Successfully reported this slideshow.

Liver and biliary tract pathology

39

Share

Upcoming SlideShare
Liver Basics
Liver Basics
Loading in …3
×
1 of 48
1 of 48

More Related Content

Related Books

Free with a 14 day trial from Scribd

See all

Related Audiobooks

Free with a 14 day trial from Scribd

See all

Liver and biliary tract pathology

  1. 1. Liver and Biliary Tract Fadel Muhammad Garishah School 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. http://www.niaaa.nih.gov
  4. 4. Which one is the central vein? Which one is the triad portal?
  5. 5. Microstructure of Liver Between the plates of hepatocytes are vascular sinusoids. The sinusoids are lined by fenestrated and discontinuous endothelial cells. Deep to the endothelial cells lies the space of Disse, into which protrude abundant microvilli of hepatocytes. Scattered Kupffer cells of the mononuclear phagocyte system are attached to the luminal face of endothelial cells, and fat-containing hepatic stellate cells (HSCs) are found in the space of Disse. Between abutting hepatocytes are bile canaliculi, these channels drain into the canals of Hering, ductular structures that connect the bile canaliculi 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 spleen when they get old or damaged. This releases hemoglobin, which is broken down to heme as the globin parts are turned into amino acids. The heme is then turned into unconjugated bilirubin, not soluble in water, bound to albumin and sent to the liver. Conjugated (direct): In the liver it is conjugated with glucuronic acid by the enzyme glucuronyltransferase, making it soluble in water. (bilirubin covalently bound to albumin, which appears in serum when hepatic excretion of conjugated bilirubin is impaired in patients with hepatobiliary disease).
  9. 9. Perbedaan Antara Bilirubin Indirek/Direk Bilirubin 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. Jaundice 1. Prehepatik/Hemolitik 2. Hepatik/Parenkim 3. Posthepatik/Obstruktif
  11. 11. 1. Ikterus Akibat Kenaikan Produksi Bilirubin a. 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 Liver Laboratory Assessment – Biochemistry – Immunology/Serologic Histopathologic Biopsy Radiologic diagnostic
  14. 14. Biochemistry Bilirubin unconjugated and conjugated Hepatic enzymes: ALT, AST and γ-GT Albumin: a low serum albumin concentration is an important manifestation of liver failure, which results in peripheral oedema and contributes to the presence of ascites, 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 hepatitis Characteristics: – '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 excreted before the jaundice (isolation of patient absence) Specific diagnosis is made by seeking an IgM-class antibody to HAV in the patient's serum; this indicates recent infection. A carrier state does not exist.
  22. 22. Hepatitis B Virus (HBV) – serum hepatitis Characteristics: – 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 countries and 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 surface antigen (HBsAg, formerly known as 'Australia antigen' because it was first detected in the serum of an Australian aborigine).
  23. 23. Hepatitis C Virus (HCV) – serum hepatitis Characteristics: – 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 blood product administration is much less common now that donors are screened for HCV. The initial illness is often asymptomatic and the abnormalities of liver biochemistry (e.g. raised serum transaminases) are usually fluctuant. However, despite these misleadingly benign signals, the infection is prone 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 viruses There are other authentic hepatitis viruses. The best characterised is a water-borne agent, distinct from HAV, that has been responsible for outbreaks of hepatitis in India; it has been designated hepatitis E virus (HEV). Fortunately, the disease rarely progresses to chronicity and, 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 blood transfusions and blood products include hepatitis G virus and the TT virus. Their role in liver disease appears to be relatively minor.
  25. 25. Delta agent and other nonhepatitis viruses Delta agent is a defective RNA virus that requires the presence of HBV, which supplies the outer layers of the viral coat, for its replication and assumed role as a pathogen. Its main effect is to aggravate the consequences of HBV infection.
  26. 26. Alcoholic Hepatitis Cellular energy is diverted from essential metabolic pathways, such as fat metabolism, to the metabolism of alcohol so fat accumulates in the liver cells. Acetaldehyde, the main product of alcohol metabolism, binds to liver cell proteins, resulting in injured hepatocytes and an inflammatory reaction. Alcohol stimulates collagen synthesis in the liver, leading to fibrosis and eventually cirrhosis.
  27. 27. Drug-induced Hepatic Injury Approximately 10% of all adverse reactions to drugs involve the liver. This is not surprising in view of the central role played by the liver in metabolism and in the conjugation and elimination of toxic substances from the body. Through injury to the liver cells (hepatocellular), which is pathologically indistinguishable from viral hepatitis, or to bile production or excretion (cholestatic). Predictable reactions will occur in any individual if a sufficient dose is administered; examples include coagulative centrilobular necrosis due to paracetamol overdose and cholestatic jaundice due to methyl testosterone
  28. 28. Acute Biliary Obstruction Acute obstruction of the main bile ducts is most commonly due to gallstones. Clinically, it usually results in colicky pain and jaundice. If there is superimposed infection of the biliary tract, the ducts become inflamed (cholangitis) and the patient develops a fever. Cholangitis can lead to the formation of liver abscesses.
  29. 29. Chronic Hepatic Injury
  30. 30. Chronic Hepatic Injury Chronic Hepatitis Injury: HBV, HCV, Alcoholic Hepatis, Drugs induced, Autoimmune Iron 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. Wilson's disease (hepatolenticular degeneration) α1-Antitrypsin deficiency
  31. 31. Autoimmune Liver Disease Sclerosing cholangitis: a chronic inflammatory process affecting intrahepatic, and sometimes extrahepatic, bile ducts. Initially, the ducts are surrounded by a mantle of chronic inflammatory cells, but this is eventually replaced by fibrosis and obliteration of the ducts. Steatohepatitis is used for liver biopsies in which the only abnormalities are steatosis (fat vacuoles in hepatocytes) and inflammation. Fatty liver (e.g. diabetes mellitus, obesity, hyperlipidaemia).
  32. 32. Cirrhosis Hepatis Aetiology: – viral hepatitis (HBV and HCV) – alcohol – haemochromatosis – autoimmune liver disease (autoimmune hepatitis and primary biliary cirrhosis) – recurrent biliary obstruction (e.g. gallstones) – Wilson's disease. micronodular-nodules up to 3 mm diameter macronodular-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 disease Oedema Reduced albumin synthesis resulting in hypoalbuminaemia Ascites Hypoalbuminaemia, secondary hyperaldosteronism, portal hypertension Haematemesis Ruptured oesophageal varices due to portal hypertension Spider naevi Gynaecomastia Hyperoestrogenism Purpura and bleeding Reduced clotting factor synthesis Coma Failure to eliminate toxic gut bacterial metabolites ('false neurotransmitters') Infection Reduced Kupffer cell number and function
  35. 35. Hepatic Failure Liver Failure Ascites Portal Tension Splenomegaly Caput Medusae Varices Oesophageii Renal Failure Cirrhosis Hepatis
  36. 36. Tumors of the Liver Benign 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 Liver simple cysts hydatid cysts: due to the parasite Echinococcus granulosus choledochal cysts
  38. 38. Gall Bladder Pathology Fadel Muhammad Garishah School of Medicine, Diponegoro University
  39. 39. Topography of Gallbladder
  40. 40. Hepatobilier ductal system
  41. 41. Congenital Gall Bladder Pathology biliary atresia, in which there is failure of the biliary tree to develop and normally anastomose with intrahepatic structures choledochal cysts (see above), sometimes associated with congenital hepatic fibrosis.
  42. 42. Diseases of Gall bladder Cholelithiasis Cholesterosis Cholecystitis Mucocele Carcinoma of the gallbladder Carcinoma of the bile duct Biliary 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. Cholesterosis Cholesterosis is the name given to the clinically unimportant occurrence of cholesterol-laden macrophages in the lamina propria of the gallbladder mucosa. This occurrence gives the mucosa a yellow-speckled appearance known as 'strawberry gallbladder'.
  45. 45. Cholecystitis Cholecystitis is an inflammatory condition of the gallbladder. Acute: – Usually associated with gallstones – Initially sterile, then infected – Complications include empyema and/or rupture Chronic: – Invariably associated with gallstones – Fibrosis and Aschoff-Rokitansky sinuses
  46. 46. Mucocele A mucocele of the gallbladder is the result of sterile obstruction of the neck by a gallstone. The lack of inflammation permits the gallbladder to distend with mucus without rupturing. Carcinoma of Gallbladder Usually an adenocarcinoma Invariably associated with gallstones Carcinoma of Bile Ducts/Cholangiocarcinoma Adenocarcinoma Increased incidence in ulcerative colitis Presents with jaundice
  47. 47. Biliary obstruction Bile 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. A raised serum alkaline phosphatase with only modest elevation of transaminases is usual. If the biliary obstruction persists, there is a risk that the static bile becomes infected, causing cholangitis and liver abscesses. Lack of bile in the small intestine interferes with the absorption of fat and fat-soluble substances (e.g. some vitamins). Diseases of intrahepatic bile ducts : A clinical picture similar to that of biliary obstruction can result from diseases of intrahepatic bile ducts such as: – biliary atresia – primary biliary cirrhosis – sclerosing cholangitis.

×