Aetiology and Pathophysiology of Chronic Liver Disease Flashcards by Alyx McGregor

what is chronic liver disease

duration > 6 months

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outcome of chronic liver disease

cirrhosis

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symptoms and signs of chronic liver disease

dependent on underlying disease or features of cirrhosis

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pathology of chronic liver disease

recurrent inflammation
repair with fibrosis and regeneration = cirrhosis compensated
cirrhosis eventually becomes decompensated

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what are kupffer cells

specialised macrophages lining the walls of sinusoids

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causes of chronic liver disease - cirrhosis causes

alcohol 
NAFLD
HCV
primary biliary cholangitis 
autoimmune hepaititis 
HBC
haemochromatosis 
primary sclerosing cholangitis 
wilson's disease
alpha 1anti-trypsin 
budd-chiari
methotrexate

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diseases affecting the liver which are chronic

amyloid
rotor syndrome
they are not causes of chronic liver disease as they do not causes cirrhosis

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causes of NAFLD

metabolic syndromes;
obesity
type II diabets (insulin resistance)
HDL cholesterol

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progression of NAFLD

steatosis
NASH (fibrosis)
steatohepatitis with fibrosis
cirrhosis

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pathogenesis of NAFLD

unknown

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treatment of NAFLD - steatosis

limited options
weight loss
exercise

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die causes of NAFLD

energy intake
density
fat
fructose

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histologic features of NASH

inflammation
hepacyte degeneration
fibrosis

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inflammation features in NASH

mild
lobular
mixed mononuclear and neutrophilic

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hepatocyte degeneration features in NASH

ballooning

mallory bodies

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fibrosis features in NASH

initially pericellular

later bridging

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risk factors of NAFLD

triglycerides

hypertension

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tests for NAFLD - steatosis

ultrasound

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complications of NAFLD - steatosis

increased CVD risk

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tests for NAFLD - NASH

liver biopsy

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complications of NAFLD - NASH

progression to cirrhosis

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treatment for NAFLD - NASH

weight loss
exercise
experimental treatments

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types of autoimmune liver disease

primary biliary cholangitis (PBC) (cirrhosis)
auto-immune hepatitis 
primary sclerosing cholangitis 
alcohol related liver disease 
drug reactions

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PBC aetiology

genetic mutation - M2-E2 E3 subunits of PDC-E2 in inner leaflet of mitochondrial membrane
middle aged woman

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immunopathology of PBC

T cell mediated - CD4+ react to M2 target resulting in loss of tolerance

symptoms of PBC

asymptomatic fatigue itch without rash Xanthesalma

tests for PBC

anti-mitochondrial antibodies cholestatic LFTs liver biopsy

treatment for PBC

Urseo deoxycholic acid | Obeticholic acid

outcomes of PBC

many patients may not develop symptoms or liver failure | many liver failures caused by PBC will be unfit for transplant

describe auto-immune hepatitis

affects woman more than men type 1 - adult poor prognosis if untreated cirrhosis likely to develop

describe type 2 aut-immune hepatitis

affects children and young adults | very rare

immunology of type 2 auto-immune hepatitis

LKM-1 | anti-mitochondrial antibodies

describe type 1 auto-immune hepatitis

affects adults (young and elderly) more common in females uncommon

immunology of type 1 auto-immune hepatitis

anti nuclear antibody anti-smooth muscle antibodies soluble liver antigens antibodies severity

extra hepatic manifestations of autoimmune hepatitis

``` Autoimmune thyroiditis graves disease chronic UC Less commonly with; RA pernicious anemia systemic sclerosis ITP SLE ```

symptoms of autoimmune hepatitis

``` acute onset of symptoms similar to toxic hepatitis or acute viral hepatitis; malaise fatigue lethargy nausea abdominal pain anorexia ```

LFTs of autoimmune hepatitis

elevated AST and ALT | elevated PT

signs of autoimmune hepatitis

hepatomegaly jaundice stigma of chronic liver disease splenomegaly

tests for autoimmune hepatitis

LFTs elevated IgG presence of autoimmune antibodies liver biopsy

histology of autoimmune hepatitis

chronic hepatitis with marked piecemeal necrosis and lobular involvement interface hepatitis and plasma cells

genetic predisposing factors of autoimmune hepatitis

HLA-DR3 - early onset, severe HLA-DR4 - late onset, extrahepatic manifestations, good response to steroids IgG T cell receptors

environmental triggers of autoimmune hepatitis

certain viruses drugs toxins

drugs triggering autoimmune hepatitis

``` Oxyphenisatin Methyldopa Nitrofurantoin Diclofenac Minocycline statins ```

treatment for autoimmune hepatitis

prednisone - high and taper down | azathioprine

complications autoimmune hepatitis

oesophageal varies | cirrhosis

what is primary sclerosing cholangitis

autoimmune destructive disease of large and medium sized bile ducts recurrent cholangitis

epidemiology of primary sclerosing cholangitis

men | patients usually have colitis (UC)

tests for primary sclerosing cholangitis

imaging of biliary tree - MRCP and ERCP

treatment for primary sclerosing cholangitis

maintain bile flow | monitor for cholangiocarcinoma and colo-rectal cancer

what is haemochromatosis

genetic iron overload syndrome - mono genetic autosomal recessive

mutated gene in haemochromatosis

HFE gene

pathology of haemochromatosis

cirrhosis cardiomyopathy pancreatic failure

treatment of haemochromatosis

venesection

what is Wilsons disease

lenticular hepatic degeneration - mono genetic autosomal recessive disease

mutated gene is Wilsons disease

loss of function or loss of protein muationsin caeruloplasmin; copper binding protein loss of copper regulation massive tissue deposition of copper, especially liver and basal ganglia

clinical features of Wilsons disease

Neurological- chorea-atheitoid movements Hepatic – cirrhosis or sub-fulminant liver failure Kaiser Fleisher rings

treatment for Wilsons disease

copper chelation drugs

describe alpha 1 anti-trypsin deficiency

genetic mutations in A1AT genes at multiple sites - causing variable phenotype protein function lost excess tryptic activity

clinical features of alpha 1 anti-trypsin deficiency

lung emphysema | liver disposition of mutant protein, cell damage

treatment for alpha 1 anti-trypsin deficiency

supportive management

what is Budd-chiari

thrombosis of hepatic veins; congenital webs thrombotic tendency, protein C or S deficiency

clinical features of budd-chiari

acute - jaundice, tender hepatomegaly | chronic - ascites

tests for Budd-chiari

ultrasound of hepatic veins

treatment for Budd-chiari

recanalization or TIPS

what is methotrexate

drug used to treat rheumatoid arthritis and psoriasis

effect of methotrexate on the liver

dose dependent liver toxin - progressive fibrosis | stop drug to prevent fibrosis

describe cardiac cirrhosis

secondary to high right heart pressures

causes of cardiac cirrhosis

incompetent tricuspid calve congenital rheumatic fever constrictive pericarditi

cardiac cirrhosis effect on the liver

congestive heart failure causing; ascites liver impairment

Aetiology and Pathophysiology of Chronic Liver Disease Flashcards

(69 cards)