Cell Injury 2023 PDF

Cell injury1 Assistant professor Noora Mustafa  Objectives Cellular responses to stress: ✓Adaptation ✓Reversible cell injury ✓Cell death : Apoptosis vs. necrosis  OVERVIEW OF CELLULAR RESPONSES TO STRESS Normal cell function requires a balance between physiologic demands and the constraints...

Cell injury1 Assistant professor Noora Mustafa  Objectives Cellular responses to stress: ✓Adaptation ✓Reversible cell injury ✓Cell death : Apoptosis vs. necrosis  OVERVIEW OF CELLULAR RESPONSES TO STRESS Normal cell function requires a balance between physiologic demands and the constraints of cell structure and metabolic capacity; the result is a steady state, or homeostasis. Cells can alter their functional state in response to modest stress to maintain the steady state More excessive physiologic stresses, or adverse pathologic stimuli (injury), result in : (1) adaption, (2) reversible injury, or (3) irreversible injury and cell death  definitions Reversible injury denotes pathologic cell changes that can be restored to normalcy if the stimulus is removed or if the cause of injury is mild. Irreversible injury occurs when stressors exceed the capacity of the cell to adapt (beyond a point of no return) and denotes permanent pathologic changes that cause cell death. Cell death occurs primarily through two morphologic and mechanistic patterns denoted necrosis and apoptosis  CELLULAR ADAPTATIONS TO STRESS Adaptations are reversible changes in the number, size, phenotype, metabolic activity, or functions of cells in response to changes in their environment. Physiologic adaptations usually represent responses of cells to normal stimulation by hormones or endogenous chemical mediators (e.g., the hormone-induced enlargement of the breast and uterus during pregnancy).  Pathologic adaptations are responses to stress that allow cells to modulate their structure and function and thus escape injury. Such adaptations can take several distinct forms These changes include: Hypertrophy (increased cell mass) Hyperplasia (increased cell number) Atrophy (decreased cell mass) Metaplasia (change from one mature cell type to another  Hypertrophy Hypertrophy is an increase in the size of cells resulting in increase in the size of the organ there are no new cells, just bigger cells, enlarged by an increased amount of structural proteins and organelles. Hypertrophy can be physiologic or pathologic and is caused either by increased functional demand or by specific hormonal stimulation  Hypertrophy the striated muscle cells in both the skeletal muscle and the heart can undergo only hypertrophy in response to increased demand because in the adult they have limited capacity to divide. Therefore, the weightlifter can develop a rippled physique only by hypertrophy of individual skeletal muscle cells induced by an increased workload. Examples of pathologic cellular hypertrophy include the cardiac enlargement that occurs with hypertension or aortic valve disease  hyperplasia hyperplasia takes place if the cell population is capable of replication; it can be physiologic or pathologic, The two types of physiologic hyperplasia are: (1) hormonal hyperplasia, exemplified by the proliferation of the glandular epithelium of the female breast at puberty and during pregnancy (2) compensatory hyperplasia, that is, hyperplasia that occurs when a portion of the tissue is removed or diseased. For example, when a liver is partially resected, mitotic activity in the remaining cells begins as early as 12 hours later, eventually restoring the liver to its normal weight. Pathological : like endometrial hyperplasia which can lead to endometrial carcinoma  example. Hypertrophy and hyperplasia can also occur together, and obviously both result in an enlarged (hypertrophic) organ. Thus, the massive physiologic enlargement of the uterus during pregnancy occurs as a consequence of estrogen- stimulated smooth muscle hypertrophy and smooth muscle hyperplasia  Atrophy Shrinkage in the size of the cell by the loss of cell substance is known as atrophy. When a sufficient number of cells is involved, the entire tissue or organ diminishes in size, becoming atrophic , it may be diminished in function but not dead  Causes of atrophy decreased workload (e.g., immobilization of a limb to permit healing of a fracture), loss of innervation, diminished blood supply, inadequate nutrition, loss of endocrine stimulation, aging (senile atrophy)  Metaplasia a reversible change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type. In this type of cellular adaptation, cells sensitive to a particular stress are replaced by other cell types better able to withstand the adverse environment. Metaplasia is thought to arise by genetic "reprogramming" of stem cells rather than transdifferentiation of already differentiated cells  example Epithelial metaplasia is exemplified by the squamous change that occurs in the respiratory epithelium in habitual cigarette smokers. The normal ciliated columnar epithelial cells of the trachea and bronchi are focally or widely replaced by stratified squamous epithelial cells  Disadvantages of metaplasia Although the metaplastic squamous epithelium has survival advantages, important protective mechanisms are lost, such as mucus secretion and ciliary clearance of particulate matter. Epithelial metaplasia is therefore a double-edged sword; if persistent, may predispose to malignant transformation of the epithelium.  example in chronic gastric reflux, the normal stratified squamous epithelium of the lower esophagus may undergo metaplastic transformation to gastric or intestinal-type columnar epithelium. Metaplasia may also occur in mesenchymal cells but less clearly as an adaptive response. For example, bone is occasionally formed in soft tissues, particularly in foci of injury  the morphology of Reversible injury Cellular swelling : the first manifestation of almost all forms of injury to cells, is difficult to appreciate with the light microscope; it may be more apparent at the level of the whole organ. When it affects many cells in an organ it causes some pallor, and increase in weight of the organ. Microscopic examination may reveal small, clear vacuoles within the cytoplasm; these represent distended and pinched-off segments of the ER. This pattern of nonlethal injury is sometimes called hydropic change or vacuolar degeneration. Swelling of cells is reversible  example Fatty change is manifested by the appearance of lipid vacuoles in the cytoplasm. It is principally encountered in cells participating in fat metabolism (e.g., hepatocytes and myocardial cells) and is also reversible. Injured cells may also show increased eosinophilic staining, which becomes much more pronounced with progression to necrosis  The ultrastructural changes of reversible cell injury 1) plasma membrane alterations such as blebbing, blunting or distortion of microvilli, and loosening of intercellular attachments; (2) mitochondrial changes such as swelling and the appearance of phospholipid-rich amorphous densities; (3) dilation of the ER with detachment of ribosomes and dissociation of polysomes; (4) nuclear alterations, with clumping of chromatin. Reversible injury  apoptosis Apoptosis occurs when a cell dies by activation of an internal “suicide” program, involving; there is minimal disruptiondisassembly of cellular components of the surrounding tissue and there is minimal, if any, inflammation. Morphologically, there is chromatin condensation and fragmentation.  necrosis Necrosis is the more common type of cell death, involving: severe cell swelling, denaturation and coagulation of proteins breakdown of cellular organelles, and cell rupture. Usually, a large number of cells in the adjoining tissue are affected, and an inflammatory infiltrate is recruited. Thank you