Cell Injury

Mechanism of cell Injury. General Pathology

1. Cell Injury By Dr. Amnah Shaukat

2. Outline: Introduction Causes of C ell Injury Reversible & Irreversible Cell Injury Cell Death Necrosis Apoptosis

3. 1. Introduction: Cellular injury occurs when a stress exceeds the cell’s ability to adapt. The extent of injury depends upon type of stress, severity of stress and the type of cell affected. For example neurons suffer cell injury by ischemic(shortage of blood) stress while skeletal muscles may adapt & survive.

4. 1. Introduction: Similarly slow developing ischemia may cause atrophy while acute(sudden) ischemia results in cell injury. Causes of cell injury: Inflammation Nutritional deficiency Hypoxia Trauma Genetic mutations

5. 2. Causes of Cell Injury 1. Hypoxia 2. Inflammation 3. 4. Trauma 5. Gene Mutations

6. Hypoxia: Low oxygen delivery to tissues. Causes of hypoxia are; Ischemia(decreased blood supply to tissues) Hypoxemia(low partial pressure of oxygen in blood; on high altitude areas) Decreased Oxygen carrying capacity of blood; Anaemia(low H b levels) or Carbon monoxide poisoning.

7. 3 . Reversible & Irreversible cell Injury: Process of cell injury Hypoxia impairs the oxidative phosphorylation in the cell which leads to decreased ATP production ATP deficiency disrupts cell functions like Na+ K+ pump and aerobic glycolysis(use of glucose and oxygen to make energy/ATP). Cells switch to anaerobic glycolysis (anaerobic: in the absence of oxygen ).

8. 3. Reversible & Irreversible cell Injury: 4. At first the injury is reversible. Hallmark of reversible injury is C ellular S welling 5. Eventually the injury becomes irreversible. The hall mark of irreversible injury is M embrane D amage. 6. The end result of irreversible injury is Cell D eath .

9. 4. Cell death: The morphological hall mark of cell death is loss of Nucleus. Nucleus is lost by; Pyknosis (nuclear condensation) + Karyorrhesis (nuclear fragmentation) + Karyolysis (dissolution of nucleus)

10. 4. Cell death: There are two mechanisms of cell death; Necrosis (defined as death of large group of cells followed by acute inflammation. Due to some underlying pathology, never physiological). Apoptosis (energy dependent, genetically programmed cell death involving single cell of small group of cells).

11. 4(A). Necrosis:

12. 4(a). Necrosis: Gross patterns of necrosis include; Coagulative Necrosis Liquefactive Necrosis Gangrenous Necrosis Caseous Necrosis Fat Necrosis Fibrinoid Necrosis

13. 1. Coagulative necrosis: A type of necrosis in which the basic architecture of the cell and organ remains intact. The structure of organ is preserved by coagulation of proteins but the Nuclei disappear. Seen in ischemic infarction of organs except brain. A. Necrosis

14. Coagulative necrosis in kidney Wedge shaped infarction pointing to the area of occlusion of artery A. Necrosis

15. 2. Liquefactive Necrosis: Type of necrosis in which the necrotic tissue become liquefie d . Enzymatic degradation of proteins results in liquefaction. Infarction of brain, abscess formation and pancreatitis are examples of liquefactive necrosis. A. Necrosis

16. Liquefactive Necrosis in brain Area of ischemic infarction is liquefied A. Necrosis

17. 3. Gangrenous Necrosis: Ischemia of lower limb and GIT shows this pattern of necrosis. Dry gangrene: coagulative necrosis that resembles mummified tissue. Wet gangrene: infection of necrotic tissue causes liquefactive necrosis. A. Necrosis

18. A. Necrosis

19. 4. Caseous Necrosis: Soft and friable necrotic tissue with cottage cheese like appearance. It is a combination of coagulative and liquefactive necrosis. Examples are granulomatous inflammation in Tb and Fungal infection. A. Necrosis

20. Caseous Necrosis in Lung A. Necrosis

21. 5 . Fat Necrosis: Necrosis of adipose tissue with chalky-white appearance due to calcium deposition. Seen in trauma to fat tissue. For example breast tissue and peri-pancreatic fat. A. Necrosis

22. 6. Fibrinoid Necrosis: Necrotic damage to blood vessel wall. Leakage of proteins(including fibrin) into the vessel wall results in bright pink staining on microscopy. Seen in malignant hypertension and vasculitis. A. Necrosis

23. Fibrinoid Necrosis A. Necrosis

24. b. apoptosis: Energy(ATP) dependent, genetically programmed cell death involving single cell or small groups of cells. Examples include; Removal of cells during embryogenesis Killing of virally infected cells by immune system. Morphology includes; Dying cells shrink in size and cytoplasm becomes more eosinophilic(pink).

25. b. apoptosis: 2. Nucleus condenses and fragments in an organized manner. 3. Apoptotic bodies are formed from the cell and are eaten up by macrophages. 4. There is no inflammation after apoptosis.