in suboptimal physiologic function that can be
prevented or reversed by supplementation with
physiologic levels of the element

Calcium metabolism
5th most abundant element crystalline form with phosphorous in a

proteinaceous matrix
Major structural component of body
Total calcium in body 100 to 170gm
99%-bones
0.5%-soft tissue
0.1%- extracellular fluid
Normal serum ca level-9-11 mg/dl
Calcium in plasma 3 foms-1.ionized calcium 40%,active form
2.protein bound calcium-albumin
3.complexed calcium-phosphate&
carbonate

Requirements & Absorption

Daily dietary ca intake-

newborns- 360mg
children and adults -800mg
adolecents, pregnant and lactating women -1200mg
Source: Milk, cereals, vegetables
Ca in diet taken as ca phosphate, carbonate, tartrate
1/3rd of daily dietary intake of ca is absorbed-normal
40% absorbed fm gut-duodenum, first half of the jejunum
99% of calcium stored in bones& part of this available for
exchange with extracellular fluid- imp for maintanance of
plasma cal.

Functions: Formation of bones & teeth.

Maintenance of skeletal structure& tooth

structure
Normal membrane permeability
Normal heart rhythm
Neuromuscular excitability
Coagulation of blood
Muscle contraction
Formation of glandular secretions- saliva

Thyroid
gland

Calcium Metabolism

Calcitonin

ca
BLOOD
ca

Ca2+

2+

BONE

Deposition
Resorption

SMALL
INTESTI
NE

2+

Vit D
PTH
1,

Parathyroi
d gland

PTH

KIDNEY

SKIN

)2
H
O
5(

25(OH)D3

Vit D

D3

LIVER

Hypocalcaemia
Hypoalbuminemia renal failure
Surgically induced Hypoparathyroidism
Hypocalcaemia Hyper irritability
Tetany with carpopedal
spasm
Hypercalcaemia
Primary hyperparathyroidism
Malignancy
Endocrine causes acute adrenal insufficiency and renal failure
Hypercalcaemia- Neurological disturbances
Cardiac arrhythmias

Etiologies of Hypercalcemia

Increased GI Absorption
Milk-alkali syndrome
Elevated calcitriol
Vitamin D excess
Excessive dietary intake
Granulomatous diseases
Elevated PTH
Hypo phosphatemia

Etiologies of hyper
calcemia
Increased Loss From Bone
Increased net bone resorption
Elevated PTH
Hyperparathyroidism
Malignancy
Osteolytic metastases
PTHrP secreting tumor
Increased bone turnover
Pagets disease of bone
Hyperthyroidism

Etiologies of Hypocalcemia
Decreased GI Absorption
Poor dietary intake of calcium
Impaired absorption of calcium
Vitamin D deficiency
lack of exposure to sun light
Malabsorption syndromes
Decreased conversion of vit. D to calcitriol
Liver failure
Renal failure
Low PTH
Hyperphosphatemia

Etiologies of
hypocalcemia
Decreased Bone Resorption/Increased Mineralization
Low PTH (hypoparathyroidism)
PTH resistance (pseudohypoparathyroidism)
Vitamin D deficiency / low calcitriol
Hungry bones syndrome
Osteoblastic metastases

Osteoporosis and calcium deficiency

Lack of adequate bone matrix

Negative calcium balance
Skeletal mass in older age is proportional to skeletal mass at
maturity
Androgen and estrogen
Calcium along with strontium and sodium fluoride

Pathologic calcifications

Dystrophic calcifications - Calcium salts deposited in dead or

degenerated tissue
Tuberculous necrosis, blood vessels in atherosclerosis, scars, areas of
fatty degeneration
Not dependent on calcium in blood but a change in the local
condition of the tissues
A local alkalinity in damaged tissue
Orally in the gingiva, tongue, cheek and also in the pulp
Benign fibromas of mouth and adjacent tissues

Pathologic calcifications
Teeth of elderly
Occur in the blood vessels or in the perineural connective

tissue of the pulp or diffusely scattered in pulp chamber

and root canal appear as fine fibrillar calcifications
coalesce to form large masses
Hill classified 2 types
a)nodular type
calcification of hyalinized
connective tissue perivascular or perineural increased
fibrosis. Found in the coronal portion of the pulp chamber
and increase in size by accretion and deposition of
calcium along the collagenous fibrils.
.

b) found in and around the necrotic cells and corpora

amylacea multicentric manner frequently in radicular

portion of the pulp canal.
Calcification nidus at the center and increases in size by
concresence
Found in the degenerative process of the pulp and in pulps
with deep seated inflammatory processes

Pathologic calcifications
Metastatic calcifications

Calcium salts in undamaged tissues

Due to excess of blood calcium in hyperparthyroidism,
hyper vitaminosis D
Mainly in the kidneys, gastric mucosa, and blood vessels
Calcinosis calcifications

Presence of calcifications under the skin

Calcinosis circumscripta - circumscribed
Calcinosis universalis scleroderma dermatomyositis

PHOSPHORUS METABOLISM
Total content of human body-500-600 mg
85% - 90% in skeleton 100mg in soft tissues.
Also a main constituent of both teeth and bone.
But their turnover rate is lowest
It is present in all cells of the body as organic phosphorous

compounds in combination with proteins, lipids and carbohydrates.

It is a constituent of ATP and has a unique role in energy storage
and transformation.
Normal inorganic phosphate level of blood in adults range from 2
-4 mg/dl and children 3 5mg/dl
Blood Phosphorus Total blood phosphorus is 40mg/100ml.
The RBCs contain more phosphorus than plasma

Sources Milk, eggs

Brain, liver, egg yolk
Muscles
Dietary requirements 240mg(infants) 800mg(adults) growing children,
pregnant women and lactating mothers require higher
intake of about 1200mg.
Regulation of calcium and phosphorous controlled by
kidny with respect to parathormone and vit D

Blood levels maintained by a balance of various

factors parathyroid hormone, phosphate
activity and vit D.
Absorption of phosphorus 70% is absorbed by small intestine.
Absorption takes place in the form of soluble

inorganic phosphate.
PTH causes a decrease in tubular phosphate
reabsorption and thus a promotion in the excretion of
phosphate.
Excretion It is mainly excreted through urine. But calcium

Three forms of phosphorus

Inorganic phosphate-present in plasma-2.5-4.5 mg/dl.
Ester phosphate-absent in plasma present in RBCs-

0.1-0.7mg/100ml present.
Lipid phosphorus-also known as phospholipids-

present both in cells and plasma.7-15 mg/100 ml of

blood.

Functions Formation of teeth and bone.

Formation of phospholipids and phosphoproteins.
Plays important role in fat and carbohydrate metabolism

by functioning in phosphorylation. Thus helps in

oxidization of glucose.
Formation of ATP
It is a constituent of DNA & RNA.
Formation of nerve phophatides.
Cephalin a phospholipid take part in blood clotting.
Regulates hydrogen ion conc. of cells, blood and urine.
Helps in enzymatic functions of vit B complex.

Etiologies of
Hyperphosphatemia
Increased GI Intake
Decreased Urinary Excretion
Renal Failure
Low PTH (hypoparathyroidism)
s/p thyroidectomy
s/p I131 treatment for Graves disease of thyroid
cancer
Autoimmune hypoparathyroidism
Cell Lysis
Rhabdomyolysis
Tumor lysis syndrome

Etiologies of Hypophosphatemia
Decreased GI Absorption
Decreased dietary intake (rare in isolation)
Diarrhea / Malabsorption
Phosphate binders (calcium acetate, Al & Mg containing
antacids)
Decreased Bone Resorption / Increased Bone Mineralization
Vitamin D deficiency / low calcitriol
Hungry bones syndrome
Osteoblastic metastases

Etiologies of Hypophosphatemia
Increased Urinary Excretion
Elevated PTH (as in primary hyperparathyroidism)
Vitamin D deficiency / low calcitriol
Fanconi syndrome
Internal Redistribution (due to acute stimulation of
glycolysis)
Refeeding syndrome (seen in starvation, anorexia, and
alcholism)

Sodium

Maintanence of acid base equilibrium

Sodium deficiency is rare
Gradual weakness, fatigue, lassitude, apathy, anorexia, exhaustion,
nausea, muscle cramps, peripheral vascular collapse.
Potassium
Muscular activity
Acid base equilibrium
Nerve conduction
Cardiac or respiratory failure
Muscular weakness
Hyperkalemia- adrenal insufficiency, dehydration excessive absorption of
potassium
Mental confusion, numbness, tingling of extremities, pallor, cold skin,
weakness, cardiac rhythm disturbance and peripheral collapse

Trace elements
Iodine - thyroid hormone

goitre
Copper - Normal erythropoiesis
Deficiency - Wilsons disease
Kinky hair syndrome
Iron - anemias
Excess of iron - Bronze diabetes
Sideroblastic anemia,
thalassemia
Zinc - Acrodermatitis enteropathica
Keratogenesis, bone growth, wound healing and
reproduction disorders.

Protein metabolism
Proteins complex biological compounds high

molecular weight containing nitrogen, hydrogen, oxygen,

carbon and small amounts of sulphur
All tissues plants and animals proteins
Substances of high molecular weight proteins, nucleic
acids, carbohydrates are hydrolyzed to yield smaller
molecules which are absorbed and assimilated.
Normal adult has about 12 - 18% protein.

Protein requirement
1gm of protein for each kilogram of body weight
Protein is required in increased quantity in the last half of
pregnancy and during lactation and in even greater
amounts in infancy and childhood and adolescence
Proteins and their constituent amino acids are of importance
in the formation of hormones, enzymes, plasma proteins,
antibodies and numerous other physiologically active
substances.

Proteins
Complete proteins contain sufficient amts of essential

amino acids for normal metabolic reactions and are

usually found in foods of animal origin.
Incomplete proteins are those that have insufficient
quantities of one or more essential amino acids. Ex:- Corn
protein low in lysine and legume low in methionine.
Complimentary proteins are proteins that when ingested
singly are incomplete but when combined, provide
sufficient essential amino acids.

Build up of body protein is active during growth, late pregnancy

and lactation.
A constant flux of tissue break down and tissue formation
producing a dynamic equilibrium
Proteins have an important bearing on the pre eruptive and post
eruptive effects on teeth
Form an integral part of cells necessary for the normal
development of tooth and specifically for the formation of the
matrix of hard tissues of the teeth.
The chemical nature of protein foods can neutralize the acids
produced by oral bacteria

Protein energy malnutrition

PEM a spectrum of diseases with kwashiorkar an

essential feature of deficiency of protein and nutritional

marasmus total inanition of infant due to severe and
prolonged restriction of all food.
Marasmic kwashiorkar clinical features of both
Children adapt to prolonged energy and
protein shortage by nutritional dwarfism
Marasmus is of greater clinical importance
than kwashiorkar.

Causes
Prolonged febrile illness, in massive burns and

large chronic ulcers, in stress, hyperthyroidism

and other hypermetabolic states.

Classification of Vitamins

Water soluble
Vit C

Fat soluble
B complex
Thiamine B1
Riboflavin B2
Niacin B3
Biotin
Pantothenic acid
Folic acid
Vit B 12
Pyridoxine B6

Vit A
Vit D
Vit E
Vit K

VITAMIN A
1. Eye sight
2. Growth bone growth slow
3. Reproduction spermatogenesis in

males;preventing fetal resorption in females

4. Maintenance of epithelial cells
Sources Carotenoids brightly colouredcarrots,pumpkins,papayas,tomatoes etc
Daily requirements Adults 5000 IU
Children 2-3000 IU
1 IU = 0.3 mg of retinol.

 CLINICAL IMPLICATIONS dietary insufficiency

1.Night Blindness/Nyctalopia
2.Xeropthalmia
3.Keratomalacia
4.Follicular hyperkeratosis of the skin.
.
Others Acne & Psoriasis Rx with tretinoin.(all trans retinol)
carotenes immmunity,antioxidants
Hypervitaminosis - > 7.5 mg / day
C/f :-skin dry and pruritic
liver enlarged
drowsiness,sluggishness,vomiting,falling of hair etc

VITAMIN D
Group of closely related sterols
Nutritionally imp forms Calciferol(D2) and

Cholecalciferol(D3)
Source Sunlight and animal fats,fish liver
oils

VITAMIN D
Clinical implications
Poor intestinal
absorption hypocalcemia
new bone fails to
mineralize.
Children Rickets
Adults Osteomalacia &
Osteoporosis
(mainly in women)

 Hypervitaminosis D chronic ingestion of large doses (50,000 IU/day)

manifestations due to plasma Ca and ectopic

deposition
- Hypercalcemia, weakness, fatigue, ectopic Ca
deposition
(soft tissues,blood vessels etc) renal stones,
hypertension etc.
Rx - with holding the vitamin, low Ca diet, fluids,corticosteroids.
Therapeutic Uses Rickets- 1000-5000 IU/day

Osteomalacia
Osteoporosis
Hypoparathyroidism

Interactions

Phenytoin and phenobarbitone

calcitriol;

responsiveness of tissues to

prolonged use rickets and osteoporosis

Vitamin E
Tocopherol
Source
N Plasma level - 0.8 1.4 mg/100 ml
Daily req. 25 30 mg
Functions Antioxidant
Clinical Implications deficiency is rare

1. Neuromuscular diseases in children & neurological manifestations

(altered
gait, depressed tendon reflexes) in adults with hepatobiliary disease
2. Increased oxidative fragility of erythrocytes;hemolytic anemia in
premature infants and malabsorption syndrome
3.Nocturnal muscle cramps
Therapeutic uses G-6-PD deficiency-100mg/day - survival time of
erythrocytes

Vitamin K
2 major forms- K1 fresh green vegs,fruits

K2 intestinal bacteria.

Functions stimulate the production &/ or release of certain coagulation

factors

Daily req.- 0.03 mg/kg adults

met by dietary intake & microbial synthesis

Clinical Implications
Deficiency of Vit K-

in the prothrombin content of blood CT

Newborn infants- deficient in Vit K; lack of established intestinal flora

0.1-0.2 mg of Menadione sod bisulphite or 0.5 mg of vit K1 i.m

Water Soluble Vitamins

VITAMIN C ascorbic acid anti scorbutic properties 1933
Sources

Daily req.-Infants 35mg

Adults 45 mg
Pregnancy and lactating mother 60-80 mg

N conc in blood plasma 0.6 1.5 mg/100ml

 Functions Hydroxylation of proline hydroxyproline - collagen

1.Oxidative and metabolic reactions

2.Formation and stabilization of collagen triple helix
3.Biosynthesis of adrenal steroids,catecholamines,oxytocin,ADH
4.Stimulates collagen synthesis and maintenance of intercellular
connective tissue
Clinical implications

Scurvy history - sea voyages

 Symptoms Connective tissue defect

increased capillary fragility,

Swollen,bleeding gums,
loosening of teeth
perifollicular hemorrhages,
petechial hemorrhages,
spontaeneous bruises,
impaired wound healing etc
Therapeutic uses-

Prophylactic- 50 100 mg/day

Scurvy 0.5 1.5 g / day
Postoperative 500 mg/day
Anemia Vit C enhances iron
absorption
Toxicity

Oxalate metabolite of ascorbic acid - conc.

Urinary stones

 Deficiency lack of collagen formation hydroxylation of proline &

permeability of endotoxin from the oral mucosa

Enhances motility of PMN s & thus deficiency

s the host immune response

Affects the severity of gingivitis but not the pd attachment

Vit C concs in human neutrophils are very high

- enhancement of chemotaxis
-facilitation of oxidative destruction of micro orgs.
-preservation of neutrophil integrity
- protection of host tissue by acting as a reducing agent neutralize
oxidation products produced by neutrophils during the metabolic
resp.burst

ANTIOXIDANTS
Combat oxidation
Substances that protect other chemicals of the body from damaging

oxidation reaxns

free radicals & O2 species

Free radicals atom or molecule impaired electron acquires electron

chain rxn highly reactive

Types of antioxidants

non enzym
Vit E
B carotene
Vit C
Trace elements
Se,Mn,Cu,Zn

enzymatic
superoxide dismutase,catalase
glutathione peroxidase etc

 Mode of action

1.Interrupt lipid peroxidation

chain reaxn
death
2.Reducing conc of reactive O2 species
3.Scavenging initiating radicals

O2

life

free radicals

cell damage and

 Vit E prevents peroxidation of membrane phospholipids cell damage

lipophilic nature interior of cell memb lipid bi layers

vit E + ascorbic acid
tocopherol OH

semidehydroascorbic acid +

reactive oxygen intermediates

Carotene quench singlet O2

scavenge free radicals

protect cell memb. lipids
Vitamin C water soluble chain breaking antioxidant

scavenges free radicals & reactive O2 molecules

metabolic
pathways of detoxification
prevents formation of carcinogens from precursor
compds.

Thiamine (b1)
1926 Jansen and Donath vit B1 from rice polishings
Chemical structure made of pyrimidine and thiazole ring linked by

methylene bridge
Sources
Daily Req.

Infants & children 0.3-1.2mg

Adults 1.2 1.5 mg
N conc in plasma

1g/100ml
Functions

- Growth
- Nerves
Active form thiamine pyrophosphate

- coenzyme in carbohydrate metabolism,decarboxylation

of ketoacids,hexose monophosphate shunt

 Deficiency symptoms

Beriberi I Cannot dry and wet increased levels of pyruvic & lactic acids
Dry beri beri neurological symptoms
1.Polyneuritis with numbness
2.Tingling
3.Muscular weakness and atrophy wrist drop
4. Paralysis of limb
5.Mental changes sluggishness,poor memory
6.Loss of apetite
Wet beri beri
Cardiovascular system affected
1.Palpitation
2.Breathlessness
3.High output cardiac failure
Wernicke s Encephalopathy - alcoholics ; psychiatric

 Therapeutic Uses
1. Prophylactic 2 10mg / day

2.Beri beri,Wernicke s encephalopathy 100mg/day i.m or iv till

symptoms subside.

Adverse effects - Thiamine is nontoxic

excess - urine

Riboflavin (b2)
Earlier lactoflavin milk
Sources anaerobic fermenting bacteria,milk,liver,heart,fish etc
Daily req.

Infants & children 0.4-1.2 mg

Adults 1.5 1.8 mg
Functions
flavin adenine mononucleotide (FMN) & FAD oxidation-reduction

reactions
Deficiency

associated with other vit deficiencies

angular stomatitis,sore,raw tongue,
ulcers in mouth,dry scaly skin

Niacin (b3)

Nicotinic acid, Nicotinamide

Sources liver,fish,cereals,nuts,pulses etc
Tryptophan

nicotinic acid

( 60mg of T = 1mg nicotinic acid )

Daily req.

Infants & children 5-16mg

Adults 16-20 mg
N conc in whole blood 0.5 0.8 mg/100ml
Functions

NAD & NADPH Oxidation reduction reactions

H2 receptors-tissue respiration,glycolysis
fat synthesis
Nicotinic acid in large doses vasodilator

 Deficiency Pellagra

3D s Dermatitis
Diarrhoea
Dementia
Anemia,hypoproteinemia

Therapeutic uses

Prophylactically 20 50 mg/day
Pellagra 200 500 mg / day

Pyridoxine (b6)
Pyridoxine,Pyridoxal and Pyridoxamin
Sources liver,meat,egg,soybean,vegs & whole grain
Functions

Pyridoxine & pyridoxamine

pyridoxal

pyridoxal phosphate
Transaminases,decarboxylases
synthesis of nonessential aa
s,tryptophan,dopamine,histamine,GABA

Drug Interactions isoniazid

pyridoxine level
hydralazine,cycloserine and pencillamine
Deficiency along with other B vits

glossitis,growth retardation,mental confusion,etc

Pantothenic
acid
(b5)

Organic acid

Sources liver,mutton,egg yolk,vegs

Component of Coenzyme A CHO, fat, steroid and porphyrin

metabolism
Clinical deficiency not known

BIOTIN
Sulfur containing organic acid
Sources egg yolk, liver, nuts
Antagonist avidin egg white
Deficiency alopecia, anorexia, glossitis, muscular pain

Folic
acid

Pteroyglutamic acid, folacin

N level in serum 3 - 25g/l of serum

Sources yeast, liver, kidney, fish, green leafy vegetables
Daily req.- children 100 300 g

Adults - 400g
pregnant and lactating women - 800g
Deficiency- Megaloblastic anemia

Other manifestations retardation of growth

weakness
infertility
Treatment 5mg/week
Folic acid + vit B12

Vitamin b12
Cyanocobalamin , Hydroxycobalamin Co containing compounds
Castle (1927-32) extrinsic factor in diet + intrinsic factor in the body

hemotopoietic principle
1948 Vit B 12 was isolated EF
Sources-

only pulses are a source in vegs

Daily req.

Infants & children 1 - 2g

Adults - 3g
Pregnancy,lactation - 4g
Functions

active forms
deoxyadenosyl-cobalamin
methylcobalamin

 Vit b 12 is linked to folate metabolism

Others

1. Homocysteine

methionine

methionine methyl group donor in many metabolic rxns and

protein
synthesis
2. also imp for making THFA available for reutilization
B 12 deficiency THFA gets trapped- 1 C-transfer rxns get
affected
3.Ribonucleotide

deoxyribonucleotide

4.Biosynthesis of proteins
Utilization of B12

Absorption is in ileum

- depends upon HCl & Intrinsic factor(parietal cells)

- free B12 (cobalamin) + IF

2 mol of cobalamin & 1 mol IF

- resists intestinal digestion

transported in combination with transcobalamin

 Deficiency -

Occurs due to 1.Addisonian pernicious anemia absence of IF inability

to
absorb B 12
2.Gastric disorders
3.Malabsorption
4.Nutritional deficiency
Manifestations
1.Megaloblastic anemia neutrophils with hypersegmented
nuclei,giant platelets
2.Glossitis GI disturbances
3.Neurological
Treatment

Hydroxycobalamin parenteral 1000g initially

Vit B12 + folic acid advised