API

Relationship: 1830

Title

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N/A, Cell injury/death leads to Necrotic Tissue

Upstream event

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N/A, Cell injury/death

Downstream event

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Necrotic Tissue

Key Event Relationship Overview

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AOPs Referencing Relationship

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AOP Name Adjacency Weight of Evidence Quantitative Understanding
IKK complex inhibition leading to liver injury adjacent High High

Taxonomic Applicability

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Sex Applicability

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Life Stage Applicability

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Key Event Relationship Description

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Cell death can help the maintenance of the organ, for example by avoiding cancer. However, in the KER, cell death will lead to necrotic tissue. If too many cells die, the tissue will fall apart.

There are several types of necrotic tissue caused by cell death:

Apoptosis (individual cell necrosis), spotty and focal necrosis, zonal necrosis confluent necrosis. Every type can have a different underlying disease. All types can occur by drug induced liver injury.(Krishna 2017).

Evidence Supporting this KER

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Biological Plausibility

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It has been well established that cell death can lead to necrotic tissue.

Reviews:

(Guicciardi et al. 2013): Apoptosis and necrosis in the liver.

(Luedde et al. 2014): Cell death in liver disease.

Empirical Evidence

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Uncertainties and Inconsistencies

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Quantitative Understanding of the Linkage

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Response-response Relationship

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Time-scale

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Known modulating factors

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Known Feedforward/Feedback loops influencing this KER

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Domain of Applicability

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References

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Krishna, M., 2017. Patterns of Necrosis in Liver Disease. , 10(2), pp.53–56.

Guicciardi, M.E. et al., 2013. Apoptosis and Necrosis in the Liver. Comprehensive Physiology, 3(2), pp.977–1010. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3867948&tool=pmcentrez&rendertype=abstract.

Luedde, T., Kaplowitz, N. & Schwabe, R.F., 2014. Cell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance. Gastroenterology., 14(11), pp.871–882.