Hepatobiliary - non-neoplastic liver conditions Flashcards
hepatic diseases (6)
- Infectious disorders
- Viral hepatitis
- Bacterial, parasitic and helminthic - Drug- and toxin induced liver injury (DILI)
- Alcoholic liver disease - Cholestatic / biliary diseases
- Large bile duct obstruction
- Neonatal cholestasis
- Autoimmune cholangiopathies - Autoimmune hepatitis
- Metabolic diseases
- Non-alcoholic fatty liver disease (NAFLD)
- Haemochromatosis
- Wilson disease
- a1-antitrypsin deficiency
- Neonatal hepatitis - Circulatory disorders
- Hepatic venous outflow obstruction
acute hepatitis symptoms
- Jaundice
- Poor appetite
- Dark-coloured urine
- Nausea and vomiting
- Fever
- Abdominal pain
- Fatigue
causes of viral hepatitis
Hepatotropic: Hepatitis A, B, C, D, E
Non-hepatotropic (no effect on liver): EBV, CMV
hepatitis A
- mode of transmission
- where does it affect
- malignancy
- fecal-oral transmission
- affects countries w/ poor hygiene/ sanitation, close quarters
- consumption of raw shellfish
- benign: self-limiting,
gives lifelong immunity
hepatitis B
- modes of transmission **
- pathogenesis
- diagnosis
- malignancy
- carrier state
- histo features
global health problem:
- Vertical transmission
- Horizontal transmission esp. early childhood
- Sexual and IV drug abuse
- injury to hepatocytes caused by immune response -> CD8+ cytotoxic T cells attacking infected cells
- HBsAg (acute), HBcAg (chronic) postive**
- risk of causing hepatocellular carcinoma
- healthy carrier w/ no inflammation -> normal ALT/AST
- ‘ground-glass’ hepatocyte
hepatitis C
- modes of transmission **
- pathogenesis
- carrier state
- histo features
- diagnosis**
- IVDA, sexual, needle-stick injury, vertical
but 1/3 have no identifiable risk factors - HCV is genomically unstable + has multiple strategies to evade host anti-viral immunity
- > causes hepatic damage (persistent infection and chronic hepatitis)
- no carrier state - all presents as chronic hepatitis
- no lifelong immunity - HCV RNA (RT-PCR) very persistent **
- histo features:
lymphoid follicle
fatty change
hepatitis D
- mode of transmission
- where does it affect
- pathogenesis
- diagnosis
- vaccine/ treatment
- blood-borne (IVDA, blood transfusions)
- prevalence highest in Amazon basin, Middle East, Mediterranean and central Africa
- Superinfection:
severe acute hepatitis in a HBV carrier/
exacerbation of preexisting chronic Hep B infection - diagnosis: IgM anti-HDV antibody
- vaccine: prevent HBV infection also prevents HDV cause HDV is developed from HBV
self-limiting (like HBV)
hepatitis E
- mode of transmission
- who should take special caution
- diagnosis
- vaccine/ treatment
- fecal oral transmission
- zoonosis: monkeys, cats, pigs, dogs
- immunocompromised pts - chronic infection
- pregnancy: high mortality rate
- diagnosis: HEV RNA and virions can be detected by PCR in stool and serum
- self-limiting disease
acute vs chronic viral hepatitis
difference is the pattern of injury
both are mononuclear T cells
acute: lobular hepatitis
chronic: portal hepatitis
lobular hepatitis (acute) histo features
- Hepatocyte degeneration (hydropic swelling)
- Apoptosis, spotty necrosis with hepatocyte dropout to confluent necrosis
(perivenular, bridging) - Kupffer cell (macrophage) hypertrophy
- Lymphoplasmacytic infiltrate
- Cholestasis (cause of bile duct obstruction)
portal hepatitis (chronic) histo features
- Lymphoplasmacytic portal infiltration
- Portal and periportal (interface) hepatitis to bridging hepatic necrosis
- Fibrosis to cirrhosis; regression may occur
grading and staging of liver disease
grading: extent of injury and inflammation
staging: progression of fibrosis
Non-hepatotropic viral hepatitis
- viral types
multi organ involvement
- opportunistic infection:
- CMV, HSV, EBV, adenovirus
localised diseases caused by bacterial, parasitic and helminthic infections (2)
- Abscess (bacterial or amoebic)
- Hydatid cyst
diffused diseases caused by bacterial, parasitic and helminthic infections (3)
- Mild hepatic inflammation w/ varying hepatocellular cholestasis
- Granulomatous disseminated disease (Schistosoma – ‘pipe stem fibrosis’, miliary TB)
- Dilated intrahepatic ducts (liver flukes: high rate of cholangiocarcinoma)
amoebic abscess (localised liver disease)
Large cavity lined by necrotic shaggy tissue
- Abscess contents have lack of inflammatory cells due to process of liquefactive necrosis
- caused by protozoa
miliary TB of liver
- histo features
- diagnosis
- granuloma: Epithelioid histiocytes, lymphocytes and multinucleated giant cells
- Ziehl-Neelsen stain for acid-fast bacilli
- Culture and sensitivity for Mycobacterium tuberculosis
autoimmune hepatitis
- antibodies present
- affect who more
Chronic progressive disease
- autoantibodies: ANA, SMA, anti-SLA/LP, AMA, anti-LKM1
genetic association: HLA genotype
affects females more
autoimmune hepatitis
- diagnosis
- histo features
- presence of autoantibodies
- elevated IgG level
histo:
1. interface hepatitis with lymphoplasmacytic predominance
2. Emperipolesis
3. Hepatic rosette formation
Drug- and toxin induced liver injury (DILI)
- pathogenesis
- Direct toxicity
- hepatic conversion of xenobiotic -> active toxin
- immune-mediated mechanisms
DILI (Drug- and toxin induced liver injury) diagnostic criteria
- temporary liver damage upon drug/toxin exposure
- recovery upon stopping the drug
alcoholic liver disease
- factors determining severity of ALD
- Dosage and duration: 6 beers/day + > 10-20 yrs
- Gender: females more susceptible
- Ethnic and genetic differences (in production of detoxifying enzymes)
- Comorbid conditions (viral hepatitis)
alcoholic liver disease
- complications
- steatosis
- Dysfunction of mitochondrial and cellular membranes
- Hypoxia and oxidative stress
- increase in inflammatory response
- decrease hepatic sinusoids perfusion
alcoholic liver disease
- histo features (6)
- Centrilobular steatosis (reversible with abstention)
- Hepatocyte swelling (ballooning degeneration) and necrosis
- Mallory-Denk bodies
- Neutrophilic reaction
- Pericellular/perisinusoidal fibrosis (“Chicken-wire fence” pattern)
- Cirrhosis (micronodular)
Non-alcoholic fatty liver disease (NAFLD) [metabolic disease]
- progression
only for individuals who drink very little alcohol
healthy -> steatosis -> NASH (steatohepatitis) -> NASH w/ fibrosis -> cirrhosis
NASH: hepatocyte injury
2 causes of NAFLD
metabolic diseases:
- Insulin resistance -> decreased lipid metabolism + increased production of inflammatory cytokines
- Oxidative injury -> liver cell necrosis
as fat laden cells are highly sensitive to lipid peroxidation products
haemochromatis definition
Caused by excessive iron absorption, depositing in parenchymal organs (liver, pancreas, heart, joints, endocrine organs, skin)
wilson’s disease definition
Autosomal recessive disorder caused by ATP-7B gene mutation (chr 13)
- > impaired copper excretion into bile + failure to secrete copper into blood
- > accumulation of copper in the tissues and organs
A1-antitrypsin deficiency
Autosomal recessive:
disorder of protein folding
-> impaired secretion and very low serum α1AT
(α1AT is important in inhibition of proteases, particularly those released from neutrophils)
-> so high protease activity
