Title : LiverObjectives: to1. Describe anatomy and microarchitecture of liver.2. Out line liver biopsy.3. Study infectious disorders of liver .4. Explain fulminant hepatitis.
Anatomy: Liver lies in right hypochondrium. Topographic division of liver into right, left, caudate,and quadrate lobes. Physiologicaly or functionaly: divided in to right andleft lobes. Surgically: divided into eight segments.
Adult liver weighs 1400 to 1600 gm,representing 2.5% of body weight. Incoming blood arrives portal vein and hepatic arterythrough hilum of liver (porta hepatis). Major bile ducts exit in porta hepatis. Blood from all sources is collected into hepatic veinwhich exits into inferior vena cava.
Microarchitecture: Liver is divided into 1 to 2 mm hexagonal lobules. In lobule, parenchyma is divided into three zones:o zone 1 being closest to portal tract (periportal).o zone 2 being intermediate ( midzone ).o zone 3 abutting central vein (centrilobular ).o This zonation is important since many hepatic disordersexhibit a zonal distribution.
Liver Biopsy There are four methods :1. blind percutaneous needle biopsy.2. peritoneoscopy .3. open surgery .4. transvenous (transjugular or less often transfemoral). C T or U/S guided Fine Needle Aspiration (FNA) :for diagnosing focal hepatic lesions.
Infectious Disorders: Most hepatic infections are viral in origin. Others include: miliary tuberculosis, malaria,staph , salmonella , candida, and amebiasis.VIRAL HEPATITIS : caused by:(1) infectious mononucleosis (Epstein-Barr virus).(2) cytomegalovirus: newborn or immunosuppression.(3) yellow fever: tropical countries.(4) rubella, adenovirus, herpesvirus, or enterovirus :children and immunosuppression.(5) Hepatotropic viruses (most important).
Viral hepatitis caused by Hepatotropic virusesVIRUS TYPE INFECTION ROUTE DISEASEHepatitis A (HAV) RNA Fecal–oral AcuteHepatitis B (HBV) DNA Parenteral Acute, chronicHepatitis C (HCV) RNA Parenteral Acute, chronicHepatitis D (HDV) RNAPathogenic whencombined with HBVAcute, chronicHepatitis E (HEV) RNA Fecal–oral Acute
Acute viral HepatitisPathology:Parenchymal changes:• Hepatocyte injury: swelling (ballooning degeneration).• Cholestasis (canalicular bile plugs).• Hepatocyte necrosis: isolated cells or cell clusters.• Cytolysis (rupture), or apoptosis (shrinkage) withacidophil bodies (Councilman bodies) formation.
• If severe: bridging necrosis ( portal-portal,central-central, portal-central ).• Lobular disarray: loss of normal architecture.Regenerative changes:• Hepatocyte proliferation.Sinusoidal cell reactive changes:• phagocytosed cellular debris in Kupffer cells.• Influx of mononuclear cells into sinusoids.Portal tracts:• Inflammation: predominantly mononuclear.• Inflammatory spillover into adjacent parenchyma.
Chronic Hepatitis: Symptomatic, biochemical, or serologicevidence of continuing or relapsinghepatic disease for more than 6 months, withhistologically documented inflammation and necrosis. Hepatitis viruses (HBV, HCV, and HBV+HDV)are responsible for most cases. Other causes include :o chronic alcoholism.o Wilson disease.o α1-antitrypsin deficiency.o drugs ( isoniazid, α-methyldopa, methotrexate ).o autoimmunity.
Chronic viral Hepatitis:Pathology:Changes shared with acute hepatitis:• Hepatocyte injury, necrosis, and regeneration.• Sinusoidal cell reactive changes.Portal tracts:• Inflammation: Confined to portal tracts. Spill over into adjacent parenchyma, with necrosis ofhepatocytes (interface hepatitis originally termedpiecemeal necrosis). Bridging inflammation and necrosis.
Fibrosis: Portal deposition. Portal and periportal deposition. Formation of bridging fibrous septa.HBV : ground-glass hepatocytes ( accumulations of viralantigen in endoplasmic reticulum ). sanded nuclei ( nuclear viral inclusions ).HCV : bile duct epithelial cell proliferation. lymphoid aggregate formation .Cirrhosis : The end-stage outcome.
Chronic viral hepatitisground glasshepatocytes in chronic HBV
Lymphoid follicles in portal tract of patientwith chronic hepatitis C.Sanded nuclei (nuclear inclusions) areseen in HBV-replicative hepatocytes.
Serologic Diagnosis in viral hepatitisHAV: Incubation period(2–6 wks).IgM: appears in bloodat onset of symptoms,constituting a reliableMarker of acute infection .Fecal shedding of virus endsas IgM titer rises.IgM begins to decline in fewmonths and is followed byappearance ofIgG which persists for years,perhaps for life, providingProtective immunity againstReinfection by all strains ofHAV, Hence HAV vaccine iseffective.
HBV: ( incubation period 6 to 8 wks)HBsAg : appears before onset ofsymptoms, peaks during overtdisease, declines in 3 to 6 months.HBeAg: appear soon after HBsAg, and signifyactive viral replication.IgM anti-HBc : shortly before onset ofsymptoms, concurrent with onset of elevationof serum aminotransferases. Over months,IgM antibody is replaced by IgG anti-HBc.Anti-HBe : shortly after disappearance ofHBeAgIgG anti-HBs : after disappearance of HBsAg.and may persist for life, conferring protection.The carrier state is defined by presence ofHBsAg in serum for 6 months or longer afterinitial detection.The persistence of circulating HBsAg, HBeAg ,usually with anti-HBc and occasionallyanti-HBs indicate progressive liverdamage.
HCV : incubation period 6 and 12 wks .HCV is detectable in blood for 1 to 3weeks, coincident with elevations inSerum transaminases (ALT) .anti-HCV antibodies emerge after 3 to 6weeks.In chronic HCV infection, circulating HCVpersists in many patients despitepresence of neutralizing antibodies,Hence, in patients with symptoms ofchronic hepatitis, HCV testing must beperformed to confirm diagnosis ofHCV infection.A clinical feature that is quitecharacteristic of chronic HCV infectionis episodic elevations in serumaminotransferases, with interveningnormal or near-normal periods.
Fulminant hepatitis and hepatic failure:Hepatic insufficiency progresses from onsetof symptoms to hepatic encephalopathy within2 to 3 weeks.Causes :o HAV or HBV.o Drug and chemical toxicity : acetaminophen , isoniazid ,halothane, and methyldopa.o Miscellaneous : mycotoxins of mushroom.o Unknown : 18% of cases
Clinical features: Jaundice , encephalopathy, and fetor hepaticus. Mortality rate ranges from 25% to 90% in absenceof liver transplantation.Morphology : Grossly: necrotic areas have a muddy red appearance . Microscopically : complete destruction of hepatocytesin contiguous lobules leaves only a collapsed reticulinframework and preserved portal tracts.there may be surprisingly little inflammation.
Massive hepatic necrosis in fulminant hepatitis
Summary:1. Liver lies in right hypochondrium anddivided in to right and left lobes.2. Microarchitecture : liver is divided into1 to 2 mm hexagonal lobules.3. There are four methods for liver biopsy.4. Most hepatic infections are viral in origin.5. In fulminant hepatitis hepatic insufficiencyprogresses from onset of symptoms to hepaticencephalopathy within2 to 3 weeks.
Questions:1. What are the pathological changes in chronicviral hepatitis?2. Draw a table for hepatotropic viruses including theirtypes, infectious routes, and diseases they cause?THANK YOU