Cellular Injury and Responses to stress Faculty of Medicine Department of Pathology Hussam Telfah, MBBS, FRCPath

Cellular Response to Stress Normal cell needs special conditions “environment” to function properly. Homeo-stasis : similar-standing still. Range of Temperature, PH, Glucose etc

Cellular Responses Adaptation: hypertrophy, hyperplasia, atrophy, metaplasia. Injury: reversible and irreversible. Intracellular accumulation; calcification Cellular aging.

Cellular Adaptations Reversible changes in size, number, phenotype, metabolic activity or function in response to changes in environment. Adaptation can be both physiologic and pathologic.

Hypertrophy Hypertrophy is an increase in cell size resulting in an increase in the size of the organ. Alone in nondividing cells or coexisting with hyperplasia in dividing cells. Physiologic vs pathologic. Increased functional demand (workload) or stimulation by hormones or growth factors.

Hypertrophy Muscle

Hypertrophy Heart: left ventricle hypertrophy.

Hypertrophy Uterus

Hypertrophy There is a limit for hypertrophy beyond which the muscle is no longer able to compensate for the increased burden. Some times subcellular organelle may undergo selective hypertrophy. Example: drugs lead to hypertrophy of smooth endoplasmic reticulum only.

Hyperplasia Increased number of cells resulting in increase of the size of the organ or tissue. Takes place in cells capable of dividing. Physiologic vs pathologic.

Hyperplasia Physiological Hyperplasia (hormonal or compensatory), Examples: Uterine enlargement during pregnancy Female breast in puberty & lactation Compensatory hyperplasia in the liver Pathological Hyperplasia of the endometrium (excessive hormone stimulation). Wound healing (Effects of growth factors). Infection by papillomavirus Hyperplasia can be a fertile soil for development of neoplasia

Hyperplasia Prostate

Hyperplasia Endometrium

Atrophy Reduced size of an organ or tissue as a result from a decrease in cell size and number. Physiologic : Embryonic development. Pathologic: Decreased workload (Disuse atrophy) Loss of innervation (Denervation atrophy) Diminished blood supply. Inadequate nutrition. Loss of endocrine stimulation. Pressure.

Metaplasia Metaplasia is a “reversible” change in which one differentiated cell type (epithelial or mesenchymal) is replaced by another cell type. New epithelium is better in dealing with the current stress or irritation. Persistence of factors causing metaplasia may lead to progression into malignant transformation. Examples: respiratory , GIT, cervix, muscle.

Metaplasia Replacement of ciliated columnar epithelium with stratified squamous epithelium in the respiratory tract of a smoker.

Causes of Cell Injury Oxygen Deprivation: hypoxia and ischemia Chemical agents & Drugs. Physical agents: mechanical trauma, changing T⁰. Infection Agents: viruses to worms. Immunological reactions: autoimmune. Genetic derangement: chromosomal to single amino acid defect Nutritional Imbalances: Deficiency vs excess.

Morphologic alterations in cell injury Reversible injury Generalized swelling of the cell: failure of energy-dependent ion pumps in the plasma membrane result in disturbances in ionic and fluid homeostasis. It is usually the first manifestatioin. Another names hydropic change or vacuolar degeneration. Plasma membrane alterations: blebs, blunting or loss of villi and loosening of intercellular attachments.

Morphologic alterations in cell injury Reversible injury Mitochondrial changes: swelling and appearance of small amorphus densities. Dilatation of ER and detachment of polysomes (ribosomes) with possibility of myelin figure formation. Nuclear alterations: nuclear chromatin clumping.

Kidney tubules Downloaded from: StudentConsult (on 24 September 2011 08:38 PM) © 2005 Elsevier

Figure 1-8 Schematic illustration of the morphologic changes in cell injury culminating in necrosis or apoptosis. Downloaded from: StudentConsult (on 24 September 2011 08:56 PM) © 2005 Elsevier

Morphologic alterations in cell injury irreversible injury (Necrosis) Result from denaturation of intracellular proteins and enzymatic digestion of cells. Loss of membrane integrity. Digestion enzymes: lysosomes of dying cells and leukocytes.

Morphologic alterations in cell injury irreversible injury (Necrosis) Increased eosinophilia in H&E stain. Vacuolation due to digestion of cytoplasmic organelles. Myelin figures: aggregates of damaged cell membranes (phospholipids). Then they are either phagocytosed by other cells or further degraded into fatty acids and calcify. Plasma and organelle membrane discontinuities.

Morphologic alterations in cell injury irreversible injury (Necrosis) Marked dilatation of mitochondria and appearance of large densities. Nuclear changes: breakdown of DNA - Karyolysis: loss of DNA, fade of basophilia. - Pyknosis: nuclear shrinkage and increased basophilia. - Karyorhexis: fragmentation of the pyknotic nucleus. - Disappearance of the nucleus.

Patterns of tissue necrosis Coagulative necrosis: preservation of the architecture of dead tissue for at least some days. Denaturation of structural proteins and enzymes. Eosiniphilic anucleated cells Cells are removed by inflammatory leukocytes.

Patterns of tissue necrosis Ischemia in any organ except the brain may lead to coagulative necrosis. Infarction: localised area of coagulative necrosis.

Patterns of tissue necrosis Liquifactive necrosis: digestion of the dead cells resulting into a liquid jelly-like mass. In focal bacterial or fungal infections and in hypoxic death in central nervous system. Creamy yellow due to accumulation of dead leukocytes (pus).