Cell Injury and Causes Quiz

Cell injury occurs when the cell's ability to adapt to stress or stimuli is exceeded.
Two principal patterns of cell death:
- Necrosis: Cell death due to noxious conditions characterized by swelling, protein denaturation, and organellar breakdown.
- Apoptosis: Programmed cell death occurring in normal or physiologic conditions.

Hypoxia: Insufficient oxygen supply to the blood.
Physical agents: Trauma, extreme temperatures, radiation, electric shock, and sudden changes in atmospheric pressure.
Chemicals and drugs: Alter membrane permeability, osmotic homeostasis, or enzyme cofactor integrity.
Microbiologic agents: Viruses, bacteria, fungi, and parasites.
Immunologic reactions: Immune system responses causing cell injury, such as anaphylactic reactions.
Genetic defects: e.g. Down's syndrome and sickle cell anemia.
Nutritional imbalances: Protein-calorie insufficiency, vitamin deficiencies, and diets rich in animal fat.
Aging: The natural process of aging contributes to cellular changes and vulnerability to injury.

Four intracellular systems are vulnerable to injury:
- Cell membrane integrity
- Aerobic respiration
- Protein synthesis
- Genetic apparatus
Calcium influx: Ischemia or toxins cause an influx of calcium from the extracellular space and release of mitochondrial calcium, activating enzymes that damage cells.
Free radical generation: Important mediators of cell death.

Reversible Injury:
- Reduced ATP
- Influx of extracellular calcium
- Reduced plasma membrane sodium pump
- Accumulation of intracellular sodium
- Diffusion of potassium out of the cell
- Cellular swelling
- Decreased intracellular pH
Irreversible Injury:
- Severe vacuolization and calcium accumulation in mitochondria
- Extensive damage to the plasma membrane
- Swelling of lysosomes
- Continued loss of essential cellular components
- Activation of lysosomal enzymes

Free radicals are chemically unstable species involved in various processes:
- Chemical injury
- Radiation injury
- Oxygen toxicity
- Cellular aging
- Microbial killing
- Inflammatory damage
- Tumor killing
Generation of free radicals:
- Absorption of radiant energy
- Redox reactions
- Enzymatic catabolism

Mechanisms:
- Combining with critical molecular components or cellular organelles
- Conversion to reactive toxic metabolites
Example: Carbon tetrachloride (CCl4): Converted to a toxic free radical that causes membrane peroxidation and liver damage.

Reversible Injury:
- Light microscopic changes: Cell swelling, cytoplasmic eosinophilia, and fatty change.
- Ultrastructural changes: Plasma membrane blebbing, mitochondrial swelling, dilatation of endoplasmic reticulum, nuclear alterations.
Necrosis:
- Morphologic changes resulting from enzymatic digestion and protein denaturation.
- Cytoplasmic changes: Eosinophilia, glassy appearance, vacuolation, and calcification.
- Nuclear changes: Karyolysis, pyknosis, and karyorrhexis.

Coagulative necrosis: Preservation of structural outlines of the coagulated cell or tissue.
Liquefactive necrosis: Caused by bacterial or fungal infections, resulting in the accumulation of white blood cells.
Gangrenous necrosis: Ischemic coagulative necrosis with superimposed infection and liquefactive necrosis.
Caseous necrosis: Characteristic of tuberculous infection, characterized by a cheese-like appearance.
Fat necrosis: Focal areas of fat destruction following acute pancreatitis.

Programmed cell death occurring in various physiologic and pathologic conditions.
Morphologic features:
- Nuclear chromatin condensation,
- Karyorrhexis
- Formation of apoptotic bodies
Apoptosis does not elicit an inflammatory response.
Initiation of apoptosis:
- Withdrawal of growth factors or hormones
- Engagement of specific receptors
- Injury by radiation, toxins, and free radicals
- Intrinsic protease activation

Abnormal substances accumulate in cells either transiently or permanently.
Categories of accumulations:
- Normal endogenous substance produced at an increased rate
- Normal or abnormal endogenous substance that can't be metabolized
- Abnormal exogenous substance deposited due to inability to transport it to other sites.

Accumulation in macrophages, smooth muscle cells leading to foam cells and atheromas.
Xanthomas: Accumulation of fat within macrophages of subcutaneous connective tissues.

Accumulation can occur in various conditions, such as glomerular diseases with proteinuria.

Cells adapt to changing conditions, often responding to stress or stimuli.
Atrophy: Shrinkage in cell size due to loss of cell substance.
Hypertrophy: Increase in cell size due to increased synthesis of structural proteins and organelles.
Hyperplasia: Increase in the number of cells in an organ or tissue.
Metaplasia: Reversible change in which one adult cell type is replaced by another.