Essentials: Liver Pathology (Summary Slides) Flashcards
Microvesicular steatosis (definition)
Accumulation of numerous small lipid droplets in hepatocytes (liver cells).
Pathogenesis: Microvesicular steatosis is associated with 3 conditions/etiologies
- Acute fatty liver of pregnancy (AFLP)
- Reye’s syndrome
- Drugs (aspirin)
How dangerous is microvesicular steatosis?
Acute liver failure is common with this condition! This is a life-threatening condition (emergency)!
Macrovesicular steatosis (definition)
Accumulation of large fat vacuoles in hepatocytes (liver cells)
Pathogenesis: Macrovesicular steatosis is associated with 4 main etiologies
- Alcohol abuse
- Obesity
- Drug abuse
- Type II diabetes & hyperlipidemia
Alson seen in hepatitis C
Macrovesicular steatosis can progress to…
steatohepatitis (if inflammation and liver injury develop)
Steatohepatitis (definition)
fat buildup in the liver that leads to inflammation of the liver.
3 types of steatohepatitis
Alcohol
ASH: Acoholic steatohepatitis
Metabolic syndromes:
NASH: Non-alcoholic steatohepatitis
Alcoholic and non-alcoholic steatohepatitis: macroscopic appearance
Pale, greasy & enlarged liver
Alcoholic and non-alcoholic steatohepatitis: key histologic features (3)
- Injured hepatocytes (balloon cells)
- Mallory-Denk bodies
- Chicken wire fibrosis
- Inflammation! (lymphocytes, neutrophils)
Non-alcoholic fatty liver disease (NAFLD) (definition)
NAFLD is a spectrum of liver disease (metabolic syndrome) that includes NASH (non-alcoholic steatohepatitis)
Autoimmune Hepatitis (definition)
Chronic liver disease characterized by immune-mediated hepatocyte damage.
3 key histologic features of autoimmune hepatitis
- Interface hepatitis (inflammation at the junction of the portal tracts and hepatic lobules)
- Plasma cell infiltration
- Rosetting of liver cells (hepatocytes form flower-like pattern)
How do we treat autoimmune hepatitis?
Autoimmune hepatitis responds very well to STEROIDS.
Autoimmune hepatitis is more common in…
more common in (Caucasian) women than men
3 auto-antibodies present in autoimmune hepatitis
ANA
SMA
Anti-LKM1
Primary biliary cholangitis (PBC) (definition)
Autoimmune attack on intra-hepatic bile ducts causing inflammation.
Key histological feature of primary biliary cholangitis (PBC)
Florid duct lesions with granulomas (around the intra-hepatic bile ducts)
Antibody that is a hallmark of primary biliary cholangitis (PBC)
AMA
(presence of AMA is highly specific for PBC)
Primary biliary cholangitis is most commonly seen in…
middle-aged females (50s)
3 main symptoms of primary biliary cholangitis
- Fatigue
- Pruritus (itching)
- Jaundice
Key histological feature of primary sclerosing cholangitis (PSC)
Onion skin fibrosis
Primary sclerosing cholangitis (definition)
Chronic liver disease that causes inflammation and scarring of the bile ducts
Which type of cholangitis affects both intra and extra hepatic ducts
Primary sclerosing cholangitis
Primary sclerosing cholangitis usually affects…
young males (30s)
How do we confirm primary sclerosing cholangitis (PSC)?
By identifying fibrosis and structuring of medium-large bile ducts on ERCP or MRCP
70% of patients with primary sclerosing cholangitis (PSC) also have…
ulcerative colitis (IBD)
Patients with primary sclerosing cholangitis (PSC) are at risk of…
cholangiocarcinoma
Hereditary hemochromatosis (definition)
Genetic disorder (homozygous recessive) that causes the body to store too much iron in organs and tissues (iron overload disease).
Iron depositis in the liver, pancreas, skin (bronzed colour), etc.
Most common gene mutation causing hereditary hemochromatosis
HFE gene mutations (C282Y)
Form of diabetes caused by hereditary hematochromatosis
“Bronzed” diabetes
How does hereditary hematochromatosis affect the liver and heart?
Liver: cirrhosis
Heart: cardiomyopathies
If a patient develops liver cirrhosis secondary to hereditary hemochromatosis, they are at very high risk of developing…
hepatocellular carcinoma
How do we treat hereditary hemochromatosis?
Phlebotomy (draw blood)
Screen the patient’s family!
Alpha-1 antitrypsin deficiency (definition)
Autosomal recessive genetic disorder causing decreased levels of alpha-1 antitrypsin (a protein which normally protects the liver and lungs from damage).
Key histologic feature of alpha-1 antitrypsin deficiency
Hyaline globules within zone 1 hepatocytes, representing misfolded alpha-1 antitrypsin protein aggregates.
Visualized using the PAS-diastase stain!!!
What is alpha-1 antitrypsin
An anti-protease
What is a common genotype of alpha-1 antitrypsin deficiency? Describe it
PiZZ (abnormally folded alpha-1 antitrypsin protein cannot migrate from organelles and cannot exit the cytoplasm, so it accumulates in liver cells)
What is the #1 genetic cause of pediatric liver disease (hepatitis)?
Alpha-1 antitrypsin deficiency
How can alpha-1 antitrypsin deficiency affect the lungs?
It can cause emphysema
Wilson’s disease (definition)
Autosomal recessive genetic disorder characterized by the excess buildup of copper in the body.
What mutation causes Wilson’s disease? Explain.
Mutations in ATPB7 gene (the enzyme that normally incorporates copper into ceruloplasmin and excretes copper into bile).
How does Wilson’s disease affect the liver?
Copper overload in the liver leads to cirrhosis and acute liver failure/necrosis.
Key histological feature of Wilson’s disease?
Copper in zone 1 hepatocytes
How can Wilson’s disease affect the eyes?
Causes Kayser-Fleischer ings in the cornea
Budd Chiari syndrome (definition)
Vascular disease causing impaired blood flow OUT from the liver due to THROMBOSIS of major hepatic veins!!
What blood vessels are affected by budd-chiari syndrome?
Outflow veins: central veins/IVC
Budd-chiari syndrome usually affects…
women (30s)
2 common causes of budd-chiari syndrome
Polycythemia rubra vera (rare blood cancer that causes the body to produce too many red blood cells, which thickens the blood and can lead to blood clots)
Drugs
Drug-induced liver injury: What is the #1 drug that can cause liver toxicity?
Acetaminophen (#1 cause of fulminant hepatic failure)
1 cause of fulminant hepatic failure
Acetaminophen (drug toxicity)
How does acetaminophen injure the liver?
Causes massive hepatic necrosis (zone 3)
Causes of fulminant hepatic failure (medical emergency, severe liver injury) (6)
1 ACETAMINOPHEN
Viral (Hep A, Hep B)
Wilson’s disease
Ischemia
Microvesicular steatosis
Malignancy
Cirrhosis (definition)
Acute condition of the liver in which the liver is scarred and permanently damaged.
Common causes of liver cirrhosis (3)
- Alcohol
- Hep C
- Non-alcoholic fatty liver disease
Rare causes of liver cirrhosis (4)
- Hepatitis B
- Hemochromatosis
- Biliary disease
- Autoimmune hepatitis
Key symtpoms of liver cirrhosis (2)
- Failure of liver metabolic functions
- Portal hypertension
Cirrhosis increases the risk of…
hepatocellular carcinoma (HCC)
3 key histologic features of liver cirrhosis
- diffuse liver involvement
- fibrous septation
- nodular regeneration
Name 5 types of liver growths neoplasms (benign and malignant)
- Focal nodular hyperplasia
- Hemangioma
- Adenoma
- Metastasis
- HCC
Focal nodular hyperplasia is…
a) neoplastic
b) non-neoplastic
b) non-neoplastic
Name benign liver neoplasms (2)
Hemangioma
Adenoma
Name malignant liver neoplasms (2)
Hepatocellular carcinoma
Metastasis
Focal Nodular Hyperplasia (definition and cause)
Asymptomatic benign liver tumour due to vascular hyperperfusion to the liver.
Focal nodular hyperplasia usually affects…?
women
Focal nodular hyperplasia treatment?
Treatment is rarely required (NO resection).
Monitor, watch and wait.
Focal nodular hyperplasia appearance
Solitary, well-circumscribed tumour with central scar
Hemangioma (definition)
Non-cancerous neoplastic tumour causing benign vascular lesions
1 liver tumour
Hemangioma
How can we diagnose hemangioma?
Easily diagnosed on CT
Hepatocellular adenoma (definition)
Uncommon solitary neoplastic tumour of the liver, usually affecting women (oral contraceptive pill is a risk factor).
What is the risk of a hepatocellular adenoma becoming malignant?
low risk of malignancy
Hepatocellular adenoma treatment
Stop OCP (oral contraceptive pill)
Surgery (resect the tumour)
1 liver MALIGNANCY in Canada
Metastasis (it is more common than primary liver malignancy)
Cancer metastasis to the liver is usually caused by…
ADENOCARCINOMA of…
* lung
* colon
* pancreas
* breast
Describe the appearance of metastases in the liver
You will see multiple masses and liver enlargement (potentially with liver failure)
Hepatocellular carcinoma (definition)
Primary cancer of the liver
Hepatocellular carcinoma stains positively with…
alpha fetoprotein (normal hepatocytes do not)
Rare variant of hepatocellular carcinoma: Name and description
Fibrolamellar HCC (large solitary mass in young patients, no cirrhosis)
Main risk factor for hepatocellular carcinoma
CIRRHOSIS (any cause of cirrhosis)
