Cell Injury 2 (2023) PDF

Cell injury (part2) Assistant professor Noora Mustafa  Objectives Causes of cell injury Mechanism of cell injury Morphologic alteration of cell injury Pathogenesis of cell injury Patterns of necrosis what causes apoptosis?  Causes of Cell Injury 1.Oxygen deprivation (h...

Cell injury (part2) Assistant professor Noora Mustafa  Objectives Causes of cell injury Mechanism of cell injury Morphologic alteration of cell injury Pathogenesis of cell injury Patterns of necrosis what causes apoptosis?  Causes of Cell Injury 1.Oxygen deprivation (hypoxia) affects aerobic respiration and therefore ability to generate adenosine triphosphate (ATP). This extremely important and common cause of cell injury and death occurs as a result of: Ischemia (loss of blood supply) Inadequate oxygenation (e.g., cardiorespiratory failure) Loss of oxygen-carrying capacity of the blood (e.g., anemia, carbon monoxide poisoning 2.Physical agents, including trauma, heat, cold, radiation, and electric shock 3. Chemical agents and drugs, including therapeutic drugs, poisons, environmental pollutants, and “social stimuli” (alcohol andnarcotics) 4.Infectious agents, including viruses, bacteria, fungi, and parasites 5.Immunologic reactions, including autoimmune diseases and cell injury following responses to infection 6. Genetic derangements, such as chromosomal alterations and specific gene mutations 7.Nutritional imbalances, including protein–calorie deficiency or lack of specific vitamins, as well as nutritional excess Ultra structural changes of reversible and irreversible cell injury Reversible vs. irreversible Morphologic changes in reversible and irreversible cell injury (necrosis). A, Normal kidney tubules with viable epithelial cells. B, Early (reversible) ischemic injury showing surface blebs, increased eosinophilia of cytoplasm, and swelling of occasional cells. C, Necrotic (irreversible) injury of epithelial cells, with loss of nuclei and fragmentation of cells and leakage of contents. Mechanisms of Cell Injury Cell injury results from disruption of any of the five essential cellular elements: ATP production (mostly through effects on mitochondrial aerobic respiration) Mitochondrial integrity independent of ATP production Plasma membrane integrity, responsible for ionic and osmotic homeostasis Protein synthesis, folding, degradation, and refolding Integrity of the genetic apparatus Sources and consequences of increased cytosolic calcium in cell injury  Necrosis Necrosis is the sum of the morphologic changes that follow cell death in living tissue or organs. Two processes underlie the basic morphologic changes: Denaturation of proteins Enzymatic digestion of organelles and other cytosolic components  Pattern of necrosis Coagulative necrosis: is the most common pattern, predominated by protein denaturation with preservation of the cell and tissue framework. This pattern is characteristic of hypoxic death in all tissues except the brain. This is normal kidney tubules to compare with the above image  Liquefactive necrosis occurs when autolysis or heterolysis predominates over protein denaturation. The necrotic area is soft and filled with fluid. This type of necrosis is most frequently seen in localized bacterial infections (abscesses) and in the brain. Caseous necrosis is characteristic of tuberculous lesions; it appears grossly as soft, friable, “cheesy” material and microscopically as amorphous eosinophilic material with cell debris.  Fat necrosis is seen in adipose tissue; lipase activation (e.g., from injured pancreatic cells or macrophages) releases fatty acids from triglycerides, which then complex with calcium to create soaps. Grossly, these are white, chalky areas (fat saponification); histologically, there are vague cell outlines and calcium deposition. Late stage of fat necrosis shows peripheral dystrophic calcifications in the dense fibrotic cystic wall.  Fibrinoid necrosis is a pathologic pattern resulting from antigen-antibody (immune complex) deposition in blood vessels. Microscopically there is bright-pink amorphous material (protein deposition) in arterial walls, often with associated inflammation and thrombosis. Normal blood vessle  Causes of apoptosis Apoptosis in Physiologic Situations : Death by apoptosis is a normal phenomenon that serves to eliminate cells that are no longer needed and to maintain a steady number of various cell populations in tissues. It is important in the following physiologic situations: The programmed destruction of cells during embryogenesis including implantation, organogenesis, developmental involution, and metamorphosis.  Apoptosis in Pathologic Conditions Apoptosis eliminates cells that are genetically altered or injured beyond repair without eliciting a severe host reaction, thus keeping the damage as contained as possible. Death by apoptosis is responsible for loss of cells in a variety of pathologic states: DNA damage. Radiation, cytotoxic anticancer drugs, extremes of temperature, and even hypoxia can damage DNA, either directly or via production of free radicals. If repair mechanisms cannot cope with the injury, the cell triggers intrinsic mechanisms that induce apoptosis. In these situations, elimination of the cell may be a better alternative than risking mutations in the damaged DNA, which may progress to malignant transformation. These injurious stimuli cause apoptosis if the insult is mild, but larger doses of the same stimuli result in necrotic cell death Thank you