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Flashcards in liver disease Deck (58):

acute vs chronic liver injury

acute injury can lead to liver failure, resolution or chronic injury. Chronic injury can lead to cirrhosis then liver failure, cirrhosis then resolution, or directly to resolution


signs of liver failure

jaundice, icterous, acites (hypoalbuminemia), spyder angiometa, palmar erythema, gynecomastia, coagulopathy, encephalopathy, and renal failure


What is Cirrhosis

scarred liver, end point to many chronic liver diseases. Result of chronic recurring death of hepatocytes, deposition of extracellular matrix, and architectural and vascular reorganization. Can be compensated (functional) or decompensated (failing functions)


Cirrhosis histology

diffuse fibrous septation that divides the liver parenchyma into nodules


signs of liver cirrhosis

portal hypertension due to vascular reorganization in liver and increased sinusoidal pressure. Ascites, hemorrhoids, splenomegaly, esophageal varices, hepatic encephalopathy


Causes of jaundice and cholestasis

excessive extrahepatic bilirubin production, reduced hepatocyte uptake, impaired conjugation, decreased hepatocellular excretion and impaired bile flow


common causes of chronic liver disease in US adults

viral hepatitis C > alcoholic liver dz > non-alcohol fatty liver disease > viral hepatitis B


What is hepatitis

•Inflammatory injury and death of hepatocytes resulting from steatohepatitis or viral causes


Hepatitis histology

swelling/degeneration of hepatocytes, apoptosis/lobular cells with a clear interface separating apoptotic and non-apoptotic cells, bridging necrosis, coagulative necrosis,


Types of inflammation in hepatitis

Lymphocytes – many hepatitides; common in viral. Neutrophils – common in steatohepatitis (fatty liver). Eosinophils – common in drug injury. Plasma cells – common in autoimmune hepatitis


•Be able to compare and contrast acute and chronic hepatitis time course

acute: New onset (< 6 months) of symptomatic disease and laboratory evidence of hepatocyte injury. Chronic: hepatocyte injury and inflammation >6 months.


•Be able to compare and contrast acute and chronic hepatitis time causes

acute: Common causes include acute viral hepatitis and drug injury. Chronic: Caused by chronic viral hepatitis, autoimmune hepatitis and drug injury


•Be able to compare and contrast acute and chronic hepatitis microscopic findings

acute: Micrscopic findings include lobular disarray, marked inflammation throughout, widespread hepatocyte injury and necrotic hepatocytes, no fibrosis. Chronic: Microscopic findings include less prominent inflammation and injury (lymphoid aggregates), preponderance of portal tract-based inflammation, fibrosis


Cytoplasmic accumulations in liver injury

Fat – Steatosis. Bile (yellow inclusions) – Cholestasis. Iron – Hemosiderosis/ genetic hemochromatosis. Copper – Wilson Disease / chronic cholestasis. Viral particles (ground glass) – Viral hepatitis


Regeneration and fibrosis cycle in liver injury

Chronic injury and regeneration > activated stellate cells deposit collagen > architectural and vascular reorganization > cirrhosis


How is disease progression tracked in chronic hepatitis

liver biopsies: grade indicates amount of inflammation and injury. Stage indicates amount of fibrous tissue deposition


Stages of liver fibrosis

no fibrosis (stage 0) > portal fibrosis (stage 1) > periportal fibrosis (stage 2) > bridging fibrosis (stage 3) > cirrhosis (stage 4)


grades of liver inflammation and injury

grade 1: focal inflammation, no necrosis. Grade 2: focal necrosis with mild inflammation. Grade 3: confluent necrosis without bridging and moderate inflammation. Grade 4: bridging necrosis with severe inflammation


Hepatitis A transmission, frequency of chronic liver dz, diagnosis

fecal oral contaminated food or water, NEVER causes chronic liver dz only causes acute hepatitis, detection of serum IgM Abs


Hepatitis B type of virus, transmission, frequency of chronic liver dz, diagnosis

Partially dsDNA (only hepatic virus that can integrate into host genome), parenteral, sexual contact or perinatal. 10% develop chronic liver dz. Diagnosed with HBsAg or Ab to HBcAg


Hepatitis C transmission, frequency of chronic liver dz, diagnosis

Parenteral (blood and body fluids), intranasal cocaine use is risk factor. 80% develop chronic liver dz. PCR for HCV RNA, or 3rd generation ELISA for Ab detection


Hepatitis D diagnosis and transmission

Detection of IgM and IgG Abs. HDV RNA serum. HDAg in liver. IV drug use most common mode


Hepatitis E transmission, frequency of chronic liver dz, diagnosis

Fecal-oral. Never causes chronic liver dz, only causes acute hepatitis. PCR for HEV RNA, detection of serum IgM and IgG Abs


hepatitis C antibodies

Hep C is geneticall unstable with multiple genotypes and subtypes. Anti-HCV Abs are made, but antibodies are not neutralizing


Outcomes of Hep C

85% develop chronic hepatitis, 15% resolve and rarely fulminant hepatitis results.


Discuss appearance of important Hep B Abs and Ags

Hep Be Ag and HBV-DNA signifies active disease and viral replication. Hep B surface Ag appears before onset of symptoms and peaks during overt dz. IgM Abs rise before IgG


compare serum markers of Hep B in infection with recovery compared to chronic carrier

Infection with recovery: HBeAg, HBV-DNA and HBsAg reach peak during active disease, then drop to zero in 4-12 weeks. IgM anti-HBc and anti-Hbe rise immediately then decrease in 4-20 weeks. Anti-HBs and anti-HBc IgG rise over period of years. Chronic: HBeAg, HBV-DNA and HBsAg all rise and stay elevated. IgM rises and stays elevated. IgG rises later and stays elevated


Hepatitis B histology

ground glass hepatocytes, sanded nucleus


Hepatitis D viral infection

•Replication incompetent, completely dependent on HBV coinfection. Potentiates effects of HBV with : increased risk of fulminant hepatitis, increased activity, and faster progression to end stage liver disease.


Autoimmune hepatitis presentation and serology, histology

78% women. Indolent to severe. Presents with other autoimmune dz. Serology: autoantibodies (ANA, ASMA, anti-LKMB) and elevated IgG. Histology: plasma cell rich, centrolobular necroinflammation


Primary biliary cirrhosis cause, presentation, serology, prognosis

•Immune-mediated attack of intrahepatic small caliber bile ducts. Pruritus, middle aged women, elevated ALP, GGT and bilirubin, jaundice. Serology: anti-mitochondrial Ab and elevated IgM. 25% have liver failure in 10 yrs


primary biliary cirrhosis histology

lymphocyte mediated bile duct damage, granulomatous duct destruction


primary sclerosing cholangitis cause, presentation, diagnosis and prognosis

•Presumed immune-mediated obliterative fibrosis of intrahepatic and extrahepatic bile ducts (generally large caliber bile ducts). Men > women, 70% have ulcerative colitis, ALP elevation, progressive fatigue, pruritis and jaundice. Diagnosis: cholangiography shows alternating biliary strictures and dilation. Increased risk for cholangiocarcinoma


primary sclerosing cholangitis histology

periductal onion-skin fibrosis, fibrous obliteration of bile ducts


intrinsic vs idiosyncratic drug induced liver injury

intrinsic is dose related, idiosyncratic is unpredictable


acetaminophen liver injury

major cause of acute liver failure. Acetaminophen is an intrinsic hepatotoxin that causes centrilobular necrosis in zone 3


list metabolic liver dz

steatosis, hereditary hemochromatosis, wilsons dz and alpha-1-antitrypsin deficiency


What is steatosis

•Accumulation of fat in hepatocytes. Metabolic derangement of hepatocytes


causes of steatosis

•metabolic syndrome, alcohol, drug effect, Wilson disease, viral infection. Lipid influx is greater than lipid clearance


Steatohepatitis definition and causes

•Hepatocellular injury in association with steatosis, +/- overt inflammation. Triad of steatosis, lobular inflammation and hepatocyte ballooning degeneration. Causes: alcohol, metabolic syndrome, drug injury


steatohepatitis histology

ballooning degeneration, inflammation and steatosis. Pericentral and pericellular fibrosis


What causes alcohol steatosis/steatohepatitis

Defects in beta oxidation of hepatic lipids into CO2 and ketones, and defects in generation of VLDL.


Alcoholic steatohepatitis histology

neutrophilic infiltrates, mallory bodies,


What is non-alcoholic steatosis/steatohepatitis

fatty liver dz associated with obesity, diabetes type II, hypertriglyceridemia. Increased lipolysis and decreased beta oxidation/VLDL production


Hereditary hemochromatosis cause and presentation

genetic iron overload dz throughout body manifests as liver disease, diabetes, heart failure in middle age. AR inheritance, HFE gene mutations lead to abnormal regulation of iron absorption resulting in increased absorption


hereditary hemochromatosis histology

progressive iron deposition within the cytoplasm of hepatocytes, beginning in the periportal region first. Over time, iron acts as an oxidant and results in hepatocyte injury and fibrosis.


Wilson disease

genetic copper overload throughout body causing liver dz and neuropsych problems. Due to mutations in ATP7B gene involved in bile excretion of copper.


alpha-1-antitrypsin deficiency

•Alpha-1-antitrypsin is a protease inhibitor that prevents actions of proteases released by neutrophils and limits tissue damage. PiMM is normal genotype; PiZZ is the common disease and most people have pulmonary emphysema, 10% develop liver dz.


alpha-1-antitrypsin deficiency histology

PASD stain shows intracytoplasmic accumulation,


Abnormalities of blood flow affecting liver

impaired blood inflow causes intestinal congestion. Impaired intrahepatic blood flow causes ascites, hepatomegaly and elevated aminotransferases. Hepatic vein outflow obstruction causes ascites, hepatomegaly, elevated aminotransferases and jaundice


malignant and benign liver masses in adults

malignant: hepatocellular carcinoma and cholangiocarcinoma. Benign: hemangioma, focal nodular hyperplasia and hepatocellular adenoma.


Hepatocellular carcinoma cells, risks, prognosis

Malignant neoplasm of hepatocytes. Most common 1° malignant liver tumor. Occurs mostly in patients with chronic liver disease (HCV, HBV, alcohol) and cirrhosis. In general, dismal long-term survival


hepatocellular carcinoma gross and microscopic appearance

gross: Invasion of main branch of portal vein or hepatic artery. May have green-yellow color (bile). Micro: Thickened hepatic plates, Endothelialization of sinusoids, Invasion of fibrous tissue/vessels, Unpaired arteries, No true portal areas


Cholangiocarcinoma cells affected, risk factor, prognosis

Malignant neoplasm of bile ducts, May be intrahepatic or extrahepatic, Major risk factor is primary sclerosing cholangitis, In general, dismal long-term survival


Cholangiocarcinoma gross and microscopic appearance

gross: -Densely fibrotic mass in the hilar region with infiltrative edges, Tan-white in color. Micro: Invasive gland forming tumor with abundant desmoplastic response


Hemangioma structures affected, presentation

Benign neoplasm of dilated vascular spaces. Most common primary hepatic tumor. Small and asymptomatic usually, but can cause vague RUQ pain, early satiety, nausea, vomiting


Focal nodular hyperplasia structures affected, Sx

•Benign mass-like proliferation of hepatocytes. Arises due to local vascular flow anomaly. Usually asymptomatic


Hepatocellular adenoma structures affected, risk, Sx

Benign neoplasm of hepatocytes. Occurs mostly in women of child-bearing age and associated with oral contraceptive use. Asymptomatic or RUQ abd pain. Low risk of malignant transformation