pathophysiology of chronic liver disease Flashcards
(45 cards)
what are some of the causes of chronic liver disease
>alcohol >NAFLD >hep C/B >primary biliary cholangitis >autoimmune hepatitis >primary sclerosis cholangitis >wilsons disease >alpha 1 anti-trypsin >budd-chiari >methotrexate
what is NAFLD
non-alcoholic fatty liver disease
>more common in obesity (60%)
>more in western populations
>about 20% will have cirrhosis within 20 years
how do we get from a normal liver to a fatty liver
normal»_space; obesity, insulin resistance»_space; steatosis»_space;steatohepatitis»_space; steatohepatitis with fibrosis»_space; cirrhosis
what is NASH
non-alcoholic steatohepatitis
what are characteristics of steatohepatitis
- inflammation, usually mild, lobular and mixed mononuclear and neutrophilic
- there is hepatocyte degeneration - ballooning and malory bodies
- fibrosis - initially pericellular, later bridging
what is metabolic syndrome
medical term for a mixture of diabetes, obesity and hypertension
>that makes patients more predisposed to coronary heart disease
**NAFLD is a common manifestation of metabolic syndrome
how would you diagnose simple steatosis
> by ultrasound
having increased CV risks
no liver outcomes
how would you diagnose NASH
> liver biopsy
>there is a risk of progression to cirrhosis
how to treat simple steatosis
weight loss and exercise
how would you treat NASH
weight loss and exercise
what is steatosis
fatty liver disease
name autoimmune liver diseases
- primary biliary cholangitis (cirrhosis)
- auto-immune hepatitis
- primary sclerosing cholangitis
- alcohol related liver disease
- drug reactions
describe the autoimmune actions of PBC
T cell mediated, CD4 cells reactive to M2 target that’s why there is a loss of tolerance ?
how does PBC present
usually asymptomatic/incidental
fatigue
itch without rash
xanthelasma and xanthomas
how would you diagnose PBC
positive AMA
cholestatic LFTs
liver biopsy
how would you treat PBC
urseo deoxycholic acid
obeticholic acid
what are the general outcomes for PBC
-most people with PBC symptoms do not develop liver failure
who typically gets autoimmune hepatitis
> affects women more than men
if untreated people will usually die within 6 months
40% of people who have autoimmune hepatitis will go on to develop PBC
- there are two types of autoimmune hepatitis
Who’s more likely to get type 1 ?
there is a bimodal age distribution ie ages 10-20 and 45-70
>females are about 4x more likely to get it
>associated with extrahepatic manifestations ie autoimmune thyroiditis, graves disease, chronic UC
> > less common with RA, pernicious anemia, systemic sclerosis, ITP, SLE
usually have onset symptoms similar to toxic hepatitis or acute viral hepatitis
who’s more likely to get type 2 autoimmune hepatitis
children and young adults LKM-1 exclusive AMA very rare
RA
ITP
= rheumatoid arthritis
= immune thrombocytopenic purpura
what are the clinical presentations of type 1 autoimmune hepatitis
hepatomegaly jaundice stigmata of chronic liver disease splenomegaly elevated AST and ALTs elevated PT and non-specific symptoms such as malaise, fatigue, lethargy, nausea, abdominal pain and anorexia
how would you diagnose type 1 autoimmune hep
> elevated AST and ALTs
elevated IgGs
presence of autoimmune antibodies
liver biopsy
> > would also need to rule out other causes
what is the pathogenesis of type 1
-genetically predisposed individual with exposure to an environmental agent triggers the autoimmune pathogenic process
> the genetically predisposing factors include
HLA-DR3/4
IgG
T cell receptors
> the environmental triggers
certain viruses
toxins
drugs (oxyphenisatin, methyldopa, nitrofurantoin, diclofenac, minocycline, statins)
