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

Liver Pathology Flashcards by Libby Halligan

Normal liver size?

1400g-1600g

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Functional unit

acini
Have three zones
1, 2 and 3
Based around terminal hepatic vein(central vein)

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anatomical component

Hepatic Lobule

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Porta Hepatis

Main entry point into the liver.

A fissure where the Bile Duct, Hepatic portal vein and Proper hepatic artery enter/exit

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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

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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

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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)

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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

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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)

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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

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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.

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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

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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

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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)

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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

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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)

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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)

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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

…

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

...

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.