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Flashcards in Hepatic & Biliary Pathology Deck (67):

Causes of Chronic Liver Disease

- nonalcoholic fatty liver disease, viral hepatitis, alcohol, toxins, hereditary disorders, immune mediated disorders, drug reactions


Nonalcoholic Fatty Liver Disease (NAFLD) is associated with __________ and __________.

- obesity and type II diabetes
- the metabolic syndrome (insulin resistance)
- HTN and dyslipidemia are also linked


T or F: in viral hepatitis, the viruses do NOT directly injure the liver cells.

- true!
- instead, the immune system targets the infected cells and is responsible for the damage


What are three inherited disorders that can lead to Chronic Liver Disease?

- hemochromatosis
- Wilson's disease
- alpha-1 anti-trypsin deficiency


Compare the duration, symptoms, and hepatic liver enzymes in acute viral hepatitis vs. chronic viral hepatitis.

- acute: less than 6 months duration, jaundice is slightly more common, ALT and AST are in the 1000's, ALT greater than AST
- chronic: greater than 6 months duration, jaundice uncommon, ALT and AST are in the 100's, ALT greater than AST
- symptoms common to both: malaise, lethargy, RUQ discomfort (**symptoms in viral hepatitis are RARE**)


Which hepatitis viruses are DNA viruses?

- only HBV
- (all others are RNA viruses)


Which hepatitis viruses can cause chronic hepatitis? How is each transmitted?

- (obviously, all can cause acute hepatitis)
- A: ssRNA, not chronic, fecal-oral
- B: dsDNA, chronic, parenteral
- C: ssRNA, chronic, parenteral
- D: ssRNA, chronic, requires HBV to be present
- E: ssRNA, not chronic, fecal-oral


Other than the hepatitis viruses, list three other viruses that are known to cause hepatitis.

- cytomegalovirus, Epstein-Barr virus, herpes virus
- (these viruses are associated with more systemic infections)


What are the top three most common types of hepatitis?

- hep A, then hep C, then hep B


Hepatitis ___ most commonly affects children. Why? What prophylaxis or treatment is there?

- hep A most commonly affects kids because of their hygiene (HAV is spread fecal-orally)
- there is a hep A vaccine (although the virus is rarely fatal)


How is hepatitis C spread parenterally? What percentage of patients will spontaneously clear the virus? Develop a chronic infection? Develop cirrhosis? What prophylaxis or treatment is there?

- hep C is spread parenterally via blood-to-blood transmission
- 30% with spontaneously clear the virus, 70% will develop chronic infection, 10% of whom will develop cirrhosis
- no vaccine, treat with PEGylated interferon and Ribavirin (for genotypes 3, 4, 5, 6; for genotype 1 and 2, replace PEGylated interferon with oral antivirals)


How is hepatitis B spread parenterally? What prophylaxis or treatment is there?

- hep A is spread parenterally via blood, birthing, and baby-making
- there is a hep B vaccine, treat with PEGylated interferon and nucleoside analogs


T or F: treating hepatitis B and hepatitis C has a 60% cure rate.

- true and false!
- cure rate for hep C IS 60%
- cure rate for hep B is very low, the goal of treatment being viral suppression rather than curative


Neonates infected with HBV will most likely develop ACUTE/CHRONIC hepatitis, while infected adults will most likely develop ACUTE/CHRONIC hepatitis.

- neonates w/ HBV: most (90%) will develop chronic hepatitis
- adults w/ HBV: most will develop acute hepatitis and then get better (10% will develop chronic disease)


Which serology marker indicates an ongoing HBV infection? Which indicates an immunity to HBV?

- HBsAg (the HBV surface antigen) indicates an ongoing infection
- aHBs (anti-HBV surface antigen antibody) indicates immunity


What is Hemochromatosis? What mutation is involved? What causes the damage? When does it typically present?

- an autosomal recessive inherited defect (C282Y mutation of the HFE gene on chromosome 6p) that can lead to chronic liver disease
- mutations result in excess iron deposition and storage, especially in the liver, pancreas, heart, skin, and gonads
- iron generates free radicals, which damage these organs
- typically presents in late adulthood as the accumulation takes a while


What is used to screen for Hemochromatosis? What is the classic triad of symptoms/clinical findings?

- transferrin saturation (if greater than 0.45 --> indicative of hemochromatosis)
- classic triad: cirrhosis (liver), diabetes (pancreas), and bronze skin
- (also: cardiac arrhythmia and gonadal dysfunction)


What is Wilsons' Disease? What mutation is involved? When does it typically present?

- an autosomal recessive inherited defect that can lead to chronic liver disease
- mutations in ATP7B gene (chromosome 13) coding for ATP-mediated hepatocyte copper transport result in excess copper accumulation (in liver, brain, cornea, kidneys, and joints), resulting in acute liver failure, cirrhosis, and neurological disease
- copper fails to enter the circulation as ceruloplasmin
- presents in childhood, unlike hemochromatosis
- much more rare than hemochromatosis


Which phenotype is responsible for alpha-1 anti-trypsin deficiency?

- a recessive PiZ/PiZ phenotype
- (normal allele is PiM)
- (note that only 10% of patients will develop liver disease; emphysema is much more common)


Give three examples of immune disorders that can cause chronic liver disease.

- autoimmune hepatitis (AIH)
- primary biliary cirrhosis (PBC)
- primary sclerosing cholangitis (PSC)


Autoimmune Hepatitis (AIH) usually involves elevated ____ levels. What do we use to treat it?

- AIH usually has elevated IgG levels
- treat with prednisone


Primary Biliary Cirrhosis (PBC) usually involves elevated ____ levels. What do we use to treat it? What is targeted in this autoimmune disorder?

- PBC usually has elevated IgM levels
- treat with ursodeoxycholic acid
- targets the mitochondria of intrahepatic/intralobular bile ducts (granulomatous destruction)


What is meant by "impaired synthetic function" and "decompensated liver disease"?

- impaired synthetic function: abnormalities in prothrombin time and serum albumin
- decompensated liver disease: issues w/ fluid accumulation, ascites, edema, and encephalopathy


Why does liver disease cause encephalopathy? What are the 4 grades of encephalopathy?

- in severe liver disease, blood is shunted past the liver, so many toxins in the blood are unable to be cleared; when this toxic blood enters the brain/nervous system = impaired consciousness
- grade 1: sleep inversion --> grade 2: asterixis --> grade 3: progression into a coma --> grade 4: coma


3 Major Life-Threatening Complications of Cirrhosis

- variceal hemorrhages, spontaneous bacterial peritonitis, and hepatocellular carcinoma


How can we differentiate between ascites due to portal hypertension or due to another cause?

- ascites in portal hypertension: albumin gradient increases, but total protein is decreased
- ascites in another setting: albumin gradient increases, and total protein increases


What is Spontaneous Bacterial Peritonitis (SBP)?

- infection of the ascitic fluid
- it is very dangerous and often asymptomatic


Why are patients with varices commonly given antibiotics?

- it's used as a prophylaxis against sepsis if the varices rupture (variceal rupture is often associated with sepsis)


What are the main causes of cirrhosis in the Western world? What about worldwide?

- western world: alcoholic and metabolic liver disease
- worldwide: viral hepatitis B and C


4 Main Biliary Diseases (and the age group they most commonly affect)

- primary biliary cirrhosis (PBC): adults (female)
- primary sclerosing cholangitis (PSC): adults (male)
- congenital biliary atresia: infants/neonates
- bile duct obstruction: all ages


Congenital Biliary Atresia

- failure of the common bile duct to develop normally, leading to complete obstruction of the biliary tract --> rapid cirrhosis occurs
- elevated CONJUGATED bilirubin in neonates (neonatal jaundice/cholestasis)


What is the most common liver malignancy? Why?

- metastases are the most common (especially from colon, pancreas, lungs, and breasts)
- because the liver receives a ton of blood from many different organs


3 Patterns of Injury that can Cause Liver Failure

- acute liver failure with massive hepatic necrosis (drugs, hepatitis)
- chronic liver disease (most common; cirrhosis usually involved)
- hepatic dysfunction without overt necrosis (least common; hepatocytes are viable but non-functional)


5 Major Clinical Features of Hepatic Failure (due to chronic liver disease)

- jaundice, hypoalbuminemia, palmar erythema, spider angiomas, hyperestrogenemia (hypogonadism and gynecomastia in men)
- (in acute liver failure, patients may be jaundiced w/ encephalopathy)


Jaundice in the eyes is known as:

- sclerae icterus


What is Cholestasis?

- the retention of bilirubin and other bile solutes (bile salts and cholesterol)
- manifests as pruritis and xantholasma


What is Cirrhosis?

- cirrhosis is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into abnormal nodules


What are the three main characteristics of a cirrhotic liver?

- diffuse involvement, bridging fibrous septa, and parenchymal nodules


What are the main symptoms of cirrhosis? What do most cirrhotic patients die from?

- symptoms are non-specific: weight-loss, fatigue, anorexia (loss of appetite)
- death due to liver failure, portal HTN, HCC


What causes the portal hypertension in liver failure?

- increased resistance to portal blood flow, mainly at the sinusoids, results in the hypertension


What type of shunt can develop with portal hypertension? What 4 areas are at risk?

- portosystemic shunts can develop wherever the systemic and portal circulations share capillary beds
- can occur around and within the rectum (hemorrhoids), at the cardioesophageal junction (esophageal varices), in the retroperitoneum, and at the falciform ligament of the liver


Caput Medusae

- abdominal wall collaterals that develop in response to portal hypertension


What is the predominant cell infiltrate in acute hepatitis? What about in chronic?

- in BOTH types, the infiltrate is mainly mononuclear (T-cell mediated immune response)
- (this differs to normal acute inflammation being neutrophilic in nature)


What is a ground-glass cell?

- a hepatocyte with HBsAg in its cytoplasm; this cell morphology is seen in hepatitis B
- it occurs when the viral genome that encodes HBsAg is integrated into the host cell's DNA


Why does hepatitis D require HBV?

- because it is replicative defective and requires encapsulation by HBsAg in order to replicate


What unique morphology is seen in histology of hepatitis C?

- fatty change
- (it often resembles alcoholic/non-alcoholic steatosis)


List the stages of acute viral hepatitis.

- incubation period --> symptomatic pre-icteric phase (malaise, fatigue, anorexia) --> symptomatic icteric phase (jaundice) --> convalescence


Which three drugs have toxic effects that mimic hepatitis?

- acetaminophen, isoniazid (used to treat TB), and some toxins


What serology finding lets you know a patient is immune to hepatitis B via vaccination? What about immune due to a previous exposure?

- vaccine: HBsAg neg, aHBc neg, aHBs pos
- previous infection: HBsAg neg, aHBc pos, aHBs pos


Major diagnostic use for ALP, GGT, AST, and ALT.

- ALP = alkaline phosphatase; obstructive hepatobiliary diseases, HCC, bone disease
- GGT = gamma-glutamyl transpeptidase; similar to ALP but without bone disease, associated with alcohol
- AST + ALT = aminotransferases; when AST is greater than ALT: alcoholic hepatitis (but neither will be greater than 300); when ALT is greater than ALT: viral hepatitis (acute is in the 1000s, chronic in the 100s)


Major diagnostic use for amylase, lipase, ceruloplasmin, and transferrin.

- amylase: acute pancreatitis, mumps
- lipase: acute pancreatitis (the most specific!)
- ceruloplasmin: decreases in Wilson's disease
- transferrin: increases in hemochromatosis


What is Reye Syndrome? What is it highly associated with? What are the symptoms?

- rare, often fatal childhood hepatoencephalopathy associated with viral infection treated with aspirin
- symptoms: hypoglycemia, nausea, vomiting, coma


Where does steatosis and fibrosis usually begin?

- both begin in the centrilobular hepatocytes (zone III)


What is a Mallory-Denk body? What pathology is it associated with? What does it look like on histology?

- a tangle of intermediate filaments in the cytoplasm of degenerating hepatocytes
- found in steatohepatitis (alcoholic fatty liver and NAFLD)
- look for a twisted rope abnormality in the cytoplasm of the cell


What is meant by the "chicken-wire fence" pattern?

- associated with hepatic fibrosis (due to alcoholic fatty liver and NAFLD)
- fibrosis begins at the centrilobular hepatocytes (zone III), first sclerosing the central vein and then spreading out to the sinusoids = chicken-wire fence


What percent of heavy drinkers will develop alcoholic steatosis? Alcoholic hepatitis? Alcoholic cirrhosis?

- 90-100% will develop steatosis (reversible)
- 10-35% will develop hepatitis
- 8-20% will develop cirrhosis (irreversible)


What other liver pathology is a major accelerating factor of liver disease in alcoholics?

- hepatitis C


What is the most common primary malignant tumor of the liver? What is is associated with? Are there any serum markers?

- hepatocellular carcinoma (HCC)
- associated with HBV, HCV, cirrhosis, Wilson disease, hemochromatosis, a1AT deficiency, aflatoxins from Aspergillus spp.
- in Oz, 70% of cases are due to chronic HCV
- serum marker: alpha-fetoprotein (AFP)


What percentage of patients with alpha-1 anti-trypsin deficiency present with hepatic involvement?

- only 10-20% (emphysema is a much more common ailment)


What's a secondary cause of Hemochromatosis?

- chronic blood transfusions
- (ex: in patients with beta-thalassemia, they have non-functional Hb and require chronic transfusions. each transfusion is essentially bringing in iron into the body, as RBCs are an iron reservoir)


Primary Sclerosing Cholangitis (PSC) usually involves elevated ____. What is targeted in this autoimmune disorder? What pathology is it associated with?

- IgM antibodies are involved and elevated
- targets both intra- and extrahepatic bile ducts (fibrotic destruction --> onion skin appearance)
- associated with ulcerative colitis


In hemochromatosis, affected hepatocytes will have a brown pigment from iron accumulation - what else gives hepatocytes a similar color? What can be used to distinguish between these on histo?

- lipofuscin also gives a brown color similar to iron (it's basically from old cells being broken down)
- distinguish with a Prussian blue stain (if it's iron, it will stain blue)


What is colelithiasis? What are the general causes? What are the two types of stones? What are four main risk factors?

- gallstones; precipitation of cholesterol and/or bilirubin in bile
- due to stasis, excess cholesterol or bilirubin, and/or decreased bile acids
- 2 types of stones: cholesterol stones (more common, yellow, radio-lucent) and bilirubin stones (black, radio-opaque)
- risk factors are the 4 F's: female (estrogen activates HMG CoA reductase, which makes cholesterol), fat (obesity), fertile (pregnant0, forties (age)


What are the major symptoms/complications of colelithiasis?

- biliary colic pain: waxing and waning pain in the RUQ (when the gallbladder is contracting against the stones)
- *cholecystitis*: due to elevated pressures; RUQ pain that radiates to the right scapula, fever, nausea)
- *ascending cholangitis*: bacterial infection of bile ducts via stasis
- *acute pancreatitis*
- gallstone ileus: stone enters the small bowel, causing an obstruction
- fistula between gallbladder and small intestine
- gallbladder carcinoma


Long-standing cholelithiasis can result in cholecystitis, which can progress to chronic cholecystitis. What is the hallmark morphology of chronic cholecystitis? What complication can result?

- Rokitansky-Aschoff sinus formation: mucosal outpouchings found in the smooth muscle of the gallbladder wall
- can result in calcification of the gallbladder due to the chronic time frame = "porcelain gallbladder"


What percent of cholecystitis is due to cholelithiasis? What percent of patients with cholelithiasis will also have choledocholithiasis?

- 90% of cases of cholecystitis is due to gallstones (cholelithiasis)
- 15% of patients with cholelithiasis also have choledocholithiasis (biliary tract stones)


What is the triad of symptoms associated with acute cholangitis? The pentad of symptoms associated with suppurative ascending cholangitis?

- acute: Carchot triad; RUQ pain, fever, jaundice
- suppurative: Reynold pentad: the triad + mental status changes and hypotension
- (cholangitis is infection of the biliary ducts)