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Digestive System > Liver Pathology > Flashcards

Liver Pathology Flashcards

1
Q

Normal liver size?

A

1400g-1600g

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2
Q

Functional unit

A

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

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3
Q

anatomical component

A

Hepatic Lobule

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4
Q

Porta Hepatis

A

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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5
Q

Purpose of zones? Other names for zones are?

A

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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6
Q

What are the Four general features of Hepatic disease

A

1: the patterns of hepatic injury
2: hepatic failure
3: cirrhosis (distinct to liver)
4: portal hypertension

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7
Q

1 Patterns of hepatic injury are?

A

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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8
Q

2 Hepatic Failure

A

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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9
Q

Clinical Features of Hepatic Failure

A

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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10
Q

Paracetamol in excessive dosage is? What would you see with this?

A

‘Hepatotoxic’

  • Hepatocellular necrosis (loss of normal hepatocyte structure) near hepatic /central vein
  • Normal anatomy/tissue around portal triad
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11
Q

Cirrhosis

A

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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12
Q

Physical features of Cirrhosis

A

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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13
Q

What mediates Cirrhosis

A

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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14
Q

Complications of Cirrhosis

A

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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15
Q

What is portal hypertension?

A

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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16
Q

Causes of Portal Hypertension

A

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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17
Q

Consequences of Portal hypertension

A

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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18
Q

Ascites?

A

accumulation of fluid in abdomen due to increased PV pressure, often with decreased serum albumin levels

19
Q

Portosystemic Shunts

A

Bypasses where systemic and portal circulation share capillary beds

20
Q

Viral Hepatitis

A

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)

21
Q

Hepatitis A

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
22
Q

Hepatitis B and C can develop to

A

chronic Hepatitis > cirrhosis > hepatocellular carcinoma)

23
Q

Hepatitis B

A
  • 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
24
Q

Draw flow diagram of Hep B outcomes pg 163

A

…

25
Q

Hepatitis C

New Treatment

A
  • 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

26
Q

Autoimmune Hepatitis

A

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
27
Q

What would you see?
How can you treat?

(AI hepatitis)

A

You will see an inflammatory infiltrate with lymphocytes and plasma cells

Treat via immunosuppresion

28
Q

Drug and Toxin-induced Liver insults are classified as?

A

Predictable Hepatotoxins: act in dose-dependant matter and occur in most individuals eg paracetamol

Unpredictable Hepatotoxins

29
Q

Hepatotoxins can act

A

1) directly cell toxic
(to hepatocytes)
2) Act through hepatic conversion to an active toxin or activate immune mechanisms

30
Q

Drug and toxin-induced liver insults patterns of injury are?

What are the most common cause for acute and chronic

A

Varies from: Cholestasis, hepatocellular necrosis, Fatty liver disease, fibrosis, granulomas, neoplasms

Acute liver failure: paracetamol
Chronic Liver damage: alcohol

31
Q

Alcoholic Liver Disease.

Pathological effects

A

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
32
Q

The pathological effects of Alcoholic Liver disease can lead to??

A
  • Hepatic Steatosis (fatty change/accumulation)
  • acute Alcoholic Hepatitis (post alcohol binge)
  • Cirrhosis
33
Q

Draw diagram pg 166

A

…

34
Q

Can Hepatitis, steatosis and Cirrhosis be reversed to normal with abstinence from alcohol

A

Hepatitis and Steatosis can over time

Cirrhosis cannot.

35
Q

Non-Alcoholic Fatty Liver Disease (NAFLD)

A

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

36
Q

NASH

A

Non-Alcoholic Steatihepatitis

37
Q

NAFLD is associated with

A

obesity
metabolic syndromes
Type 2 Diabetes
hypertension

38
Q

Haemocromatosis

A

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

39
Q

Cholestatic Diseases of the liver

A

Obstuctive liver damage
INTRAHEPATIC: Obstruction occurring to bile ducts or canalicculi within liver

EXTRAHEPATIC: Obstruction at the CBD or head of the pancreas

40
Q

What are the two ways cholestasis of the liver can be caused?

A

1) Autoimmune Cholangiopathies:

2) Cholestasis of Sepsis

41
Q

Autoimmune Cholangiopathies

A

Body acts against liver
Primary Biliary Cirrhosis- AI leads to destruction of bile canaliculi
Primary sclerosing cholangitis- AI leading to scarring of bile ducts

42
Q

Cholestasis of Sepsis

A

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)
43
Q

Circulatory Disorders of the Liver.

Draw diagram pg 169

A

…

44
Q

Liver Tumors

A

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.

Digestive System (27 decks)

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