Cirrhosis PDF

Hepatobiliary Disease: Cirrhosis & Liver Cell Cancer; Biliary Diseases Dr Kabiru Abdullahi MBBS, FMCPath Associate Professor MORBID ANATOMY DEPARTMENT CHS, BAZE UNIVERSITY, ABUJA...

Hepatobiliary Disease: Cirrhosis & Liver Cell Cancer; Biliary Diseases Dr Kabiru Abdullahi MBBS, FMCPath Associate Professor MORBID ANATOMY DEPARTMENT CHS, BAZE UNIVERSITY, ABUJA 14/10/2024 10/14/2024 1  Basic Anatomy of the liver: EMBRYOLOGY arises as the hepatic diverticulum from the endodermal lining of the most distal portion of the foregut during the third to fourth week of gestation ✓Parenchyma from: proliferating hepatic cords ✓Stroma from: mesenchyme of the septum transversum ✓ Hematopoietic tissue and Kupffer cells also derive from splanchnic mesenchyme of the septum transversum ✓The epithelium of the intrahepatic bile ducts arises from the proximal part of the primitive hepatic cords 10/14/2024 2  Basic Anatomy: Gross Morphology The liver resides predominantly in the abdominal right upper quadrant and is completely protected by the rib cage The liver of an adult weighs 1400 to 1600 g ✓2% of the body weight ✓It is relatively larger in infancy ✓one-eighteenth of the birth weight 10/14/2024 3  Basic Anatomy: Gross Morphology ❑It is divided by deep grooves into two ❑Functionally large lobes division into eight segments right (lateral to falciform ligament) do not correspond to the anatomical left (medial to falciform ligament) division into lobes ✓and two smaller lobes: ✓is more important the caudate and quadrate lobes ✓is only of topographical significance 10/14/2024 4  Basic Anatomy: Gross Morphology ❑dual blood supply three-fourths via the portal vein ✓the remainder via the hepatic arteries Venous outflow is by the right, middle, and left hepatic veins Bile ducts accompany the hepatic artery and portal vein ✓Bile is formed in hepatocytes, steadily secreted into bile canaliculi, canals of Hering, and then to the intra- and extrahepatic bile ducts 10/14/2024 5  Basic Anatomy: Gross Morphology ❑Lymphatics The liver represents the largest single source of lymph in the body, producing 15 to 20% of the overall total volume ✓hepatic lymph has an unusually high protein content The capsule and the stroma is rich in lymphatic structures 10/14/2024 6 10/14/2024 7 10/14/2024 8 10/14/2024 9 10/14/2024 10 10/14/2024 11  Liver Disease ❑The enormous functional reserve of the liver masks the clinical impact of mild liver damage ❑Diseases of the liver are numerous: 1. Congenital anomalies 2. Acquired diseases 10/14/2024 12  Congenital Anomalies 1. Agenesis of the liver is incompatible with life is usually associated with other severe congenital anomalies in stillborn fetuses ✓Agenesis of one lobe of the liver, usually the right, is seen infrequently and is rarely associated with clinical symptoms 2. Situs inversus totalis the liver, its peritoneal and vascular connections, and the gallbladder and extrahepatic 10/14/2024 ducts have a mirror-image configuration to normal situs 13  Congenital Anomalies 3. Asplenia-polysplenia syndromes ✓liver may be midline and bilaterally symmetrical 4. herniation through defects in the diaphragm a. Diaphragmatic defects are more common on the left side the liver often herniates into the left pleural cavity ✓Intrapericardial herniation of the liver occurs rarely ✓may result in massive pericardial effusion in neonates b. In cases of omphalocele, the liver is often herniated into the omphalocele sac 10/14/2024 14 liver herniates through defect in the diaphragm 10/14/2024 15  Acquired Diseases Of The Liver 1. Major Primary Diseases Of The Liver: viral hepatitis alcoholic liver disease nonalcoholic fatty liver disease (NAFLD) Cirrhosis hepatocellular carcinoma (HCC) 2. Hepatic damage secondary to some of the most common diseases cardiac decompensation disseminated cancer Extra-hepatic infections 10/14/2024 16  Response of the liver to injury ❑The liver is vulnerable to a wide variety of metabolic, toxic, microbial, circulatory, and neoplastic insults A spectrum of changes are seen ✓None is diagnostic, rather, a combination of changes are used: i. Hepatocyte degeneration and intracellular accumulations ii. Hepatocyte necrosis and apoptosis iii. Inflammation iv. Regeneration v. Fibrosis 10/14/2024 17 10/14/2024 18 10/14/2024 19 10/14/2024 20 10/14/2024 21 kn 10/14/2024 22  IRON DEPOSITS: PEARL’S PRUSSIAN BLUE 10/14/2024 23 ACUTE LIVER INJURY ❑Aetiology: i. viral infections ii. high alcohol consumption iii. adverse drug reactions iv. biliary obstruction, commonly due to gallstones. Direct physical injury to the liver (eg, laceration following trauma) contrasts with the diffuse injury produced by the agents listed above. Recovery from acute liver injury, focal or diffuse, is attributable to the capacity of the organ for cellular regeneration 10/14/2024 24  ACUTE LIVER INJURY: consequences 1. Apoptosis: Death of individual liver cells ✓is the most frequent pattern in viral hepatitis 2. interface hepatitis or piecemeal necrosis: Death of periportal hepatocytes or entire acinar zones, usually zone 3 (bridging necrosis) ✓risk of cirrhosis developing 3. panacinar necrosis: Liver cell death substantially affecting the entire acinus ✓leads to liver failure and a significant risk of immediate death 10/14/2024 25 ACUTE LIVER INJURY: morphology 10/14/2024 26 Acquired Liver Diseases: inflammatory disorders ❑Hepatitis ❑pathologically classified into: 1. Acute liver injury/ acute hepatitis 2. Chronic liver disease/ chronic hepatitis 3. Cirrhosis 10/14/2024 27  Chronic Liver Disease: ❑Definition: symptomatic, biochemical, or serologic evidence of continuing or relapsing hepatic disease for more than 6 months ✓The clinical features are extremely variable and are not predictive of outcome 10/14/2024 28  Chronic Liver Disease: Physical findings are few: Laboratory studies may reveal: ✓spider angiomas ✓prolongation of the prothrombin ✓palmar erythema time ✓mild hepatomegaly ✓Hyperglobulinemia ✓hepatic tenderness ✓Hyperbilirubinemia ✓mild splenomegaly ✓mild elevations in alkaline phosphatase levels 10/14/2024 29  Chronic Liver Disease: etiology 1. Hepatitis C virus ✓is by far the most common cause of chronic viral hepatitis in developed countries 2. Hepatitis B virus ✓More common in developing world ✓Age at the time of infection is the best determinant of chronicity ✓maternal-to-infant transmission is a major risk factor for chronic HBV infection ✓The younger the age at the time of infection, the higher the probability of chronicity 10/14/2024 30  Chronic Liver Disease: etiology 3. Autoimmune hepatitis (AIH) 4. Drug-induced chronic hepatitis 5. Cryptogenic chronic hepatitis 6. Combined infection with HBV and HCV 7. Triple infection with HBV, HDV, and HCV 10/14/2024 31 10/14/2024 32 10/14/2024 33  Chronic Liver Disease: Histologic Features 1. mild forms 2. Moderate to sever forms Liver architecture is usually well interface hepatitis preserved bridging necrosis between portal portal tract inflammation tracts and portal tracts-to-terminal lymphocytes, macrophages, plasma hepatic veins cells ✓are harbingers of progressive liver hepatocyte apoptosis damage. deposition of fibrous tissue ✓hallmark of chronic liver damage is the Continued loss of hepatocytes and fibrosis results in cirrhosis 10/14/2024 34 Chronic Liver Disease: Histologic Features 10/14/2024 35 Chronic Liver Disease: Histologic Features 10/14/2024 36 Chronic Liver Disease: Histologic Features 10/14/2024 37 Chronic Liver Disease: Classification 1. Morphologic i. Chronic Persistent Hepatitis (CPH) ii. Chronic Active Hepatitis(CAH) iii. Chronic Lobular Hepatitis(CLH) ✓Due to limitations is being surpassed by: 2. Prognostic: the Knodell Histologic-Activity Index Assesses i. Inflammation ii. Necrosis ACTIVITY: GRADING iii. fibrosis STAGE 10/14/2024 38 Chronic Liver Disease: Classification 10/14/2024 39 Chronic Liver Disease: Classification 10/14/2024 40 Chronic Liver Disease: Classification 10/14/2024 41 Chronic Liver Disease: classification 10/14/2024 42 Chronic Liver Disease: classification 10/14/2024 43 CIRRHOSIS Definition Epidemiology Aetiology Pathogenesis Morphology Clinical features/complications 10/14/2024 44  Cirrhosis: Definition ❑the end stage of chronic liver disease with three main morphologic characteristics: i. Bridging fibrous septa ii. Parenchymal nodules containing hepatocytes encircled by fibrosis iii. Disruption of the architecture of the entire liver (“diffuse”) 10/14/2024 45 Cirrhosis: Epidemiology ❑is the twelfth most common cause of death in the United States, accounting for most liver-related deaths 10/14/2024 46  Cirrhosis: Aetiology 1. alcohol abuse 2. viral hepatitis 3. non-alcoholic steatohepatitis (NASH) 4. Other etiologies: i. biliary disease ii. iron overload 10/14/2024 47 Cirrhosis: Aetiology 10/14/2024 48  Cirrhosis: Pathogenesis ❑The central pathogenic processes i. death of hepatocytes ii. extracellular matrix (ECM) deposition iii. vascular reorganization 10/14/2024 49 Cirrhosis: Pathogenesis 10/14/2024 50 Cirrhosis: Morphology 10/14/2024 51 Cirrhosis: Morphology 10/14/2024 52 Cirrhosis: Clinical features/complications 10/14/2024 53 Cirrhosis: Clinical features/complications ❑major complications of cirrhosis are: ✓liver failure ✓portal hypertension ✓liver cell carcinoma 10/14/2024 54 investigation of a patient with liver disease: 1. analysis of serum concentrations of i. Bilirubin ii. hepatic enzymes iii. Albumin iv. clotting factors, etc. 2. immunological testing for auto-antibodies 3. liver biopsy 4. imaging techniques 10/14/2024 55