Liver Diseases. Yasmine Lashine MD, PhD

Transcription

1 Liver Diseases Yasmine Lashine MD, PhD

2 ILOs Recognize different causes of Live failure Recall and understand clinical picture and complication of Liver failure Discuss causes and clinical picture of hepatic encephalopathy Discuss Liver cirrhosis in terms of, etiology morphology, pathogenesis and complication. Discuss and understand portal hypertension in terms of etiologic factors, pathogenesis clinical features, and course. Understand and recall Hepatocellular Carcinomas in terms of epidemiology, etiology, pathogenesis, clinical pictures and diagnostic tools

3 Outline I. Hepatic Failure II. Jaundice and Cholestasis III. Hepatic Encephalopathy IV. Cirrhosis V. Portal Hypertension VI. Portosystemic Shunt VII. Hepatocellular Carcinomas 3

4 Overview 4

5 Overview The liver contains ~1,000,000 lobules 5

6 Laboratory Evaluation of Liver Disease *The most commonly performed tests are in italics. Liver biopsy representing the gold standard for diagnosis 6

7 Hepatic Failure Hepatic failure occurs when 80% to 90% of hepatic function are lost. Acute liver failure with massive hepatic necrosis Uncommon Progresses to hepatic encephalopathy in 2-3 weeks Massive hepatic necrosis. Fetal and requires hepatic transplantation Chronic liver disease Most common Occurs due to chronic damage to the liver which often ends in cirrhosis Hepatic dysfunction without overt necrosis Less common Viable Hepatocytes but unable to perform their function acute fatty liver of pregnancy, and some drug- or toxinmediated injuries. 7

8 Hepatic Failure Clinical Features: Chronic liver faliure Jaundice/icterus (bilirubin >2.0 mg/dl) Hypoalbuminemia Hyperammonemia Palmar erythema Spider angiomas Hyperestrogenemia Acute liver failure Jaundice Encephalopathy 40% recover spontanously Spider angiomas Jaundice Palmer Erythema 8

9 Clinical consequences Hepatic Failure Hyperammonemia Hyperestrogenemia Hypoalbuminemia Coagulopathy Coma Fetor hepaticus Liver flap Asterixis Palmar erythema Spider angiomas Testicular atrophy Gynecomastia Ascitis Ascites Ankle edema Edema acut fatty liver pregn soe drugor toxinedinjuries. Bleeding tendency Ecchymoses Anemia

10 Hepatic Failure 10

11 Complications of Liver Failure Coagulopathy Respiratory failure Hepatic encephalopathy Renal failure

12 Hepatic Encephalopathy Hepatic encephalopathy may develop rapidly in acute liver failure or insidiously with gradually evolving chronic liver failure. Two factors seem to be important in the genesis of this disorder: Severe loss of hepatocellular function Shunting of blood from portal to systemic circulation Hepatic encephalopathy occurs due to: Elevation in blood ammonia impairs neuronal function and promotes generalized brain edema in acute liver failure (e.g. Acute hepatitis B infection) Deranged neurotransmitters production such as GABA (γaminobutyric acid ) leading to neuronal dysfunction in case of chronic liver failure (e.g. hepatic cirrhosis ).

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14 Hepatic Encephalopathy Clinical manifestation : Brain dysfunction: Behavioral abnormalities Marked confusion Stupor, Deep coma and Death. Neurologic signs : Rigidity, hyperrfelexia and seizures Asterixis (flapping tremor) Nonrhythmic, rapid extensionflexion movements of the head and extremities, best seen when the arms are held in extension with dorsiflexed wrists.

15 Cirrhosis Cirrhosis is defined as a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules. Causes of Cirrhosis : Chronic viral infections Alcoholic or nonalcoholic steatohepatitis (NASH) Autoimmune diseases affecting hepatocytes and/or bile ducts

16 The three main characteristics of cirrhosis are (1) Involvement of most or all of the liver (2) Bridging fibrous septa (3) Parenchymal nodules containing a mix of senescent and replicating (often stem/progenitor cell-derived) hepatocytes. 16

17 Clinical features: Cirrhosis clinically silent nonspecific symptoms as : anorexia, weight loss and weakness. Hepatic failure mainfestions Clinical outcome : liver failure portal hypertension hepatocellular carcinoma 17

18 Portal Hypertension 18

19 Portal Hypertension 19

20 Portal Hypertension Causes: Prehepatic: congenital stenosis of PV, PV thrombosis (malignancy, hypercoagulable states, pancreatitis), extrinsic compression (tumors). Intrahepatic: cirrhosis, chronic hepatitis, schistosomiasis, massive fatty change, diffuse granulomatous diseases. Posthepatic: hepatic vein obstruction, constrictive pericarditis, right heart failure. The dominant intrahepatic cause is cirrhosis, accounting for most cases of portal hypertension. 20

21 Portal Hypertension Pathogenesis: Increased resistance to portal flow at the level of the sinusoids. Compression of central veins by perivenular fibrosis. Expanded parenchymal nodules. Hyperdynamic splanchnic circulation leading to an increase in portal venous blood flow (increased production of NO due to intrahepatic shunting of blood from portal to systemic circulation). 21

22 Ascites: Portal Hypertension Ascites is defines ad fluid collection in the peritoneal cavity. clinically detectable when at least 500 ml have accumulated. Turbid ascetic fluid due to Influx of neutrophils is due to secondary infection Bloody ascetic fluid is associated with intra-abdominal cancer. long-standing ascites, leads to passage of peritoneal fluid through transdiaphragmatic lymphatics leading to hydrothorax, more often on the right side. 22

23 Portal Hypertension Pathogenesis of Ascites: Increased movement of intravascular fluid into the extravascular space due to sinusoidal hypertension and hypoalbuminemia. Renal retention of sodium and water due to secondary hyperaldosteronism (decreased renal blood flow following decreased plasma volume) 23

24 Portal Hypertension Porto systemic shunts Abdominal wall collaterals Esophagogastric varices Hemorrhoid caput medusa Hematemesis Melena

25 Portal Hypertension caput medusae

26 Hepatocellular Carcinomas Epidemiology : Worldwide, HCC accounts for approximately 5.4% of all cancers. More than 85% of cases occur in countries with high rates of chronic HBV infection: Asian countries (southeast China, Korea, Taiwan) and sub-saharan African countries in which HBV is transmitted vertically. Moreover, many of these populations are exposed to aflatoxin, which when combined with HBV infection increases the risk of HCC dramatically. The peak incidence of HCC in these areas is between 20 and 40 years of age, and in almost 50% of cases, the tumor appears in the absence of cirrhosis. In Western countries the incidence of HCC is rapidly increasing, largely owing to the hepatitis C infection. 26

27 Hepatocellular Carcinomas Pathogenesis : Three major etiologic associations have been established: infection with HBV or HCV, alcoholic cirrhosis, and aflatoxin exposure. In many parts of the world, including Japan and Central Europe, chronic HCV infection is the most important risk factor in the development of liver cancer. In certain regions of the world, such as China and southern Africa, especially Mozambique, where HBV is endemic, high-level exposure to dietary aflatoxins derived from the fungus Aspergillus lavus is common. These carcinogenic toxins are found in moldy grains and peanuts. Aflatoxin can bind covalently with cellular DNA, resulting in mutations in genes such as TP53. 27

28 Hepatocellular Carcinomas Pathogenesis : In most cases, it develops from small-cell, high-grade dysplastic nodules in cirrhotic livers. Distinguishing high-grade dysplastic nodules from early HCC is difficult even in biopsies, because there are no molecular markers specific for these stages. Nodule vascularization, visualized by imaging, which is almost always a clear indication of malignancy. The presence of structural and numeric chromosomal abnormalities is a universal feature of HCC and are indicative of genomic instability. 28

29 Hepatocellular Carcinomas Morphology : HCC may appear grossly as A unifocal, usually massive tumor. A multifocal tumor made of nodules of variable size. A diffusely infiltrative cancer, permeating widely and sometimes involving the entire liver. On histologic examination: HCCs range from well differentiated lesions to poorly differentiated lesions, often composed of large, multinucleate anaplastic giant cells. There is little stroma in most hepatocellular carcinomas, explaining their soft consistency. 29

30 Hepatocellular Carcinomas Clinical Features : Although HCC may manifest with silent hepatomegaly, it is more often encountered in persons with symptomatic cirrhosis of the liver. In these persons, the following features call attention to the development of a tumor: A rapid increase in liver size A sudden worsening of ascites The appearance of bloody ascites Fever Pain 30

31 Hepatocellular Carcinomas Clinical Features : The most commonly used marker is serum alpha-fetoprotein level, but it rises only with advanced tumors and only in 50% of patients. Many non-neoplastic conditions lead to an increased level of AFP such as cirrhosis, chronic hepatitis, normal pregnancy, and massive liver necrosis. Alpha-fetoprotein level is neither specific nor sensitive. Radiologic screening of patients with cirrhosis at 6-month intervals, looking for dysplastic nodules or early, small HCC, is the current clinical frontier. 31

32 References ROBBINS Basic Pathology 9 th Edition Source of the cover: 32

33 Thank you 33

34 Palmer Erythema Spider Navi Caput mudosa

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