Liver Pathology Flashcards
What are the main functions of the liver?
Protein synthesis and coagulatory factors synthesis
When are AST and ALT released?
When there is injury or inflammation, they are released
In which other pathologies is serum lactate dehydrogenase released (LDH)?
In hemolytic anemia
What is hepatitis?
Inflammation of the liver, can be acute or chronic
What are the causes of hepatitis?
Hepatotropic viruses: A, B, C, D, E
What are the other causes of hepatitis?
Other viruses like EBV, CMV, and yellow fever
Autoimmune hepatitis
Drugs and toxins
What is the most common type of hepatitis?
Viral
What do hepatitis viruses cause?
Acute hepatitis that can progress to chronic
What does acute hepatitis usually present with?
Jaundice
Dark urine
Fever
Malaise
Nausea
Elevated liver enzymes (ALT> AST)
What causes the jaundice of viral hepatitis?
Both the conjugated and the unconjugated bilirubin
What does conjugated bilirubin indicate?
Problem with the biliary system
What does unconjugated bilirubin indicate?
Usually hemolytic anemia, especially in infants
When can chronic hepatitis progress into cirrhosis?
When the symptoms last over 6 months
What is the purpose of performing a biopsy exam?
Important for grading (inflammation) and staging (fibrosis) of the disease, which is then used to diagnose whether a patient needs antiviral treatments.
Why do doctors try to avoid performing a biopsy?
Because it is an invasive procedure, so unless it is a chronic case, doctors try to avoid it
What does HEV case in pregnancy?
Fulminant hepatitis
Which hepatitis virus kinds are considered to be acute?
Hepatitis A & E
What can HBV cause?
Acute hepatitis with joint pain and skin rash
What is the most common cause of chronic hepatitis?
Hepatitis C that can cause cryoglobulinemia
What is cryoglobulinemia?
When cryoglobulin is increased in the blood, abnormal proteins are elevated in the blood, and those proteins thicken in cold temperatures
What is a specific HDV characteristic?
HDV is dependent on HBV, superinfection is more severe than co-infection
What is the difference between co-infection and superinfection?
Co-infection: both infections occur at the same time
Superinfection: firstly infected with HBV and later on infected with HDV
What are the main clinical features of hepatitis?
Abdominal pain (caused by hepatomegaly, which is caused by inflammation)
Fever
Jaundice
What are the lymphocytes like in viral hepatitis?
Abnormal or enlarged from antigen stimulation
What are the pathological features of acute viral hepatitis?
Characterized by ballooning degeneration, apoptosis or lobular hepatitis
Portal infiltrate is minimal (T-lymphocytes)
What are the pathological features of acute viral hepatitis in severe cases?
Confluent or bridging necrosis with pan-lobular lymphocytic inflammation
What causes apoptosis in acute viral hepatitis?
Councilman body decrease triggered by cytotoxic T cells
Why is there pan-lobular inflammation in severe cases of acute viral hepatitis cases?
There are a lot of lymphocytes within the liver, so in severe cases, many of them are affected, leading to panlobular inflammation
What are the pathological features of chronic viral hepatitis?
The portal infiltrates are dense and prominent, also interface hepatitis and lobular hepatitis
Bridging necrosis and fibrosis
Ductular reactions
What is the hallmark of progressive chronic liver damage?
Bridging necrosis and fibrosis
Why is there fibrosis in the chronic viral hepatitis cases?
Infection will not be completely cleared, there will be some residue of chronic hepatitis
How do ductular reactions progress with the progression of chronic hepatitis?
Minimal in early stages of scarring but becomes extensive in late-stage disease
What does chronic viral hepatitis due to HCV show characteristically?
Portal tract expansion by a lymphoid cell forming lymphoid follicle
May show fatty change of scattered hepatocytes
Bile duct injury
What are the pathological features of HBV?
Ground-glass hepatocytes
Large, pale, finely granular cytoplasmic inclusions on H&E staining
What are ground glass hepatocytes and what causes them?
When you cannot see through the hepatocytes, caused by the accumulation of hepatitis B surface antigen
What does immunostaining confirm in HBV?
Presence of surface antigen (brown colour)
What are the different possible outcomes of hepatitis infection?
Subclinical
Acute hepatitis
Chronic hepatitis
Asymptomatic carrier
What is the definition of subclinical?
Not noticed during the infection period, but the patient has acquired antibodies
What are the possibilities of subclinical infection?
Recovery
What are the possible outcomes of acute hepatitis?
Recovery
Fulminant hepatitis –> Death or transplant
What are the possible outcomes of chronic hepatitis?
Recovery
Cirrhosis –> Hepatocellular carcinoma –> Death or Transplant
What is autoimmune hepatitis?
Autoimmune progressive hepatitis with genetic predisposition, associated with another auto-immune disease, with antibodies and response to immunosuppression therapy
What are the two types of autoimmune hepatitis?
Type 1: middle-aged women, antinuclear & anti-smooth muscle antibodies
Type 2: children & teenagers, anti-liver kidney microsomal & anti-liver cytosol antibodies
What happens if autoimmune hepatitis is not treated?
May follow indolent course, if untreated may cause liver failure or cirrhosis
What are the clinical and microscopical features of autoimmune hepatitis?
Share features of viral hepatitis, but plasma cells (unlike viral –> lymphocytes) predominate with hepatocyte rosettes
What are hepatocytes rosettes?
Hepatocytes that look like roses
What is the predictable drug and toxin-induced liver injury?
Acetaminophen, the toxic agent, is a toxic metabolite produced by the CYP450 system that causes acute liver failure that requires transplantation
What is the unpredictable (idiosyncratic) drug and toxin inducer liver injury?
Chlorpromazine, an agent that causes cholestasis in patients who are slow to metabolize it, and halothane and its derivatives can cause fatal immune-mediated hepatitis after repeated exposure
What is alcohol liver disease?
Damage to hepatic parenchyma due to consumption of alcohol
What is the progression of alcohol liver disease?
Alcohol fatty change –> Alcoholic or steatohepatitis –> Alcoholic steatofibrosis (cirrhosis)
What is fatty liver (steatosis)?
Accumulation of fat in hepatocytes (micro & macrovesicular steatosis)
What is the result of fatty liver?
Heavy, greasy liver
How is fatty liver disease resolved?
With abstinence
What is alcoholic steatohepatitis?
Characterized by hepatocellular damage seen as swelling of hepatocytes (ballooning) and necrosis
What is the result of alcoholic steatohepatitis?
Formation of Mallory-Denk bodies, acute inflammation due to netrophils
What is alcohol steatofibrosis?
Starts around the central vein, spread outwards in chicken wire fence pattern
What is the result of alcoholic steatofibrosis?
Central portal fibrous septa end by microvesicular cirrhosis
What are the lab results of Alcohol liver disease like?
Increase of GGT in serum
What are the macroscopic and microscopic findings of alcohol liver disease?
Macroscopic: larger liver with more pronounced steatosis
Microscopic: lipid accumulates in the hepatocytes as vacuoles, lipid droplet expanding the cell and displacing the nucleus
What are the symptoms of alcoholic steatohepatitis?
Minimal to severe: malaise, anorexia, weight loss, upper abdominal discomfort, tender hepatomegaly, and fever
What are the lab results like for alcoholic steatohepatitis?
Increase in direct bilirubin
Increase in liver enzymes (AST > ALT)
Increase in alkaline phosphatase and neutrophilic leukocytosis
Increase in PT and PTT
What are the results of a liver biopsy in alcohol steatohepatitis?
Intracytoplasmic Mallory-Denk bodies
What do Mallory-Denk bodies consist of?
Dense eosinophilic intracytoplasmic material (damaged cytokeratin filaments/intermediate filament)
What is non-alcoholic liver disease / non-alcoholic steatohepatitis?
Fatty change, steatohepatitis, and or cirrhosis that develop without exposure to alcohol
What is non-alcoholic liver disease associated with?
Metabolic syndromes
What are examples of the metabolic syndromes that are associated with non-alcoholic liver disease?
Obesity
Hyperlipidemia
Hypertriglyceridemia
DM
HTN
How is non-alcoholic liver disease diagnosed?
Diagnosis of exclusion; ALT> AST
What is the histological finding of non-alcoholic liver disease?
The same as alcoholic liver disease, steatosis, steatohepatitis and steatofibrosis
What is the definitive diagnosis of NASH?
A liver biopsy is not commonly done; a good history and physical examination will provide clues in most cases
What will an US and CT show in the case of NASH?
US: diffusely increased echogenicity
CT: diffusely decreased attenuation
What is cirrhosis?
End-stage liver damage characterized by disruption of the normal hepatic parenchyma by bands of fibrosis and regenerative nodules of hepatocytes
What is fibrosis mediated by?
TGF-β from stellate, which lies beneath the endothelial cells that line the sinusoids
What are the causes of cirrhosis? (8)
Chronic hep B and C
Autoimmune hepatitis
Drugs
Alcoholic liver disease
Non-alcoholic steatohepatitis
Metabolic disease
Biliary disease
Cryptogenic cirrhosis
What are the clinical features of cirrhosis?
Early stage: may be asymptomatic (compensated cirrhosis)
Later stage: non-specific symptoms and then symptoms related to portal hypertension, decreased detoxification and decreased protein synthesis
What are the complications of cirrhosis?
Liver failure or complicated by HCC
What is the role of fibrosis?
Disrupts vascular function, liver is going to be filled with new, generating cells in order to make up for the blood vessels that are daamged
What is the pathogenesis of cirrhosis?
Death of hepatocytes (by stellate cells; fibrosis)
Extracellular matrix deposition
Vascular reorganziation
What does the Kupfer cell activation during cirrhosis cause?
It leads to the secretion of multiple cytokines, which then activate the stellate cells and acquire a myofibroblastic state, a major source of collagen
Also, a major source of TNF released into system circulation
What is portal hypertesnion?
Absolute increase in portal venous pressure or increase in the pressure gradient between the portal vein and the IVC
What is considered an increase in the portal gradient?
6 mmHg or more
What are the consequence of portal hypertension? (5)
Ascites
Portosystemic venous shunts cause bleeding
Congestive splenomegaly/hypersplenism
Diminished liver function
Hepatic encephalopathy
Why is ascites a complication of portal hypertension?
Dilation of blood vessels, increased blood flow, an increase of aldosterone and renin
What kind of bleeding is caused as a consequence of portal hypertension?
Esophageal varices
Hemorrhoids
Caput medusae
What are the causes of portal hypertension?
Prehepatic (portal vein thrombosis)
Hepatic (cirrhosis, schistosomiasis)
Post hepatic (hepatic venous thrombosis, Budd Chiari syndrome)
What is hepatic encephalopathy?
Mental status changes, asterixis & flapping tremors, and eventually coma
What causes hepatic encephalopathy?
An increase in serum ammonia metabolic may be triggered by an increase in NH3 production, as in GIT bleeding, or decreased NH3 removal, as in renal failure
What are clinical signs of decreased detoxification and excretion?
Gynecomatia, testicular atrophy, spider angiomata and palmar erythema due to hyperstrinism in males and hypogonadism in females
Jaundice
What causes hepatorenal syndrome?
Decrease in GFR leading to decreased urine output & increase in blood urea nitrogen and creatinine
What are the effects of decreased synthesis?
Hypoalbuminemia with edema and ascites (controlled by hydrostatic and osmotic pressures)
What is coagulopathy, and what causes it?
Due to decreased synthesis of clotting factors –> bruising and bleeding & DIC
Also thrombocytopenia due to decrease thrombopoietin and sequestration by spleen
What are the lab results like in indication of liver function?
Increased PT
Decreased albumin
Increased bilirubin
What are the indications of liver injury
Increased ALT & AST
Increased alkaline phosphotase
Increased GGT
What are the prognostic factors in cirrhotic patients?
PT
Albumin levels
Increased bilirubin
What are the diagnostic exams for cirrhosis?
Liver biopsy
Lab findings
What are the lab findings of cirrhosis like?
Elevated bilirubin
Elevates enzymes (AST > ALT)
Thrombocytopenia
What are the microscopic findings of cirrhosis?
Regenerative nodules of hepatocytes are surrounded by fibrous connective tissue that bridges between portal tracts, within collagenous tissues, there are scattered lymphocytes and the proliferation of bile ducts
What is the stain used to highlight the fibrous/collagen tissue around the nodules?
Masson trichrome stain
What are the different metabolic diseases?
Primary hemochromatosis
α1 antitrypsin deficiency
Wilson disease
What is primary hemochromatosis?
Autosomal recessive
Accumulation of iron in the liver, pancreas, heart, pituitary gland & joints
What causes primary hemochromatosis?
Mutations in the HFE gene, which encodes a protein that influences intestinal iron uptake, iron will generate free radicals
What does primary hemochromatosis present with?
Cirrhosis, DM, bronze skin, cardiac arrhythmia, and gonadal dysfunction
What does hepatocellular iron appear like under Prussian stain?
Appears blue
What is α1 antitrypsin deficiency?
Autosomal recessive
Accumulation of α1AT protein increases elastase activity
What does α1 antitrypsin deficiency present like under microscope?
Round-oval cytoplasmic globular inclusions in hepatocytes that are strongly periodic acid-Schiff positive and diastase-resistant
What is Wilson disease?
Autosomal recessive
Caused by a mutation in metal iron transporter ATP7B
Hepatic copper accumulation –> free copper into the bloodstream & copper deposition into extrahepatic tissue
What is the role of ATP7B?
Without it, copper cannot be excreted into bile for elimination from the body
What are examples of extrahepatic tissue in which copper accumulates?
Basal ganglia
Cornea
What are the effects of Wilson’s disease?
Primarily affects the basal ganglia –> neurologic symptoms
Eye lesions called Kayser-Fleischer ring
What are the lab results like in Wilson disease?
Increased urinary copper
Decreased serum ceruplasmin
Increased liver copper
What is liver failure?
Most severe consequence of liver diseases
80 to 90% function of the liver is lost
What is the mortality rate of liver failure?
High if there is no liver transplant
In which three clinical scenarios does liver failure occur?
Acute liver failure
Chronic liver failure
Acute on chronic liver failure
What is another name acute liver failure is known by?
Fulminant liver failure
What causes acute liver failure?
Sudden and massive liver destruction
What is acute liver failure?
Liver disease that produces hepatic encephalopathy & coagulopathy within6 months of initial liver injury with no pre-existing liver disease
Fulminant if 2 after jaundice
What is the etiology of acute liver disease?
Ingestion of acetaminophen, autoimmune hepatitis, other drugs and toxins, acute Hep A, B and E
what are the gross findings of acute liver failure?
Massive hepatic necrosis, liver is small and shrunken due to loss of parenchyma
What is the histology of acute liver failure like?
Large zones of destruction surrounding occasional islands of regenerating hepatocytes
What are the clinical features of acute liver necrosis? (8)
Nausea
Vomiting
Jaundice
Fatigue
Onset of life-threatening encephalopathy
Coagulation defects
Portal hypertension with ascites
Hepatorenal syndrome
What happens to a patient if they do not receive a transplantation liver in acute liver failure?
They die
What are the serum transaminases levels in acute liver failure?
Increase initially and then decrease suddenly
What is Reye syndrome?
Fulminant liver failure with encephalopathy in children with viral infection who take aspirin
What is the pathogenesis of Reye syndrome?
Aspirin metabolites decrease β oxidation by reversible inhibition of mitochondrial enzymes
What are the clinical features of Reye syndrome?
Fatty liver, hepatomegaly, vomiting, hypoglycemia, coma and death
What is chronic liver failure usually associated with?
Cirrhosis
What is the etiology of Chronic Liver Disease?
Chronic Hep B and C, non-alcoholic fatty liver disease, alcoholic liver disease
What are the clinical features of chronic liver disease?
Same acute liver disease, but patients may also have severe chronic jaundice, hyperestrogenemia in males, hypogonadism in females, and portal hypertension
What can cause the severe chronic jaundice in chronic liver failure?
Pruritus that can be complicated by secondary bacterial infection
What is acute on chronic liver failure?
So individuals, after years of stable, well-compensated, chronic disease, suddenly develop signs of acute liver failure
What are the causes of acute on chronic liver disease?
HDV infection in those with chronic HBV
Resistance to medical therapy (viral hepatitis)
Ascending bacterial cholangitis in patients with primary sclerosing cholangitis
Sepsis, drugs, toxins, acute cardiac failure
Replacement of liver parenchyma by primary or metastatic carcinoma
What does imapired blood inflow cause, like portal vein obstruction, intra or extra hepatic thrombosis?
Esophageal varices
Splenomegaly
Intestinal congestion
What does impaired intrahepatic blood flow (cirrhosis and sinusoid occlusion) cause?
Ascites (cirrhosis)
Esophageal varices (cirrhosis)
Hepatomegaly
Elevated aminotransferases
What does hepatic vein outflow obstruction cause? (hepatic vein thrombosis, sinusoidal obstructive syndrome)
Ascites
Hepatomegaly
Abdominal pain
Elevated aminotransferases
Jaundice
What is sinusoidal obstruction syndrome?
Veno-occlusive disease due to consumption of pyrrolizidine alkaloid containing Jamaican bush tea, allogeneic hematopoietic stem cell transplant, a cancer patient receiving chemotherapy
What is Budd-Chiari syndrome?
Occurs when two or more major hepatic vein branches are obstructed due to a hypercoagulable state, Primar biliary cholangitis, HCC, postpartum and oral contraceptives
What are the clinical features of Budd-Chiari syndrome?
Hepatomegaly
Varices
Ascites
Abdominal pain
Liver failure with ABSENT JVD
What does liver biopsy show in Budd-Chiari syndrome?
Centrilobular congestion and fibrosis
