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Hepatitis_ Gall Bladder and Biliary Tract Diseases

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									Hepatitis, Gall Bladder &
 Biliary Tract Diseases
   Gall Bladder and
Biliary Tract Diseases
                 Objectives
► Causes,clinical features, effects and
 complications of acute and chronic
 cholecystitis

► Causes,clinical features, effects and
 complications of cholangitis

► Types   of gallstones

             factors, pathogenesis, effects
► Predisposing
 and complication of gall stones
                Introduction
Biliary system
     -intrahepatic and extrahepatic bile ducts
     -gallbladder
                        mucus-
► -lined by glandular mucus-secreting
  epithelial cell layer
                    liver-
► Bile secreted by liver->right and left hepatic
  ducts-                   duct-       duct-
  ducts-> common bile duct-> cystic duct->
  gall bladder
             Introduction( cont’d)
Bile
► Consists of micelles of cholesterol
                phospholipid
                bile salts
                bilirubin
► Stored and concentrated in the gallbladder
► In response to high fat food content; the
  gallbladder contracts by stimulation of
  cholecystokinin and expelled bile into the second
  part of duodenum through the ampulla of Vater as
  the sphincter of Oddi relaxes
         Cholelithiasis ( gallstones)

►   Common condition in which gallstones form within
    the biliary system

►   Types of gallstones
       1. cholesterol stones*
       2. pigment stones*
                                        +/-
       3. Mixed cholesterol + pigment ( +/- calcium
           carbonate)

* Different risk factors, different pathogenesis
Gallstones
Gallstones
      Predisposing factors for cholesterol
                    stones
►   Demography-
    Demography- Northern Europe , North and South
    America, native Americans; Mexican Americans
►   Advancing age
►   Female sex hormones-Female gender
                           -Oral contraceptives
                           -Pregnancy
►   Obesity
►   Rapid weight reduction
►   Gallbladder stasis
►   Inborn disorder of bile acid metabolism
►   Hyperlipidaemic syndromes
      Pathogenesis of cholesterol stones

►   Cholesterol stones can be pure (100%) or mixed with
    calcium carbonate, phosphates and bilirubin

►   Imbalance between the ratio of cholesterol and bile
    salts
       - excess of cholesterol
       -a deficit of bile salts

►   When cholesterol concentration exceeds the
    solubilising capacity of bile ( supersaturation)
    cholesterol nucleates into solid cholesterol
    monohydrate crystals
Cholesterol stones formation involves 4
   simultaneous defects:

1. Bile supersaturation with cholesterol

2. Gallbladder hypomotility promoting nucleation

3. Cholesterol nucleation in bile is accelerated

4. Mucous hypersecretion in gallbladder traps the
    crystals permitting their aggregation into stones
Cholesterol stones


                     Cholesterol
                        stones
                     Inflammed
                        mucosa
                     Thickened gall
                        bladder
                        wall
► Gallstones
► Cholesterolstones
► Inflammed mucosa
► Thickened wall
    Predisposing factors for pigment stones

► Demography:      Asian>Western;
                   rural>urban

► Chronic    hemolytic syndromes

► Biliary   infection

► Gastrointestinal  disorders: ileal disease (eg Crohn’s
  disease), ileal resection or bypass cystic fibrosis
  with pancreatic insufficiency
           Pathogenesis of pigment stones

►   Complex mixtures of abnormal insoluble calcium
    salts of unconjugated bilirubin with inorganic calcium
    salts

►   Biliary tract infection( E. coli, Ascaris lumbricoides,
    Opisthorchis Sinensis ) causes increase of
    unconjugated bilirubin in bile

►   Intravascular hemolysis causes increased hepatic
                            bilirubin-
    secretion of conjugated bilirubin- deconjugated in
            tree-
    biliary tree-> exceeds the aqueous solubility of free
    bilirubin
Pigment stones



                 - Pigment
                   stones
                 - Inflammed
                   mucosa
                 - Thickened wall
Pigment stones
    Effects and complications of
             gallstones
►   May be asymptomatic for years before develop
    symptoms
►   Inflammation of gallbladder (cholecystitis)
►   Mucocoele*
►   Predisposition to carcinoma of gallbladder
►                          system-
    Obstruction of biliary system- biliary colic and
    jaundice
►   Infection-
    Infection- cholangitis and liver abscess;
                 gallbladder-
    empyema of gallbladder->perforation and
    fistula
►   Gallstone ileus
►   Pancreatitis
Pathological
effects
of gallstones
Gallstone ileus
                   Mucocoele

► Sterileobstruction of the neck of gallbladder
  by a gallstone

► Lack    inflammation-
       of inflammation-> gallbladder distend
  with mucous without rupturing

► Careful  handling during surgery to avoid
  spillage of mucous into peritoneal cavity thus
  risk of pseudomyxoma peritonei#
# Peritoneum becomes seeded with mucous –producing
  epithelial cells and the cavity filled with mucous
► Mucocoele
             Cholecystitis
► Inflammation   of the gallbladder
► May   be
           acute
           chronic or
           acute superimposed on chronic
► Almost always occur in association with
  gallstones
► One of the most common indication of
  abdominal surgery in U.S
            cholecystitis-
      Acute cholecystitis-Cause

Acute calculous cholecystitis
► Acute inflammation of the gallbladder
  due to obstruction of the gallbladder
  outflow by a gallstone
                 cholecystitis-
           Acute cholecystitis-Cause

Acute acalculous cholecystitis
► Occur in the absence of gallstones eg:
                                    non-
  1.postoperative state after major non-biliary surgery
  2.severe trauma
  3.severe burns
  4.multiorgan system failure
  5.sepsis
  6.prolonged intravenous hyperalimentation
  7.postpartum state
       Pathogenesis ( acute calculous
               cholecystitis)
► Gallbladder   outflow obstruction

► Inflammatory    reaction ( irritant effects of bile)

► Disruption   of protective mucosal layer

► Gallbladder stasis-
              stasis-> distension compromised
  blood flow to mucosa

► Later,   maybe bacterial contamination
    Pathogenesis( acute acalculous
            cholecystitis)
► Thought   to result from ischaemia
                                   transfusion-
► Dehydration and multiple blood transfusion-
  > pigment load
► Gallbladder stasis
► Accumulation of microcrystals of cholesterol,
  viscous bile and mucous=>cystic duct
  obstruction
► Inflammation and oedema of the wall
► Bacterial contamination and generation of
  lysolechitins
                   Clinical features

►   Right upper quadrant or epigastric pain

►   Mild fever, anorexia, tachycardia, sweating, nausea
    and vomitting

►   Tender upper abdomen

►   Hyperbilirubinaemia

►   Mild-
    Mild-moderate leucocytosis

►   Mild increased of serum alkaline phosphatase
              Acute cholecystitis




Inflammed mucosa
            Chronic cholecystitis

► May  develop insidiously or after repeated
  episodes of acute cholecystitis
► Is associated with cholelithiasis in 90% of
  cases
► Evolution is obscure
► ? Gallstones direct role
► Chronic acalculous cholecystitis exhibits
  symptoms and histology similar to chronic
  calculous cholecystitis
► Bile supersaturation predisposes to chronic
  inflammation and stone formation
► Obstruction of gallbladder outflow is NOT a
  prerequisite
► Most gall bladders removed at elective surgery for
  gallstones exhibit features of chronic cholecystitis
  suggesting long term coexistence of gallstones
       low-
  and low-grade inflammation
          cholecystitis-
  Chronic cholecystitis-Clinical features

► Recurrent attacks of steady or colicky
 epigastric or right upper quadrant pain

► Nausea,   vomitting, fatty food intolerance
                          Morphology

►   Thickened gallbladder wall

►   Rokitansky-
    Rokitansky-Aschoff sinuses, mucosal herniations(diverticula)

►   Variable degrees of chronic inflammatory cell infiltrate

►   Stone may be found in Hartmann’s pouch (pathological
    dilatation of the gallbladder neck due to increased intraluminal
    pressure or stone impaction)

►   Xanthogranulomatous cholecystitis#
►   Hydrops of gallbladder*
Chronic cholecystitis with cholelithiasis




        Cholesterol stones
        Thickened gall bladder wall
        Inflamed mucosa
Chronic cholecystitis




  Thickened gall bladder
  Inflammed mucosa
Chronic cholecystitis
-histology
 Rokitansky-
-Rokitansky-Aschoff
 sinuses (arrow)
- chronic inflammatory
   cell infiltration in the
   lamina propria
#- rare;
             lipid-
  abundant lipid-laden macrophages and
  giant cells accumulate within the
  fibrotic wall
* atrophic, chronically obstructed
  gallbladder , containing only clear
  secretions
                cholecystitis-
        Chronic cholecystitis-Effects and
                 complications
►              superinfection-
    Bacterial superinfection- cholangitis or sepsis
►   Gallbladder perforation and local abscess formation
►   Gallbladder rupture with diffuse peritonitis
►                    fistula-
    Biliary enteric fistula-drainage of bile into adjacent
    organ, entry of bacteria and air into biliary tree,
    gallstone ileus
►               gallbladder-
    Porcelain gallbladder-extensive dystrophic
                      gallbldder-
    calcification of gallbldder-increased risk of carcinoma
►                      pre-
    Aggravation of pre-existing medical illness with
    cardiac, pulmonary, renal or liver decompensation
                             Cholangitis

►   Inflammation of the bile ducts usually due to bacterial infection

►   Usually precipitated by biliary obstruction most commonly
    choledocholithiasis# with secondary bacterial infection

►   Other causes ( uncommon)
       Indwelling stents/catheters
       Tumours
       Acute pancreatitis
       Benign strictures

# presence of stones within the bile ducts of the biliary tree
  Cholangitis-
  Cholangitis- Effects and complication

► Fever
► Chills
► Abdominal   pain
► Jaundice
► Inflammed  bile ducts
► Neutrophils infiltration
► Suppurative cholangitis
► Liver abscess
► Cholesterosis  @
  strawberry gallbladder
  Yellow-
► Yellow-pecked
  appearance of the
  gallbladder mucosa
  due to the presence of
  cholesterol-
  cholesterol-laden
  macrophages
► Clinically unimportant!
Disorders of the extrahepatic bile
              ducts
► Choledocholithiasis
► Ascending   cholangitis
► Biliary atresia
► Choledochal cyst
            Choledocholithiasis
► Presence   of stones within the bile ducts of
  the biliary tree
► Asymptomatic or cause symptoms due to
► Obstruction           Secondary biliary cirrhosis
► Pancreatitis          Cholangitis
► Hepatic abscess
► Acute calculous cholecystitis
           Ascending cholangitis
► Bacterial   infection of bile ducts = cholangitis

► Result   from any obstruction to bile flow

► Ascending  cholangitis=infection of the
  intrahepatic radicals due to bacteria
  entering the biliary tracts through the
  sphincter of Oddi
            Biliary atresia
Complete obstruction of the lumen of the
extrahepatic biliary tree within the first 3
months of life
2 forms
        (20%)-
1.fetal (20%)- associated with other
anomalies
2.perinatal-
2.perinatal- presumed normal at birth but
destroyed following birth
            Choledochal cyst
► Congenital  dilatation of the bile ducts
► Children before the age of 10
► Predispose to stone formation,stenosis and
  stricture, pancreatitis
► May occur in association with cystic
  dilatation of the biliary tree ( Caroli disease)
►*  Caroli disease
► The larger ducts of the intrahepatic biliary
  tree are segmentally dilated and may
  contain inspissated bile
► Pure form is rare
► Usually associated with portal tract fibrosis
  of the congenital hepatic fibrosisi type
HEPATITIS
            OBJECTIVES
   Drugs, toxins and viruses which
   Drugs,
► 1.
 commonly leads to hepatitis

► 2.Pathogenesis and morphology of the
 liver caused by alcoholism

   Clinicopathological features of viral
► 3.
 hepatitis
        Microanatomy




Acinar concept   Lobular concept
Microanatomy



          Acinar concept
                   Hepatitis

Definition
► Injury to the liver associated with an influx of
  acute or chronic inflammatory cells

Causes
  Infection-Viral,
► Infection-Viral, bacterial, parasitic, helminthic
► Drug and toxin induced
► Alcoholic liver disease
► Metabolic
► Autoimmune
  Viral-
► Viral-foremost in hepatic infection
  Others-
► Others- miliary tuberculosis
        - malaria
        - staphylococcal bacteraemia
        - salmonellosis
        - candidiasis
        - amebiasis
                       Viral hepatitis
Infection of the liver caused by a group of viruses having a
   particular affinity for the liver
1. Hepatitis A virus        4. Hepatitis D virus
2. Hepatitis B virus        5.Hepatitis E virus
3. Hepatitis C virus        6. Hepatitis G virus


Systemic viral infection that can involve the liver include
1. Infectious mononucleosis (EBV)        Others-
                                      4. Others-rubella, adenovirus
2.Cytomegalovirus                          herpesvirus, enteroviruses
3.Yellow fever virus
                 Hepatitis A
► May  occur sporadic or epidemic
► Does not cause chronic hepatitis or a carrier
  state
  Transmission-Faecal-
► Transmission-Faecal-oral spread
  -nurseries/institution, water contaminated sewage,
  ingestion of sewage contaminated shellfish
► Direct cytopathic effect on the liver
► Diagnosis: Serology
     IgM antibody ( recent infection)
     IgG antibody (protective immunity against
     reinfection by all strains of HAV)
                  Hepatitis B
► Spread  by blood, blood contaminated instruments,
  blood products and venereally
           transmission-           child-
► Vertical transmission- mother to child- in utero;
  during delivery or intimate post natal contact
  ( responsible for most cases of carrier state in
  underdeveloped countries

► Liver   damage by antiviral immune reaction

► Carrier   state exists
                  B-
        Hepatitis B-Serologic Diagnosis
1.HBsAg-
1.HBsAg- appears before onset of symptoms
            - during overt disease
                                                   3-
            - declines to undetectable levels in 3-6 months
          HBV-
2.HBeAg, HBV-DNA and DNA polymerase
            -appear in serum soon after HBsAg
            -all signify active viral replication
      anti-HBc-
3.IgM anti-HBc- detectable in serum shortly before onset
                       of symptoms; replaced by IgG anti HBc
                       over months
   Anti-Hbe-
4. Anti-Hbe- detectable shortly after the disappearance of HBeAg
      anti-HBs-
5.IgG anti-HBs- does not rise until the acute disease is over
                 -is usually not detectable for a few weeks to
                   several months after the disappearance of HBsAg
                                                  protection;
                 - may persist for life ; confer protection; is the
                                                            non-
                    basis for vaccination strategies using non-
                    infectious HBsAg
► HBV                                 cells,
       is not directly toxic to liver cells, instead
 it is the immune response to viral antigen
 expressed on the infected hepatocytes that
 cause liver cell injury
     Five clinical patterns of HBV infection

► Asymptomatic   infection –may progress to
  chronic hepatitis or carrier
        self-
► Acute self-limiting hepatitis but majority
  recover and have lifelong immunity
                    hepatitis-
► Fulminant acute hepatitis->massive liver
  necrosis
           hepatitis-
► Chronic hepatitis-may progress to cirrhosis
  or aymptomatic carrier
                         state-
► Asymptomatic carrier state-may develop
  chronic hepatitis
Potential outcome of hepatitis B infection in
                  adults
                     Hepatitis C

Main characteristics
► Spread by blood, blood contaminated
  instruments, blood products and possibly
  venereally
►                  transmission-
    Major route of transmission- innoculations and blood
    transfusions
► Relatively   short incubation period (2 –26
  weeks)
► Often asymptomatic
► Fluctuating liver biochemistry
► Tendency to chronicity
Potential outcome of hepatitis C infection
                in adults
           Hepatitis D virus
► Causinginfection only when it is
 encapsulated by HBsAg

► Dependent  on HBV genetic information
 for multiplication

► Cause   hepatitis only in the presence of
 HBV
             Hepatitis D virus
Delta hepatitis arises in two setting
1.         coinfection-
    Acute coinfection- exposure to both HBV and HDV
2.  Superinfection of a chronic carrier of HBV with
    inoculum of HDV
Three possible outcomes
1.  Acute, severe hepatitis in a previously healthy HBV
    carrier
2.  Mild HBV hepatitis may be converted to fulminant
    disease
3.  Chronic, progressive disease=> cirrhosis
            Hepatitis E virus
► Enterically                water-
                transmitted, water-borne infection

► High   mortality rate among pregnant women

  Self-
► Self-limiting   disease

► Not associated with chronic liver disease or
  persistent viraemia
      Other Hepatitis Viruses
Hepatitis G virus (HGV)
► Flavivirus
► Blood, blood products; possibly sexual contact
          infection-
► 75% of infection-clear ; the remainder= chronic
► Site of replication is most likely mononuclear cells
► Not hepatotropic; does not cause elevation of serum
  aminotransferases
               co-
► Commonly co-infects HIV pts; this dual infection is
  somewhat protective against HIV disease
Morphology of acute and chronic
          hepatitis
Morphology of acute and chronic hepatitis are
 shared among hepatotropic viruses ; can be
 mimicked by drug reactions

A few histologic features may be indicative of
  particular viruses eg
►                cytoplasm-
    ground glass cytoplasm- hepatitis B
►                           steatosis-
    Lymphoid aggregate and steatosis- Hepatitis C
       Histological features of acute viral
                    hepatitis
►   Ballooning degeneration
►   Cholestasis
►   Macrophage aggregate
►   Apoptotic liver cell death ( Councilman bodies)
►   Bridging necrosis( in severe acute hepatitis)
►   Kupffer cell hyperplasia and hypertrophy
►   Portal tract infiltration by mixed inflammatory cells
►             hepatitis-
    Interface hepatitis-necrosis of periportal hepatocytes
►   Ductular reaction (esp in Hepatitis C)
Ground-
Ground-glass hepatocytes
Acute viral hepatitis
Diagrammatic
representation
Of morphologic
features of
acute hepatitis
   Hepatitis-
   Hepatitis-Clinicopathologic
           syndromes
► Acute asymptomatic infection with
  recovery-
  recovery- serologic evidence only
           -HAV and HBV infection
► Acute symptomatic hepatitis with
  recovery; anicteric or icteric*
► Chronic hepatitis without or with
  progression to cirrhosis
► Fulminant hepatitis
  Acute symptomatic infection with
             recovery
4 phases
1. Incubation period

               pre-        phase-
2. Symptomatic pre-icteric phase-fatigue, nausea,
   LOA, LOW, low grade fever, headache, arthralgia,
   rash

                       phase-
3. Symptomatic icteric phase-jaundice; dark urine
                ( conjugated hyperbilirubinaemia)
4. Convalescence
         Chronic hepatitis
Definition:

 Symptomatic, biochemical or serologic
 evidence of continuing or relapsing
 hepatic disease for more than 6 months
 with histologically documented
 inflammation and necrosis
   Clinical features of chronic hepatitis

► Variable  and are not predictive of outcome
► Fatigue, malaise, loss of appetite, occasional
  bouts mild jaundice
► Spider angiomas, palmar erythema, mild
  hepatomegaly, hepatic tenderness, mild
  splenomegaly
  Occasionally-
► Occasionally- immune complex disease ie
  vasculitis; glomerulonephritis ( in HBV and
  HCV)
   Histological features of chronic
              hepatitis
► Lymphoid   aggregates
► Bile duct damage
► Steatosis
► Interface hepatitis
► Bridging necrosis
  Fibrosis-
► Fibrosis-portal tracts, periportal
  ;bridging fibrosis (linking of fibrous
  septae between lobules)
Chronic hepatitis
Diagrammatic
representation of
morphologic features of
chronic
hepatitis
                 Fulminant hepatitis

►   Occurs when hepatic insufficiency progresses from
    onset of symptoms to hepatic encephalopathy within
    2-3 weeks
►   Less rapid course ( up to 3 months) is called
    subfulminant hepatic failure
►   * fulminant hepatic failure may be caused by other
    than viral hepatitis ie drug ( acetaminophen overdose,
               antidepressant-
    isoniazid, antidepressant- MOI, halothane and
    methyldopa), mycotoxin-Amanita phalloides
                  mycotoxin-
►   When it is due to viral hepatitis; usually it is due to
    hepatitis A or Hepatitis B virus .
               hepatitis-
     Fulminant hepatitis- morphology

  Microscopically-
► Microscopically-  complete destruction of
  hepatocytes in contigous lobules
► Collapsed of reticulin network and preserved
  portal tracts
► With patient survival => time to regenerate
  surviving hepatocytes and bile ducts
► May recover completely
► However, fibrous scarring may occur in
  submassive or patchy necrosis resulting in
  post-
  post-necrotic cirrhosis
           hepatitis-
 Fulminant hepatitis-clinical features

► Jaundice,   encephalopathy, fetor hepaticus

► Absence  of stigmata of chronic liver disease
  ie gynaecomastia , spider angiomas

  Life-
► Life- threatening extrahepatic complications
  include-
  include-coagulopathy and bleeding,
  cardiovascular instability, renal failure, ARDS,
                  acid-
  electrolyte and acid-base imbalances, sepsis
            Autoimmune hepatitis
►   Chronic form of hepatitis

►           20-40year-
    Female; 20-40year-olds

►   Absence of viral serologic markers

►   Elevated serum IgG and γ globulin levels

►                                         cases-
    High serum autoantibodies in 80% of cases-
    antinuclear (ANA), antismooth muscle (SMA)
    antiliver/kidney (antiLKM1) antibodies

►   Negative antimitochondrial antibody (AMA)
        Autoimmune hepatitis

► Prominent    lymphocytes and plasma cell
  infiltrates in the liver
► Relapsing and remitting course
► Treatment: steroids
  Non-
► Non-responder to treatment: Progress
  to cirrhosis
         transplant-
► Liver transplant-excellent prospect in
  severe case
        Alcoholic liver disease
► Chronic disorder featuring steatosis,
 hepatitis, progressive fibrosis, cirrhosis and
 marked derangement of vascular perfusion
 due to chronic excessive alcohol
 consumption.
        Alcoholic liver disease
► Hepatic  steatosis*
► Alcoholic hepatitis*
► Cirrhosis


*May develop independently
 Not necessarily represent a continuum of
 changes
                       disease-
       Alcoholic liver disease-morphology

► Hepatic   steatosis- fatty change
                      -perivenular fibrosis

► Alcoholic   hepatitis- hepatocyte swelling and necrosis
                        - Mallory bodies
                        - neutrophilic reaction
                          fibrosis-
                        - fibrosis- sinusoidal and perivenular

► Alcoholic   cirrhosis -fibrosis
                        -hyperplastic nodules
Fatty liver
Fatty change
Alcoholic hepatitis
Mallory bodies
Mallory bodies
                    Pathogenesis
► Only  10-15% of alcoholics develop cirrhosis
        10-
► Women more susceptible to hepatic injury
► No clear understanding of the pathogenetic factors
  influencing liver damage (? Genetic factors)
►   Steatosis results from
    1. Shunting of normal substrate away from catabolism and
       toward lipid biosynthesis
    2. Impaired assembly and secretion of lipoprotein
    3. Increased peripheral catabolism of fat
► Impaired                         methionine-
            hepatic metabolism of methionine->
                                     levels-
  decreased intrahepatic glutathione levels->
  susceptible to oxidative injury
                     induction-
► Cytochrome p450 induction-increased conversion
  of drugs to toxic metabolites; produces reactive o2
  species
► Affects microtubular and mitochondrial function
  and membrane fluidity
                                      epitopes-
► Hepatocellular proteins create new epitopes->
                   reacts-
  immune system reacts->inflammation and
  immune-
  immune-mediated hepatocellular injury
              Other effects of alcohol

► Malnutrition,   vitamins deficiencies

► Impaired   digestive function

► Chronic   gastric and intestinal mucosal damage

► Pancreatitis


► Induces   release of bacterial endotoxin into portal
  circulation from the gut=>inflammation in the liver
                     Clinical features

►           steatosis-
    Hepatic steatosis-mild hepatomegaly with mild elevation of
    serum bilirubin and alkaline phosphatase

►             hepatitis-
    Alcoholic hepatitis-usually acute; after bouts of heavy
    drinking

►   Malaise, anorexia, wt loss, upper abdominal discomfort,
    tender hepatomegaly

►   Cirrhosis-
    Cirrhosis- symptoms related to portal hypertension and
    chronic liver disease
Pathogenesis of
alcoholic liver
disease
Interrelationships among hepatic steatosis, hepatitis
                    and cirrhosis
           toxin-
  Drug and toxin-induced Liver disease

Mechanisms of injury

1. Direct toxicity

2. Hepatic conversion of a xenobiotic to an
    active toxin

          mechanism-
3. Immune mechanism- drug as hapten
          ( predictable) or idiosyncratic
► Intrinsic
  (unpredictable)

► Injury   may take weeks to months to develop

► Hepatocyte   necrosis, cholestasis or insidious onset
  of liver dysfunction

  Drug-
► Drug-induced    chronic hepatitis is clinically and
  histologically indistinguishable from chronic viral
  hepatitis
          reaction-
Intrinsic reaction-examples of drug and toxin
► Acetaminophen (Paracetamol)
► Amanita phalloides toxin
► Carbon tetrachloride
► Alcohol
Idiosyncratic reaction
► Sulphonamide
► A-methyldopa
► Allopurinol
► Acetylsalicylic acid (aspirin)
Drug and toxin-induced
liver injury
       Metabolic Liver Disease
► Nonalcoholic   fatty liver disease

► Wilson   disease

► Haemochromatosis


      anti-
► α-1-anti-trypsin   deficiency
         Nonalcoholic fatty liver disease and
                  steatohepatitis

►             alcoholic-
    Resemble alcoholic-induced liver disease but patients
    are not heavy drinkers

►   Strong association between obesity, dyslipidaemia,
    hyperinsulinaemia and insulin resistance and overt
    type 2 diabetes

►   Diagnosis of exclusion

►   Steatosis, parenchymal inflammation,Mallory bodies,
    hepatocyte death

►   May progress to cirrhosis
                Wilson disease
► Autosomal    recessive
► Accumulation of toxic level of copper in brain,
  liver, eye
► Decreased serum caeruloplasmin
► Liver: fatty change, acute and chronic
  hepatitis, cirrhosis
► Brain: atrophy and cavitation of basal ganglia
  (putamen)
► Eye: ggreen-brown copper deposits in Descemet’s
  membrane in the limbus of cornea
Kayser-
Kayser-Fleischer Ring

              Green-brown copper deposits
              in Descemet’s membrane in
              the limbus of cornea
        Haemochromatosis
► Excessive  accumulation of body iron;
  deposited in parenchymal organs eg liver and
  pancreas
► Hereditary (primary) haemochromatosis
► Homozygous recessive
► Loss of intestinal regulation of dietary iron
  absorption
► Fully developed case:micronodular cirrhosis,
  diabetes mellitus, skin pigmentation
        Haemochromatosis
Secondary haemochromatosis

► Parenteral    iron overload

► Ineffective   erythropoiesis

► Increased    oral iron intake
    α1-antitrypsin deficiency
► Autosomal   recessive
► Low serum levels of α1- antitrypsin (protease
  inhibitor)
  Abnormally-
► Abnormally-folded polypeptideretained in
  ER- autophagocytosis-
  ER-> autophagocytosis-> liver injury
► Presents with neonatal hepatitis with
  cholestatic jaundice
  Adolescence-
► Adolescence-hepatitis/cirrhosis
                  2-
► HCC develop in 2-3% of PiZZ individual

								
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