wk 6 6 Aetiologies and Pathophysiology of chronic liver disease Flashcards
t/f chronic liver disease is of a duration greater than 3 months
false 6 months
t/f chronic liver disease can present acutely q
true
duration (6mnths) may be sub clinical
signs/symptoms dependent on underlying disease/features of cirrhosis
describe the pathology of chronic liver disease
recurrent inflammation and repair with fibrosis and regeneration
fibrosis of the liver is due to the activation of hepatic stellate cells, how does this occur
quiescent HSC is activated through hepatocyte Kupffer inflammatory cells
TIMP is what turns the activated HSC into an apoptic HSC, what does it do
TIMP - Tissue Inhibitor of Metalloprotinease, determines the degradation of cells through MMP (matrix metalloprotineases)
other than alcohol, autoimmune disease and hepatitis, what else can cause Chronic liver disease
NAFLD (non-alcoholic fatty liver disease)
Primary Biliary/sclerosing Cholangitis
Haemochromatosis (iron overload)
WIlsons Disease (copper overload)
Alpha 1 anti-trypsin (pancreatic enzyme)
Budd-Chairi (hepatic portal occlusion)
Methotrexate
2 examples of chronic diseases that affect the liver (but arent chronic liver disease)
amyloid rotor syndrome (hyperbilirubinaemia)
what is the commonest disease in the world
NAFLD (simple steatosis)
NAFLD vs NASH
NASH is a type of NALFD
there is Non-alcoholic steatohepatitis, or simple steatosis
NALFD initiates due to excess fat accumulation, what does this cause 3
inrtrahepatic oxidative stress
lipid peroxidation
TNF-alpha/cytokine cascade
t/f progression to NASH can occur with/without increased expression of ARE-genes
true
with - large inc in ROS leads to greater expresssion
without - multiple factors (Fatty acids) instead cause
both lead to activation of NF–kB
how is a simple steatosis diagnosed
ultrasound
simple steasosis increases the risk of
cardiovascular disease
treatment for simple steatosis
weight loss
exercise
in NASH, there is a risk of progression to
cirrhosis
difference between primary biliary and primary sclerosing choangitis
primary biliary - interlobular bile ducts affected by granulomatous immune cells, leading to cholangitits
primary sclerosing - progressive inflammation of bile ducts leading to strictures
how does PBC present?
middle aged woman usually asymptomatic but may feel - fatigue -itch and no rash - xanthesalma and xanthomas
what antibodies are produced in PBC which allow it to be diagnosed
Antimitochondrial Antibodies (AMAs)
other thn AMAs, give 2 ways PBC may be diagnosed
Cholestatic LFTs
Liver Biopsy
treatment of PBC
urseo deoxycholic acid
t/f auto-immune hepatitis affects woman more than men
true
3:1`
auto-immune hepatitis can be subtyped into Type 1 and 2, which one occurs in children/young adults? which is diagnosed through AMA alone? which will see IgG present?
type 2
type 2
type 1
clinical presentation of type 1
patient: <40 yrs
hepatosplenomegaly
jaundice
stigmata of chronic liver disease
Elevated AST, ALT, PT (aspartate/alanine aminotransferase) (prothrombin time)
non specific - malaise,nausea,ab pain, anorexia
how is type 1 diagnosed
elevated AST,ALT,IgG
rule out wilsons, antitrypsin, vira hep, drug induced liver disease, NASH, PBC/PSC
presence of autoimmune antibodies
liver biopsy
what is the hallmark finding of type 1 autoimmune hepatitis histologically
interface hepatitis
also have chronic hepatitis with marked necrosis and lobular involvement with numerous plasma cells
which drugs can trigger autoimmune hepatitis
methyldopa diclofenac statins minocycline oxyphenistatin nitrofurantoin
treatment of autoimmune hepatitis
prednisone (coritcosteroid) + azathioprine (immunosuppressant)
what worsens the prognosis in AIH
if present with ascites or hepatic encephalopathy (brain damage due to irremoval of toxins in liver)
recurrent cholangitis is most likely
primary sclerosing Cholangitis
2 cancers which need to be monitored for in PSC
cholangiocarcinoma
colo-rectal carcinoma
how is PSC diagnosed
imaging of biliary tree
which inflammatory disease is PSC most typically seen inb
Ulcerative Colitis
haemochromatosis is …..
and is treated using
iron overload
maintenance venesection for life, diets reducing iron
wilsons disease is due to the poor regulation of deposition of which metal? how is it treated?
copper
copper chelation drugs
alpha 1 anti-trypsin defiency causes what
deregulation of neutrophil elastase (leading to emphysema)
Budd-chiari is the
thrombosis of hepatic veins
3 defiencies which lead to budd-chairi
thrombotic defiency
protein C
protein S
acute budd-chairi presents as jaundice and tender hepatomegaly, when woulld it be considered chronci
ascite formation
how is budd-chairi diagnosed
Ultrasound of hepatic veins
treatment for budd-chairi
recanalisation or TIPS (transjugular Intrahepatic Portosystemic Shunt)
methotrexate is used to treat Rheumatoid arthritis and proriasis (skin condition) what can it cause
cirrhosis
treatment - stop drug
cardiac cirrhosis is secondaruy to high right heart pressures (incompetent valves, congenital, rheumatic, pericarditis) how does it present and how is it treared
heart failure with ascites/liver impairment
treat underlying cardiac condition
