ENDOCRINE DISEASE

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ENDOCRINE DISEASE

• Prof. M.K.Hamam
• Oral Medicine
• Diagnosis Treatment
• Burkets
• Tenth Edition

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• 1- Endocrine Disorders
•  
• Importance of hormones
• Endocrine system
• Hormonal disorders
• Adrenal gland disorders
• Addisons disease
• Dental evaluation, management
• Thyroid disorders
• anatomy -
  Location
• Hormone
• Hypothyroidism
• Hyperthyroidism
• Dental evaluation and management
• Diabetes mellitus
• 2- liver diseases

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• Introduction
• Endocrine system are inherently hierarchically
  organized .
• The hypothalamus controls the pituitary gland
  activities which in turn regulate other endocrine
  gland secretions .
• Hypothalamus secretes releasing and inhibiting
  factors .
• Among the releasing hormone is corticotrophin
  releasing factor
• ( CRF ) , which stimulates the release of adreno
  corticotrophic hormone ( ACTH ) from the
  pituitary gland .

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• Hierarchical arrangement
• ACTH acts on adrenal cortex to cause the release
  of cortisol
• ( hydrocortisone )
• Hypothalamus secretes ? CRF stimulates ?
  pituitary gland secretes? ACTH
• stimulates ? Adrenalcortex ? Secretes ?
  Cortisol .

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Negative feed back regulatory

• All endocrine system functions as a closed loop
  . In most endocrine system ,negative feed back
  regulatory their function .
• For example , hypothalamus and pituitary gland
  stimulate the secretion of cortisol from adrenal
  cortex . While cortisone inhibits hypothalamus
  and pituitary gland secretion
• ( negative feed back ).

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Pituitary gland

• The anterior lobe of pituitary gland produces .
• 1- Adreno Corticotrophic Hormone ( ACTH )
• 2- Melanocyte Stimulating Hormone ( MSH )
• 3- Thyroid Stimulating hormone .( TSH )
• 4- Growth Hormone ( GH )
• 5- Follicle Stimulating Hormone ( FSH )
• 6- Luteinizing Hormone ( LH )
• 7- Prolactin

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• A- Disorders of pituitary gland ( Dwarfism )
• General manifestation
• 1- Impaired growth of child ( GH )
• 2- Hypoadrenocorticism ( ACTH )
• 3- Hypothyroidism ( TSH )
• 4- Failure of ovulation , amenorrhea . ( FSH )
• 5- Impotence , defective spermatogenesis .( LH
  )
• 6- Failure of lactation
  ( - prolactin )

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• Oral manifestation -
• 1- Delayed shedding eruption of teeth .
• 2- Microdontia if occurs before odontogensis .
• 3- Crowding and malocclusion with normal size of
  teeth. If occurs after odontogenesis.
• Dental implication -
• Stress, surgery , GA,infection ,sedative
  ,hypnotic , and trauma
• May precipitate hypo pituitary coma .
• Hypo pituitary is related to decrease TSH ACTH
  , so the patient cannot tolerate stress.
• Hypo pituitary coma is manged by -
• 1- 200 mg hydrocortisone sodium succinate I.V.
• 2- 25-50 mg dextrose ( if there is hypoglycemia
  )
• 3- Oxygen
• 4- Call ambulance for hospital admission .

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B- Hyperpituitarism

• Children ( before epiphysis closure ) ? Gigantism
  
• 1- well proportional individual but huge .
• 2- teeth spacing ( if occur after odontogensis )
• Adult - ( after epiphyseal closure ) ?
  Acromegaly
• 1- large hand , feet , malar bone , supraorbital
  ridges , tongue , lip, mandible prognathism )
• 2- Teeth spacing ( food impaction )
• hyper cementosis ( teeth
  fracture , or difficulty in extraction )

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A 12 year old boy, 65, with his mother, and his
hand (left) in comparison with that of a grown
man, 61 All long bones in the body effected
before closure of epiphyseal growth plates
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• Dental implication
• 1- systemic problem associated with
  hyperpituitrism may complicate the dental
  treatment as -
• Hypertension
• Diabetes mellitus
• Hypercalcemia
• Cardiomyopathy .
• 2- Hazards of GA related to breathing problem
  where -
• Tongue is large
• Epiglottic opening is narrow .
• Kyphosis .
• Thymus gland is enlarged
• So it is better to avoid supine position .

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Adrenal gland

• Adrenal gland secrete -
• A - From medulla
• 1- Epinephrine ( adrenaline )
• 2- nor epinephrine ( noradrenalin )
• B- From Cortex
• 1- Glucocorticoids ( cortisol )
• 2- Mineralocorticoids ( aldosterone )
• 3- Sex hormones .

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• Disorders of adrenal gland
• 1- Adrenal cortex insufficiency
• Etiology
• 1- Congenital
• 2- Acquired
• A- Primary Addisons disease
• B- Secondary - ? to exogenous steroid
  therapy .
• ? to pituitary
  insufficiency .
• ( ACTH
  deficiency )

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• 11-Adrenal cortex hyperfunction
• Etiology
• A- Cushing disease
• It is due to pituitary gland adenoma resulting in
  increase ACTH
• That stimulate adrenal cortex .
• B- Cushing syndrome
• It is due primary adrenal adenoma .
• C- Iatrogenic Cushing syndrome
• It is due to exogenous corticosteroid therapy .

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• Clinical Features of Cushings Syndrome
• Round (moon) face.
• A hump on upper back Buffalo hump
• stretch marks on their abdomen (striae)
• Hypertension
• Prolonged wound repair
• Obesity
• Mental depression

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Easy bruising Thinning skin Poor wound
healing Acne Purple striae Hirsutism Female
balding Menstrual irregularity Sleep
disorders Excessive hunger Excessive
thirst Frequent urination Sweating Anxiety Confus
ion Concentration loss Memory loss Depression Suic
idal thoughts Panic attacks
Abdominal weight gain Red, round moon
face Thinning extremities Buffalo hump High
blood pressure High blood sugar Muscle
weakness Osteoporosis/Fractures Infections Bloo
d clots Visual field defects
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A Primary Adrenal cortex insufficiency
Addisons disease

• Definition
• It is adrenal cortex insufficiency ( atrophy )
  leading to failure of cortisol and aldosterone
  secretion .
• Auto immune disease due to circulating
  antibodies directed against adrenal cortex .
• Tuberculosis
• Sarcoidosis
• Hemorrhage
• Histoplasmosis
• Malignancy . Amyloidosis

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• Clinical Features
• Manifestations related to low level of
  aldosterone
• 1- Sodium water depletion
• 2- Reduced extracellular volume hypotension .
• 3- Retained potassium hydrogen ions
• 4- Hyperkalemia acidosis .
• Manifestaion related to low level of cortisol
• 1- Stimulation pituitary gland to secrete
  pro-opio melanocortin . So there is increased
  level of -
• Melanocyte stimulation activity which lead to
  increase skin oral melanin pigmentation .
• ACTH .

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• PeutzJeghers syndrome multiple pigmented spots
  on -

• Addison disease pigmentation of the -.

the skin.
the lower lip.
buccal mucosa
gingiva
the buccal mucosa.
lower lip
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• 2- Hypoglycemia
• 3- Weight loss , weakness
• 4- Addisonians Crisis ( adrenal crisis )
• It is manifestation by sever exacerbation of
  symptoms as hypotension , headache , dehydration
  , weakness , nausea , vomiting .
• It is precipitated by factors that increase the
  body demand for cortisol such -
• as surgery , stress , infection , trauma ,
  G.A .
• The patient may die if not treated immediately .
  
• Laboratory finding
• Cortisol , Sodium
  
  
• ACTH , Potassium .
  
  
  
  

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B- Secondary adrenal cortex insufficiency
( patient on glucocorticoid therapy )

• Pharmacological action of glucocorticoids
• 1-Owing to their anti- inflammatory and immune-
  suppressive action ,
• There are prescribed for management of -
• Allergic diseases .
• Autoimmune diseases ( Lupus erythematosus ,
  pemphigus vulgaris ,..)
• 2- they are prescribed as replacement therapy in
  patients with Addison s disease

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• Complications of glucocorticoid therapy
• A- Adreanal cortex atrophy -
• The long term low dose steroid ( 10 mg prednisone
  for one month ) or short term high dose steroid
  results in adrenal cortex suppression ( atrophy
  ).
• Adrenal cortex secretion is under the control of
  ACTH secreted by pituitary gland .
• Exogenous steroid received by the patient for
  management of certain allergic or skin disease
  results in suppression of ACTH release . In turn
  , endogenous adrenal cortex secretion is
  suppressed and the adrenal glands under atrophy .
• .

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• Patients with adrenal cortex atrophy cannot
  tolerate stress , surgery , G.A , infection , and
  trauma . There is increase in the body with
  such high levels of endogenous corticosteroids (
  300 mg ) , so the patient suffers adrenal crisis
  .
• Causes of adrenal crisis -
• 1-Adrenal insufficiency (A- cong. Adrenal ins .B-
  Primary Addison's disease . C-Secondary
  ,exogenous steroid , surgical excision of gland ,
  pituitary insufficiency ) certain condition (
  stress, G.A ., infection , surgery , trauma ) ?
  adrenal crisis .
• 2- Sudden withdrawal of exogenous steroid

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• How to avoid adrenal atrophy ?
• 1- alternate day on the day off therapy , the
  adrenal pituitary axis is allowed to function and
  produce endogenous cortisol .
• 2- single morning dose of exogenous steroid 1.5
  hrs. after arising . Cortisol level is normally
  high in the morning . Thus if steroid is given at
  this time it does not to tend to suppress ACTH
  and adrenal gland secretion .
• How to avoid adrenal crisis ?
• 1- Careful case history -
• It should be remember that not only patient under
  current treatment are not at risk of adrenal
  crisis but also patient who had steroid therapy
  during the last year ( normal function of
  adrenal gland is restored within 9-12 month. )
• 2- Supplementary corticosteroid should be given
  before and during period of stress ( G.A. Trauma
  , )
• 3- Gradual withdrawal of steroid therapy to allow
  for the restoration of adrenal function.

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• Management of patient on steroid therapy .
• Under local anaesthesia
• 1- patient on total replacement therapy
  Addisons disease
• Hospitalization
• It is better to over treat ( i.e. high dose of
  steroid ) during surgery rather that to have
  Adrenal crisis .
• 2- patient received steroid during the previous
  12 months .
• 200 mg hydrocortisone orally 2 hours
  pre-operative or
• 200 mg hydrocortisone I.V . Immediately pre
  operative .
• 3- patient currently on steroid therapy -
• A- Short appointment ( lt 1hr. )
• Emergency ? 200 mg hydrocortisone I.V . ?
  immediately before appointment
• No emergency ? double the steroid dose the night
  and the whole day of app.

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• B- long appointment ( gt 1 hr. )
• Emergency ? 200 mg hydrocortisone I.V.
  immediately before app.
• 200 mg hydrocortisone
  I.M. 6 hrs . For 24 hrs .
• No emergency ? Triple the dose the night before
  and the whole day of app.
• then gradual
  tapping to regular dose over the 2th of
  3rd postoperative days

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• 11- Under General Anaesthesia
• 1- patient on total replacement therapy
  Addisons disease
• 2- patient received steroid during the previous
  12 months .
• 100 - 200 mg I.V. hydrocortisone sodium
  succinate with pre-medication and then every 6
  hrs . For 24-72 hrs . Then continue normal
  medication .
• 3- patient currently on steroid therapy -
• Monitor blood pressure during surgery
  recovery .
• I.V. steroid should be given if there is fall in
  blood pressure

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Thyroid gland

• ?Thyroid glands secrete thyroxin ( T4 )and Tri-
  iodothyronine ( T3 ).
• Thyroid gland secretion is under the control of
  pituitary gland which secrete ( TSH ) . The
  release of TSH from pituitary gland is regulated
  by thyrotrophine releasing factor ( TRF ) from
  hypothalamus .
• Negative feed back mechanism similar to the
  pituitary adrenal axis is also regulating the
  thyroid gland secretion and the axis is called
  pituitary thyroid axis.
• Hypothamus ?? secretes TRF ? ? Stimulates
  pituitary ?? secrete ?? stimulates TSH ? Thyroid
  
• Inhibit ( -ve feed back )
  T3
  T4 secretes
  
  
  stimulate
• 
  
  Thyroid
• The precise role of thyroid hormones is not
  known . However , excessive secretion increases
  the basal metabolic rate ( BMR )
  
  
  

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• Disorders of thyroid gland -
• Hyperthyroidism ( thyrotoxicosis )
• Types -
• Grave s disease characterized by diffused
  enlargement of thyroid
• 
  gland .
• 
  exophthalmos .
• Nodular Goiter characterized by less sever
  nodular enlargement of
• 
  thyroid gland .
• 
  No exophthalmos
• General manifestation
• Warm moist skin
  
• Tremors of hands and tongue
• Exophthalmoses which may persist even after
  treatment .
• Nervousness
• Tachycardia . Due to increase BMR .

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Hyperthyroidism Graves Disease
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• Oral manifestation
• Normal growth of jaws
• Early shedding of deciduous teeth
• Early eruption of permanent teeth .
• Osteoporosis .
• Dental implication
• 1-Treated thyrotoxic patient present no problem
  in dental treatment .
• Untreated patient may have tachycardia and
  arrhythmia that can lead to heart failure .
• Adrenergic receptors are very sensitive to
  adrenaline , so local anesthesia should be free
  from adrenaline . Prilocaine containing
  octapressin is an alternative .
• 2- G.A ( risk of arrhythmia )
• 3- anti- thyroid drugs ( thiocarbamides ) induces
  agranulocytosis ?oral oropharyngeal ulceration .

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3- Thyroid crisis

• It is an exaggerated manifestation of
  hyperthyroidism .
• Precipitation factors . Stress , infection ,
  surgery .
• Clinical manifestation -
• nausea , vomiting , profuse sweating ,Tremor
  ,Tachycardia ,Fever , hypotension ,Finally heart
  failure and death.
• How to avoid thyroid crisis .
• Stress , ( Tranquilizers benzodiazepine
  potentiate the antithyroid drugs )
• Acute infection should be managed immediately .
• How to manage thyroid crisis ?
• call ambulance for hospitalization since medical
  treatment will include -
• Hydrocortisone 200 mg i.v
• Glucose i.v
• Ice pack , wet pack , fans
• Antithyroid drugs and adrenergic antagonizer (
  propanolol )
• N.B - The dentist should cool the patient with
  cold towels and give 100-300 mg .i.v .
  Hydrocortizone and will be ready to initate
  cardiopulmonary resuscitation if indicated.

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2- Hypothyroidism

• Less common than hyperthyroidism
• Females.
• Children ? Cretinism (inherited or acquired)
• Adult ? Myxedema (acquired).
• Causes
• Thyroid ,Congenital absence or defect
• Iatrogenic
• Iodine deficiency
• Chronic thyroditis
• Pituitary ( secondary)
• Hypothalamic (tertiary )

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• Cretinism
• In childhood? severe developmental defects
  (unless recognized and treated early).
• Clinical manifestations
• Growth retardation
• Mental retardation
• Mongoloid faces.
• Protuberant abdomen
• Delayed bony and dental development.
• Defective development and maturation of the CNS
• Delayed eruption of teeth.
• Micrognathia
• Macroglossia
• Malocclusion , anterior open bite
• Puffy , enlarged , protruded lip.
• Short flat nose

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• Myxedema
• Myxedema is defined as hypothyroidism acquired
  (not inherited) in the adult.
• Decreased metabolism hypothyroid state.
• Facial edema(myxedema).
• Coarse skin.
• Decreased mental acuity.
• Physical activity, and tolerance to cold, as well
• Very uncommon ? coma die.
• loss of hair
• Weight gain

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• Dental implication
• Myxedema coma
• Precipitating factor
• Trauma , surgery , infection , G.A
• Sedative ( diazepam ) analgesic ( codeine ) . The
  respiratory center is hypersensitive to these
  drugs , they should be avoided or the dose must
  be reduced .
• Manifestation
• Hypothermia , Hypofuntion , Bradycardia ,
  Epileptic seizures
• Management
• Call ambulance for hospitalization
• Artificial respiration
• 200 mg hydrocortisone i.v.

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Diabetes Mellitus

• Definition
• It is an endocrine disorder , characterized by
  persist rise in blood glucose level ,
• Resulting from absolute or relative deficiency
  of insulin . Insulin reduces blood sugar level by
  -
• Glucose oxidation
• Glycogensis .
• Increase uptake of glucose by cells
• Etiology -
• 1- Primary ( idiopathic )
• A- insulin dependent ( juvenile onset )
• B- Non insulin dependent ( maturity onset )
• 2- Secondary
• A- Pancreatic damage ( Chronic pancreatitis ,
  Hemochromatosis . )
• B- Genetic syndrome ( insulin resistance )
• C- Endocrinal ( Acromegaly , Cushing ,
  pheochromocytoma , Steroid therapy )

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Comparison of Insulin-Dependent and Non-Insulin
Dependent Diabetes Mellitus
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• Manifestations of diabetes are due to -
• 1- hyperglycemia
• 2- Ketoacidosis
• 3- vascular wall disease
• 4- Advanced glycosylated end products ( AGEs )
• 5- hyperlipidemea
• Diagnosis
• 1- Glucose tolerance test .
• 2- High glycsylated hemoglobin ( reflects blood
  sugar level in the last 3 months ). If -
• A- lt 7 it is normal , patient is not diabetic
• B- 7-9 patient is controlled .
• C- gt 13 patient is not controlled .
• 3- Ketoacidosis
• 4- Glucosuria

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• Oral manifestations .
• No specific pathogonomic features .
• More obvious in uncontrolled diabetics .
• 1- Dry mouth
• 2- Atrophy of filiform papilla enlarged
  hyperemic fungiform papillae .
• 3- Burning sensation of the tongue .
• 4- Periodontal disease ( periodontal abscess in
  uncontrolled )
• 5- Occasionally enlarged salivary glands .
• 6- Increased rate of dental caries .
• 7- odontalgia ( due to pulp necrosis )
• 8- Grinspan syndrome ( it consists of )
• Diabetes
• Hypertension
• Lichenoid reaction.

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• Mangement of diabetic patients
• A- Patient controlled by diet or diet ant
  diabetic drugs .
• The dentist should reassure the patient to take
  his meal ant diabetic drugs
• B - Patient controlled by diet insulin .
• These measurements are undertaken for the
  controlled patient only .but the uncontrolled
  patient should be to the physician before any
  dental procedure .
• 1- Dental appointment should be in the morning
  about 1-2 hours after breakfast
• And after the usual insulin dose .
• 2- Premedication - sedative or tranqllizer ( to
  decrease endogenous adrenaline )
• 3- Antibiotic cover when surgery is indicated .
• 4- Avoid long appointments .
• 5- Avoid excessive trauma during surgical
  procedure .
• 6- Remove all septic foci and maintain good oral
  hygiene .

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• 7- Local anesthesia - the lowest concentration
  of adrenaline ( vasoconstrictor is essential to
  decrease pain ) or use prilocaine plus
  octapressin .
• 8- G.A ( by anaesthetist )
• 9- Hospitalization ( multiple extraction, massive
  infection , patient is receiving more than 60
  units insulin / day .
• 10 Unconsciousness in dental surgery is
  frequently due to hypoglycemia . 25 gm glucose
  orally or 20 ml of 20 dextrose i.v. will relieve
  hypoglycemia rapidly .
• If this is ineffective , call the ambulance .

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• Effect of low glucose level
• Brain use only glucose , if its level falls
• 1- neuroglycopenia ? irritability , tremor ,
  confusion loss of concentration .
• 2- Adrenaline release ? tachycardia , palpation
  sweating .
• Hypoglycemic shock is more dangerous than
  hyperglycemic shock because of neuroglycopenia .

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6- Diseases of the Liver
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A- Jaundice (icterus)

• Jaundice excessive bilirubin in the
  circulation.
• Hemolytic jaundice hemolysis of red blood cells.
• Obstructive jaundice obstruction in the biliary
  tree stones, infectious or neoplastic lesions.
• Hepatocellular jaundice liver disease.

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Morbilliform
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Symptoms

• Excess of bilirubin.
• Color of the skin, oral mucous membrane, and
  sclera.
• Hepatocellular disease a deficiency of
  prothrombin and clotting factors.
• Decreased tolerance to anesthetics and
  medications.
• History of contact with hepatitis pt. ? Refer to
  physician.

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Symptoms

• Symptoms of all hepatitis A, B, C, D, and Non- B
  are same (hepatitis A).
• More than half of all the types of hepatitis are
  either subclinical or mild enough to escape
  diagnosis.
• Malaise, arthralgia, myalgia, anorexia, nausea
  and fever.
• Morbilliform skin rash.

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Hepatitis

• It may be induced by -
• Chemical agents phosphorus
• Drugs isoniazed hyrochloride
• Collagen disease lupus erythematous
• Viral infection -
• Infection mononucleosis
• Cytomegalovirus
• Coxsackie virus
• Hepatitis A,B,C,D,E Viruses .

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What Is Hepatitis?

• Hepatitis means inflammation of the liver
• Hepat (liver) itis (inflammation) Hepatitis
• Viral hepatitis means there is a specific virus
  that is causing liver to inflame (swell or become
  larger than normal)

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Inflammation
Walls ofscar tissue begin to form.
Healthy liver cells become trapped by a wall of
scar tissue
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• Definition -
• Inflammation in the liver induced by viral
  infection
• Types -
• Hepatitis A transmitted by food , not serious
  .
• Hepatitis B
• Hepatitis C
• Hepatitis D ( delta )
• Hepatitis E water borne spread .

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HBV HCV
Type DNA virus RNA virus
Reverse transcriptase enzyme Present Absent
Present in All body fluids, saliva, CNS ,tears , semen , amniotic fluid All body fluids except semen ( still under study )
Mode of transmission Parental , sexual Parental. Sexual ( still under study )
Target cell Liver cells Liver cell lymphocyte
Vaccination Available Not available
Oncogenicity can cause hepatocellular Can cause hepatocellular carcinoma
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• Clinical manifestations
• Prodromal phase - high fever , malaise ,
  anorexia , nausea
• Icteric phase -
• 1- Jaundice develops within 5 days then fever
  gradually subsides .
• 2- cteric colour of sclera , nail bed , oral
  mucous membrane specially floor of mouth and
  palate .
• 3- Hepatomegaly tenderness of liver .
• 4- Spleenomegaly lymphadenopathy .
• 5- Spider angioma
• 6- Cholesterol deposition along lower eye lid .
• 7- Bleeding tendency
• 8- Dark urine and light colored stools .

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• Recovery phase -
• It is very long with HBV , HCV and the disease
  may be complicated by -
• 1- Acute fulminate infection .
• 2- Chronic infection .
• 3- Liver cirrhosis .
• 4- Hepatocellular carcinoma .
• Diagnosis -
• Case history ( blood trasfusion , contact with
  infected individual )
• Clinical examination icteric colour
• Laboratory investigation .

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• 1- Serological tests
• There are 3 antigens characteristic for HBV .
• HBsAg Surface antigen .
• HBcAg Cora antigen .
• HBeAg Envelope antigen .
• There are 3 antibodies produced in response to
  the previously mentioned antigens
• Anti-HBs antibody
• Anti- HBc antibody
• Anti- HBe antibody

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Antigen Appear Disappear Indicate
HBsAg Up to 6 weeks after exposure May disappear 1-6 w.after infection . Or lasts for 25 years in carriers Acute infection Chronic carriers
HBcAg Active stage of disease After resolution of disease .
HBeAg Active stage of disease After resolution of disease may persist for long time Highly infective individuals
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• Generally , the antibodies rise after
  disappearance of their antigens
• N.B . The presence of -
• Anti HBs antibodies means -
• 1- past infection with HBV
• 2- Vaccination of HB .
• Anti HBe and HBs Ag means -
• Healthy carrier ( will not manifest the
  disease )
• HBsAg then later Anti HBc level rise means .
• Active hepatitis .
• Anti HBc , HBsAg and absence of anti- HBs means
  
• Chronic carrier ( may manifest the disease
  )

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• 2- liver function test - elevation of -
• A- serum glutamic pyruvic transaminase ( SGPT )
• Alanine aminotransferase ( ALT )
• B- Serum glutamic oxaloacetic transaminase ( SGOT
  )
• Aspartic transferase ( AST )
• C- Serum alkaline phosphatase .
• D- Serum bilirubin .
• 3- Polymerase Chain Reaction ( PCR )
• Indicated mainly for diagnosis of HCV

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Dental implications

• There are 3 major problems facing the dentists ,
  when dealing with hepatitis patients .
• 1- Bleeding and clotting disorders due to liver
  disease.
• 2- Cross infection .( infection control
  ,vaccination , accidental needle prick )
• 3- Defective detoxification of drugs .