Liver and biliary tract pathology


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Lecture slide of Pathology of Liver and Biliary Tract

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Liver and biliary tract pathology

  1. 1. Liver and Biliary Tract Fadel Muhammad GarishahSchool of Medicine, Diponegoro University 50 Years Anniversary
  2. 2. Macrostructure of Liver The liver is the largest visceral organ in the body and is primarily in the right hypochondrium and epigastric region, extending into the left hypochondrium The right lobe of liver is the largest lobe, whereas the left lobe of liver is smaller. The porta hepatis serves as the point of entry into the liver for the hepatic arteries and the portal vein, and the exit point for the hepatic ducts• Vascularization from the Hepatic Artery• Venous drainages come into Liver from Portal Hepatic Vein, receiving drainage from intestines (Mesenteric Veins, and Splenic Vein)• From Liver, the sinusoids united into Hepatic Vein, that drainages into Inferior Cava Vein
  3. 3. Microstructure of Liver The Lobule Model: hexagonal lobules oriented around the terminal tributaries of the hepatic vein (terminal hepatic veins), with portal tracts at the periphery of the lobule. The hepatocytes in the vicinity of the terminal hepatic vein are called “centrilobular”; those near the portal tract are “periportal”• The acinar model: the hepatocytes near the terminal hepatic veins are the distal apices of roughly triangular acini, whose bases are formed by the penetrating septal venules from the portal vein extending out from the portal tracts. In the acinus the parenchyma is divided into three zones, zone 1 being closest to the vascular supply, zone 3 abutting the terminal hepatic venule and most remote from the afferent blood supply, and zone 2 being intermediate.
  4. 4. Which one is thecentral vein? Which one is the triad portal?
  5. 5. Microstructure of LiverBetween the plates of hepatocytes are vascular sinusoids. The sinusoids are linedby fenestrated and discontinuous endothelial cells. Deep to the endothelial cellslies the space of Disse, into which protrude abundant microvilli of hepatocytes.Scattered Kupffer cells of the mononuclear phagocyte system are attached to theluminal face of endothelial cells, and fat-containing hepatic stellate cells (HSCs) arefound in the space of Disse. Between abutting hepatocytes are bile canaliculi, thesechannels drain into the canals of Hering, ductular structures that connect the bilecanaliculi to bile ductules in the periportal region.
  6. 6. • Zonation of the parenchyma is an important concept because of the gradient of activity displayed by many hepatic enzymes, and the zonal distribution of certain types of hepatic injury.• While the acinar model best describes the physiologic relationships between hepatocytes and their vascular supply, the histopathology of the liver is usually discussed on the basis of a lobular architecture.
  7. 7. Metabolism of Bilirubin• Classic Theory Hb---(release Globin)---Hematin--- (release Fe)---Protoporphyrin--- (Oxidized)---Biliverdin--(Reduction)- -- Bilirubin• Lamberg Theory Hb---(Oxidized)---Choleglobin--- (release Fe and Protein)--- Biliverdin---(reduction)---Bilirubin
  8. 8. Bilirubin(s)Unconjugated (indirect): Erythrocytes (red blood cells)generated in the bone marrow are disposed of in the spleenwhen they get old or damaged. This releases hemoglobin, whichis broken down to heme as the globin parts are turned intoamino acids. The heme is then turned into unconjugatedbilirubin, not soluble in water, bound to albumin and sent to theliver.Conjugated (direct): In the liver it is conjugated with glucuronicacid by the enzyme glucuronyltransferase, making it soluble inwater. (bilirubin covalently bound to albumin, which appears inserum when hepatic excretion of conjugated bilirubin isimpaired in patients with hepatobiliary disease).
  9. 9. Perbedaan Antara Bilirubin Indirek/DirekBilirubin Indirek/Unconjugated bilirubin Bilirubin Direk/Conjugated Bilirubin• Afinitas otak, toksik • Tidak memiliki afinitas dengan SSP,• Tidak mewarnai jaringan kurang toksik dibanding Indirek• Tidak larut dalam air • Mewarnai jaringan lain• Hijman/Bergh positif dengan alkohol • Larut air • Hijman/Bergh positif tanpa alkohol
  10. 10. Jaundice1. Prehepatik/Hemolitik2. Hepatik/Parenkim3. Posthepatik/Obstruktif
  11. 11. 1. Ikterus Akibat Kenaikan Produksi Bilirubina. Ikterus hemolitik: peningkatan hemolisis eritrosit, akut/kronik. Hemolytic Anemia, Sickle Cell Anemia, Malaria, Thalassemia, Keracunan dan Hipersplenisme. a. Pada bayi yang baru lahir, destruksi eritrosit tinggi, tapi enzim Glukoronil transferase masih rendah. b. Defisiensi GT menyebabkan bilirubin indirek meninggi, terikat albumin, larut lemak, toksisitas SSP, menyebabkan kernikterus (ikterus dan kejang).b. Diseritropoietik (shunt) hiperbilirubinemia: maturasi abnormal eritrosit, destruksi prematur pada sumsum tulang. Tapi di perifer tetap normal.
  12. 12. 2. Ikterus Akibat Gangguan Uptake Bilirubin Hepatosit Penyakit Gilbert: Familial inherited, Autosomal Dominan, Gangguan Uptake Bilirubin, menyebabkan nonfamilial hemolitik acholuric.3. Ikterus Akibat Gangguan Konjugasi Bilirubin Hepatosit a. Fisiologik pada neonatus, membaik 2-3 minggu setelah kelahiran b. Sindroma Crigler Najj
  13. 13. Diagnostic Of LiverLaboratory Assessment– Biochemistry– Immunology/SerologicHistopathologic BiopsyRadiologic diagnostic
  14. 14. BiochemistryBilirubin unconjugated and conjugatedHepatic enzymes: ALT, AST and γ-GTAlbumin: a low serum albumin concentration is animportant manifestation of liver failure, which results inperipheral oedema and contributes to the presence ofascites, due to a reduction in plasma oncotic pressure.Blood clotting factors: the risk of unexpected haemorrhage
  15. 15. Laboratory Assessment
  16. 16. Laboratory Assesment
  17. 17. Histopatologic Biopsy
  18. 18. Acute Liver Injury
  19. 19. Hepatitis
  20. 20. Immunopathogenesis HAV menunjukkan injury yang direct pada hepatosit HBV menunjukkan immune mediated hepatosit injury HCV juga menggunakan mediasi sistem immune dalam prosesnya
  21. 21. Hepatitis A Virus (HAV) - infectious hepatitisCharacteristics:– faecal-oral spread– relatively short incubation period– sporadic or epidemic– directly cytopathic virus– no carrier state– mild illness, full recovery usual.Young people, often mild, jaundice rarely appear, virus excretedbefore the jaundice (isolation of patient absence)Specific diagnosis is made by seeking an IgM-class antibody toHAV in the patients serum; this indicates recent infection. Acarrier state does not exist.
  22. 22. Hepatitis B Virus (HBV) – serum hepatitisCharacteristics:– spread by blood, blood-contaminated instruments, blood products and venereally, narcotics needle, tattoo needle, transmitted between homosexual males via anal sexual acts– relatively long incubation period– liver damage by antiviral immune reaction– carrier state exists– relatively serious infection.high incidence of the carrier state in underdeveloped countriesand the virus can be transmitted vertically from mother to child-in utero, during delivery or through intimate post-natal contact.Specific diagnosis is made by seeking the hepatitis B surfaceantigen (HBsAg, formerly known as Australia antigen because itwas first detected in the serum of an Australian aborigine).
  23. 23. Hepatitis C Virus (HCV) – serum hepatitisCharacteristics: – spread by blood, blood-contaminated instruments, blood products and possibly venereally – relatively short incubation period – often asymptomatic – fluctuating liver biochemistry – tendency to chronicity.In many countries, transmission of HCV by blood transfusion and bloodproduct administration is much less common now that donors arescreened for HCV.The initial illness is often asymptomatic and the abnormalities of liverbiochemistry (e.g. raised serum transaminases) are usually fluctuant.However, despite these misleadingly benign signals, the infection isprone to chronicity and cirrhosis is a frequent consequence eventually.Specified diagnosis via PCR will be recognized the serotype of virus.
  24. 24. Hepatitis E virus and other non-A, non-B virusesThere are other authentic hepatitis viruses. The bestcharacterised is a water-borne agent, distinct from HAV,that has been responsible for outbreaks of hepatitis inIndia; it has been designated hepatitis E virus (HEV).Fortunately, the disease rarely progresses to chronicityand, as with HAV, full recovery is usual except in pregnancy,when it is associated with a high mortality rate.Other non-A, non-B viruses associated with bloodtransfusions and blood products include hepatitis G virusand the TT virus. Their role in liver disease appears to berelatively minor.
  25. 25. Delta agent and other nonhepatitis virusesDelta agent is a defective RNA virus that requires thepresence of HBV, which supplies the outer layers of theviral coat, for its replication and assumed role as apathogen. Its main effect is to aggravate the consequencesof HBV infection.
  26. 26. Alcoholic HepatitisCellular energy is diverted from essential metabolic pathways, such as fatmetabolism, to the metabolism of alcohol so fat accumulates in the livercells.Acetaldehyde, the main product of alcohol metabolism, binds to liver cellproteins, resulting in injured hepatocytes and an inflammatory reaction.Alcohol stimulates collagen synthesis in the liver, leading to fibrosis andeventually cirrhosis.
  27. 27. Drug-induced Hepatic InjuryApproximately 10% of all adverse reactions to drugs involve theliver.This is not surprising in view of the central role played by theliver in metabolism and in the conjugation and elimination oftoxic substances from the body.Through injury to the liver cells (hepatocellular), which ispathologically indistinguishable from viral hepatitis, or to bileproduction or excretion (cholestatic).Predictable reactions will occur in any individual if a sufficientdose is administered; examples include coagulativecentrilobular necrosis due to paracetamol overdose andcholestatic jaundice due to methyl testosterone
  28. 28. Acute Biliary ObstructionAcute obstruction of the main bile ducts is most commonlydue to gallstones. Clinically, it usually results in colicky painand jaundice. If there is superimposed infection of thebiliary tract, the ducts become inflamed (cholangitis) andthe patient develops a fever. Cholangitis can lead to theformation of liver abscesses.
  29. 29. Chronic Hepatic Injury
  30. 30. Chronic Hepatic InjuryChronic Hepatitis Injury: HBV, HCV, Alcoholic Hepatis,Drugs induced, AutoimmuneIron overload in Liver:– Haemosiderosis is the name given to the mere presence of excess iron, in the form of haemosiderin, in the liver. The liver architecture is usually normal.– Haemochromatosis is a more serious disorder in which the presence of excess iron, as haemosiderin, is associated with a risk of progression to cirrhosis.Wilsons disease (hepatolenticular degeneration)α1-Antitrypsin deficiency
  31. 31. Autoimmune Liver DiseaseSclerosing cholangitis: a chronic inflammatory processaffecting intrahepatic, and sometimes extrahepatic, bileducts. Initially, the ducts are surrounded by a mantle ofchronic inflammatory cells, but this is eventually replacedby fibrosis and obliteration of the ducts.Steatohepatitis is used for liver biopsies in which the onlyabnormalities are steatosis (fat vacuoles in hepatocytes)and inflammation. Fatty liver (e.g. diabetes mellitus,obesity, hyperlipidaemia).
  32. 32. Cirrhosis HepatisAetiology:– viral hepatitis (HBV and HCV)– alcohol– haemochromatosis– autoimmune liver disease (autoimmune hepatitis and primary biliary cirrhosis)– recurrent biliary obstruction (e.g. gallstones)– Wilsons disease.micronodular-nodules up to 3 mm diametermacronodular-nodules greater than 3 mm diameter.
  33. 33. The major complications of cirrhosis are:– liver failure– portal hypertension– liver cell carcinoma.Liver Failure– inadequate synthesis of albumin, clotting factors, etc.– failure to eliminate endogenous products such as bilirubin, hormones, nitrogenous waste, etc.
  34. 34. Pathophysiological basis of clinical features of chronic liver diseaseOedema Reduced albumin synthesis resulting in hypoalbuminaemiaAscites Hypoalbuminaemia, secondary hyperaldosteronism, portal hypertensionHaematemesis Ruptured oesophageal varices due to portal hypertensionSpider naevi Gynaecomastia HyperoestrogenismPurpura and bleeding Reduced clotting factor synthesisComa Failure to eliminate toxic gut bacterial metabolites (false neurotransmitters)Infection Reduced Kupffer cell number and function
  35. 35. Hepatic FailureLiver FailureAscitesPortal TensionSplenomegalyCaput MedusaeVarices OesophageiiRenal FailureCirrhosis Hepatis
  36. 36. Tumors of the LiverBenign tumours of the liver include: liver cell adenoma,angioma, bile duct hamartoma , focal nodular hyperplasia.Malignant– Primary malignant tumours of the liver include: • liver cell carcinoma (hepatocellular carcinoma) • cholangiocarcinoma (adenocarcinoma of bile ducts) • angiosarcoma (malignant neoplasm of vascular endothelium) • hepatoblastoma (primary liver tumour in childhood).– Secondary metastases include the entire gastrointestinal tract including pancreas and bowel, the lung and the breast.
  37. 37. Cysts of Liversimple cystshydatid cysts: due to the parasite Echinococcus granulosuscholedochal cysts
  38. 38. Gall Bladder Pathology Fadel Muhammad GarishahSchool of Medicine, Diponegoro University
  39. 39. Topography of Gallbladder
  40. 40. Hepatobilier ductal system
  41. 41. Congenital Gall Bladder Pathologybiliary atresia, in which there is failure of the biliary tree todevelop and normally anastomose with intrahepaticstructurescholedochal cysts (see above), sometimes associated withcongenital hepatic fibrosis.
  42. 42. Diseases of Gall bladderCholelithiasisCholesterosisCholecystitisMucoceleCarcinoma of the gallbladderCarcinoma of the bile ductBiliary obstruction
  43. 43. Cholelithiasis Cholesterol stones may form if there is an imbalance between the ratio of cholesterol and bile salts; normally, the latter form micelles which have a hydrophilic exterior enclosing the hydrophobic cholesterol. Thus, gallstones can result from: an excess of cholesterol or a deficit of bile salts. Bile pigment, Cholesterol, or mixture of cholesterol and bile pigment
  44. 44. CholesterosisCholesterosis is the name given to the clinicallyunimportant occurrence of cholesterol-laden macrophagesin the lamina propria of the gallbladder mucosa. Thisoccurrence gives the mucosa a yellow-speckled appearanceknown as strawberry gallbladder.
  45. 45. CholecystitisCholecystitis is an inflammatory condition of thegallbladder.Acute:– Usually associated with gallstones– Initially sterile, then infected– Complications include empyema and/or ruptureChronic:– Invariably associated with gallstones– Fibrosis and Aschoff-Rokitansky sinuses
  46. 46. MucoceleA mucocele of the gallbladder is the result of sterileobstruction of the neck by a gallstone. The lack ofinflammation permits the gallbladder to distend withmucus without rupturing. Carcinoma of GallbladderUsually an adenocarcinomaInvariably associated with gallstones Carcinoma of Bile Ducts/CholangiocarcinomaAdenocarcinomaIncreased incidence in ulcerative colitisPresents with jaundice
  47. 47. Biliary obstructionBile duct obstruction is a fairly common event and may be due to: – gallstones – carcinoma of the common bile duct – carcinoma of the head of the pancreas – inflammatory stricture of the common bile duct – accidental surgical ligation of the common bile duct.The patient becomes jaundiced, deeply so if the obstruction is not relieved,with a raised conjugated serum bilirubin, pale stools and dark urine. Araised serum alkaline phosphatase with only modest elevation oftransaminases is usual.If the biliary obstruction persists, there is a risk that the static bilebecomes infected, causing cholangitis and liver abscesses. Lack of bile inthe small intestine interferes with the absorption of fat and fat-solublesubstances (e.g. some vitamins).Diseases of intrahepatic bile ducts : A clinical picture similar to that ofbiliary obstruction can result from diseases of intrahepatic bile ducts suchas: – biliary atresia – primary biliary cirrhosis – sclerosing cholangitis.