pathology sheet # 4

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pathology sheet # 4

Post by Shadi Jarrar on 28/9/2010, 11:57 pm

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- Pathology Sheet #4
- Dr. Fatima Obeidat
- 26.9.2010
- Done by: Dania Salhab

* Slide no. 64...Ischemia-reperfusion injury…
- For example if we have a thrombus in the coronary artery this can cause ischemia in the heart which is reversible initially and with the restoration of the blood supply the cells will return to normal, but if the injury to the cells was irreversible, the cells will remain dead.

- As we know not all the cells undergo cell death at the same time, we have cells that are in the center of the legion that are irreversibly injured but surrounded by reversibly injured cells, for example in myocardial ischemia/necrosis some cells will undergo cell death before others.

- If we did a thrombolysis (lysis for the thrombus) with normal restoration of the blood supply, the reversibly injured cells will return to normal in the majority of the patients, but in other patients the reversibly injured cells will undergo irreversible cell injury which means that the size of the infarct will increase…what we call (Ischemia-reperfusion injury).

* Slide no. 65-66…Mechanisms of Ischemic-reperfusion injury…
1. As we said before, with the restoration of the blood supply (oxygen) to reversibly injured cells, when the mitochondria functions fully and normally, the injury will completely reduced, but with irreversible injured cells there will be some dysfunction mitochondria that will cause partial reduction to the oxygen that comes from the blood resulting in oxygen free radicals.

2. With the restoration of the blood supply the neutrophils will accumulate at the side of the injury because of the expression of adhesion molecules, this will produce free radicals and that will damage the reversibly injured cells, convert them into irreversible injured cells and increase the size of necrosis.

3. In ischemic tissues there will be increased deposition of IGM for unknown reasons. With the restoration of the blood supply, the IGM will bind with complement resulting in activation the complement system and production of certain substances…that will cause more damage and will lead to convert the reversible injured cells into irreversible injured cells.

* Slide no. 67…Chemical injury…
- Some chemicals might cause injury by direct action that doesn’t need any previous activation by certain enzymes, other chemicals should be activated by certain enzymes to be converted into active substances that might cause injury.

- Mercuric Chloride can bind directly to the proteins of the cell membrane resulting in damage to the membrane which will increase the permeability to (Ca++ ) so activation of many enzymes we took before.

* Slide no. 68…CCl4…
- Correction for the slide:
Point no.3…dissociation of ribosomes from the ROUGH endoplasmic reticulum…

- CCl4 will be activated by the enzyme P450 (which presents in the smooth endoplasmic reticulum) into free radicals CCl3.
- The injury mainly will be to the liver because the metabolism of CCl4 occurs there.

- CCl3 will cause lipid peroxidation of the membranes which is an autocatalytic reaction that produce another free radicals, which called Aldehyde free radicals, and these free radicals will also cause lipid peroxidation to other membranes in the cell, one of them is the rough endoplasmic reticulum which causes a decrease in the protein synthesis and that will cause accumulation of triglycerides in the cell, so we will have a fatty change.

- Also the damage to the plasma membranes will cause increase in the influx of (Ca++ ) and this will activate enzymes that will cause cell death by necrosis.

- Another damage will be to the mitochondria that will lead to more depletion of the ATP synthesis…more damage will occur to the cell.

* Slide no. 70…Apoptosis…
- As mentioned in the slide, the plasma membrane of the cell will remain intact (differs from necrosis) so there will be no leakage of the intracellular component into the outside environment, so no host reaction.

* Slide no. 71…
- As mentioned before apoptosis can occur in association with necrosis in certain pathological situations, if the injury was severe the apoptosis may progress into necrosis.

- The apoptotic cells will express certain molecules on their surfaces so they will rapidly phagocytosed by the macrophages without inducing any host reaction, and because of this sometimes we can’t see apoptosis by microscope.

* Slide no. 72…Differences…
- Because of protein cleavage in apoptosis, there will be shrinkage in the cell and the organelles will be compact to each other, so the size of the cell will be small.

- Most important feature is that the plasma membrane will remain intact, so no leakage of the contents of the cell…no inflammation.

* Slide no. 73…Causes of apoptosis…
- During embryogenesis we need constant number of cells, so there will be loss of cells by the process of apoptosis.

- During menopause there will be loss of involution of the follicles, also by the process of apoptosis.

- When the immune reaction finishes the lymphocytes will be lost also by the process of apoptosis.

* Slide no.74…
- Patients that have cancer take radiation and anticancer chemotherapy, and sometimes these can cause damage to the DNA of the normal cells by the free radicals, but we have a repair mechanism to repair this and if these mechanisms failed to repair, the cell will kill itself by activation of apoptotic mechanisms.
- Sometimes because of mutations in the gene or maybe because of free radicals, there will be improper folded proteins and this can cause injury to the cell, the cell will kill itself by the process of apoptosis.

* Slide no. 75…
- In cases of vital hepatitis (especially hepatitis B) the viral infected cells will be killed by the process of apoptosis, and killing of these cells will be by cytotoxic lymphocytes.

- Also in some viral infections by certain viruses (like HIV) the cell will kill itself by the process of apoptosis.

* Slide no. 76…Morphology of apoptosis…
- Correction for the slide:
Pint no.3…Formation of cytoplasmic BUDS and apoptotic bodies…
Shadi Jarrar
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عدد المساهمات : 997
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تاريخ التسجيل : 2009-08-28
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الموقع : Amman-Jordan

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