The Liver

Question 1

T or F. The liver has a massive reserve and has to have massive hepatocyte loss to see clinical change

Answer 1

T, in addition, the liver has the ability to repair itself. Even at the fibrotic stage.

Question 2

Answer 2

Question 3

What is this showing?

Answer 3

Hepatocyte necrosis

• osmotic regulation: fluid flows into the cell, which swells and ruptures.
• macrophages clean up

Question 4

______ is the predominant mode of death in ischemic/hypoxic injury and a significant part of the response to oxidative stress.

Answer 4

Hepatic necrosis

Question 5

What is this?

Answer 5

Hepatocyte apoptosis- active form of “programmed” cell death resulting in:

hepatocyte shrinkage,

nuclear chromatin condensation (pyknosis),

fragmentation (karyorrhexis), and

cellular fragmentation into acidophilic apoptotic bodies (Councilman bodies; acidophil bodies)

Question 6

What is this?

Answer 6

Confluent Necrosis = widespread parenchymal loss – zones matter

•Histologic manifestations are cellular debris, macrophages, and remnants of the reticulin meshwork.

Question 7

What is this?

Answer 7

•In bridging necrosis this zone may link central veins to portal tracts or bridge adjacent portal tracts

•In some cases there is scar regression as depicted in the figure

Question 8

How does hepatocyte regeneration occur?

Answer 8

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 and thus stem cell replenishment is usually not a significant part of parenchymal repair.

Question 9

•The principal cell type involved in scar deposition is the _____ cell.

Answer 9

hepatic stellate

Question 10

What are the functions of hepatic stellate cells?

Answer 10

In its quiescent form, it is a lipid (vitamin A) storing cell. However, in several forms of acute and chronic injury, the stellate cells can become activated and are converted into highly fibrogenic myofibroblasts.

Question 11

How are stellate cells activated to induce liver fibrosis?

Answer 11

First, Kupffer cell activation from injury leads to secretion of multiple cytokines, including PDGF and TNF, which activate stellate cells. and promote chemotaxis of activated stellate cells to areas of injury via PDGF and monocyte chemotactic protein-1 (MCP-1).

Contraction of the activated stellate cells is stimulated by endothelin-1 (ET-1) and fibrosis is stimulated by TGF-β

Question 12

What is this?

Answer 12

Cirrhosis

Question 13

How does cirrhosis arise on a molecular level?

Answer 13

Zones of parenchymal loss from fibrosis transform into dense fibrous septa due to a combination of the collapse of the underlying reticulin where large swaths of hepatocytes have irrevocably disappeared and hepatic stellate cells have been activated.

Eventually, these fibrous septa encircle surviving, regenerating hepatocytes in the late stages of chronic liver diseases that give rise to diffuse scarring described as cirrhosis.

Question 14

Describe the immune system in the liver

Answer 14

• Antigens in the liver are taken up by antigen presenting cells, including, Kupffer cells and blood-derived dendritic cells, and presented to lymphocytes.
• Toll-like receptors detect host molecules, and also those derived from foreign invaders such as bacteria and viruses.

Question 15

How does immune response affect the liver?

Answer 15

These processes lead to elaboration of proinflammatory cytokines, which have diverse effects on the liver, including recruitment of inflammatory cells, hepatocyte injury, vascular disturbances, promotion of scarring, and perhaps even malignant transformation.

Question 16

Adaptive immunity plays an even more critical role in viral hepatitis. Give some examples

Answer 16

• Antigen-specific and CD8+ T cells are involved in eradication of hepatitis B and C, the primary causes of chronic viral hepatitis, largely through elimination of infected hepatocytes.
• Lymphocytes, however, not only play a destructive role, but also help induce local hepatocyte replication through secretion of cytokines.

Question 17

Which hepatic zone has the lowest O2 and nutrient supplies? Is this zone very susceptible to anoxic, toxic and nutritional injury?

Answer 17

Zone III

Question 18

Answer 18

Question 19

What is this?

Answer 19

Diffuse microvesicular steatosis- Diffuse poisoning of liver cells without obvious cell death and parenchymal collapse

Question 20

What are some causes of diffuse microvesicular steatosis?

Answer 20

•Examples: fatty liver of pregnancy or idiosyncratic reactions to toxins – however now known to be seen in a large variety of diseases

Question 21

What causes microvesicular steatosis?

Answer 21

Not much is known regarding the pathogenesis of microvesicular steatosis but in many instances the primary defect could be a mitochondrial lesion, and inhibition of the mitochondrial beta oxidation of fatty acids has been the most frequently implicated defect

Question 22

Steatosis

Question 23

Question 24

T or F. Regression can occur in fully established cirrhosis

Answer 24

T, does occur; this is another reason why cirrhosis should not be automatically equated with end stage disease

Question 25

Describe the regression of cirrhosis

Answer 25

scars can become thinner, more densely compacted, and eventually fragment. As fibrous septa break apart, adjacent nodules of regenerating parenchyma coalesce into larger islands

Question 26

Answer 26

Hep B ground glass Hepatocytes

Question 27

Answer 27

Question 28

Describe Autoimmune Hepatitis

Answer 28

•Chronic, progressive hepatitis with all the features of autoimmune diseases in general: genetic predisposition, association with other auto­immune diseases, presence of autoantibodies, and therapeutic response to immunosuppression.

Question 29

There are two primary types of autoimmune hepatitis, Types I and II. Describe type I

Answer 29

•Type 1 autoimmune hepatitis is most often seen in middle-aged women and is most characteristically associated with antinuclear and anti–smooth muscle antibodies (ANA and ASMA)

Question 30

There are two primary types of autoimmune hepatitis, Types I and II. Describe type II

Answer 30

•Type 2 autoimmune hepatitis is most often seen in children or teenagers and is associated with anti-liver kidney microsomal autoantibodies (anti-LKM1)

Question 31

What is a prominent and characteristic component of autoimmune hepatitis?

Answer 31

Plasma cells