Liver Pathology Flashcards

1
Q

What are the 2 scenarios when a biopsy is useful in liver pathology?

A

Establish primary diagnosis when not clear from other diagnostic modalities i.e. different modalities are suggesting different diagnoses

Provide additional information in cases where primary diagnosis already been made
I.e. grading inflammation or staging fibrosis

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2
Q

What are the 3 different methods of taking a liver biopsy?

A

Percutaneous (most common)

Transjugular
-helpful in cases of portal hypertension

Open
-occurs opportunistically during open surgery

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3
Q

What are the 3 components of portal tracts?

How can you differentiate between them histologically

A

Portal =vein

  • thin walled
  • larger than others
  • might contain RBC

Bile duct

  • lined with biliary epithelium i.e. tube surrounded by lining of single layer of cells
  • doesn’t contain any RBC

Hepatic artery

  • thick wall
  • might contained RBC

Surrounded by tissue= quiescent fibroblast

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4
Q

What is a hepatic sinusoid and what is its primary function?

What is a key characteristic of the endothelium lining the sinusoids?

A

Microvascular structure between portal vein and terminal hepatic vein which seperate hepatocytes

Site of exchange between the blood and perisinusoidal space (space of Disse)

Lined with fenestrated endothelium (sinusoidal epithelium

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5
Q

What is the space of Disse?

A

Perisinusoidal space containing stellate cells (lipocytes) which contain lipids and act to moderate fibrosis in disease

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6
Q

What are Kupffer cells?

A

Liver-resident macrophages

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7
Q

What are the 3 different zones in the liver parenchyma and what are the features/difference of each zone?

A

Zone 1= Periportal

  • best oxygenated-> most resistant to ischaemia
  • 1st effected by viral hepatitis or toxic substance i.e. will recieve then 1st preferentially to the other zones

Zone 2= Intermediate zone
-affected in yellow fever

Zone 3= pericentral/centrilobular zone

  • least oxygenated-> most susceptible to ischaemia
  • most sensitive to metabolic toxins due to being the furthers away from blood supply to remove the toxins
  • highest amount of CYP450

I.e. zone 1 receives oxygen 1st and zone 3 receives oxygen last

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8
Q

What are the different histological manifestations of liver disease?

A

Reversible liver injury

  • ballooning
  • steatosis
  • cholestasis

Inflammation

Cell death

Healing and repair

Neoplasia

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9
Q

Why does ballooning occur in liver pathology?

A

Occurs due to dysfunction of hepatocytes membrane due to damage leading to entry of sodium and water into the cell leading to accumulation of intracellular fluid and swelling of organelles

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10
Q

What are Mallory-Denk bodies and when do they occur?

A

Cytoplasmic inclusions within ballooned heptaocytes due to collapse of the cytoskeletal frame work leading to accumulation of keratins and ubiquitin
-pinky staining of ballooned hepatocytes

Can occur in NAFLD and ALD

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11
Q

What is steatosis and how does it appear histologically?

A

Accumulation of fat droplets within hepatocytes

White round circles which distend hepatocytes and displace nucleus to the edge

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12
Q

How does cholestasis present histologically?

A

Accumulation of bile in liver= bilirubinostasis
-appears as “bile plugs” in bilary tracts in liver parenchyma i.e. not normally present due to bile being excreted

Accumulation of copper
-due to copper normally being excreted in bile

Hepatocyte ballooning
-appears feathery due to cellular damamge from accumulated bile salts

Ductular reaction

  • proliferation of bilary tracts in portal tracts to try and regeneration bile structures and remove static bile
  • will see clusters of multiple biliary ducts when would only expect to see individual
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13
Q

What special stain is used to highlight copper deposition in hepatocytes?

A

Orcein stain

-makes copper deposists appear like dark granules within hepatocytes

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14
Q

What special stain can be used to better highlight ductular reaction?

A

Immunoperoxidase for CK7

I.e. CK7 is a marker for biliary epithelium

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15
Q

What are the 3 native antigen presenting cells in the liver?

A

Dendritic
Sinusoidal endothelial cells
Kupffer cells

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16
Q

Where does immune cell recruitment occur in the liver?

How does the process of acute inflammation and immune cell recruitment differ from the normal process?

A

Sinusoids and portal tracts

Vasodilation does not play significant role
Fenestrated endothelium means there does not need to be increased permeability
Plasma cells > neutrophils in most cases of acute hepatitis

17
Q

What are the 2 different locations of inflammation?

A

Lobular
-associated with sinusoids

Portal
-due to interface hepatits (spill over) or bile duct inflammation

18
Q

What is interface hepatits and what is the key histological feature?

A

Process of inflammation and erosion of hepatic parenchyma at junctiom with portal tracts

Leads to hepatocytes forming “rosset” pattern

19
Q

What would be the histological sign of apoptosis in liver histology?

A

Programmed cell death leading to cell shrinkage and formation of nuclear debris in single hepatocyte
I.e. hepatocytes becomes dark staining

20
Q

How would necrosis present in liver histology?

A

Cytoplasmic swelling and fragmentation of the nucleus

Affects many contiguous hepatocytes

21
Q

What is the mechanism behind the livers ability to regenerate?

A

Proliferation of differentiated cells
-hepatocyte adjacent to damage able to re-enter the cell cycle and proliferate

Proliferation of progenitor cells in canal of Hering
-stem cell niche located between bile canaliculi and ducts

22
Q

Why does chronic liver disease occur?

A

Persistant severe injury preventing the liver from regenerating properly leading to progessive fibrosis and vascular remodelling

23
Q

What is the underlying pathophysiology of fibrosis?

What occurs when portal tracts become damaged?

A

Damage to hepatocytes stimulates Kupffer cells to produce chemical mediators:
-TNF + PDGF= stimulate proliferation of stellare cells in space of Disse and quiescent fibroblast surrounding the portal tract
TGF-beta= stimulates collagen deposition and fibrogenesis

Leads to perisinusoidal fibrosis-> causes portal-central and central-central fibrous septa

Damaged portal tracts leads to activation of portal fibroblasts
-causes fibrous expansion of portal tracts and fibrous bridging

24
Q

What is the consequences of perisinusoidal deposition of collagen?

A

Inhibits the exchange of nutrients due to the collagen preventing movement between sinuisoids and hepatocytes

25
Q

What stain is used to highlight the collagen in fibrotic liver samples?

A

Hameatoxylin van Gieson stain

-stains collagen PINK

26
Q

What are the different histological fibrotic patterns?

A

Perisinusoidal fibrosis

Portal-based
-fibrous expansion of portal tract

Bridging fibrosis (2 portal tracts connected by fibrous bridge)

Periductal fibrosis

27
Q

What are the 3 characteristic features of cirrhosis?

A

Loss of normal liver architecture on micro and macro level

Nodular regeneration of hepatocytes

Fibrosis

28
Q

What vascular changes occur in cirrhosis?

A

Capillarisation of sinusoidal endothelium due to loss of fenestrations

Increased resistance in portal tracts and hepatic venules due to fibrosis

Formation of septal shunts within portal-central fibrous septa

Intrahepatic portal and hepatic vein thrombi
-possibly due to decreased ADAMTS13 production by stellate cells

29
Q

What are septal shunts?

A

New vessels form to bypass the damaged parenchyma leading to tissue become underperfused

30
Q

What are the clinical complications of cirrhosis?

A

HEPATOCELLULAR FAILURE
Jaundice
Hypoalbuminaemia
Bleeding tendency-> decreased producing of clotting factors
Hepatic encephalopathy
Impaired oestrogen metabolism
Hepatorenal and hepatopulmonary syndromes

PORTAL HYPERTENSION
Acites
Splenomegaly
Porto-systemic shunts

HEPATOCELLULAR CARCINOMA

31
Q

What do porto-systemic shunts form and what are examples of them?

A

The shunts open when the pressure in the portal venous system increases too much

Lower oesophageal varices
Rectal haemorrhoids
Umbilical caput medusae
Retroperitoneal shunts