The Liver Flashcards
T or F. The liver has a massive reserve and has to have massive hepatocyte loss to see clinical change
T, in addition, the liver has the ability to repair itself. Even at the fibrotic stage.
What is this showing?
Hepatocyte necrosis
- osmotic regulation: fluid flows into the cell, which swells and ruptures.
- macrophages clean up
______ is the predominant mode of death in ischemic/hypoxic injury and a significant part of the response to oxidative stress.
Hepatic necrosis
What is this?
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)
What is this?
Confluent Necrosis = widespread parenchymal loss – zones matter
•Histologic manifestations are cellular debris, macrophages, and remnants of the reticulin meshwork.
What is this?
•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
How does hepatocyte regeneration occur?
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.
•The principal cell type involved in scar deposition is the _____ cell.
hepatic stellate
What are the functions of hepatic stellate cells?
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.
How are stellate cells activated to induce liver fibrosis?
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
What is this?
Cirrhosis
How does cirrhosis arise on a molecular level?
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.
Describe the immune system in the liver
- 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.
How does immune response affect the liver?
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.
Adaptive immunity plays an even more critical role in viral hepatitis. Give some examples
- 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.
Which hepatic zone has the lowest O2 and nutrient supplies? Is this zone very susceptible to anoxic, toxic and nutritional injury?
Zone III
What is this?
Diffuse microvesicular steatosis- Diffuse poisoning of liver cells without obvious cell death and parenchymal collapse
What are some causes of diffuse microvesicular steatosis?
•Examples: fatty liver of pregnancy or idiosyncratic reactions to toxins – however now known to be seen in a large variety of diseases
What causes microvesicular steatosis?
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
Steatosis
T or F. Regression can occur in fully established cirrhosis
T, does occur; this is another reason why cirrhosis should not be automatically equated with end stage disease
