CELL INJURY AND CELL DEATH

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Martina Day
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1 CELL INJURY AND CELL DEATH INTRODUCTION Cell Injury is a result of the sequence of events that occur if the limits of the adaptive capability of cells are exceeded or there is no adaptive response is possible, for specific stimuli or injurious agents. There are several of factors or occurrences that cause cell injury such as ischemia, hypoxia, chemical injury and infectious stimuli like bacteria and viruses. Different changes inside the cell s environment and organelles occur when it is injured and different mechanisms of cell injury can be observed. Depletion in ATP, mitochondrial damage, influx of Calcium, presence of free radicals and defects in the permeability of cells. In order for cells to adapt to these stresses, cells developed different cellular adaptations. These are the reversible changes in the number, size, phenotype, metabolic activity or functions of cells in response to the changes in their environment. Hypertrophy, hyperplasia, atrophy and metaplasia are some of the adaptations that are being utilized by the cells in the body as the need arises. However, if the cells weren t able to adapt to stress, it leads to cell death, to either necrosis or apoptosis. Necrosis is the type of cell death that is associated with loss of membrane integrity and leakage of cellular contents resulting to dissolution of cells. There are several types of necrosis: coagulative, liquefactive, gangrene, caseous, fat and fibrinoid necrosis. As for apoptosis, or the process of programmed cell death is a pathway of cell death that is induced by a tightly regulated suicide program in which cells destined to die activate enzymes that degrade the cells' own nuclear DNA and nuclear and cytoplasmic proteins. This case study includes photographs and micrographs of different diseases. It aims to help the students to explain descriptively the gross and histopathologic changes seen in clinical examples of cellular adaptation and cell injury. Another objective of this activity is to link the microscopic findings of specific examples of cellular adaptation and cell injury to its pathologic causes and clinical presentation. CASE 1 Clinical History: R.M., 48-year-old, male died of cerebral hemorrhage. He had a longstanding history of poorly controlled hypertension (BP = 210/140). Gross specimen: Postmortem examination of his heart showed that it weighed 835 grams (Normal = grams). The heart was cut in cross-sectional "bread loaf" slices. In this image, the rounded left ventricle is on the right and the triangular right ventricle is on the left. The wall of the left ventricle concentrically measured approximately 2.5 cm in width (normal width, ~1 cm).

(Photograph of the heart specimen) Normal

2 (Photograph of the heart specimen) Normal Histology Before you look at the case, you may wish to review the histology of the normal myocardium at several increasing powers of magnification. Observe the intracytoplasmic striations and central nuclei.

Histological Section of Patient's Heart This is a transmural histological

For orientation, the ventricular cavity is to the left (marked with a heart

(The endocardium is not evident at this magnification.

3 Histological Section of Patient's Heart This is a transmural histological section of the patient's heart removed at autopsy (Virtual Slide 001). For orientation, the ventricular cavity is to the left (marked with a heart icon). An arrow indicates a papillary muscle. (The endocardium is not evident at this magnification.) To the right is the epicardium, with a star icon indicating the epicardial fat. Look at this slide at higher magnification in the area marked by the box.

Case Study Questions: 1. What pathological diagnosis (of the heart tissue) would appear on the report? 2. Explain your answer above by defining the pathological diagnosis you had made 3.

4 Compare the patient's myocardium (on the left) with the normal myocardium (on the right) observed at the same magnification. Study Questions: 1. Describe the cytoplasmic and nuclear changes in the cells compared to normal. 2. What subcellular (organelle) component would be most likely to have been increased in the cells? Case Study Questions: 1. What pathological diagnosis (of the heart tissue) would appear on the report? 2. Explain your answer above by defining the pathological diagnosis you had made 3. Is this morphological change indicative of cell death? If not, what cellular change is this? Explain your answer 4. What specific clinical cause could explain the myocardial change in this patient? 5. What are the other etiologies that can produce similar histological changes in the heart? Additional Questions on Cellular Change The following are photographs and micrographs of different organs that had undergone cellular adaptations, identify each adaptation, identify the possible etiology and describe your answers briefly. 1. Breast

5 2. Trachea 3. Kidney

6 (ANSWER SHEET) STUDY QUESTIONS CASE STUDY QUESTIONS: ADDITIONAL QUESTIONS ON CELLULAR CHANGE PHOTO # Cell Adaptation/Change Description Etiology (END)

Mechanisms of Cell Injury

Mechanisms of Cell Injury Causes of Cell Injury 1- oxygen deprivation (anoxia) 2- physical agents 3- chemical agents 4- infections agents 5- immunologic reactions 6- genetic defects 7- nutritional imbalances Mechanisms of Cell