Cirrhosis Flashcards
Definition
Implies irreversible liver damage resulting from the necrosis of liver cells followed by fibrosis and nodule formation.
Three key characteristics
- chronic hepatic necrosis
- chronic inflammatory process with fibrosis
- nodules
Aetiology
Vitamin
- vascular
- infective - hep C and B
- Trauma
- Autoimmune - ALD - PBC, Autoimmune hepatitis
- Metabolic (drugs, toxins, alcohol) - alcoholic steatohepatits, and NASH
- Iatrogenic
- Neoplastic
Metabolic- Alcoholic steatohepatitis
- 10-20% alcoholics affected
- characterised by steatosis(retention of lipids), inflammation and fibrosis
- Clinical - AST, ALT, fever, hepatomegaly and jaundice
Metabolic - Non-alcoholic steatohepatitis (NASH)
- metabolic syndrome (diabetes, obesity)
- characterised by steatosis, inflammation and fibrosis
- cirrhosis takes longer to develop than alcoholic steatohepattis
Infective -Hep C virus
- chronic >6 months
- transmission: blood contact
- Asymptomatic (silent)
- diagnosis - Hep C ABs or Viral RNA - cannot detect antigen
- treat with interferons
Infective hepatits B virus
- Chronic > 6 months
- transmission - blood, seme, vagina
- vaccine is available to prevent
- diagnose with HbsAg
- treat with interferons
Primary Biliary cirrhosis definition
Autoimmune disease of the liver causing fibrosis and scarring of the biliary tract - Intrahepatic ducts
cholestasis - bile blockage
Mixed portal inflammation with granulomas (florid duct lesion
Primary bilary cirrhosis Clinical features
- middle aged women
- mainly asymptomatic
- Fatigue
- itching
- jaundice
- hepatomegaly
Investigations PBC
Bilirubin is secreted an eliminatinated in bile but as bile duct flow os blocker, Bilrubin will enter the bloodstream and cause jaundice
- Alk phosph, bilirubin, chol increases in blood
- diagnosis - anti-mitochondrial antibodies
Treatment PBC
ursodeoxycholic acid
liver transplant
osteoporosis prophylaxis
Primary sclerosing cholangitis definition
- Chronic cholestatic LD
- characterised by progressive obliterating fibrosis of intra and extra hepatic duts, eventually leading to cirrhosis
- portal inflammation and fibrosis (periductal onion skinning)
Diagnosis of PSC
diagnosis:
- asymptomatic- routine blood test in patient with IBD
- symptomatic - pruritis, jaundic or cholangitis
- P- ANCA -60%
- MRCP or liver biopsy
PSC clinical features
Pruritis +/- fatigue, if advanced ascending cholangitis, cirrhosis and end-stage hepatic failure
middle aged men
uknown cause - assoc with ulcerative collitis
treatment of PSC
Treatment - management of complications with eventual transplantation
high risk for cholangiocarcinoma
Management and prognosis
- treat the underlying cause and comolications
- liver transplant in selected
- surveillence using endoscopy to screen for varices every 2 years
- USS to detect HCC
- prognosis linked to severity
Congenital - wilsons disease
- Normally copper absorbed by the stomahc, processed in the liver and excreted in bile
- mutation in P-Type ATPase (catson transport enzyme) normally transports copper into bile
- copper then accumulates in liver and brain
- causes liver disease and neuropschyiatric symptoms
Signs of congenital wilsons disease
- Liver disease (Hepatitis, cirrhosis, fulminant liver failure)
- CNS signs - tremour, dyarthria, dysphagia, dyskinesia
- mood - depression, personality change
- cognition- memory decreases; quick to anger
- Kayser-fleischer rings - cooper in iris
Investigations of wilsons disease
- urine: 2hr copper excretion studies need expert interpretation
- LFT increase
- serum cooper
- serum caeruoplasmin decrease
- falsely low caeruoplasms: protein defiiency states
- falsely high caeruoplasmim: acute phase reactant
- molecular genetic testing
- slip lamp: KF rings
- liver biopsy: hepatic copper
Management of Wilson disease
Diet - avoid eating foods with a high copper content (e,g liver,chocolate, nuts, mushrooms, legumes and shellfish)
Drugs - life long penicillamine
SE: nausea, rash, WCC decrease, Hb down, lateelts decrease
Monitor FBC and urinary CU
Liver transplant
Hereditary haemochromatosis definition
Inherited disorder of iron metabolism in which increased intestinal iron absoprtoin leads to iron deposition in joints, heart, pancrease and pitaru
Congenital haemochromotosis
- Accelerated rate of iron absorption from intestines
- progressive iron deposition in various tissue
- hepatic cirrhosis along with
- cardiomyopathy
- diabetes
- arthirits
- hyperpigmentation
- hypopituitarism
Clinical features
- can be entirely asymptomatic
- weakness, fatigue, muscle cramps, weight loss, non specific *weight loss, nausea and vomitting
- liver is hard, irregular and non-tender (liver is smaller)
- spider naevi- strong indicator of liver diease
Genetics of HH
HFR gene on chromosome 6
Clinical features of HH
- Early - NIl or tiredness, arthralgia
- later - slate-grey skin pigmentation, signs of CLD, hepatomegaly, cirrhosis
- endocrinopathies - DM bronze diabetes - iron deposition in pancreas
HH investigations
- Bloods - increase LFT
- increased serum ferritin
- transferrin saturation >45%
- glucose - DM
Imaging - chondrocalcinosin
Liver biopsy - Perl stain
ECHO if cardiomyopathy suspected
Management of HH
Venesection for life
monitor LFTS and diabetes
diet low in iron
Autoimmune hepatitis definition
autoimmune liver disease of unknown cause characterized by suppressor T-cell defects with autoantibodies directed against hepatocyte surface antigens
Clinical features of autoimmune hepatitis
- young or middle aged women
- 40% - acute hepatitis and signs of autoimmune disease e.g fever, malaise, ruticarial rash
Investigations with AIH
- serum bilirubin, AST, ALT and ALK phosp all increase
- hypergammaglobulinaemia + ve autoantibodies
- liver biopsy - mononclear infiltrate or portal and periportal areas
- MRCP - helps exclude PSC
Management of autoimmune hepatitis
- immunosuppresant therapy - prednsiolone
- azathioprine can be used as a steroid-sparing agent to maintain remission
- liver transplant
Alpha 1 anti-trypsin deficency
Inherited conformation disease than can be fatal. It commonly affects lung (emphysema) and liver (cirrhosis and HCC) and can present in homozygous or heterozygous forms. A1AT is a glycoprotein and one of a family of serine protease inhibitor made in the liver that control inflammatory cascades. Deficency is called a serpinopathy. It makes up 90% of serum alpa 1 - globulin on elettrophoresis
Genetics of alpha 1 antitrypsin
Autosomal recessive disorder is found on chromosome 14 carrier frequency of 1:10
Genetic types by electrophoretic mobility
(M)- medium
Slow
very slow
Investigations of alpha 1 anti-trypsin
- serum alpha 1 antitrypsin
- liver biopsy - periodic acid schiff
- phenotyping by isolectrc focusing
Management of alpha 1 anti-trypsin
- GP
- lung
- liver specialists ad geneteicists
- supprotive for emphysema and liver disease may be suffienct for some
- quit smoking
- liver transplant
