Liver Pathology Flashcards
Normal liver size?
1400g-1600g
Functional unit
acini
Have three zones
1, 2 and 3
Based around terminal hepatic vein(central vein)
anatomical component
Hepatic Lobule
Porta Hepatis
Main entry point into the liver.
A fissure where the Bile Duct, Hepatic portal vein and Proper hepatic artery enter/exit
Purpose of zones? Other names for zones are?
Pathologists can describe changes specific to each zone, which helps clinicians to identify/ diagnose the disease
1 = periportal
2 = mid-zonal
3 = centrilobular
What are the Four general features of Hepatic disease
1: the patterns of hepatic injury
2: hepatic failure
3: cirrhosis (distinct to liver)
4: portal hypertension
1 Patterns of hepatic injury are?
5 general responses (limited # of responses)
1) Degeneration and intracellular accumulation (fat-steatosis, or bilirubin-cholestasis)
2) Necrosis and apoptosis (consequence of toxins/drugs)
3) Inflammation (hepatitis)
(viral, infection, autoimmune issues)
4) Regeneration
5) Fibrosis (leads to cirrhosis > portal hypertension)
2 Hepatic Failure
relatively unncommon
- Sudden and massive destruction OR endpoint of chronic damage
- Only seen when loss ~80-90%
- Decompensation associated with increased demand (infection, GI bleeding, sepsis) triggered by ‘co-morbidity’ so the liver has less ability to compensate and HF will occur at
Clinical Features of Hepatic Failure
Failure of normal function:
- Jaundice (failure to metabolise bilirubin)
- Hypoalbuminaemia (low albumin > peripheral edema)
- Elevated Ammonia (not removed/detox. leads to neurological dysfunction)
- Bleeding (decreased coagulation factors)
Paracetamol in excessive dosage is? What would you see with this?
‘Hepatotoxic’
- Hepatocellular necrosis (loss of normal hepatocyte structure) near hepatic /central vein
- Normal anatomy/tissue around portal triad
Cirrhosis
a chronic disease of the liver marked by degeneration of cells, inflammation, and fibrous thickening of tissue. It is typically a result of alcoholism or hepatitis.
Physical features of Cirrhosis
Bridging Fibrous Septae: link portal tracts
Parenchymal Nodules: Proliferating hepatocytes encircled by fibrosis
- micronodules less then 3mm
- macronodules upto a few cm
Disruption of entire architecture
- vascular architecture > shunts that avoid HPV and HA blood bypasses
- progressive fibrosis
What mediates Cirrhosis
A number of inflammatory Cytokines (particularly Kupffer cells, also know as alveolar macrophages in lungs).
Activated Kupffer cell releases inflamm. CK release > fibrosis , changes in BVs
These all cause damage to normal hepatocytes (necrosis and apoptosis)
and initiate an inflammatory response (from fibrosis)
FIBROSIS > CIRRHOSIS
Complications of Cirrhosis
1) Impairment of Normal Hepatic Function- synthetic/detoxification fuunction
2) Impairment of Normal blood pressures/flow in the portal vein (those with chronic liver disease > portal hypertension)
What is portal hypertension?
Increased resistance to portal blood flow, due to increase in the blood pressure within a system of veins called the portal venous system leading to eventual reversal of blood flow
Causes of Portal Hypertension
Prehepatic: Obstructive Thrombosis (block in PV)
Post Hepatic : Severe right sided heart failure (rised r.side pressure)
Intrahepatic: Cirrhosis (90% cases)
Consequences of Portal hypertension
1) Porto-systemic Shunts: lead to
- Congestive Splenomegaly (big spleen)
- Eosophageal varices (loss of blood)
- Varices around umbilicus
And due to failure of liver to do normal function
2) Ascites
3) Hepatic encephalopathy (neurodegeneration)
Ascites?
accumulation of fluid in abdomen due to increased PV pressure, often with decreased serum albumin levels
Portosystemic Shunts
Bypasses where systemic and portal circulation share capillary beds
Viral Hepatitis
1) Hepatitis A, B, C (these most common 90-95%), D and E
2) Cytomegalovirus (herpes virus in immuno-suppressed patients)
3) Epstein-Barr Virus (glandular fever)
Hepatitis A
- Benign self-limited disease
- Incubation period= 2-6 weeks
- DOESN’T cause chronic hepatitis or cirrhosis (usual for it to progress)
- infection of hepatocytes due to poor hygiene
- by person-person, faecal/oral transmission
- asymptomatic or mild febrile illness +/- jaundice
- May have some hepatocellular damagemild elevated liver enzyme levels
Hepatitis B and C can develop to
chronic Hepatitis > cirrhosis > hepatocellular carcinoma)
Hepatitis B
- big global issue (350mill carriers)
- spread via body fluids
- can result in acute hepatitis with resolution OR damage and chronic hepatitis due to the bodies immunological response to infection
- CH > cirrhosis
Draw flow diagram of Hep B outcomes pg 163
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Hepatitis C
New Treatment
- Major Cause of Liver Disease
- vaccinations and blood transfusion
- acute infec. usually undetected
- Majority is CHRONIC DISEASE > (can havefibrosis > cirrhosis > Hep.carcinoma)
- > 20% will develop cirrhosis 5-10 years post infection
New Hep C antiviral treatment now available
Autoimmune Hepatitis
Chronic Progressive Hepatitis
Body is tricked immunologically to create an immune response against itself (self-antigens).
Features:
- genetic predisposition
- ass. with other autoimmune diseases
- presense of auto antibodies
What would you see?
How can you treat?
(AI hepatitis)
You will see an inflammatory infiltrate with lymphocytes and plasma cells
Treat via immunosuppresion
Drug and Toxin-induced Liver insults are classified as?
Predictable Hepatotoxins: act in dose-dependant matter and occur in most individuals eg paracetamol
Unpredictable Hepatotoxins
Hepatotoxins can act
1) directly cell toxic
(to hepatocytes)
2) Act through hepatic conversion to an active toxin or activate immune mechanisms
Drug and toxin-induced liver insults patterns of injury are?
What are the most common cause for acute and chronic
Varies from: Cholestasis, hepatocellular necrosis, Fatty liver disease, fibrosis, granulomas, neoplasms
Acute liver failure: paracetamol
Chronic Liver damage: alcohol
Alcoholic Liver Disease.
Pathological effects
Leading cause of liver disease in most western countries.
Pathological effect
- direct hepatocyte injury
- cell injury via ROS and cytokines
- changes lipid metabolism
- less export of lipoproteins
The pathological effects of Alcoholic Liver disease can lead to??
- Hepatic Steatosis (fatty change/accumulation)
- acute Alcoholic Hepatitis (post alcohol binge)
- Cirrhosis
Draw diagram pg 166
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Can Hepatitis, steatosis and Cirrhosis be reversed to normal with abstinence from alcohol
Hepatitis and Steatosis can over time
Cirrhosis cannot.
Non-Alcoholic Fatty Liver Disease (NAFLD)
Initially Hepatic Steatosis only (30% adults in western countries)
MAY (~20% cases) progress to steatosis + inflammation (NASH)
over 15years ~11% of patients will NASH will progress into cirrhosis
NASH
Non-Alcoholic Steatihepatitis
NAFLD is associated with
obesity
metabolic syndromes
Type 2 Diabetes
hypertension
Haemocromatosis
Excess accumulation of iron, which is stored in liver and pancreas
If it reaches critical levels it becomes toxic to hepatocytes and pancreatic islet cells
90% of the time it’s due to autosomal recessive genetic condition: Cys282Tyr mutation in the HFE gene
Leads to micronodular cirrhosis, diabetes, skin pigmentation
Cholestatic Diseases of the liver
Obstuctive liver damage
INTRAHEPATIC: Obstruction occurring to bile ducts or canalicculi within liver
EXTRAHEPATIC: Obstruction at the CBD or head of the pancreas
What are the two ways cholestasis of the liver can be caused?
1) Autoimmune Cholangiopathies:
2) Cholestasis of Sepsis
Autoimmune Cholangiopathies
Body acts against liver
Primary Biliary Cirrhosis- AI leads to destruction of bile canaliculi
Primary sclerosing cholangitis- AI leading to scarring of bile ducts
Cholestasis of Sepsis
Sepsis can affect the liver through
- Direct effects of intrahepatic infection (liver absess)
- Ischemia related to hypotension/shock
- Circulating microbial products. (particularly with gram-negative bacteria, E.coli)
Circulatory Disorders of the Liver.
Draw diagram pg 169
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Liver Tumors
Benign Neoplasms:
hepatocellular adenomas
Malignant Neoplasms: Hepatocellular carcinoma (common complication with cirrhosis of the liver) 'primary tumor'
BUT most common cancer is secondary usually from colon cancers.
