Liver Pathology Flashcards
Demographic of liver disease?
1.9% of all deaths due to liver disease
Eight leading cause of death
7.2/100.000/year chronic liver disease
57% Hepatitis C
24% Alcohol related
9% Non-alcoholic fatty liver
4% Hepatitis B
Indications and purpose of a liver biopsy?
Indications:
Acute and chronic liver dysfunction
Hepatomegaly
Space occupying lesions
Purpose
Cause
Severity (stage of progression)
Liver biopsy methods?
Open (per-operative)
Laparoscopic
Trans-jugular
Fine needle aspiration cytology
Per-cutaneous
blind
targeted
Diagnosis of liver disease?
Functional abnormalities:
Metabolism
Protein
Carbohydrate
Lipid
Bile acid
Bilirubin
Hormone and drug
Removal of microbes/toxins
Exctretion
Immunological function
Pathological manifestations:
Limited number of pathological response patterns to injury
Manifestation of liver disease?
Intracellular accumulation
Fatty change (steatosis)
Iron
Copper / Copper assoc. protein
Storage disease
Liver cell necrosis
Liver cell apoptosis
Inflammation
Cholestasis
Fibrosis
Pathogenesis of liver regen and damage?
Aetiology of acute liver diease?
ACUTE
Infective Hepatitis
Autoimmune
Toxic
Vascular Damage
Biliary Obstruction
gall stones
tumours
Metabolic
Aetiology of chronic liver injury?
CHRONIC
Infective Hepatitis
Autoimmune
Toxic
Vascular Damage
Biliary Disease
primary biliary cirrhosis
sclerosing cholangitis
graft vs host disease
transplant rejection
Metabolic
Causes of acute hepatitis?
Hepatitis viruses
EB Virus, CMV
Leptospirosis
Tell me about the hep viruses?
Tell me about he hep viruses and IG response in acute liver injury?
Tell me about hep and IG response in chronic viral injury?
Visual diff in acute and chronic hepititis?
Hep B stats?
Hep C stats?
Autoimmune hep?
Acute, fulminant onset
chronic active hepatitis (anti SM, ANA, LKM1 antibodies)
Describe changes in alcoholic liver disease?
Fatty change (steatosis)
Steatohepatitis:
Spotty (focal) liver cell necrosis
Neutrophils
Mallory’s hyaline:
eosinophilic globules of intermediate filaments in hepatocytes
Perivenular fibrosis
Micronodular cirrhosis
What causes Non-Alcoholic Steato-Hepatitis (NASH)Non-Alcoholic Fatty Liver (NAFL)?
Diabetes mellitus
Drugs
Parenteral nutrition
Intestinal by-pass surgery
Describe Drug-induced hepatotoxicity?
Intrinsic hepatotoxins
e.g. paracetamol
Idiosyncratic hepatotoxins
hypersensitivity
metabolic
May lead to
hepatitis
cholestasis
fatty change (steatosis)
fibrosis
Causes of hepatocellular damage?
Vascular pathology that causes liver disease?
acute:
hypotension
right sided cardiac failure
hepatic venous outflow obstruction (Budd-Chiari)
Chronic:
right sided cardiac failure
venoocclusive disease
Hepatic venous outflow obstruction and veno-occlusive diease?
Membranous obstruction
Tumours
Hepatic venoocclusive disease
alkaloids
Senecio (ragwort)
Crotalaria (bush tea)
alcoholic liver disease
blood disorders
radiotherapy
cytotoxic drugs
Biliary obstruction, acute and chronic?
Acute:
Gallstones
tumours
Chronic:
primary biliary cirrhosis
Antimitochondrial antibodies
sclerosing cholangitis With IBD (UC)
graft vs host disease
transplant rejection
Metabolic
iron overload - Genetic haemochromatosis (chromosome 6p) C282Y mutation HFE gene (see pic)
Chronic anaemia
increased absorption
multiple transfusions
High dietary intake
Alcoholic liver disease
Chronic liver failure
Porphyria cutanea tarda
-1-antitrypsin deficiency
PiZ mutation; PiZZ phenotype
Cathepsin, elastase, proteinase inhibition
Wilson’s disease (copper overload)
Chr 13 Copper transporting ATPase
List metabolic diseases for carb, protein, glycoprotein and lipid?
Carbohydrate: glycogen storage disease
galactosaemia
Protein: tyrosinaemia
urea cycle disorders
Glycoprotein: mucopolysaccharidoses
Lipid: lipidoses
What is Cirrhosis?
diffuse process in which the normal lobular architecture is destroyed and the parenchyma is converted into structurally abnormal nodules of liver cells separated by bands of fibrosis
It is an irreversible condition that represents the end stage of chronic liver cell damage and regeneration occurring simultaneously
Causes of cirrhosis?
Alcoholic liver disease 60%-70%
Non-Alcoholic Fatty Liver Disease ? high
Viral Hepatitis 10%
Autoimmune hepatitis
Chronic cholestatic liver disease 5-10%
Iron and copper overload 5%
Drugs & toxins Rare
-1-antitrypsin deficiency Rare
Idiopathic 10-15%
types of nodules in cirrhosis?
Micronodular:
nodules up to 3mm
Macronodular
nodules more than 3mm (up to 30mm)
Consequences of cirrhosis
Impaired liver function:
hypoalbuminaemia
oedema
reduced synthesis of coagulation factors
bleeding
decreased metabolism of endogenous oestrogens
testicular atrophy
gynaecomastia
spider naevi
failure of detoxification
encephalopathy (decompensated cirrhosis)
alcohol binge
intercurrent infection
gastrointestinal bleed
shock
hepatocellular carcinoma
hepatorenal syndrome
Portal hypertension:
varices at sites of porto-systemic anastomosis
oesophageal
rectal
peri-umbilical (caput medusae)
splenomegaly
portal vein thrombosis
