Cell Injury and Death PDF

CELL INJURY AND CELL DEATH Ng’walali P.M. (MD, PhD, FCPath (ECSA)  CAUSES OF CELL INJURY The causes of cell injury range from the gross physical trauma to the single gene defect that results in a nonfunctional enzyme underlying a specific metabolic disease Most injurious stimuli c...

CELL INJURY AND CELL DEATH Ng’walali P.M. (MD, PhD, FCPath (ECSA)  CAUSES OF CELL INJURY The causes of cell injury range from the gross physical trauma to the single gene defect that results in a nonfunctional enzyme underlying a specific metabolic disease Most injurious stimuli can be grouped into the following categories:  Oxygen Deprivation: Hypoxia, or oxygen deficiency, interferes with aerobic oxidative respiration common cause of cell injury and death  Chemical Agents: An increasing number of chemical substances; even innocuous substances such as glucose, salt, or even water, if absorbed in excess  Immunologic Reactions: Although the immune system defends the body against pathogenic microbes, immune reactions can also result in cell and tissue injury  Infectious Agents: Submicroscopic viruses to meter-long tapeworms; rickettsiae, bacteria, fungi, and protozoans  Genetic Factors: Genetic defects may cause cell injury as a consequence of deficiency of functional proteins, such as enzymes in inborn errors of metabolism, or accumulation of damaged DNA  Nutritional Imbalances: Protein–calorie insufficiency among underprivileged populations  Physical Agents: Trauma, extremes of temperature, radiation, electric shock, and sudden changes in atmospheric pressure  Aging: Cellular senescence leads to alterations in replicative and repair abilities of individual cells and tissues; result in a diminished ability to respond to damage Reversible Cell Injury:  The two main morphologic correlates of reversible cell injury are cellular swelling and fatty change  Cellular swelling is the result of failure of energy- dependent ion pumps in the plasma membrane, leading to an inability to maintain ionic and fluid homeostasis  Fatty change occurs in hypoxic injury and in various forms of toxic/metabolic injury and is manifested by the appearance of lipid vacuoles in the cytoplasm  Irreversible Cell Injury (Death) Necrosis:  Is the type associated with loss of membrane integrity and leakage of cellular contents culminating in dissolution of cells  The leaked cellular contents often elicit a local host reaction, called inflammation Morphology of necrosis  Necrosis is characterized by changes in the cytoplasm and nuclei of the injured cells  Cytoplasmic changes: Necrotic cells show increased eosinophilia (pink staining from the eosin [H&E] stain)  Nuclear changes: Nuclear changes assume one of three patterns, all due to breakdown of DNA and chromatin: 1. Basophilia of the chromatin may fade (karyolysis), presumably secondary to deoxyribonuclease (DNase) activity 2. Pyknosis, characterized by nuclear shrinkage and increased basophilia; the DNA condenses into a solid shrunken mass 3. Karyorrhexis, the pyknotic nucleus fragments. In 1 to 2 days, the nucleus in a dead cell may completely disappear  Patterns of Tissue Necrosis Coagulative necrosis: is a form of necrosis in which the underlying tissue architecture is preserved for at least several days.  Leukocytes are recruited to the site of necrosis, and the dead cells are digested by the action of lysosomal enzymes of the leukocytes  The cellular debris is then removed by phagocytosis Nuclei have become pyknotic (shrunken and dark) and have then undergone karorrhexis (fragmentation) and karyolysis (dissolution) - Heart The renal cortex: anoxic injury at the left so that the cells appear pale and ghost-like. Normal renal parenchyma at the far right Liquefactive necrosis:  A form of necrosis in which the underlying tissue architecture is preserved for at least several days.  Seen in focal bacterial or fungal infections, microbes stimulate the accumulation of inflammatory cells and the enzymes of leukocytes digest the tissue  The dead cells transforming the tissue into a liquid viscous mass. The digested tissue is removed by phagocytes Cerebral infarction at the upper left in the distribution of the middle cerebral artery The liver shows a small abscess filled with many neutrophils (purulent exudate) Caseous necrosis:  Most often in foci of tuberculous infection. Caseous means “cheese-like,” referring to the friable yellow- white appearance of the area of necrosis  The area of caseous necrosis is often enclosed within a distinctive inflammatory border; forming a granuloma Caseous necrosis, with confluent cheesy tan granulomas in the upper portion of this lung in a patient with tuberculosis. Gross appearance of caseous necrosis in a hilar lymph node infected with tuberculosis Caseous necrosis is characterized by acellular pink areas of necrosis, at the upper right, surrounded by an inflammatory cells Fat necrosis:  Refers to focal areas of fat destruction, typically resulting from release of activated pancreatic lipases  This occurs in acute pancreatitis  Histologically, the foci of necrosis contain shadowy outlines of necrotic fat cells with basophilic calcium deposits Chalky white areas seen on the cut surfaces in acute pancreatitis The necrotic fat cells at the right have lost their peripheral nuclei, and their cytoplasm has become a pink amorphous mass of necrotic material.  APOPTOSIS  Apoptosis is a pathway of cell death in which cells activate enzymes that degrade the cells’ own nuclear DNA and nuclear and cytoplasmic proteins  Fragments of the apoptotic cells then break off, giving the appearance that is responsible for the name (apoptosis, “falling off”)  Apoptotic cell death does not elicit an inflammatory reaction in the host  Causes of Apoptosis  Apoptosis occurs in many normal situations and serves to eliminate cells that are no longer needed and to maintain a constant number of cells of various types in tissues  It also occurs as a pathologic event when cells are damaged beyond repair  Apoptosis in Physiologic Situations  The programmed destruction of cells during embryogenesis  Involution of hormone-dependent tissues upon hormone deprivation (uterus in menstrual cycle)  Elimination of cells that have served their useful purpose (neutrophils in acute inflammation)  Apoptosis in Pathologic Conditions  DNA damage: Radiation, cytotoxic anticancer drugs, extremes of temperature, and even hypoxia  Cell injury in certain infections (viral)  Pathologic atrophy in parenchymal organs after duct obstruction as occurs in the pancreas