Liver Diseases Flashcards
Describe the histological features of ballooning degeneration
Swollen hepatocytes with large clear spaces in the cytoplasm
Describe the histological features of Feathery degeneration
accumulation of fat giving the swollen hepatocytes a foamy appearance; Clumping of intermediate filaments
Mallory Hyaline Is associated with which type of hepatic degeneration and condition
clumping of intermediate filaments characteristic of feathery degeneration
also known as alcoholic hyaline Because it is associated with chronic alcoholism
What other diseases are associated with feathery degeneration
Wilson’s disease and hemochromatosis;
what is the definition of steatosis
cytoplasmic accumulation of fat
Compare and contrast macro vesicular and microvascular stiatosis
macro: Nuclei are displaced by fat vacuoles
micro: fat droplets are finally distributed in the cytoplasm
What is steatohepatitis
steatosis w/ inflammatory cells
what is cholestatic hepititis?
cholestasis (billary stones) w/ inflammation
what are councilman bodies?
apoptotic hepatocytes
how is ischemic coagulative necrosis microscopically defined?
Preservation of cellular contours with disappearance of the nucleus
where can one find centrilobular necrosis
around the central vein
what are histological characteristics of confluent (massive) necrosis
Widespread perinechymal injury And degeneration of reticulum framework
What is zonal necrosis
Necrosis confined to a particular acinus zone
What is bridging necrosi
Necrosis static extends zonally from one lobby rule to another adjacent lobbyul
Describe the pathogenesis of hepatic fibrosis
Hepatitis Stellate cells are stimulated in response to inflammatory cytokines Produced by Kupffer cells
activated stellate cells undergo differentiation into myofiberblasts Stimulated by signals from PDGF receptor beta and cytokines TGF beta and IL17
50% of accidental and deliberate hepatic familiar is due to ingestion of what substance
acetaminophen
Acute liver illnesses associated with encephalopathy and coagulopathy occur how many weeks after the initial injury
WITHIN 26 weeks
What are the clinical presentations of acute hepatic failure
Elevated serum levels of liver trans anime’s; hepatomegaly; jaundice; pruritus;
Hyper ammonia anemia Is associated with what acute hepatic failure
hepatic encephalopathy
what are extra hepatic symptoms of hepatic encephalopathy
Rigidity, hyperflexia, cerebral edema, confusion
Coagulopathy induced to actue hepatic failure Can lead to what secondary complication
Disseminated intravascular coagulation
Serum levels of what plasma protein would you expect to be decreased In cases of acute hepatic failure
albuquin
what is Fetor hepatitis
Production of a musty body odor due due to the formation of mercaptans by GI bacterial metabolism of sulfur containing amino acids like methionine
Metabolism of what hormone is impaired in acute hepatic failure
estrogen
hepatic failure induced hypergastronemia leads to what extra hepatitis symptoms
palmar erythema, spider angioma, hypogonadism, & gyncecomastia in males
What are the histological features of acute hepatitis
Ballooning degeneration, colostasis, apoptosis, bridging necrosis, Kuffler’s cell hypertrophy
What is interface hepatitis
Infiltration of lymphocytes into the portal vessels
The histological characteristics of acute hepatitis
Lobular inflammation And a hepatocellular injury And bridging necrosis if severe
Describe the histological characteristics of chronic hepatitis
lymphocytic inflammation, fibrosis, regenerative hepatic nodules
What are the histological ham marks of chronic hepatitis C
Prominent lymphoid aggregates or even fully formed lymphoid follicles and porter tracks resulting in steatosis and bile duct injury
what are the histological hallmarks of chronic hepatitis b
swollen hepatocyte endoplasmic reticulums with a ground glass appearance
what is piecemeal necrosis
aka interface hepatitis is necrosis of the limiting plates by inflammatory cells
this is commonly seen in cases of chronic active hepatitis
Describe the gross characteristics of Hepatitis
Patches of pale yellow discoloration
What are the leading causes of chronic liver failure
alcoholic liver disease, Chronic hepatitis B, chronic hepatitis C and non alcoholic fatty liver disease
Describe the pathogenesis of cirrhosis
Chronic inflammation Of a liver will over time damage the reticulum framework and vascular architecture
The liver compensates by By forming fibrous caps around regenerative parent chimel nodules and bridging fibrous septi
vascular shunnting is also seen
Describe the gross characteristics of cirrhosis
Bumpy surface With depressed areas of scarring and bulging regenerative nodules
Define pre hepatic portal hypertension
Obstructive thrombosis and narrowing of the portal vein before it branches within the liver
define post hepatic portal hypertension
severe right sided heart failure, constructive pericarditis, and hepatic vein outflow obstruction
define intra hepatic portal hypertension
Most dominant cause is cirrhosis; other causes include massive fatty change, sarcoidosis, miliary tuberculosis; schistosomiasis
Describe the pathogenesis of cirrhosis induced portal hypertension
resistance to portal flow at the level of the sinusoids Due to myofibroblastic hyperplasia and scarring
body compensates By increasing blood flow into the portal system (arterial vasodilation) leading to increased Venus Eflux into the portal venous system
What are the four major consequences of cirrhosis induced portal hypertension
Asides; Portos Systemic Venus Shunts; congestive spenomegaly; hepatic encephalopathy
What are porto systemic shunts
Increased pressure in the portal circulation causes blood flow to be reversed
dilation of collateral vessels and develpment of then-walled venous shuts are created to bypass the liver
Where can porto systemic shents be found
Places where systemic and portal circulation share common capillary beds:
rectum
GE junction
falciform ligament of the liver
Porto systemic shunts in the rectum Leads to what secondary complication
hemorrhoids
Porto systemic shunts in the gastroesophageal junction leads to what secondary complication
Esophageal varices
describe the pathogenesis of esophageal varices
dilation of submucosal esophageal veins causes their errosion leading to GI hemorrhaging
Porter systemic shunts of the falcon form ligament of the liver causes what
caput meduae:
periumbilical and abdominal venous collaterals
splanchnic vasodilation induced from portal HTN decreases arterial pressure. This triggers release of what hormones.
ADH & Renin decrease renal perfusion and raise BP
what Affect does portal hypertension have on pulmonary circulation
Dilates intrapulmonary capillary vessels Resulting in a Right to left shunt through dilated vessels
this causes ventilation perfusion mismatch and hypoxemia
What lab findings are indicative of viral hepatitis
Hyperabilo rib anemia; ALT > AST
Which strain of viral hepatitis is usually self limited and does not cause chronic hepatitis in a immunocompetent individual
HEV
What strain of viral hepatitis Can only be activated in the presence of HBV
HDV
How is HAV transmitted
ingestion of contaminated food or water; outbreaks are typically assoc. w/ food handling in poor sanitatary conditions
All viral hepatitis strains are Positive single stranded RNA except for a rich strain
HBV: dsDNA
How is hepatitis B commonly transmitted
Bloodborne via sexual & subcutaneous routes
For suspected hepatitis B infection Would you order a blood or a stool culture
blood Cx
HBV is present in all bodily fluids EXCEPT FECES
What hepatitis B protein is implicated in the pathogenesis of HBV related hepatocellular carcinoma
Hepatitis BX protein
What HBV protein Persist after acute infection has subsided
hepatitis B surface antigens
Which patient population is the most high risk for acquiring chronic HBV hepatitis
Neonates and infants
Which HBV Ab wayne after acute infection has subsided
Anti-HBe
Which HBV antibody persists after acute infection has subsided
Anti-HBs
Which viral antigens become detected after HBsAg
HBeAg
HBV DNA
HBV DNA Polymerase
Which viral antigen can be detected Before symptoms occur for HBV
HBsAg
Persistence of HBV Antigens After 6 months indicates what
patient will likely become an infective chronic carrier
What HBV antibody will be positive in individuals who have never contracted hbv but have been vaccinated for it
Anti-HBs
Individuals that have had a previous infection of HBV we’ll test positive for what HBD antibodies
Anti-HBs & Anti-HBc
Patients with an active HBV infection Will test positive for what antibodies An antigens
HBsAg & Anti-HBc (IgM +)
Patients with chronic hepatitis b Will test positive for which antigens and antibodies
+ for everything EXCEPT Anti-HBs
+ Anti-HBc (IgG +)
Persistent detection of what HCV Antigen After four to six months indicates chronic hepatitis C
HCV RNA
Why has it been proven to be a challenge to develop a vaccine against HCV
HCV has genome instability and antigenic variability
Healthy HBV Carriers World Test positive for what antigens and antibodies
+ for HBsAg & anti-HBe]
- for HBeAg
Healthy hcv carriers will test positive for which antigens and antibodies
There is no such thing as a healthy carrier state for HCV
Which strains of viral hepatitis can incorporate their genome into the host genome
Only HBV has been shown to do this
Biliary obstruction increases the risk for what kind of Hepatitis
Bacterial hepatitis
Sepsis has what hepatic feature
bile plugs within hepatic ductules
What are other common causes of non viral infectious hepatitis
granulomas: mycobacteria & histoplasmosis
calcifications in the cyst walls is indicative of what
this describes the features of hydatid cysts which are caused by a tapeworm echinococcus infection
What are epidemiological risk factors for autoimmune hepatitis
Female sex; Northern European descent; Native American and Alaska native dissent;
What HLA alleles have been linked to autoimmune hepatitis
DR 3, DR4, DRB1
1 autoimmune hepatitis is positive for which antibodies
ANA; anti-SM abs
2 autoimmune hepatitis is more common in what patient population
children
Abs: LKM-1, ACL-1
What drugs are associated with autoimmune like hepatitis
minocycline, nitrofurantoin, methyldopa
Jaundice is usually preceded by what symptom of biliary dysfunction
sclearl icterus
Jaundice usually presents within what range of serum bilirubin
2-2.5 mg/dL
What hyperbil rub anemias are predominantly of the unconjugated type
Hemolytic anemias; pernicious anemia; thalassemia; hematomas & hemorrhages; Gilbert Syndrome; Jaundice of the newborn; Crigler-Najjar syndromes
What hyperbolo rub anemias are predominantly of the conjugated type
DJ & Rotor syndromes; cirrhosis, viral hepatitis; bile duct obstructions; autoimmune cholangiopathes
What is the pathogenesis of Gilbert’s syndrome & CN Type II
Mild deficiency of the udp gt; more so w/ CN type II than Gilbert’s
symptoms are relatively benign for both diseases
what is the pathogenesis of CN syndrome type one
Absence of the UDP GT; terminal without liver transplant; death by after 18 months of life by kernicterus
Why should you advise against breastfeeding for neonates with physiologic jaundice of the newborn
breast milk contains bilirubin deconjugating enzymes
How can physiologic jaundice of the newborn be treated
er therapy with blue light converts and conjugated bilirubin To the conjugated form which can be excreted in the urine
Hemolitic disease of the newborn can cause secondary unconjugated jaundice While the baby is still in utero. this can cause what bad complication
kernicterus
What is the pathogenesis of dj syndrome
mutaion of the MRP2 gene Needed for transport of non bile salt organic ions at the canalicular membranes
What is the pathogenesis of rotor syndrome
Multiple defects and hepatocellular uptake and excretion of bilirubin pigments
what are the clinical presentations of cholestasis
Pruritis; xanthomas; increased GGT & ALP; feathery degeneration; bile duct proliferation in portal tracts
What are the main causes of neonatal colostasis
Obstructive biliary diseases and extra hepatic biliary atresia
Alcohol metabolism leads to increases in NADH. increased levels of NADH can cause secondary increase of what metabolites
lactic acid; vldl; beta hydroxybutyric acid
Increase in VLDL is associated with what liver diseases
Fatty liver disease and hypertrichlyceridemia in peripheral blood
What is the pathogenesis of alcohol induced hypoglycemia
Since the body processed ethanol as a poison, use of NAD+ for alcohol detoxification takes precedence over the production of glucose which also requires NAD+
What are the histologic characteristics of a liver with alcoholism
Macrovocicular hepatic steatosis (accumulation of VLDL in the presecene of excess NADH)
How can alcohol induce hepatitis B distinguished from viral induced hepatitis
for alcohol liver: AST > ALT
for viral: ALT > AST
What metabolic effects Of alcohol make it a poison for the body
Cyp 2E1 metabolism of ethanol Produces ROS and a toxic metabolite: Acetaldehyde that encourages lipid peroxidation
inhibition of fatty acid oxidation (excessive NADH) depletes other metabolic pathways that require ATP:
impaired methionine metabolism decreases levels of glutathione sensitizing the liver to oxidative injury
What are the histologic characteristics of an alcoholic liver
ballooned hepatocytes with formation of Mallory Hyaline
Periendular fibrosis progresses to bridging fibrosis and then cirrhosis
Describe the pathological process by which Mallory bodies are formed
mallory bodies are aggregates of Cytoskeleton material and microtubules acetaldehyde renders microtubules dysfunctional leading to disruption in the cytoskeleton
What are the different stages of alcohol induced liver damage
hepatic steatosis: mild hyperbilirubinemia and elevation of ALP
Alcoholic hepatitis: hyperbilirubinemia, elevation of ALP < AST; neutrophilic leukocytosis
Alcoholic cirrhosis: all of the above + elevation of serum alkaline phosphatase, anemia, & hypoproteinemia
NASH/NAFLD is assoc. w/ what comorbidities?
obesity, type 2DM, hyperlipidemia, Chronic liver disease
Hemochromatosis can lead to long term complications
multi-organ failure due to iron deposits in liver, pancreases, myocardium, & skin
What is the pathogenesis of hereditary hemochromatosis
Most common: HFE gene mut. on Ch. 6 which regulates hepcidin synthesis
What role does hepsidden play in the metabolism of iron
degrades ferroportin when iron levels are too high to promote iron excretion through feces
Hemochromatosis increases the risk for what pancreatic dysfunction
diabetes mellitus due to destruction of islet cells caused by deposition of hemosiderin
What is the pathogenesis of Wilson disease
deficiency of ATP7B: transmembrane copper transporting ATPase expressed on hepatocyte canalicular membranes
In which organs does excess Cu aggregate in
Liver, eyes, and brain
What are the histologic characteristics of Wilson disease
Macro vesicular stiatosis, Mallory bodies, Perry sinusoidal fibrosis which can progress to cirrhosis
where in the brain does copper
aggregate basal nucleus especially the putamen
why eye lesion is assoc. w/ Wilson disease
Kayser-Fleisscher rings: green-brown deposits in the membrane surrounding the cornea
Describe the hepatotoxic process of excess copper
Excess copper in hepatocytes binds to sulfhydral groups A cellular proteins and displaces other metals That are cofactors for Metallo Enzymes in the liver
What lab findings would indicate Wilson disease
decreased serum ceruloplasmin; transferrin equivalent for copper transportation
What are the hepatic complications of alpha 1 antitrypsin deficiency
newborns: neonatal hepatitis w/ cholestatic jaundice
adults: chronic hepatitis, cirrhosis, & hepatocellular carcinoma
What is the pathogenesis of alpha 1 antitrypsin deficiency
mutant polypeptide resulting in misfolds and aggregates; gene loctated on ch. 14: mutanat PiZZ protein
What is the function of alpha 1 antitryption
protease inhibitor that inhibits elastase released from neutrophils at sites of inflammation
what is another term for primary biliary cirrhosis
cholangitis
90 to 95% of cases of primary cholangitis Involves what underlying pathological mechanism
Cell-mediated autoimmune rxn. antimitochondrial antibodies against the E-2 component of pyruvate dehydrogenase complex
Patients with these autoimmune diseases Or at an increased risk of developing primary biliary cirrhosis or colonitis
sojourn syndrome, systemic sclerosis, rheumatoid arthritis, renod phenomenon, celiac disease
what are secondary causes of choangitis
retention of biosaults due to a bio duct injury
What are the epidemiological factors of primary colonitis
Female to male ratio is 9 to 1; Middle aged Caucasians of Northern European descent that are 40 to 50 years of age
What are the clinical manifestations of primary biliary cirrhosis
Pruritus; hypercholesterolemia; splenomegaly and jaundice; XANTHELASMAS; steatorrhea, vit. D. malabsorption
What is the diagnostic criteria for primary biliary cirrhosis
Elevated alkaline phosphatase for more than six months; positive tests for antimitochondrial antibodies; characteristic histologic bindings
what are the histological hallmarks of primary biliary cirrhosis
Hypertrophic portal tract With evidence of interface hepatitis
bile ducts Contain Granulomas
destruction of intrahepatic bile ducts
What is the pathogenesis of primary sclerosing cholangitis
Thought to be cell mediated Auto antibodies against The walls of the bile ducts
What diseases are associated with primary sclerosing Colangitis
inflammatory bowel diseases such as ulcerative colitis
what are the three symptoms of chargots triad
jaundice, fever, right upper quadrant pain
What are the characteristics of primary sclerosis colangitis
irregular biliary strictures and dilations
what substance can be given for management of primary biliary cirrhosis
Ursirioxycolic acid
Auto antibodies can you expect to find in a patient with primary sclerosis and cholanginitis
pANCA
What is a histological hallmark of primary sclerosing conangitis
circumferential onion skin fibrosis around Atrophic duct lumen
What happens after the onion skin lesions disappear
Duct disappears on leaves behind a solid corlake fiber scar
What is another term for hepatic vein thrombosis
Budd-Chiari syndrome
Vascular disorders associated with intrahepatic obstruction are associated with what clinical presentations
asides and hepatomegaly
What organomegally will occur if there is potal vein obstruction
Splenomegaly
what Vascular disorder of the liver will cause jaundice
hepatic vein outflow obstruction
Diseases are associated with hepatic vein thribosis
Myloproliferative disorders; anti phospholipid syndrome; Coagulation disorders
What kind of necrosis would you expect to find for hepatic vein thrombosis
central lobular congestion
Comparing contrast that different histological features of deliver for right sided cart failure and left sided heart failure
Left sided heart failure: hypoprofusion and hypoxia at the liver around central veins causes central lobular hemorrhagic necrosis giving the liver a nutmeg like appearance
Right sided heart failure:
Hepatic congestion causes dilation of this central lobular sinusoid and sefusion of blood through this central obular region
atrophied hepatocytes
What is the pathogenesis of sinusoidal obstruction syndrome
Obliteration of hepatic venules leads to Sub endothelial swelling and formation of collagen; Microscopically you would see perivinylar fibrosis in the pericyma
What are the epidemiological factors of focal nodular hyperplasia
Young to middle aged females; benign, non-neoplastic
What are the gross characteristics of FNH
White stellate shaped scar That is well demarited
What is the most common benign liver tumor
Cavernous Hemangioma
What are the gross characteristics of cavernous hemangioma
Red blue soft nodule usually less than two centimeters located in the sub capsular layer
microscopically what would you expect to see for cavernous hemangioma
dilated thin walled vascular channels
hepatic adenoma has a strong correlation with chronic use of what drug class
Oral contraceptives
A 30 year old woman at 30 weeks gestation Presents to your clinic with an abrupt onset of severe intraperitoneal hemorrhaging. What is the most likely culprit
Rupture of a sub capsular hepatic adenoma
Inflammatory hepatocellular adenoma It’s commonly associated with what comorbidities
more common in women; assoc. w/ obesity and metabolic syndrome
What is the pathogenesis of inflammatory hepatocellular adenoma
Sporadic mutations of glycoprotein 130; this activates the JAK-STAT Pathway
What are common associations That had been correlated with beta-catenin-activated hepatocellular adenoma
Oral contraceptive use and anabolic steroids of men
What is the pathogenesis of beta cantonon activated hepatocellular adenoma
Activating mutations in B the-batenin gene (CTNNB1) And other components of the WNT pathway (such as APC)
What is the pathogenesis of HNF1alpha inactivated hepatcellular adenoma
Mutations in the H and F1 alpha gene
What is the most common malignant liver tumor in pediatric patients
hepatoblastoma
What is the pathogenesis of hepatoblastoma
pathological activation of the wnt pathway; most common symptom is abdominal swelling and jaundice
Metastatic nodules elevate serum levels of what
Alkaline phosphatase
Why is hyper bilirubinemia And elevated transamines levels not typically present for cancers that metastasize to the liver
not all of the bile ducts get obstructed by nodules
assessment of serum levels of what liver enzymes Indicates a liver disease
AST & ALT
Assessment of zero levels of what liver enzymes indicate a hepatobiliary disease
ALP & GGT
Marked elevations of amino transferase levels are indicative of what kind of liver disease
acute liver disease
mild elevation of AST is highly suggestive of what
Alcohol induced liver injury
Decrease serum levels of amino transfer raises indicates What kind of liver disease
chronic Liver diseases such as chronic viral hepatitis and cirrhosis
What subtype of hepatic adenoma has a very high risk for malignant transformation to hepatocellular carcinoma
B-catenin-activated hepatocellular adenoma
What strains of hepatitis are associated with hepatocellular carcinoma
HBV
HCV
Elevated serum levels of alpha fetoprotein In adults is highly correlated with what
onset and progression to HCC
What subtype of hepatocellular carcinoma Is seen in adolescence and young adults without preexisting liver diseases
Fibrolamellar histologic subtype
What are the histological characteristics of fibro lamellar Hcc
Nests and chords of malignant oncocytic hepatocytes that are separated by dense bundles of collagen
A list of liver diseases that have strong correlations with hepatocellular carcinoma
chronic viral hepatitis
chronic alcoholism
hereditary hemochromatosis
alpha-1 antitrypsin deficiency
NAFLD
What are the histological features of HCC
Well differentiated hepatocytes with thicker cell plates
Absent reticulum framework
trabecular (sinusoidal) pattern consistant w/ non-neoplastic liver parenchyma
cholangiocarcinoma is derived from what type of cells
Intrahepatic bile duct cells
Biliary Adenocarcinoma is arrived from what cell types
Extra hepatic bile duct cells
Intra-hepatic colangiocarcinoma is not associated with what liver disease
cirrhosis
Cholangiocarcinoma is commonly assoc. w/ what mutatoin
KRAS mutations
what is a Klatskin tumor?
Extra hepatic biliary adenocarcinoma Located at the junction of the right and left hepatic ducks
What are the histological characteristics of colangiocarcinoma
Abundant fibrous stoma w/ lymphovascular infiltration and tubular structures Lined by cubodial and columnar epithelial cells
Describe the histological features of the gallbladder
mucosa is a Single layer of columnar epithelial cells
Vessels of nerve sit in the subserosal fat layer
No musculars or submucosa
Neck of gallbladder consists of spiral valves of Heister which extend into the cystic ducts
