Flashcards in CM-Fatty Liver Disease and Cirrhosis Deck (33):
Describe the pathological difference between a normal liver and fibrotic liver in terms of cells and extra-cellular matrix.
Normal and fibrotic livers have the same parenchymal (hepatocytes) and non-parenchymal (stellate, Kupffer, endothelial) cells.
The difference is that fibrotic livers have thick sinousoidal collagen instead of a thin basement membrane and increased interstitial collagen in the space of Disse
What cells are responsible for fibrosis in diseased livers?
Stellate cells- paracrine signals from Kupffer, endothelial, tumor and inflammatory cells active them to myofibroblasts.
Inflammatory cells are mitogenic to stellate cells meaning that they also stimulate them to proliferate
What determines whether a cell will go through apoptosis or necrosis?
If there is a lack of mitochondrial production of energy (usually due to lack of oxygen) the cell will undergo necrosis.
If there is adequate mitochondrial energy, caspase system will be activated and the cell will undergo apoptosis.
What histopathologic cells are associated with necrosis? apoptosis?
Necrosis- balloon degeneration
Apoptosis- councilman bodies
What inflammatory cells are associated with inflammation due to alcohol or fatty liver?
What inflammatory cells are associated with viral, autoimmune or immunoallergic reactions?
Describe the progression from chronic liver damage to cirrhosis.
Damage--> inflammation--> stimulates stellate cells--> stellate cells become myofibroblasts and proliferate--> interstitial fibrosis and subendothelial fibrosis-->bridging (P/P, CV/CV, P/CV)--> regenerating hepatocytes form distinct nodules within the fibrous bands = cirrhosis
Why does cirrhosis lead to portal hypertension?
What are the complications of portal hypertension?
The fibrosis and nodules distort normal architecture so there is increased resistance to flow (P-Q-R), and thus increased pressure.
This leads to:
1. varices (esophageal, caput medusa, hemorroids)
What is the threshold of ethanol consumption per day needed for any liver disease to occur in women?
How many beers, wine, shots is that?
(technically about 1.5)
What is the threshold of ethanol consumption per day needed for any liver disease to occur in men?
How many beers (12), wine (5oz), or shots (1oz) is that?
Between 40 and 60 which translates to between 3 and 5 beers a day
What is required to develop alcoholic liver disease?
1. alcohol consumption
3. nutritional status
4. Hep C or other co-infections
"malnutrition and alcohol consumption in susceptible individuals"
What is implicated in most of the toxic effects of alcohol on the liver?
Acetaldehyde- the first metabolite in the breakdown of alcohol that can covalently bind to proteins, lipids and DNA
What is the proposed mechanism by which alcohol causes hepatic steatosis?
1. by-products of alcohol breakdown are substrates for triacylglycerol synthesis
2. increases release of fatty acids from adipocytes which are taken up by the liver a reesterified into triacylglycerol
3. decreased VLDL secretion
What are the main causes of NAFLD and secondary fatty liver disease?
NAFLD: obesity, diabetes, genetic and metabolic disorders, jejuno-ileal bypass, hyperlipidemia
Secondary fatty liver disease: drugs, toxins, HepC
Describe the progression spectrum of fatty liver in terms of histopathology.
1. steatosis- fat w/o inflammation. fat droplets can be macrovesicular (typically) or microvesicular (Reyes, acute fatty liver of pregnancy)
2. steatonecrosis - fat with inflammation
-PMNs & Mallory bodies = steatohepatitis
-Councilman bodies = apoptosis
- balloon degeneration = necrosis
3. Fibrosis and Cirrhosis
What is the clinical presentation of steatosis, steatohepatitis, and cirrhosis?
Steatosis- usually asymptomatic, maybe hepatomegaly
SH- fever, jaundice, ascites and encephalopathy in 10-70% of hopsitalized because it is acute decompensation of chronic disease
Cirrhosis- combo of symptoms found with SH and steatosis
In a history of a person with chronic liver disease, what is pruritis a sign of?
PBC or PSC
In a history of a person with chronic liver disease, what is arthritis a sign of?
In a history of a person with chronic liver disease, what is impotence a sign of?
What are extra-abdominal manifestations in patients with acoholic liver disease?
In fatty liver disease, what enzymes are usually elevated?
1. AST>ALT and both are usually under 400
2. GGT in 2/3 of people
Why is AST > ALT in fatty liver disease?
1. non-hepatic sources of AST (RBC, cardiac, skeletal)
2. decreased co-enzymes
3. AST is in cytosol AND mitochondria instead of just the cytosol
In fatty liver disease what happens to albumin, total protein, and coagulation?
What would a CBC show?
albumin decreases (eventually leading to ascites)
total protein is normal because of increased gammaglobulin
PT and INR are long because Vit K clitting factors decrease
CBC would show:
1. leukocytosis with PMN
2. Hb would be normal if there were no gastrointestional bleeding
3. thrombocytopenia bc of alcohol suppression of bone marrow
What are the non-invasive methods suggestive of cirrhosis?
1. splenomegaly on physical exam/radiography
2. thrombocytopenia, leukopenia
3. varices on esophageal studies
4. collarterals on US
5. serum markers of fibrosis
What are the invasive methods to test for cirrhosis?
1. trichrome stain to look for collagen
2. reticulin stain to look for glycoproteins
What is the DDx for alcoholic liver disease?
1. Genetic - hemochromatosis, Wilson's
4. chronic HepB or C
5. drug induced
What liver disease is untreatable but unimportant?
acute viral hepatitis - it will run its course and rarely goes chronic
What liver disease are treatable and important to catch?
3. autoimmune hepatitis
What liver diseases are untreatable and important?
1. fulminant hepatitis
2. alcoholic hepatitis
3. hepatocellular carcinoma
What is the management for alcoholic liver disease?
2. if they are malnourished, parenteral feeding
3. corticosteroids for severe acute decompensation
A patient has AST/ALT
1. serology for chronic viral infection
2. serology for autoimmune antibodies SMA, LKM1
3. test for genetic liver disease
Describe what iron studies would show for hemochromatosis. What would screening for genetic markers likely show?
serum iron - high
ferritin - high
homozygous for the HFE gene