patoloji-ders-notlari

Title

Serdar Balcı

General Features of Pathology of Liver

Serdar BALCI, MD

Liver

1400-1600 gr
Dual blood supply
Bile flow
Well defined 3D structure
Exocrine organ
Endocrine organ
Center for biochemistry
- Anabolism, catabolism, detoxification

Robbins Basic Pathology

Atlas of Liver Pathology

Robbins Basic Pathology

LIVER INJURY

Degenerative, potentially reversible changes

Accumulation of fat (steatosis)

Accumulation of bilirubin (cholestasis)

When injury is not reversible:Necrosis or Apoptosis

Necrosis
- Ischemic/hypoxic injury
- Response to oxidative stress
Apoptosis
- Acidophilic apoptotic bodies
- Councilman bodies (yellow fever)
- Acidophil bodies

Necrosis

Confluent necrosis
- a severe, zonal loss of hepatocytes
- widespread parenchymal loss
- begin as a zone of hepatocyte dropout around the central vein → this space is filled by cellular debris, macrophages, and remnants of the reticulin meshwork
Bridging necrosis
- Necrosis zone link central veins to portal tracts or bridge adjacent portal tracts

apoptotic hepatocytes

acidophil bodies

**focus of mononuclear infiltration **

clusters of macrophages with eosinophilic cytoplasm indicate foci where hepatocytes have undergone necrosis

Normal liver with patent portal and hepatic veins

**Extinction occurs when contiguous hepatocytes die, usually after inflammatory injury to their blood supply **

Empty parenchyma collapses and begins to scar and adjacent portal tracts and hepatic veins become approximated

Scars in regions of extinction contract and condense, becoming fibrous septa

Septa elongate by the traction caused by hyperplasia of adjacent hepatocytes

Septa are resorbed. The resulting tissue has either venoportal fibrous adhesions or hepatic veins that are closely approximated to portal tracts. Portal tracts are remnants, often with no portal vein

Regeneration of lost hepatocytes

Occurs primarily by mitotic replication of hepatocytes adjacent to those that have died, even when there is significant confluent necrosis
Hepatocytes are almost stem cell-like in their ability to continue to replicate even in the setting of years of chronic injury
- Stem cell replenishment is usually not a significant part of parenchymal repair.
In most severe forms of acute liver failure
- Activation of the primary intrahepatic stem cell niche (canal of Hering)

Robbins Basic Pathology

Robbins and Cotran Pathologic Basis of Disease

Scar Formation and Regression

Principal cell type involved in scar deposition is the hepatic stellate cell
- Normally it is a lipid (vitamin A) storing cell
- Become activated and are converted into highly fibrogenic myofibroblasts
Stellate cells are activated by
chronic inflammation, with production of inflammatory cytokines such as tumor necrosis factor (TNF), lymphotoxin, and interleukin-1β (IL-1β), and lipid peroxidation products
Cytokine and chemokine production by Kupffer cells, endothelial cells, hepatocytes, and bile duct epithelial cells
In response to disruption of the extracellular matrix (ECM)
Direct stimulation of stellate cells by toxins

types I and III collagen and other ECM components

Robbins Basic Pathology

types I and III collagen and other ECM components

Robbins Basic Pathology

ACUTE HEPATITIS

Robbins Basic Pathology

Acute Hepatitis

Mild acute hepatitis gross inspection
- Liver is normal or slightly mottled
Massive hepatic necrosis
- Shrink to 500 to 700 g
- Limp, red organ covered by a wrinkled, baggy capsule
Entire liver may be involved, or only patchy areas affected
Necrotic areas have a muddy-red, mushy appearance with blotchy bile staining
If patients survive for more than a week, surviving hepatocytes begin to regenerate
If the parenchymal framework is preserved, regeneration is orderly and liver architecture is restored
More massive destruction, regeneration is disorderly, yielding nodular masses of liver cells separated by granulation tissue and, eventually, scar, particularly in patients with a protracted course of submassive necrosis
Hepatocyte injury
Swelling (ballooning degeneration)
- empty-appearing pale cytoplasm
- rupture and undergo necrosis (cytolysis)
- Necrotic cells appear to have dropped out, leaving collapsing sinusoidal collagen reticulin framework behind
Apoptosis
- Hepatocytes shrink
- Intensely eosinophilic
- Fragmented nuclei
- Effector T cells may be present in the immediate vicinity
When located in the parenchyma away from portal tracts, these features are called lobular hepatitis

**Acute viral hepatitis showing disruption of lobular architecture, inflammatory cells in sinusoids, and apoptotic cells **

Robbins Basic Pathology

In severe cases, confluent necrosis of hepatocytes is seen around central veins

Cellular debris, collapsed reticulin fibers, congestion/hemorrhage, and variable inflammation

Increasing severity, central-portal bridging necrosis develops

Parenchymal collapse

Massive hepatic necrosis and fulminant liver failure

Massive hepatic necrosis

the wrinkled capsule and irregular nodularity of the generally necrotic liver is due to collapse of the parenchyma

Autopsy Pathology: A Manual and Atlas

Massive necrosis, cut section of liver. The liver is small (700 g), bile-stained, soft, and congested

Hepatocellular necrosis caused by acetaminophen overdose. Confluent necrosis is seen in the perivenular region (zone 3)

Robbins and Cotran’s Pathological Basis of Diseases

CHRONIC HEPATITIS

Robbins Basic Pathology

Chronic Hepatitis

Portal inflammation in acute hepatitis is minimal or absent

Dense mononuclear portal infiltrates of variable prominence are the defining lesion of chronic hepatitis

There is often interface hepatitis as well,

Distinguished from lobular hepatitis by its location at the interface between hepatocellular parenchyma and portal stroma (or scars, when present)

The hallmark of severe chronic liver damage is scarring. At first, only portal tracts exhibit fibrosis, but in some patients, with time, fibrous septa —bands of dense scar—will extend between portal tracts

In the most severe cases, continued scarring and nodule formation leads to the development of cirrhosis