Cell Injury, Cell Death & Adaptations PDF

# Cell Injury, Cell Death and Adaptations ## Cell Injury Cell injury is defined as a variety of stresses the cell encounters as a result of changes in its internal and external environment leading to morphological or functional changes or both. The cellular response to stress may vary and depend...

# Cell Injury, Cell Death and Adaptations ## Cell Injury Cell injury is defined as a variety of stresses the cell encounters as a result of changes in its internal and external environment leading to morphological or functional changes or both. The cellular response to stress may vary and depend upon the following variables: - The type of cell and tissue involved. - Extent and type of cell injury. ### Cellular Response to Injury Includes: (Fig. 2.1) * **Cellular adaptations**: As cells encounter physiologic stresses or pathologic stimuli, they can undergo adaptation, achieving a new steady state and preserving viability and function. The principal adaptive responses are hypertrophy, hyperplasia, atrophy and metaplasia. If the adaptive capability is exceeded or if the external stress is inherently harmful, cell injury develops. * **Reversible cell injury**: When the stress is mild to moderate, the injured cell may recover. * **Irreversible cell injury**: When the injury is severe or persistent, cell death may occur. * **Intracellular accumulations**. ### Cellular Adaptation Cellular 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. * **Pathologic adaptations** are responses to stress that allow cells to modulate their structure and function and thus escape injury. (Fig.2.2). ## Cellular Response to Stress **Stages in cellular response to stress and injurious stimuli:** 1. **Normal Cell (homeostasis).** External stress or increased demand leads to: * **Adaptation**. - If adaptation is unsuccessful, it results in: * **Inability to adapt**. * **Subcellular Alterations**. * **Cell Injury**. - Cell injury can be: * **Reversible Cell Injury** which results in: * **Necrosis**. * **Irreversible Cell Injury** which results in: * **Apoptosis**. ## Cellular Adaptation to Stress (Fig. 2.2) * **Atrophy** * **Hypertrophy** * **Hyperplasia** * **Metaplasia** ## Atrophy Atrophy is decrease in the size of a normally formed organ due to decrease in the size of its individual cells with or without decrease in the number of individual cells. It is distinct from abnormalities of organ development as: * **Aplasia:** is extreme failure of development so only rudimentary tissue is present. * **Agenesis:** is complete absence of an organ. **N.B.:** Apoptotic death may also be induced by the same signals that cause atrophy, and thus may lead to loss and reduction in number of cells. Although the atrophic cells may have diminished function, yet they are not dead. ### Causes: * **Physiologic atrophy:** * Atrophy of lymphoid tissue, appendix and thymus. * Atrophy of gonads after menopause. * Atrophy of brain and heart with aging (senile atrophy). * **Pathologic atrophy:** * **Disuse atrophy:** Wasting of muscles of limb immobilized in cast. * **Neuropathic atrophy:** Interruption of nerve supply leads to wasting of muscles e.g. traumatic nerve injury and poliomyelitis. * **Endocrine atrophy:** Loss of trophic hormones e.g. hypopituitarism may lead to atrophy of thyroid, adrenal and gonads. * **Pressure atrophy:** large aortic aneurysm may produce atrophy of the vertebral bodies but the intervertebral discs are spared. * **Atrophy due to lack of nutrients:** severe protein-calorie malnutrition (marasmus) results in marked muscle atrophy. ### Pathogenesis: Cells become smaller in size by decreased protein synthesis and increased protein degradation. ### Morphologic features: * The organ is small. * Cells become smaller in size due to reduction in cell organelles, chiefly mitochondria, myofilaments and ER. * There is often increase in number of autophagic vacuoles containing cell debris which may persist to form residual bodies in the cytoplasm e.g. lipofuscin pigment granules in brown atrophy. ## Hypertrophy Hypertrophy is an increase in the size of an organ or tissue due to increase in size of its parenchymal cells. It occurs in non-dividing (permanent) cells. ### Types: * **Physiologic hypertrophy:** * Uterine smooth muscle hypertrophy in pregnancy (may be accompanied by hyperplasia). * Hypertrophied skeletal muscles in athletes. * **Pathologic hypertrophy:** * Left ventricular hypertrophy in systemic hypertension, and aortic valve disease (Fig. 2.3). ### Pathogenesis: Cells become larger in size by increased protein synthesis and decreased protein degradation ### Morphologic features: The affected organ is enlarged and heavy, due to increased size of muscle fibers as well as of nuclei. ## Hyperplasia Hyperplasia is an increase in size of an organ or tissue due to increase in the number of its parenchymal cells. * Hyperplasia occurs in tissues composed of labile and stable cells. * Hyperplasia persists so long as the stimulus is present. * Both hyperplasia and hypertrophy may occur together, e.g. pregnant uterus. ### Types: * **Physiologic hyperplasia** * **Hormonal hyperplasia** * Hyperplasia of female breast at puberty, during pregnancy and lactation. * Hyperplasia of pregnant uterus. * **Compensatory hyperplasia** i.e. hyperplasia occurring following removal of a part of an organ or a contralateral organ in paired organs e.g.: Regeneration of the liver following partial hepatectomy. * **Pathologic hyperplasia** * **Hormonal hyperplasia** (due to excessive hormonal stimulation) e.g. * Fibrocystic disease of the breast (mammary hyperplasia) which results from estrogen excess unopposed by progesterone. * Endometrial hyperplasia due to increased estrogen stimulation particularly when it is not opposed by progesterone (Fig. 2.4). * Prostatic hyperplasia in old age (Fig. 2.5). * Thyroid hyperplasia (Goiter) results from increased thyroid stimulating hormone (TSH). * **Epithelial hyperplasia** due to chronic irritation or chronic inflammation as in bilharzial cystitis. ### Pathogenesis: Cells increase in number by proliferation of stem cells and parenchymal cells **N.B.:** - In the above situations, the hyperplastic process remains controlled and reversible in contrast to uncontrolled neoplastic proliferation. - Pathologic hyperplasia represents a fertile soil for neoplasia. **Fig. 2.3: Left ventricular hypertrophy (T.S. heart)**