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434 Cards in this Set
- Front
- Back
What does a "portal triad" consist of?
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Hepatic Portal Venule
Proper Hepatic Arteriole Common Hepatic Ductule |
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What does a classic hepatic lobule conist of?
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A portal triad (hepatic portal venule, proper hepatic arteriole, common hepatic ductule) + centrilobular hepatic venule ("central vein")
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The portal venous and hepatic arterial blood vessels enter the liver through the......
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porta hepatis
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How is the portal venous blood different from systemic venous blood?
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Oxygen poor, contains toxins and metabolic waste products, intestinal bacteria, liver trophic factors from pancreas
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Which supplies more blood to the liver, the portal vein or hepatic artery?
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The portal vein supplies 2/3 of blood flow, the hepatic artery supplies 1/3 of blood flow
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The R and L hepatic bile ducts exit the liver through the....
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porta hepatis
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Which two vessels provide blood flow to the portal areas of the liver?
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the hepatic artery (1/3 of flow) and portal vein (2/3 of flow)
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Sinusoids are lined by which two kinds of cells?
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Endothelial cells and Kupffer cells
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Where are stellate (ito) cells located?
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within the Space of Disse
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Kupffer cells are closely related to what kind of cell?
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macrophages
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What characteristic of the sinusoidal epithelium allows for rapid transit of substances between the hepatocytes and blood?
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fenestrations
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What are canaliculi?
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specialized grooves on the contact surface between two hepatocytes where bile is initially excreted
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What are the darkest stained cells in this image?
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bile ducts, and probably hepatic stem cells
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What are the features stained dark brown with CEA stain?
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the bile cannalicular system
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What is a limiting plate?
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hepatocytes surrounding the portal tract form an interface between the connective tissues of the portal tract and the hepatic parenchyma
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What disease is this? What are the histological findings?
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Interface Hepatitis: mononuclear infiltrate expands portal area and damages hepatocytes at the limiting plate
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What disease is this? What are the histological abnormalities?
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Lobular Hepatitis: central venule with intense inflammation in surrounding lobule.
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What is the red thing in the center of the photo?
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Acidophil body: single cell pattern of hepatocyte necrosis; cytoplasm condenses and becomes eosinophilic (hence the dark stain with H&E)
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In which zone of hepatocytes is necrosis occuring here? How do we know?
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Hepatocytes in the midzone are necrosed. We can tell because they are highly eosinophilic (pink stained) and have lost their cellular pattern.
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This is an example of _____ necrosis.
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geographic necrosis
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What is lipochrome?
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Lipochrome is the brownish pigment in the above histological specimen. It is a wear and tear pigment that is accumulated with time and indicative of older age.
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What is going on here?
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Rupture of bile duct distended with inspissated bile. The concentrated bile is toxic and is damaging hepatocytes and producing an inflammatory response. This is ass'd with cholestasis.
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Fibroedematous expansion and peripheral ductule proliferation as seen here often occurs secondary to.....
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acute obstruction of the bile duct
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What is the diagnosis? What does this typically occur secondary to?
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This is ascending cholangitis probably secondary to bile duct obstruction. Note the epithelial cells that have sloughed into the lumen of the duct and the numerous neutrophils.
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What is this called?
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steatosis
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This specimen of liver has been stained with Congo red and has an apple-green birefringence when examined by polarization microscopy. What is this?
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amyloid
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This liver specimen has been treated with an iron stain. The likely diagnosis is...
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hemachromatosis
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What are the dark stained structures? What are they associated with?
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These are Mallory Bodies (or Mallory Hyalin). They are scroll-like aggregates of eosinophilic cytokeratin filaments. They are often associated with alcoholic hepatitis.
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What is this?
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centrilobular congestion; RBC's are entering the hepatocyte plates and there is obvious hepatocyte necrosis
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Which LFT's are the most useful in assessing hepatocellular injury?
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the transaminases (ALT, AST) and lactate dehydrogenase (LD)
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Which LFT's are most useful in assessing cholestasis?
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alkaline phosphatase (ALP), gamma glutamyltransferase (GGT), and direct(conjugated) bilirubin (D-BILI)
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Which LFT's are most useful in assessing the liver's synthetic capacity?
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Albumin (ALB) and Prothrombin time (PT)
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Where is most hepatocyte AST stored?
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80% of the total hepatocyte AST is in the mitochondria; 20% is in the cytosol
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Where is most hepatocyte ALT stored?
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Almost all hepatocyte ALT is stored in the cytosol.
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Does ALT or AST tend to rise more rapidly at first in response to hepatocellular injury? Why is this?
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Initially ALT rises more quickly because almost all hepatocyte ALT is stored in the cytosol, whereas only 20% of hepatocyte AST is stored in the cytosol (the other 80% being in the mitochondria).
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Peak ALT & AST > 100 x R.I. is suggestive of............
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massive acute hepatocellular necrosis
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Peak ALT & AST > 10 x R.I. (but < 100 x R.I.) is suggestive of............
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acute viral hepatitis
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Peak ALT & AST 2-10 x R.I. is suggestive of............
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hepatocellular necrosis associated with chronic forms of liver disease
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AST/ALT ratio < 1.0 is suggestive of....
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viral hepatitis
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AST/ALT ratio > 2.0 is suggestive of...
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acute alcoholic hepatitis
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Strenuous exercise can cause (AST / ALT) to be increased, while excess weight can cause (AST / ALT) to be increased.
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Strenuous exercise can cause (AST) to be increased, while excess weight can cause (ALT) to be increased.
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Cholestasis has what effect on liver ALP?
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liver ALP activity is induced (and thus elevated) by cholestasis
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An isolated increase in ALP and a normal GGT is most likely to be...
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something other than liver disease
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If liver disease is suspected and serum ALP is high, what level of GGT would we need to find to rule out liver disease?
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A normal level of GGT with an elevated ALP typically rules out liver disease. Something else must be causing the rise in ALP.
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Which markers take longer to rise in response to hepatic injury: the transaminases (ALT/AST) or the cholestatic markers (ALP, GGT)?
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The cholestatic markers (ALP, GGT) take longer to rise. The transaminases rise fairly rapidly initially.
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An ALP> 3x R.I. and GGT > 5x R.I. is suggestive of...
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cholestasis
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A GGT/ALP ratio > 2 is suggestive of...
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liver disease
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A GGT/ALP ratio > 5 is suggestive of...
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active alcoholic liver disease
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A GGT/ALP ratio < 2 is suggestive of...
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a non-hepatic source
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Can measures of ALP or GGT differentiate between intrahepatic or extrahepatic cholestasis?
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NO - Neither the ratio nor degree of elevation in ALP and GGT can differentiate intrahepatic from extrahepatic cholestasis
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What is the most important non-hepatic source of variation in serum ALP? Why?
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Age - osteoblasts are rich in ALP, so during active bone formation (in youth) you will see elevated levels of ALP
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T-BIL =
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Bu + Bc + Bdelta
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D-BIL =
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BC + Bdelta
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I-BIL =
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T-BILL - D-BILL
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How is bilirubin normally excreted?
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bilirubin is conjugated and then excreted through the biliary system (some bilirubin is also excreted through the kidney)
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T-BIL, D-BIL, and I-BIL are all ______ whereas Unconjugated, Conjugated, and Delta bilirubin are all_______.
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tests that ordered; types of bilirubin in the blood
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In order for Bdelta to be formed, (conjugated / unconjugated) bilirubin levels in the blood must be increased for a long time.
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In order for Bdelta to be formed, (conjugated) bilirubin levels in the blood must be increased for a long time.
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What is the half-life of albumin?
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17-20 days
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What two LFT's are useful in assessing the liver's synthetic capability?
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PT, albumin
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Decreases serum albumin and elevated immunoglobulins may be suggestive of......
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chronic hepatitis
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Elevations of which immunoglobulin are common in alcoholic cirrhosis?
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IgA
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Elevations of which immunoglobulin are common in chronic hepatitis?
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IgG
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Elevations of which immunoglobulin are common in primary biliary cirrhosis?
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IgM
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Antimitochondrial antibodies are present in the majority of patients with which liver disease? They are rarely present in which liver disease?
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Antimitochondrial antibodies are present in 85-90% of patients with primary biliary cirrhosis. They are present in only 10% of patients with chronic hepatitis.
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Which new multi-marker array provides a useful index to guage the degree of heptatic fibrosis? Which markers is it composed of?
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HCV Fibrosure (alpha2-macroglobulin, apolipoprotein A1, haptoglobin, T-bili, GGT)
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What is the most common cause of acute liver failure? In which gender is it more common?
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acetaminophen overdose; more common in women
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What are the three criteria for establishing acute liver failure?
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Rapid onset of synthetic dysfunction (jaundice, coagulopathy), Encephalopathy, No prior liver disease
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Contrast fulminant hepatic failure and subfulminant hepatic failure.
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Fulminant hepatic failure: interval between jaundice and encephalopathy < 2 weeks; rapid course to recovery or death/transplant
Subfulminant hepatic failure: interval is 2 weeks - 3 months; slow course proceeding to death or transplant |
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What are the three major differential diagnoses that must be ruled out in diagnosing acute liver failure?
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Drugs (most often acetaminophen), Viruses (Hep A, B, D, E), Toxins (Amanita mushrooms, etc)
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What is icterus?
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yellow coloration of sclera and mucus membranes in jaundice
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What is asterixis?
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a neurological sign - patient is asked to dorsiflex hands and close eyes - rhythmic flapping or shaking hands are a positive sign - highly suggestive of encephalopathy secondary to hepatic failure
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ANA is a marker of.....
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autoimmunity
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The criteria used to determine whether a patient in acute liver failure needs a transplant are called...
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King's College Criteria
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What are the King's College Criteria for diagnosing acetaminophen-induced acute liver failure?
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pH<7.30 OR PT > 100s (INR > 6.5) + Cr >3.5mg/dL + stage III or IV coma
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What are the King's College Criteria for diagnosing non-acetaminophen-induced acute liver failure?
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PT > 100s (INR > 6.5) OR any 3 of the following:
age <10 or >40 unfavorable etiology (drug, Wilson's) acute/subacute presentation bilirubin > 17.5 mg/dL PT > 50s (INR > 3.5) |
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Name some of the complications of acute liver failure.
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Renal failure/Acute tubular necrosis
Cerebral edema Infections: bacterial and fungal (Candida) Pulmonary edema, pneumonia, ARDS Hypoglycemia Hemorrhage Metabolic acidosis |
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In a patient with renal failure secondary to acute liver failure (33% of patients), what tests/studies/drugs should be avoided?
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CT contrast, NSAIDS, empiric aminoglycosides
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What is the antidote to acetaminophen overdose?
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N-acetylcysteine (Mucomyst)
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Why should Fresh Frozen Plasma (FFP) be avoided in patients with acute liver failure?
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If there is a possibility of transplant, we want to minimize the amount of extra antibody floating around in the circulation.
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What is the most common cause of death in patients with fulminant hepatic failure?
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cerebral edema
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How rapidly are successful liver transplants done for cases of acute liver failure?
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80% of patients with fulminant hepatic failure undergoing successful transplants are transplanted within 48 hours
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Is a patient with previously unrecognized liver disease (eg, Wilson's Disease) who acutely decompensates considered to have acute liver failure?
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Technically no: One of the conditions for acute liver failure is no previous liver disease. The problem is that a presence of previous liver disease is not necessarily evident at time of presentation.
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Acetaminophen is an example of a(n) _________ hepatotoxin.
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Acetaminophen is an example of a(n) intrinsic hepatotoxin.
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What is an intrinsic hepatotoxin? Give one example.
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A substance that is naturally toxic to the liver and produces an injury that is reproducible and dose dependent; acetaminophen is the classic example
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What is an idiosyncratic hepatotoxin?
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A substance that produces a liver injury relatively randomly in an unpredictable and dose-independent fashion
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How can acetaminophen overdose cause hepatocellular damage?
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Metabolism of acetaminophen by the liver produces a toxic metabolite that is bound and neutralized by glutathione; an overdose overwhelms and depletes the liver's stores of glutathione
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What are some of the ways (both intentional and inadvertent) that acetaminophen overdose occurs?
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1) suicidal overdose
2) high therapeutic dose + chronic EtOH abuse (EtOH induces p450, generating more toxic metabolite) 3) high therapeutic dose + fasting or protein malnutrition (reduced glutathione stores) |
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How is an INR (PT) used in assessing hepatic function/disease?
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The INR (PT) detects the presence/severity of a coagulopathy, and as such is a sensitive marker of hepatic synthetic failure
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Serum ammonia in ALF due to acetaminophen overdose will be (elevated/decreased)
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Serum ammonia is acetaminophen overdose will be markedly (elevated)
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Serum glucose in ALF due to acetaminophen overdose will be (elevated/decreased)
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Serum glucose in ALF due to acetaminophen overdose will be (decreased) due to impaired glycogen production and gluconeogenesis
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In ALF, what kind of liver biopsy is preferred and why?
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Percutaneous liver biopsy is contraindicated in the setting of a coagulopathy. Transjugular biopsy may be performed because any bleeding that occurs will be into the hepatic vein.
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Which will rise more rapidly in ALF, albumin or PT (INR)?
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PT (INR) will rise much more rapidly because the half life of PT proteins is on the order of hours. The half life of albumin is ~17-20 days.
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Which areas in this histological liver specimen are necrotic? What pattern of necrosis is this?
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The lighter areas are viable while the darker areas are hemorrhage into necrotic liver. This is a classic example of geographic (random) necrosis.
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What type of hepatitis is rare, often overlooked, and most prevalent in the immunosuppressed and premature infants? (HINT: histological pattern of necrosis is geographic)
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herpes hepatitis
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Describe the typical histological appearance of cells in herpetic hepatitis.
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The 3 M's:
Multinucleation Molding of nuclei Margination of nuclear chromatin about central ground-glass nucleoplasm |
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Is hemochromatosis a disease of the liver?
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NO!
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Hereditary hemochromatosis results from mutations in which gene? Where is it located and what does it code for?
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HFE on chromosome 6p
HFE codes for the HFE protein, which is an MHC class I molecule found in crypt cells of the duodenum and that facilitates cellular uptake of iron |
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What are the two main genetic mutations responsible for hereditary chromatosis? Which is the most common?
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C282Y (most common) and H63D
Both are missense mutations |
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What is the most prevalent genetic disorder in Caucasians?
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hereditary hemochromatosis
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In hereditary hemochromatosis, the mutated HFE protein fails to sense the presence of ______, so it upregulates the duodenal absorption of ________.
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iron; iron
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Fe saturation =
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Fe / TIBC
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While `75% of patients with hereditary hemochromatosis present asymptomatically or with minimal symptoms, lab findings may include.....
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Elevated LFTs (ALT)
Elevated ferritin / Serum Fe Elevated Fe saturation Hepatomegaly |
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"Bronze diabetes" is a clinical feature of which disease?
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hereditary hemochromatosis
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The triad of cirrhosis + diabetes + skin pigmentation occurs late in which disease?
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hereditary hemochromatosis
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Do the symptoms of arthropathy in hereditary hemochromatosis respond to iron removal?
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no
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Can left ventricular dysfunction secondary to hereditary hemochromatosis be reversed?
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yes, by treating with phlebotomy
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What is the mechanism for hypogonadism in hereditary hemochromatosis and what are the clinical symptoms?
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iron deposition in the pituitary cells; decreased libido and impotence in men are the major symptoms in men; amenorrhea and infertility in women
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High transferrin saturation accompanied by an elevated ferritin level and a positive genetic test for mutations in HFE is likely to be diagnostic for....
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hereditary hemochromatosis
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An elevated transferrin saturation (iron/TIBC) as found in hereditary hemochromatosis is defined as (men and women):
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> 60% in men
> 50% in women |
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What is an "elevated" level of ferritin in the context of hereditary hemochromatosis? Is it specific for the disease?
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> 300 ug/L in men
> 200 ug/L in women elevated ferritin is nonspecific |
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What is the definitive test for iron overload in the context of liver disease?
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Hepatic Iron Content (HIC)
Hepatic Iron Index (HII) = HIC / age (HII > 1.9 is strongly suggestive of HHC) |
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What is first line therapy for hereditary hemochromatosis?
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phlebotomy
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Wilson's Disease is an autosomal (dominant/recessive) disorder of ______.
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autosomal recessive; copper metabolism
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Wilson's Disease stems from a genetic mutation in (name the gene) which encodes a copper-transporting ATPase.
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ATP7B
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Wilson's Disease most often affects (young/old) patients.
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Wilson's Disease most often affects (young) patients.
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Kayser-Fleischer Rings are a feature of which disease? What are they?
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Wilson's Disease; golden-brown pigment deposits around the periphery of the iris (note: they are difficult/impossible to see in a dark-eyed individual)
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How does Wilson's Disease present?
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chronic hepatitis or fulminant hepatic failure, hemolytic anemia, psychosis, seizures, childhood behavioral problems, renal abnormalities (hypercalciuria, nephrocalcinosis)
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What serological findings are characteristic of Wilson's Disease?
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low serum ceruloplasmin
high serum copper high urine copper low ALP + high T-BIL |
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What are the Sternlieb criteria for diagnosing Wilson's Disease?
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Kayser-Fleischer rings
Neuro symptoms Low serum ceruloplasmin |
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Is there a genetic test available for Wilson's Disease?
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NO
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What is the treatment for Wilson's Disease?
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copper chelation (D-penicillamine, trientine, zinc)
OR liver transplant for fulminant hepatic failure or decompensated cirrhosis |
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How does alpha-1 antitrypsin deficiency cause liver disease? Lung disease?
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Alpha-1 antitrypsin is synthesized in hepatocytes; a "deficiency" is actually an inability to secrete it from the cell; so in the liver this manifests as hepatocellular damage due to excess buildup; in the lung disease is due to elastase working unchecked by alpha1 antitrypsin
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Alpha-1 antitrypsin is an autosomal (recessive/dominant) disease due to a mutation in the gene on chromosome ______.
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Alpha-1 antitrypsin is an autosomal (recessive) disease due to a mutation in the gene on chromosome 14
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How is alpha1-antitrypsin deficiency diagnosed?
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blood test for alpha-1 antitrypsin level and phenotype (ZZ)
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How does apha-1 antitrypsin deficiency typically present?
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fatigue, signs of portal HTN (ascites or variceal bleeding), rarely pulm disease
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What is the therapy for alpha-1-antitrypsin deficiency?
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no specific therapy; treatment is guided by signs of portal htn
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In granulomatous hepatitis, elevations of which LFT is most common?
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ALP
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Which kind of hepatitis typically presents as a young patient with fatigue, jaundice, and pruritis, and generally exhibits a mixed hepatocellular-cholestatic pattern?
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granulomatous hepatitis
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What is on the differential for granulomatous hepatitis?
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infectious etiologies (TB), autoimmune (sarcoidosis), drugs (amiodarone, sulfonamides, nitrofurantion, allopurinol)
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What is the treatment for granulomatous hepatitis?
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steroids, azathioprine, ursodeoxycholic acid (bile acid that protects the liver)
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For which of these diseases does liver transplant cure a patient: Wilson's Disease, Alpha-1-antitrypsin deficiency, hemochromatosis?
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wilson't disease and alpha-1-antitrypsin deficiency
liver transplant does NOT cure hemochromatosis |
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38-year-old male with chronically elevated liver enzymes and ferritin levels in the 600-800 range presents for further evaluation. Liver biopsy with iron stain is above. What is the likely diagnosis?
|
Hemachromatosis
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Why is excess iron harmful?
|
Excess iron is harmful because it leads to the formation of damaging reactive oxygen metabolites that can injure cells and cause fibrosis
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What radiological study in particular is good at assessing liver iron content?
|
MRI - superparamagnetic property of iron leads to a darker appearance in organs containing excess iron, compared with organs that do not accumulate iron, such as spleen
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Ferritin levels are (more/less) sensitive than transferrin saturation in screening for hemochromatosis. Why is this?
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Ferritin levels are (less) sensitive than transferrin saturation in screening for hemochromatosis. This is because ferritin is an acute phase reactant and as such is elevated in many other conditions such as infection, inflammation, and liver disease unrelated to hemochromatosis
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Hereditary Hemochromatosis is diagnosed using _______. If this is inconclusive, what else can be done?
|
Hereditary Hemochromatosis is diagnosed using genetic tests. If genetic tests are inconclusive, a liver biopsy with quantitative determination of iron concentration is used.
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Excess iron storage as in hemochromatosis affects the liver and what other organs?
|
Primarily the heart and pancreas.
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In hemachromatosis, where is iron deposition initially located?
|
in the periportal hepatocytes of the liver
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What is the primary cause of death in patients with hemachromatosis?
|
hepatocellular carcinoma
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This patient was diagnosed with hemachromatosis. This liver biopsy from the patient was stained for iron. What are the two unstained nodules likely to be?
|
hepatocellular carcinoma
This is a close up of the cells in one of the nodlules: these cells are dividing too rapidly to accumulate iron Hepatocellular carcinoma is the #1 cause of death in hemochromatosis |
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In which organs can copper be deposited inWilson's Disease?
|
liver, kidney, brain, cornea, joints
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What is the key lab finding in Wilson's Disease? How can this measurement be falsely elevated/lowered?
|
low ceruloplasmin (<20 mg/dL)
Ceruloplasmin is an acute phase reactant so it can be elevated in states of inflammation, pregnancy, estrogen use, etc Falsely low ceruloplasmin levels may be seen in protein deficient states |
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A caveat to diagnosing Wilson's Disease: Copper is excreted in the _______ and for that reason it may be (elevated/lowered) in chronic cholestatic liver diseases.
|
A caveat to diagnosing Wilson's Disease: Copper is excreted in the bile and for that reason it may be (elevated) in chronic cholestatic liver diseases.
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|
27yo male with no previous history of liver disease presents with RUQ pain. Labs reveal a low ceruloplasmin level (16 mg/dL). Liver biopsy is above. What is the likely diagnosis?
|
Wilson's Disease - note the dense fibrous septa with chronic inflammatory infiltrate around the early regenerative nodules
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This is a liver biopsy treated with a copper stain from an asymptomatic patient with a low ceruloplasmin level (15mg/dL). What is the likely diagnosis?
|
Wilson's Disease
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Alpha-1-Antitrypsin is a _________.
|
serine proteinase inhibitor
|
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When alpha-1-antitrypsin is retained within hepatocytes as a result of misfolding secondary to genetic mutation, what is the result?
|
non-specific inflammatory changes leading to fibrosis and eventually cirrhosis of the liver
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What proportion of adults homozygous for the most severe phenotype (ZZ) of alpha-1-antitrypsin deficiency develop severe disease?
|
only 1/3
|
|
Name some of the ways that AAT-deficiency is diagnosed.
|
Measure serum ATT levels
Electrophoretic phenotyping Liver biopsy showing ATT globules in hepatocytes |
|
What stain is used to highly alpha-1-antitrypsin globules in hepatocytes?
|
PAS stain
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This is a liver biopsy (H&E stain) from a patient with elevated serum levels of alpha-1-antitrypsin. What are the clusters of red in the periportal area?
|
These are eosinophilc cytoplasmic inclusions of alpha-1-antitrypsin globules. This slide here is a PAS stain which highlights these inclusions.
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Granulomas are small nodular collections of activated _______ that may fuse to form ________; they are surrounded by a peripheral rim of ________
|
Granulomas are small nodular collections of activated epitheloid macrophages (histiocyte = tissue macrophage) that may fuse to form giant cells; they are surrounded by a peripheral rim of T-lymphocytes
|
|
What LFT is generally elevated in granulomas?
|
ALP
|
|
In sarcoidosis, angiotensin converting enzyme is typically (elevated/depressed).
|
In sarcoidosis, angiotensin converting enzyme is typically (elevated).
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This liver biopsy has been treated with AFB stain. What is the likely diagnosis?
|
This patient has TB.
|
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Clay-pipe stem fibrosis in the portal area is associated with.......
|
schistosomiasis
|
|
Hepatic schistosomiasis typically presents with......
|
hepatosplenomegaly
portal hypertension esophageal varices |
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Schistosomiasis is caused by.....
|
Schistosoma eggs trapped in tissues generate an immune reaction that, in longstanding disease, causes portal fibrosis and calcification (clay-pipe stem fibrosis)
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The intermediate host for schistosomiasis is the....
|
freshwater snail
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The dense fibrosis seen here around the portal areas is often characterized as having a clay-pipe stem appearance. What disease is this?
|
Schistosomiasis - these large structures in the portal area are the calcified remnants of schistosome eggs
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44yo AA woman presents with abnormal LFT's (cholestatic pattern), elevated ACE, and an enlarged liver.
This is her liver biopsy stained with trichrome. What is the diagnosis? |
sarcoidosis - note the confluent granulomas and fibrosis
|
|
Why do IV drug users often present with foreign body granulomas?
|
They are often injecting crushed talc-containing tablets and this talc causes granulomas
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Acute hepatitis is defined as.....
|
acute onset of liver inflammation with hepatocyte necrosis
|
|
Ballooning degeneration in the context of acute hepatitis refers to...
|
diffuse swelling of hepatocyte cytoplasm
|
|
Acidophil bodies are the result of....
|
cytotoxic T-cell mediated apoptosis of hepatocytes
|
|
What is interface hepatitis?
|
inflammatory infiltrate expands portal areas extending into adjacent lobular parenchyma with necrosis of hepatocytes at limiting plate
|
|
Contrast lab findings between self-limited and fulminant acute hepatitis.
|
In self-limiting hepatitis:
transaminases are moderately elevated bili is moderately elevated (rarely > 10mg/dL) ALP nl, PT nl, albumin nl In fulminant hepatitis: transaminases and bili are very elevated PT is prolonged Low albumin level Hypoglycemia Electrolyte abnormalities |
|
Do viruses typically cause fulminant acute hepatitis?
|
No, it is rare.
|
|
EBV Hepatitis is (more/less) common than HAV, HBV, HCV.
|
EBV Hepatitis is (more) common than HAV, HBV, HCV. (twice the incidence)
|
|
EBV is a _________ virus
|
lymphotrophic
|
|
What test is used to rule in/out EBV hepatitis?
|
monospot test
|
|
45yo female presents with moderately elevated transaminases but all other LFT's are normal. Monospot test is +. What is the diagnosis?
|
EBV hepatitis
|
|
Which cause of acute hepatitis is very common but difficult to diagnose because of lack of specific lab tests or clinical or histological features?
|
drugs
|
|
Chronic hepatitis is defined as....
|
the persistence of hepatitis for >6 months
|
|
The portal are on the left is normal. What kind of hepatitis is shown on the right?
|
interface hepatitis - note that the limiting plate is indistinct with numerous lymphocytes mediating hepatocyte injury
|
|
The histological finding above is suggestive of which disease?
|
Hepatitis B
|
|
HBV is what kind of virus?
|
partially double-stranded circular DNA virus
|
|
HCV is what kind of virus?
|
single stranded RNA virus with an RNA pol that has poor fidelity
|
|
Why does HCV typically circulate with multiple genotypes and subtypes?
|
HCV has an RNA pol that has very poor fidelity - several dozen mutant strains can be found in a single patient
|
|
Why is there no vaccine for HCV?
|
Two reasons:
1) HCV RNA pol replicates with poor fidelity, creating many mutant strains 2) E2 envelope protein of HCV is the ab target but is the most unstable part of the viral genome |
|
Serum transaminases are typically (high/low/fluctuating) in hepatitis C.
|
In HCV serum transaminases are fluctuating so a single measurement is not enough to rule out infection.
|
|
What type of hepatitis is this likely to be?
|
Autoimmune hepatitis (the presence of large numbers of plasma cells is suggestive of an autoimmune etiology)
|
|
What type of hepatitis is this likely to be?
|
Autoimmune hepatitis (the presence of large numbers of plasma cells is suggestive of an autoimmune etiology)
|
|
What are the three most important characteristic finding in autoimmune hepatitis?
|
1) plasma cell infiltration of the liver
2) autoimmune antibodies (ANA, SMA, etc) 3) marked hypergammaglobulinemia |
|
Is liver biopsy important in autoimmune hepatitis? Why or why not?
|
YES - used to confirm diagnosis, justify corticosteroid use, rule out other causes (eg viral)
|
|
Why is it so important to distinguish between hepatitis of a viral etiology and hepatitis of an autoimmune etiology?
|
treatment is entirely different: treatment for autoimmune hepatitis is corticosteroids, which can worsen viral infection; conversely, treatment of an autoimmune hepatitis with interferon can make the disease worse
|
|
Infiltration of the liver by eosinophils is suggestive of what kind of etiology of liver disease?
|
drugs
|
|
What is the diagnosis?
|
Hepatitis C - nodular lymphocytic aggregates in portal areas + patchy steatosis
|
|
What is the most common chronic bloodborn pathogen and leading indication for liver transplantation in the USA?
|
Hepatitis C
|
|
What is the major risk factor for Hepatitis C?
|
IVDA (70% of cases)
|
|
How do you test for Hepatitis C?
|
First test for anti-HCV ab's
Then test for HCV RNA (qualitative and quantitative PCR) |
|
What is the best way to predict likelihood of treatment response in Hepatitis C?
|
genotype
|
|
When is an HCV infection considered eradicated?
|
when there is SVR (Sustained Virologic Response, eg absence of HCV RNA in serum at end of treatment and 6 months later)
|
|
Which drugs are used to treat Hepatitis C?
|
Pegylated interferon and Ribavirin (nucleoside analog)
|
|
Interferons are produced by a wide variety of cells in response to ......
|
presence of double-stranded RNA, a key indicator of viral infection
|
|
What is the significance of pegylating interferon?
|
Pegylation is the addition of polyethylene glycol; this enhances its biologic activity and extends its half life; it also improves the pharmakinetics of interferon
|
|
What is ribavirin, how does it work, and what is it used to treat?
|
Ribavirin is a purine nucleoside analog that inhibits the replication of a wide range of RNA and DNA viruses. It is used to treat Hepatitis C (po) and severe viral pneumonia in infants/young children. The mechanism is not precisely understood.
|
|
What are the major side effects of interferon?
|
neuropsychiatric symptoms (depression)
flu-like symptoms bone marrow suppression NOTE: side effects are decreased in the pegylated version |
|
What are the major side effects of ribavirin?
|
anemia
itching skin rash nasal stuffiness/sinusitis birth defects (contraception is a must) |
|
What are the major HCV genotypes in the USA?
|
1a and 1b
|
|
What are some of the exclusionary factors for treatment of hepatitis C?
|
severe psychiatric illness
alcohol or substance abuse co-morbidities like renal disease decompensated cirrhosis organ transplant |
|
Chronic HBV infection is a well recognized risk factor for developing...
|
hepatocellular carcinoma
|
|
Infants from HBsAg positive mothers receive both the ______ and _______ vaccines.
|
HBV; HBIG (hepatitis B immune globulin)
|
|
Why are reverse transcriptase inhibitors effective at treating HBV even though HBV is a DNA virus?
|
HBV pol has reverse transcriptase and RNase H activity
|
|
HBV is what kind of virus? How does it replicate?
|
HBV is a hepadnavirus (DNA virus) that replicates by way of an RNA intermediate called the pregenome
|
|
What is the significance of the HBV pregenome replication cycle?
|
HBV, unlike other DNA viruses, uses a reverse transcriptase for replication that can be targeted in therapy
|
|
Lamivudine is used to treat ________ in some parts of the world, but not the US.
|
hepatitis B
|
|
Lamivudine:
1) Use 2) Mechanism 3) Resistance |
1) hepatitis B (not in USA)
2) incorporated into growing DNA chains resulting in premature chain termination 3) HBV mutations are the major concern with lamivudine |
|
Adefovir:
1) Use 2) Mechanism 3) Resistance |
1) hepatitis B
2) orally available pro-drug; : Inhibits both the reverse transcriptase and DNA polymerase and is incorporated into HBV DNA causing chain termination 3) occurs at slower rate compared to lamivudine |
|
Entecavir:
1) Use 2) Mechanism 3) Resistance |
1) Hepatitis B
2) inhibits HB at 3 different steps (priming of HBV DNA pol, RT from pregenome, synthesis of + strand HBV DNA) 3) rare |
|
Telbivudine:
1) Use 2) Mechanism 3) Resistance |
1) hepatitis B
2) L-nucleoside analog 3) high rate so has limited use as monotherapy (not used much) |
|
HBV resistance to Lamivudine and Adefovir most often stems from mutations in.....
|
reverse transcriptase
|
|
What are the two major goals of a drug used to treat HBV?
|
1) high potency
2) high genetic barrier |
|
Interferon has a particularly high (potency/genetic barrier).
|
Interferon has a particularly high (genetic barrier) to resistance because it upregulates the body's own immune response.
|
|
In treating HBV, you should begin treatment with a drug that has a high (genetic barrier / potency).
|
In treating HBV, you should begin treatment with a drug that has a high (genetic barrier).
|
|
Name the three drugs most often used to treat HBV.
|
Pegylated INF, adefovir, or entecavir
|
|
Which cells in particular undergo significant swelling in hepatic encephalopathy?
|
brain astrocytes
|
|
Brain uptake of ________ is significantly increased in acute and chronic liver failure.
|
ammonia
|
|
In brain astrocytes the metabolism of ammonia produces ________, which acts as an osmol and causes edema in astrocytes.
|
glutamine
|
|
Inhibiting the production of ammonia by reducing the intake of _______ and colonic cleansing are treatments for hepatic encephalopathy.
|
dietary protein
|
|
Lactulose is used to treat ______.
|
hepatic encaphalopathy
|
|
How does lactulose work in treating hepatic encephalopathy?
|
acidifies the gut leading to reduced uptake of ammonia
increases fecal excretion of nitrogen acts as a laxative |
|
Why is neomycin used to treat hepatic encephalopathy?
|
Neomycin is an antibiotic that reduces colonic bacterial populations and thus the amount of ammonia being produced.
|
|
Name some of the precipitating factors of HE that must be watched during treatment.
|
Dehydration
Electrolyte and acid/base imbalance Constipation Infection |
|
Clinically the most important collaterals in portal hypertension are _______.
|
gastro-esophageal varices (danger of hemorrhage)
|
|
Cirrhotics should be screened for varices using ........
|
endoscopy
|
|
Cirrhotics with moderate/large varices or small varices with severe liver dysfunction should be treated with the beta blocker _____. What is the mechanism of action?
|
propanolol; reduces portal pressure by unknown mechanism (postulated that it causes splanchnic vasodilation out of proportion to that in the systemic circulation)
|
|
________ is the drug of choice for treating acute variceal bleeding.
|
Octreotide (stable somatostatin agonist)
|
|
Both ______ and _______ have been shown to reduce hepatic venous pressure in cirrhotics by exerting a rapid and direct effect on smooth muscle and are superior to vasopressin therapy because _____.
|
Both somatostatin and octreotide have been shown to reduce hepatic venous pressure in cirrhotics by exerting a rapid and direct effect on smooth muscle and are superior to vasopressin therapy because they have far fewer side effects
|
|
Octreotide works by _________.
|
splanchnic vasoconstriction thus reducing portal blood flow
|
|
How is HAV transmitted and what is the peak age of infection?
|
From person to person via by way of close contact, food and water, and blood exposure (rare); peak age is in young adults
|
|
Which serological marker rises first in Hepatitis A?
|
serum ALT
|
|
Anti-HAV IgM begins to rise ________ month(s) post-exposure and peaks around ________ month(s) post-exposure.
|
Anti-HAV IgM begins to rise 1 month post-exposure and peaks around 3 months post-exposure.
|
|
By the time a person is infected with the HAV virus becomes symptomatic, he is most likely (shedding virus / not shedding virus).
|
NOT shedding virus; shedding occurs very early and the average incubation period for HAV is 30 days
|
|
HAV vaccine is now recommend between ages ____ and _____.
|
ages 1 and 2
|
|
Which groups of people are at increased risk of infection with HAV?
|
travelers to endemic countries
MSM IVDA People with chronic LD |
|
________ is currently driving the increase in HBV rates in the USA.
|
Immigration
|
|
What is the principal way that HBV is transmitted? What are the two other major modes of transmission?
|
sexually: HBV is essentially an STD
perenteral (eg IVDA) and perinatal (from mother to infant) are the two other major modes of transmission |
|
While most cases of HBV resolve in (adults / neonates), the majority of cases of HBV in (adults /neonates) become chronic infections.
|
While most cases of HBV resolve in (adults), the majority of cases of HBV in (neonates) become chronic infections.
|
|
Risk of chronic infection by HBV is highest in which population?
|
neonates
|
|
Which serological marker is the best index of current infection with HBV?
|
Hepatitis B surface antigen (HBsAg)
|
|
Which serological marker is the best index of resolution of an infection with HBV?
|
Hepatitis B surface antibody (Anti-HBs)
|
|
Which serological marker is the best index of past exposure to HBV?
|
Hepatitis B core antibody (HBcAg)
|
|
Which serological marker is the best index of HBV activity (replication)?
|
Hepatitis B e antigen (HBeAg)
|
|
Which serological marker is the best index of resolution of HBV activity (replication)?
|
Hepatitis B e antibody (Anti-HBe)
|
|
Which serological markers will be positive in acute hepatitis B?
|
HBsAg
Anti-HBc HBeAg HBV DNA |
|
Which serological markers will be positive in resolved hepatitis B?
|
Anti-HBs
Anti-HBc Anti-HBe |
|
Which serological markers will be positive in chronic hepatitis B?
|
HBsAg
Anti-HBc HBeAg HBV DNA |
|
Which serological markers will be positive in someone vaccinated against hepatitis B?
|
Anti-HBs
|
|
The so-called "window period" in the serology of infection with HBV lies between which two points? Which serological marker will be positive during the window period?
|
The window period is the period of time between the disappearance of HBsAg and the appearance of anti-HBs. The marker that will remain positive during this period is anti-HBc
|
|
In which populations should you screen for HBV?
|
people born in an endemic area
people with a family hx of HBV/HCC non-monogamous sexual practices hx of IVDA |
|
If you identify a carrier of HBV, what step as a medical provider should you take?
|
1) vaccinate susceptible household or sexual contacts
2) ascertain replicative status and need for therapy 3) screen for HCC in those at high risk (cirrhotics) |
|
What is the primary risk factor for contracting Hepatitis C
|
IVDA
|
|
While IVDA is the major mode of transmission of HCV, HCV is most prevalent in which population?
|
hemophiliacs; IVDAbusers are the population in which HCV is the second most prevalent
|
|
In contrast to HAV or even HBV, the majority HCV infections (resolve / become chronic infections).
|
In contrast to HAV or even HBV, the majority HCV infections (become chronic infections).
Only 15% of HCV infections resolve. |
|
In which patient populations should you absolutely screen for HCV?
|
anybody with an abnormal serum ALT
IVD users (even once) Anyone receiving a blood transfusion before 1992 Hemophiliacs |
|
What tests are available to confirm a diagnosis of HCV?
|
Anti-HCV
HCV Qualitative/Quantitative PCR Recombinant Immunoblot Assay (RIBA) |
|
What is the major drawback with testing for Anti-HCV as a means to diagnose HCV infection?
|
high false positive rate
|
|
What are the two main reasons for a false negative result in testing for anti-HCV?
|
patient may be in the window period prior to seroconversion
patient may be immunosuppressed (HIV, chemo, etc) |
|
How is the recombinant immunoblot assay (RIBA) used in diagnosing HCV infection?
|
It is used to resolve a possible false positive anti-HCV, particularly in low-risk groups
|
|
What is the treatment for Hepatitis C?
|
Pegylated INF + Ribavirin
|
|
Cryoglobulinemia is a common complication of _________. What are the symptoms?
|
HCV; small vessel vasculitis, purpura, arthralgias, weakness, peripheral neuropathy (50-90%), glomerulonephritis (30%)
|
|
Can hepatitis C be cured?
|
YES!
|
|
Name that clinical finding.
|
ascites
|
|
Name that clinical finding.
|
asterixis
|
|
Name that clinical finding.
|
caput medusae
|
|
Name that clinical finding.
|
palmar erythema
|
|
Name that clinical finding.
|
spider telangiectasia
|
|
What is the definition of portal hypertension? When do complications begin to arise?
|
Portal Hypertension = portal hepatic vein pressure (PHVG) > 5mm Hg
Complications arise when PHVG > 10-12mm Hg |
|
Ascites results from high _______ pressure, low _________ pressure, and overproduction of ________.
|
Ascites results from high hydrostatic pressure, low oncotic pressure, and overproduction of lymph
|
|
What is the primary cause of ascites?
|
chronic liver disease
|
|
What are the indications and contraindications for diagnostic paracentesis of ascites?
|
Indications: new onset ascites, clinical deterioration, fever, abdominal pain
Contraindications: NONE! |
|
What tests should be ordered on ascites fluid from a diagnostic paracentesis?
|
Cell count and differential
Maybe culture, albumin, total protein |
|
In cirrhosis, the Serum-Ascites Albumin Gradient (SAG) should be (low / high) indicating the protein content of the ascites is (low/high).
|
In cirrhosis, the Serum-Ascites Albumin Gradient (SAG) should be (high) indicating the protein content of the ascites is (low).
|
|
Generally, the higher the protein content of ascites, the (lower/higher) the SAG.
|
Generally, the higher the protein content of ascites, the (lower) the SAG.
|
|
The presence of > 250 PMN's in ascitic fluid is diagnostic of _________ and should be treated with _________.
|
The presence of > 250 PMN's in ascitic fluid is diagnostic of spontaneous bacterial peritonitis and should be treated with 3rd gen cephalosporins and albumin.
|
|
The majority of hepatic hydrothoraxes are (right-sided / left-sided /bilateral)
|
right sided (66%)
|
|
Initial therapy for ascites is.....
|
Na restriction
Diuretics (spironolactone +/- furosemide) Large volume paracentesis |
|
What is TIPS?
|
transjugular intrahepatic portosystemic shunt - treatment for refractory ascites
|
|
What are the indications for the TIPS procedure?
|
refractory ascites +/- hpeatic hydrothorax
variceal bleeding |
|
What is the most common complication of the TIPS procedure?
|
encephalopathy (20%-30%)
|
|
What is the prognosis for ascites?
|
5yr survival is 20% without transplant; with transplant it is more like 80%
|
|
What is hepatorenal syndrome? What is the mechanism?
|
renal failure in the setting of cirrhosis and portal hypertension when no other cause is identified; the mechanism is upregulation of the renin-angiotensin-aldosterone system in response to reduced blood volume
|
|
If you take a kidney out of someone with ascites and hepatorenal syndrome and put it into a healthy patient, will it work?
|
YES - hepatorenal syndrome isn't due to a structural or functional deficit in the kidney itself - syndrome is due to circulating factors
|
|
How do you treat hepatorenal syndrome?
|
restrict Na and H20
albumin (to establish circulatory volume) correct peripheral vasodilation (terlipressin, octreotide) dialysis/liver transplant? |
|
What aspect of a varice predicts the risk of it bleeding?
|
size
|
|
How are esophageal varices treated?
|
Secure ABC's
somatostatin or octreotide initially proton-pump inhibitors antiobiotics endoscopic ligation/banding |
|
What treatment is given to patients who have varices to keep them from bleeding?
|
beta-blockers
endoscopic ligation TIPS surgical shunts liver transplant |
|
Hepatic encephalopathy can be caused by __________ or ___________.
|
hepatic failure ("toxins" not metabolized by liver); portosystemic shunting ("toxins" shunted around liver)
|
|
Name so of the factors that can precipitate hepatic encephalopathy.
|
alcohol
infections (SBP) GI bleed medications (sedatives, diuretics) MI hepatocellular carcinoma surgery TIPS progression of underlying disease |
|
How do you treat hepatic encephalopathy?
|
identify & reverse underlying cause if possible
lactulose (traps ammonia in gut) antiobiotics (metronidazole, neomycin) diet (protein restriction) liver transplant |
|
A MELD score is used to determine....
|
liver transplant in the setting of liver disease
|
|
Acute renal failure where urine Na is low (<10 mEq/L) and CVP is elevated (>10 mm Hg) is likely to be...
|
hepatorenal syndrome
|
|
Cirrhosis (is / is not) reversible.
|
Cirrhosis (is not) reversible.
|
|
Diffuse hepatic fibrosis surrounding discrete round to oval regenerative nodules is the histological presentation of......
|
cirrhosis
|
|
Which cells undergo transformation to a fibrogenic phenotype in cirrhosis?
|
stellate cells
|
|
"Capillarization" or loss of endothelial fenestrations and subendothelial accumulation of collagen in the Space of Disse in cirrhosis has the effect of....
|
decreasing metabolic exchange between blood and hepatocytes
|
|
__________ and _________ stimulate stellate cells to develop a myofibroblastic phenotype in early cirrhosis.
|
Cytokines (TGF-B); growth factors (platelet-derived growth factor)
|
|
A low platelet count in cirrhosis is most likely indicative of.........
|
splenomegaly and splenic sequestration of platelets
|
|
Liver specimen, trichrome stain.
1) What disease process is this? 2) What are the round/oval nodules called? 3) Do we find normal portal areas within these nodules? |
1) cirrhosis
2) regenerative nodules 3) no normal portal areas within the regenerative nodules |
|
The larger nodule seen in this cirrhotic liver is likely to be....
|
hepatocellular carcinoma
|
|
Regenerative nodules in cirrhosis (do / do not) contain normal portal areas.
|
Regenerative nodules in cirrhosis (do not) contain normal portal areas.
|
|
What is the most common cancer of the liver? The second most common?
|
Most common: metastatic cancer (breast, colon, lung)
Second most common: hepatocellular carcinoma |
|
70yo male presents with facial flushing, occasional wheezing, and PMH of recently diagnosed carcinoid tumor of the ileum. Labs show elevated AST, ALT, and serotonin. Biopsy from the liver is above. What is the likely diagnosis?
|
metastatic carcinoid tumor
|
|
Elevated serotonin and flushing, wheezing, and diarrhea that is often precipitated by foods containing tyramine is suggestive of which liver neoplasia?
|
metastatic carcinoid tumor
|
|
In the Kasai procedure the _______ is transected and anastomosed to the __________.
|
In the Kasai procedure the jejunum is transected and anastomosed to the porta hepatis.
|
|
The major complication of the Kasai Procedure is......
|
bacterial cholangitis
|
|
The "puzzle piece" shape of residual liver parenchyma here is characteristic of......
|
biliary cirrhosis
|
|
What is the primary defect in Extrahepatic Biliary Atresia?
|
congenital absence or postnatal shrinkage of extrahepatic bile ducts leading to progressive portal fibrosis and biliary cirrhosis
|
|
What are the three broad categories of non-cirrhotic portal hypertension and an example within each category?
|
Prehepatic (splenic or portal vein thrombosis)
Intrahepatic (sarcoidosis, TB, etc) Posthepatic (Budd-Chiari syndrome) |
|
What is the most common complication of portal vein thrombosis?
|
hematemesis from varices
|
|
This histological liver specimen was taken from the liver (above) and portal vein (below) of a patient with esophageal varices. What is the likely cause of the varices?
|
Thrombosis of the portal vein. The dark pink area in the lower portion of the specimen is thrombus within the lumen of the portal vein. Note the focal recanalizations within the thrombus. Also note that the liver itself happens to be cirrhotic, but is probably not the cause of the portal hypertension
|
|
A 57-year-old Caucasian woman presents with a 1-2 weeks history of progressive shortness of breath, tense bulging abdomen with suggestion of liver enlargement (liver difficult to examine), lower extremity edema and chest pain. Liver biopsy above. What is the likely diagnosis?
|
amyloidosis (NOTE this image is H&E stain, NOT congo red)
|
|
In Budd-Chiari Syndrome, the _____ lobe often undergoes compensatory hypertrophy.
|
caudate
|
|
Centrilobular congestion with RBC-trabecular lesions is the common histological presentation of....
|
Budd-Chiari Syndrome (or any post-hepatic syndrome for that matter)
|
|
Centrilobular congestion with RBC-trabecular lesions secondary to hepatic venous outflow obstruction is the histological presentation of which disease?
|
Budd-Chiari Syndrome
|
|
Primary biliary cirrhosis primarily affects (men / women).
|
women (95% of cases)
|
|
Xanthelasma are deposits of ________ around the eyes and joints and is seen in ___________.
|
Xanthelasma are deposits of cholesterol around the eyes and joints and is seen in primary biliary cirrhosis.
|
|
What is Sjorgren's syndrome?
|
lack of mucus production leading to dry eyes and dry mouth
|
|
What three diseases must be on the differential for primary biliary cirrhosis?
|
1) autoimmune hepatitis
2) primary sclerosing cholangitis 3) extrahepatic biliary obstruction (gallstones, strictures, tumors) |
|
Elevated AMA (antimitochondrial antibody) is often useful in making a diagnosis of ..........
|
primary biliary cirrhosis
|
|
What procedure is of particular use in evaluating the presence and/or cause of primary biliary cirrhosis?
|
Endoscopic Retrograde Colangiopancreatogram (ERCP)
|
|
What are the major complications of primary biliary cirrhosis?
|
decreased bile acid in small bowel leading to fat malabsorption (weight loss, steatorrhea, fat-soluble vitamin deficiency)
portal hypertension (ascites, varices, encephalopathy) |
|
Which is the only FDA-approved drug for treating primary biliary cirrhosis? Are steroids indicated?
|
Ursodiol
|
|
Are steroids indicated in the treatment of primary biliary cirrhosis?
|
Steroids are NOT indicated because they may aggravate the osteoporosis
|
|
Primary Sclerosing Cholangitis is a slowly progressing disorder that results in obstruction and obliteration of the __________ and _________ biliary tree.
|
intrahepatic; extrahepatic
|
|
While primary biliary cirrhosis is primarily a disease of (men / women), primary sclerosing cholangitis is a disease of (men / women).
|
While primary biliary cirrhosis is primarily a disease of (women), primary sclerosing cholangitis is a disease of (men).
|
|
75% of people with primary sclerosing cholangitis also have _______.
|
ulcerative colitis (NOTE: only 5% of people with ulcerative colitis have PSC)
|
|
How will the following labs appear in a classic presentation of Primary Sclerosing Cholangitis?
ALP Bili Aminotransferases p-ANCA Gammaglobulins |
ALP - elevated
Bili - often elevated Aminotransferases - slightly elevated p-ANCA -elevated Gammaglobulins - elevated |
|
How is a diagnosis of Primary Sclerosing Cholangitis made?
|
Imaging: US not helpful; Cholangiography (mostly ERCP) is the gold standard
|
|
47yo male present with jaundice and pruritis. Labs show elevated ALP, bili, p-ANCA and hypergammaglobulinemia. ERCP image is above. What is the likely diagnosis?
|
Primary Sclerosing Cholangitis
|
|
Why is recurrent bacteremia a problem in Primary Sclerosing Cholangitis?
|
Bacteria love static fluid. In PSC there is obstruction of the intra- and extra-hepatic ducts leading to bile stasis
|
|
Acute decompensation in Primary Sclerosing Cholangitis often indicates the development of....
|
cholangiocarcinoma
|
|
How is Primary Sclerosing Cholangitis treated?
|
Treatment is largely ineffective and is limited to management of recurrent cholangitis with antibiotics
|
|
Chronic inflammation of the hepatic lobule with infiltration of lymphocytes and plasma cells is suggestive of...
|
autoimmune hepatitis
|
|
In Autoimmune Hepatitis, the lab presentation is primarily (cholestatic / hepatocellular).
|
In Autoimmune Hepatitis, the lab presentation is primarily (hepatocellular).
|
|
Autoimmune hepatitis with autoimmune cholangitis would present primarily (cholestatic / hepatocellular / mixed).
|
Autoimmune hepatitis with autoimmune cholangitis would present primarily (mixed).
|
|
Which of these labs will be positive in Type I Autoimmune Hepatitis?
ANA ASMA (anti-smooth muscle ab) Anti-LKM1 Anti-soluble liver antigen |
ANA (+)
ASMA (anti-smooth muscle ab) (+) |
|
Which of these labs will be positive in Type II Autoimmune Hepatitis?
ANA ASMA (anti-smooth muscle ab) Anti-LKM1 Anti-soluble liver antigen |
ANA
Anti-LKM1 (+) |
|
Which of these labs will be positive in Type III Autoimmune Hepatitis?
ANA ASMA (anti-smooth muscle ab) Anti-LKM1 Anti-soluble liver antigen |
ASMA (anti-smooth muscle ab) (+)
Anti-soluble liver antigen (+) |
|
How is Autoimmune Hepatitis treated?
|
Immunosuppression: prednisone, azathioprine
2nd line is cyclosporine, tacrolimus, MMF |
|
A benign liver cyst is (more/less) dense than liver tissue.
|
A benign liver cyst is (less) dense than liver tissue.
|
|
LFT's are typically (normal / abnormal) in the case of a simple liver cyst.
|
LFT's are typically (normal) in the case of a simple liver cyst.
|
|
LFT's are typically (normal / abnormal) in a liver hemangioma.
|
LFT's are typically (normal) in a liver hemangioma.
|
|
(MRI / CT / US / Technetium-labeled RBC) is the tool of choice for diagnosing benign liver hemangiomas.
|
(MRI) is the tool of choice for diagnosing benign liver hemangiomas.
|
|
A hemangioma of the liver has roughly the same density as the ________ in a CT scan.
|
A hemangioma of the liver has roughly the same density as the aorta in a CT scan.
|
|
On a routine CT scan a large mass is found in the R lobe of the patient's liver. All LFT's are normal and the patient reports no symptoms. Axial MRI shows a hypointense mass. When contrast dye is injected, it radiates inward towards the center of the mass. What is the likely diagnosis? How is it treated?
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hemangioma
No treatment is indicated unless there are symptoms of hemorrhage. Size is NOT an indication for surgery. |
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Focal Nodular Hyperplasia is more common in (men / women).
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Focal Nodular Hyperplasia is more common in (women).
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On a routine contrast CT of a 55yo female, a lesion in the right lower lobe of the patient's liver is found. What is the diagnosis? How is it treated?
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This is Focal Nodular Hyperplasia. Note the central scar in the lesion. We do nothing for these.
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In someone with Focal Nodular Hyperplasia, is malignant degeneration a concern.
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NO - Focal Nodular Hyperplasia does not become cancerous
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Which relatively benign lesion of the liver is typically unifocal, presents primarily in women, and is associated with oral contraceptives?
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hepatic adenoma
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How is a hepatic adenoma treated?
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STOP ESTROGENS (oral contraceptives) - should recede
surgery if large or there is no regression after cessation avoid pregnancy (elevated estrogen levels may cause it to grow and rupture) |
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A Klatskin tumor is a __________ located at the junction of the ______.
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A Klatskin tumor is a cholangiocarcinoma located at the junction of the R and L bile ducts.
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What are the five most common metastatic cancers in the liver?
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Colon
Breast Pancreas Lung Melanoma |
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80%-90% of cases of hepatocellular carcinoma occur in the presence of ______, ________, and _________.
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HBC, HCV, cirrhosis
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The 5 major risk factors for developing hepatocellular carcinoma are:
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cirrhosis
hep B hep C hemochromatosis alcoholic liver disease |
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Who do we screen for hepatocellular carcinoma?
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cirrhotics
patients with chronic hep B patients with hemochromatosis |
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What are some of the paraneoplastic manifestations of hepatocellular carcinoma?
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hypoglycemia
polycythemia hypercalcemia hypertrophic osteoarthropathy porphyria |
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What key lab value will typically be elevated in hepatocellular carcinoma?
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alpha-fetoprotein (AFP)
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What are some of the prognostic features of hepatocellular carcinoma and what are the treatment options?
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Prognostic:severity of LD, tumor size, multifocality, comorbidities, metastases
Treatment: resection, ablation, transplant |
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What is the best method for screening for hepatocellular carcinoma?
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AFP + ultrasound
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Why is percutaneous drainage of a benign liver cyst not curative?
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Cyst fluid is secreted by biliary-type epithelium lining the cyst
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What are some complications of a benign liver cyst that may warrant surgery?
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Cyst enlargement leading to compression atrophy of liver parenchyma
Intra-cystic bleeding Rupture Infection |
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Infantile polycystic liver disease is autosomal (recessive / dominant) while adult polycystic liver disease is autosomal (recessive / dominant).
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Infantile polycystic liver disease is autosomal (recessive) while adult polycystic liver disease is autosomal (dominant).
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A 44-year-old female underwent liver ultrasonography to rule out gallstones as the cause of abdominal discomfort. A solid, well-circumscribed mass was identified in the right lobe. Contrast-enhanced MRI showed large irregular nodule with central scar. What is this? What is likely to be found within the central scar?
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Focal Nodular Hyperplasia; large, tortuous blood vessels are present within the central scar
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Unlike an ademona, focal nodular hyperplasia contains _______ and there is no __________.
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Unlike an ademona, focal nodular hyperplasia contains bile ductules and there is no capsule
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Vessels like the one pictured above are common in which kind of benign epithelial tumor? Why are they referred to as "free floating?"
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Hepatic Adenoma
"Free floating" because they are not confined / supported by septal connective tissue |
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The most common causes of hepatic adenomas are......
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Steroid Treatment (estrogen and anabolic)
Type 1 glycogen storage disease |
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What causes liver lesions like the one pictured above?
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This is a hepatic adenoma (no portal areas or bile ducts) - benign
It is caused by: Steroid treatment (estrogen and anabolic) Type 1 glycogen storage disease |
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Discuss the pertinent aspects of these lab results. [NOTE: patient has palpable spleen]
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Decreased albumin and elevated PT and INR indicate loss of synthetic fxn
Low platelet count in combo with palpable spleen = splenic sequestration Elevated bili may suggest cholestatic picture AFP - only seen elevated in adults in the case of hepatocellular carcinoma Patient is Hep C positive |
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What is the typical precondition for developing hepatocellular carcinoma?
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chronically diseased and normally cirrhotic liver
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Most hepatocellular carcinomas secrete....
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alpha-fetoprotein (AFP)
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This histological specimen of a malignant lesion is most consistent with...
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hepatocellular carcinoma - almost always occurs secondary to a cirrhotic or chronically diseased liver
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This histological specimen was taken from a section of hepatocellular carcinoma. What is the darkly-stained structure in the center?
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Mallory Body
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In contrast with normal hepatocellular carcinoma, fibrolamellar HHC presents in non-cirrhotic liver in a (younger / older) age group, serum levels of _______ are usually normal, and survival rate is (lower / higher).
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In contrast with normal hepatocellular carcinoma, fibrolamellar HHC presents in non-cirrhotic liver in a (younger) age group, serum levels of AFP are usually normal, and survival rate is (higher).
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Alternating light and dark cells, absence of portal areas, and islands of erythropoeisis are characteristics of....
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hepatoblastoma
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Serum levels of AFP in hepatoblastoma are (normal / elevated / lowered).
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Serum levels of AFP in hepatoblastoma are (elevated).
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Hepatoblastoma preferentially occurs in what age group?
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children < 2yo
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What is the most common benign hepatic tumor?
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hemangioma
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Kasabach-Merritt syndrome (platelet sequestration and consumptive coagulopathy) is often associated with....
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hemangioma
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59yo female referred for RUQ pain. A CT scan shows a 5 x 3 x 3 cm subcapsular lesion in the right lobe of the liver. She continues to experience episodes of RUQ/right flank pain. Pain is not affected by deep breathing, but is sometimes worsened by body position, making it difficult to sleep on her right side. She has not had fever or chills. Histological specimen from resection above. What is the diagnosis?
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hemangioma
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What are some laboratory signs of alcohol abuse?
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"MILT"
M - elevated MCV (folate deficiency) I - elevated iron, amylase L - elevated liver enzymes T - elevated triglycerides |
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A fatty liver due to alcohol abuse is (reversible / irreversible).
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A fatty liver due to alcohol abuse is (reversible) with abstinence.
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In this histological liver specimen we see fat droplets distend hepatocyte cytoplasm in a centrilobular pattern without hepatocellular injury. This is known as....
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hepatic steatosis
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How severe is this steatohepatitis?
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this is MILD steatohepatitis
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What stage steatohepatitis is this?
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this is severe steatohepatitis
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What stage steatohepatitis is this?
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end stage
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What disease features large lipid droplets accumulate in hepatocyte cytoplasm but there is no collagen deposition, portal fibrosis, or inflammation.
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fatty liver (hepatic steatosis)
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In hepatic steatosis, the rupture of a fat-laden hepatocyte with macrophages engulfing the fat is called a ........
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lipogranuloma
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Name some of the diseases in which Mallory bodies are evident.
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Alcoholic Liver Disease
NASH Wilson's Disease PBC HCC |
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The darkly stained ropey eosinophilic material near the center of this picture is a ___________.
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Mallory body
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In alcoholic liver disease, early fibrosis is _____ and ________; later we see _______ fibrosis.
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In alcoholic liver disease, early fibrosis is centrilobular and perisinusoidal; later we see bridging portal fibrosis.
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What disease is this?
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Alcoholic Liver Disease
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Describe the mechanism of hepatic fibrosis in chronic alcohol abuse.
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Chronic alcohol abuse makes gut mucosa leaky to bacterial endotoxin; excess endotoxin in the portal circulation activates Kupffer cells, which release additional inflammatory cytokines that further stimulate stellate cell fibrogenesis
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NASH (Non-Alcoholic Steatohepatitis) is a diagnosis of ________ with a morphological appearance identical to _____________.
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NASH (Non-Alcoholic Steatohepatitis) is a diagnosis of exclusion with a morphological appearance identical to alcoholic steatohepatitis
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Lab studies (can / cannot) definitively establish a diagnosis of fatty liver.
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Lab studies (cannot) definitively establish a diagnosis of fatty liver.
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When fatty liver is suspect, an AST: ALT ratio > 2 suggests ________.
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alcohol use
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When fatty liver is suspect, an AST: ALT ratio < 1 suggests ________.
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NASH
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The only was to definitively diagnose NASH is by _________.
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liver biopsy
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_________ requires the presence of steatosis, lobular inflammation, ballooning degeneration and the presence of central sinusoidal fibrosis
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Non-alcoholic steatohepatitis (NASH)
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Hepatocytes take up unconjugated bilirubin, conjugate it with _______ using ________, then secrete it into the bile canaliculi.
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Hepatocytes take up unconjugated bilirubin, conjugate it with glucuronic acid using UDP, then secrete it into the bile canaliculi.
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In young adults, the most common cause of jaundice is _____ and the second most common cause is ________.
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In young adults, the most common cause of jaundice is viral hepatitis and the second most common cause is alcohol.
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In the elderly, the most common cause of jaundice is _____ and the second most common cause is ________.
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In the elderly, the most common cause of jaundice is malignancy and the second most common cause is drugs.
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95% of bile acids are reabsorbed in the ________.
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terminal ileum
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Cholelithiasis is....
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stones in the gallbladder
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Biliary colic is.....
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pain associated with irritation of the viscera secondary to cholecystitis and gallstones
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Choledocholithiasis is ....
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the presence of a gallstone or gallstones in the common bile duct
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Cholecystitis is....
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inflammation of the gallbladder (acute or chronic)
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Cholangitis is....
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infection or inflammation of the biliary tree
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Cholestasis is.....
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Defective excretion of bile from the liver with bile pigment in hepatocytes and inspissated bile plugging dilated canaliculi
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The majority of all gallstones are ....
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cholesterol stone
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Risk factors for gallstones are..........
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the 4 F's:
fat, fertile, female, forty |
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Black gallstones form from ________ while brown gallstone form from ______ and ________.
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Black gallstones form from calcium bilirubinate while brown gallstone form from calcium bilirubinate and free fatty acids.
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What is Charcot's triad?
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A triad of three symptoms (fever, RUQ pain, jaundice) that result from cholangitis secondary to an obstructed bile duct
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If the gallbladder doesn't appear on a radionucleotide scan, then the _______ must be obstructed.
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If the gallbladder doesn't appear on a radionucleotide scan, then the cystic duct must be obstructed.
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Ultrasound is both _______ and __________ for detecting cholelithiasis.
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Ultrasound is both sensitive and specific for detecting cholelithiasis.
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When assessing the a liver biopsy of viral hepatitis, they are scored according to stage and grade. What do "stage" and "grade" mean here?
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Stage - how much fibrosis
Grade - how much inflammation |
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Acute mechanical obstruction of the bile duct from an impacted stone or acute pancreatitis has what morphological features?
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Edematous expansion of portal area
Ductular proliferation Centrilobular cholestasis with bile-filled macrophages Zones of hepatocyte death from bile toxicity Ascending cholangitis |
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This is a histological specimen from a patient with acute mechanical obstruction of the common bile duct. What is morphologically occuring here?
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This is early ascending cholangitis as a result of the obstruction. We see:
Edematous expansion of the portal area Proliferating ductules at the limiting plate Interlobular bile duct infiltration by PMN's |
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This is a histological specimen from a patient with chronic mechanical obstruction with severe ascending cholangitis, biliary fibrosis and bile infarcts. What are some of the morphological abnormalities?
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Extensive biliary fibrosis (light patches)
Sheets of PMN's destroying a pus-filled duct (at center of light patches) Ruptured bile ducts with leakage causing hepatocyte necrosis (brown stains) |
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This cancer presents with symptoms of large duct obstruction. What is this?
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cholangiocarcinoma (bile duct carcinoma)
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The image above is from a MRCP. What is the diagnosis?
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sclerosing cholangitis
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These morphological changes are associated with which disease?
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sclerosing cholangitis (late stage)
|
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Which disease of the bile ducts is strongly associated with inflammatory bowel disease (especially ulcerative cholitis)?
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primary sclerosing cholangitis
|
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What is the only effective treatment for end-stage primary sclerosing cholangitis?
|
liver transplant
|
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Describe the lab findings in primary sclerosing cholangitis:
LFT's Globulins Others |
LFT's - GGT and ALP elevated, ALT and AST may be elevated or normal, bili is elevated in advanced disease, synthetic function becomes abnormal in advanced disease
Globulins - IgG and IgM are elevated p-ANCA is positive CA 19-9 (serum carb antigen) raises suspicion for cholangiocarcinoma |
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This is a bile duct from a patient suffering from early stage...
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Primary Biliary Cirrhosis: autoimmune attack on intrahepatic bile ducts by cytotoxic T-lymphocytes with progressive bile duct destruction
|
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What are the lab findings in Primary Biliary Cirrhosis?
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Elevated ALP, GGT
Elevated Bili AMA present Elevated IgM (variable) |
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Primary Biliary Cirrhosis affects the ________ bile ducts while Primary Sclerosing Cholangitis affects the ________ bile ducts.
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Primary Biliary Cirrhosis affects the interlobular (portal area) bile ducts while Primary Sclerosing Cholangitis affects the extrahepatic and/or intrahepatic (septal) bile ducts.
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The presence of foamy macrophages containing cholesterol in the tips of the villi of the gallbladder are diagnostic of....
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cholesterolosis
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A CT finding like the one pictured above is diagnostic for which disease? How does it occur?
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Porcelain Gallbladder: calcification of gallbladder wall after years of chronic inflammation
NOTE: increased risk for gallbladder cancer |
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What is the most common biliary tract malignancy? What are risk factors?
|
gallbladder carcinoma
porcelain gallbladder and chronic Salmonella infection of the gallbladder carry increased risk |
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What is the diagnosis?
|
Gallbladder carcinoma
|
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Cytotoxic T-cell mediated apoptosis of a hepatocyte produces a....
|
acidophil body
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