Liver path: autoimmune & metabolic Flashcards
Can autoimmune hepatitis be seen in pediatrics?
Yes
peak age is 40’s though
These two serologic markers for autoimmune hepatitis are more common in adults (type 1)
ANA (anti nuclear) and ASMA (anti smooth muscle)
These two serologic markers for autoimmune hepatitis are more common in pediatrics (type 2)
Anti-LKM (liver, kidney, muscle)
Anti-liver cytosol
pANCA, anti-actin, and anti-soluble liver Ag are less common/specific serologic markers for this condition
Autoimmune hepatitis
ANA and ASMA are serologic markers common in adults with this condition
Autoimmune hepatitis
Ant-LKM and Anti-liver cytosol are serologic markers common in children with this condition
Autoimmune hepatitis
In Autoimmune hepatitis, these cells are activated and cause fibrosis
Stellate cells
The majority of patients with Autoimmune hepatitis have this as their chief complent
Fatigue, malaise
Autoantibodies, elevated y-globulin, elevated IgG, normal IgA/IgM, +/- bilirubin / alk phos are laboratory findings of this condition
Autoimmune hepatitis
Interface hepatitis occurs when lymphs extend pass the limiting plate, and is seen in viral hepatitis as well as this condition
Autoimmune hepatitis
This type of morphology is when lymphs extend past limiting plate, and is seen in Autoimmune hepatitis and viral hepatitis
Interface hepatitis
Plasma cells in lymphocytic infiltrate is morphologically characteristic of this liver condition
Autoimmune hepatitis
In Autoimmune hepatitis, morphology will show this key cell type in lymphocytic infiltrate
Plasma cells
This condition is autoimmune destruction of small-medium size bile ducts
Primary biliary cholangitis
Does Primary biliary cholangitis occur in smaller or larger bile ducts?
Small-medium
Are males or females more likely to have Primary biliary cholangitis?
Females
This condition is characterized by T lymphocyte destruction of small bile ducts/ductules
Primary biliary cholangitis
In Primary biliary cholangitis, this cell type is involved in the destruction of small bile duct/ductules
T cells
In pathogenesis of this condition, T cells destroys small bile ducts, and bile salts are released into parenchyma
Result is hepatocyte injury, fibrosis and cirrhosis
Primary biliary cholangitis
In Primary biliary cholangitis, there is T cell destruction of small bile ducts, as well as the release of these into parenchyma
Bile salts
This is lymphocytic inflammation of duct and granulomas
Seen in Primary biliary cholangitis
Florid duct lesion
Florid duct lesion is lymphocytic inflammation of duct and granulomas, and is seen in this liver condition
Primary biliary cholangitis
Morphology of this condition will show expanded portal tracts with lymphocytes early, and then portal bile duct destruction and inflammation and necrosis that extend into parenchyma
Primary biliary cholangitis
“Jigsaw puzzle” pattern of cirrhosis is characteristic of this liver condition
Primary biliary cholangitis
In Primary biliary cholangitis, cirrhosis has this characteristic pattern
“Jigsaw puzzle”
Early manifestations of this liver condition are fatigue and pruritus
Xanthelasma, steatorrhea, RUQ pain also occur
Late manifestations include jaundice and splenomegaly
Primary biliary cholangitis
Is pruritus an early or late manifestation of Primary biliary cholangitis?
Early
In Primary biliary cholangitis, there can be abdominal pain in this quadrant
RUQ
This condition will have AMA (anti-mitochondrial antibody), alk phos, and AST/ALT values minimally elevated
Primary biliary cholangitis
In a patient with Primary biliary cholangitis, if AST/ALT is >3x normal, think of this syndrome
Overlap syndrome
(combination of autoimmune hepatitis and PBC)
Hyperbilirubinemia will occur late in pathology of this liver condition which is also characterized by AMA antibodies
Primary biliary cholangitis
This is chronic progressive destruction of larger bile ducts
Primary sclerosing cholangitis
Is Primary sclerosing cholangitis destruction of small or large bile ducts?
Larger
Does Primary sclerosing cholangitis primarily occur in men or women?
Men
Primary sclerosing cholangitis is strongly associated with this condition
Inflammatory bowel disease
Ulcerative colitis > Crohn’s disease
This liver condition is strongly associated with inflammatory bowel disease (esp. ulcerative colitis)
Primary sclerosing cholangitis
Does Primary sclerosing cholangitis have characteristic autoantibodies?
No
In Primary sclerosing cholangitis, these two cell types attack larger bile ducts and result in cholestasis (jaundice) and chronic irritation of biliary epithelium (neoplasia)
T cells and neutrophils
In this liver condition, cholestasis can occur (leading to juandice), as well as chronic irritation of biliary epithelium, which can cause neoplasia
Primary sclerosing cholangitis
Morphology of this liver condition will show concentric fibrosis and inflammation around ducts
“Onion skin” fibrosis
Primary sclerosing cholangitis
“Onion skin” fibrosis is characteristic of this liver condition
Primary sclerosing cholangitis
Lymphocytes and neutrophils in large bile duct epithelium are seen morphologically in this liver condition
Primary sclerosing cholangitis
Fibro-obliterative lesion (scar nodule at former site of duct) is seen in this liver condition
Primary sclerosing cholangitis
Beaded ductal system is seen morphologically in this liver condition
Primary sclerosing cholangitis
Asymptomatic alk phos elevated, or pruritus, jaundice, abdominal pain, and fever can indicate this liver condition
Primary sclerosing cholangitis
In this condition, cholangiography shows strictures of larger ducts
Primary sclerosing cholangitis
(pruning and beaded appearance to ducts)
What is the best test for diagnosis of Primary sclerosing cholangitis?
Cholangiography
which will show pruning and beaded appearance of ducts
Adenocarcinoma is a complication of this condition which has elevated alk phos, AST/ALT, conjugated bilirubin (depending on stage), and hyperglobulinemia
Primary sclerosing cholangitis
Primary sclerosing cholangitis can cause nutritional deficiency, specifically decrease in these vitamins
Fat soluble vitamins (A, D, E, K)
A patient with Primary sclerosing cholangitis who is now suddenly deteriorating (jaundice, weight loss, pain), may have this complication
Cholangiocarcinoma
Cholangiocarcinoma, pruritus, and cholelithiasis/cholecystitis are complications of this liver condition
Primary sclerosing cholangitis
Bile duct obstruction/destruction due to bile duct injury, such as surgical injury, infection, sarcoidosis, sickle cell
Secondary sclerosing cholangitis
Pathogenesis of this is hepatocellular dysfunction due to inflammatory mediators
Triad are not affected
Canalicular cholestasis
Cholestasis of sepsis
Is the portal triad affected in Cholestasis of sepsis?
No
Are canaliculi affected in Cholestasis of sepsis?
YES - canalicular cholestasis (bile accumulates in canaliculi in between hepatocytes)
Large duct obstruction has a risk of this condition, in which coliform bacteria extend from gut into biliary tree
Ascending cholangitis
This condition involving impaired flow has risk of ascending cholangitis and biliary cirrhosis (jigsaw pattern)
Cholestasis beginning at triad
Large duct obstruction
Is the portal triad affected in large duct obstruction?
Yes - cholestasis beginning at triad
Biliary infection due to obstruction
Ascending cholangitis
Ascending cholangitis is biliary infection due to this
Obstruction
(gallstones most commonly)
This is a set of symptoms associated with Ascending cholangitis, and includes fever/chills, RUQ pain, jaundice
Carcot triad
Carcot triad is fever/chills, RUQ pain, and jaundice, which is seen in this liver condition
Ascending cholangitis
What is the treatment for Ascending cholangitis?
Drainage and antibiotics
What is the carcot triad?
Fever/chills, RUQ pain, jaundice
Associated with Ascending cholangitis
This condition is excessive iron accumulation with deposition in target organs
Hemochromatosis
Hemochromatosis is excessive accumulation of this with deposition in target organs
Iron
In Hemochromatosis, iron deposits in these four organs
Liver, heart, pancreas, skin
What are the two categories of Hemochromatosis?
Hereditary and secondary
Iron is absorbed in this part of the body
Duodenum
Iron circulates bound to this
transferrin
If iron is not used, it is stored in the liver bound to this
Ferritin
This compound is the point of iron regulation, as it decreases intestinal absorption
Hepcidin
Iron is stored as this compound in the hepatocyte
Ferritin
What is the inheritance pattern of Hemochromatosis?
Autosomal recessive
This gene regulates iron absorption by regulating hepcidin
HFE gene
HFE gene regulates absorption of this compound by regulating hepcidin
Iron
HFE gene regulates iron absorption by regulating this compound
Hepcidin
This mutation is more common in Hereditary Hemochromatosis than H63D
C282Y
Mutation in HFE gene results in inappropriately low levels of this, despite elevated serum iron/ferritin
Hepcidin
Why does Hereditary Hemochromatosis have hepatocellular carcinoma risk?
Iron generates ROS, which is mutagenic
In Hereditary Hemochromatosis, this deposits in liver, pancreas, myocardium, joints
Hemosiderin
Is there inflammation in Hereditary Hemochromatosis?
No - iron is directly hepatotoxic
Hepatomegaly with cirrhosis, skin pigmentation, diabetes and cardiac deficiency can be seen clinically in this condition
Hereditary Hemochromatosis
Diabetes with tan skin can indicate this liver condition
Hereditary Hemochromatosis
Hepatomegaly with cirrhosis, and cardiac dysfunction, can indicate this condition
Hereditary Hemochromatosis
What is the treatment for Hereditary Hemochromatosis?
Phlebotomy or chelation
In Hereditary Hemochromatosis, are serum levels of iron and ferritin elevated or reduced?
Elevated
Condition of tissue copper deposition due to inability to excrete or transport copper
Wilson disease
What is the inheritance pattern of Wilson disease?
Autosomal recessive
In Wilson disease, copper deposits in these three regions of the body
Brain, liver, cornea
Copper is normally absorbed in this part of the body
Proximal small intestine
Circulated copper is incorporated into this compound
Ceruloplasmin
Copper is excreted into this
bile
Does Wilson disease present as acute or chronic liver failure?
Can be either
Liver failure with eventual cirrhosis, and basal ganglia atrophy (putamen especially) are seen in this condition
Wilson disease
Kayser-Fleischer rings in the eyes are seen in this condition
Wilson disease
(due to copper deposition)
Are ceruloplasmin levels increased or decreased in Wilson disease?
Decreased
Decreased serum ceruloplasmin are seen in this condition
Wilson disease
This is an inherited deficiency of WBC protease inhibitor
Alpha-1-antitrypsin deficiency
What is the inheritance pattern of Alpha-1-antitrypsin deficiency?
Autosomal recessive
Alpha-1-antitrypsin deficiency involves this chromosome
14
These are the three alleles on chromosome 14 that are involved in Alpha-1-antitrypsin
M = normal
S = slightly reduced
Z = markedly reduced
Patients with this deficiency may present with liver and/or pulmonary disease
Alpha-1-antitrypsin deficiency
This condition characterized by lack of anti-protease activity can present with emphysema and liver fibrosis/cirrhosis
Alpha-1-antitrypsin deficiency
In Alpha-1-antitrypsin deficiency, A1AT accumulates in this organelle of hepatocytes
Endoplasmic reticulum
Persistent neonatal jaundice is frequent in this condition involving emphysema at early age, hepatomegaly, and eventual cirrhosis and portal hypertension
Alpha-1-antitrypsin deficiency
Does Alpha-1-antitrypsin deficiency have a risk of malignancy?
yes - small risk of hepatocellular carcinoma
Is there treatment for Alpha-1-antitrypsin deficiency?
no
Are serum A1AT levels low or high in Alpha-1-antitrypsin deficiency?
Low
Morphology of this condition will have globular eosinophilic inclusions in periportal hepatocytes
Alpha-1-antitrypsin deficiency
In Alpha-1-antitrypsin deficiency, are globular eosinophilic inclusions seen in centrilobular or periportal hepatocytes?
Periportal
Inclusions seen in this liver condition are PAS positive
Alpha-1-antitrypsin deficiency
Inclusions in Alpha-1-antitrypsin deficiency are positive on this stain
PAS
Macronodular cirrhosis is seen morphologically in this deficiency
Alpha-1-antitrypsin deficiency
Statins can cause this liver condition
Cholestasis
Amanita can cause this liver condition
Hepatocellular injury
Most common drug induced liver injury
Acetaminophen overdose
Acetaminophen doses greater than this can cause liver injury
15g
A patient with anorexia, nausea, vomiting, and very highly elevated AST/ALT may have this liver injury
Acetaminophen overdose
AST/ALT elevations due to Acetaminophen overdose are seen this many hours later
48-72
In Acetaminophen overdose, Encephalopathy, coagulopathy, ascites, transaminases (AST/ALT) may fall with resolution of this
Necrosis
Do the majority of Acetaminophen overdose cases recover?
Yes
(but death after 4-10 days is possible)
Centrilobular coagulative necrosis is seen in this liver injury
Acetaminophen overdose
(centered on central vein)
Does acetaminophen overdose result in centrilobular or periportal coagulative necrosis?
Centrilobular (centered on central vein)
This condition causes >50% of all cirrhosis related deaths
Alcoholic liver disease
Are males or females more at risk in Alcoholic liver disease?
Females
(but men have higher rates)
This race is more at risk in Alcoholic liver disease
African
Alcohol dehydrogenase produces this compound, which disrupts cytoskeleton and mitochondria, induces fibrogenesis, and increases lipid production
Acetaldehyde
In Alcoholic liver disease, p450 induction produces this
Reactive oxygen species
(which cause lipid production, inflammation, cellular and mitochondrial damage)
Alcoholic liver disease leads to these 3 types of injury
Steatosis
Steatohepatitis
Cirrhosis
Is alcohol steatosis associated with inflammation?
No
Is alcohol steatosis reversible?
Yes
generally reversible and not fibrogenic
Is there cellular damage in alcohol steatosis?
No
(no mallory hyaline, no ballooning)
Is there cellular damage in alcoholic steatohepatitis?
Yes
and fibrogenesis
This type of injury in alcoholic liver disease may produce hepatomegaly
Steatohepatitis
The three morphologic features of this type of injury in alcoholic liver disease are fatty change, ballooning with mallory hyaline, and lobular inflammation
Steatohepatitis
Is there inflammation in alcoholic steatohepatitis?
yes
(Lipid accumulation together with inflammatory mediators)
In cirrhosis during alcoholic liver disease, ballooning degeneration and apoptosis result in hepatocyte death, then hepatocytes regenerate, and these cells produce fibrous tissue
Satellite cells
In cirrhosis from alcoholic liver disease, fibrosis begins in these structures
Sinusoids
(intrasinusoidal fibrosis)
Nonalcoholic steatosis/steatohepatitis (NASH or NAFLD) is associated with these three conditions
Diabetes, obesity, hyperlipidemia
Does steatohepatitis from alcoholic or nonalcoholic liver disease produce less mallory hyaline?
Nonalcoholic
Does steatohepatitis from alcoholic or nonalcoholic liver disease have AST:ALT >2 ?
Alcoholic
Does steatohepatitis from alcoholic or nonalcoholic liver disease have AST:ALT <2 ?
Nonalcoholic
