CELLULAR INJURY, ADAPTATION & CELL DEATHNOTES: Ex: In systemic hypertension, increase BP heart has to work against increase in peripheral resistance cardiac muscle adapts by increasing in ce ll size = Hypertrophy When there is persistent hypertension (uncontrolled), myocardial cell exceeds its limit of adaptation will decompensate and undergo changes (ex. lysis o f cells) = Irreversible cell injury (usually in the form of coagulative necrosis in the heart Myocardial Infarction) Usually apoptosis is not seen in cardiac muscle CELLULAR ADAPTATIONS OF GROWTH AND DIFFERENTIATION Occurs when excessive physiologic stresses or some pathologic stimuli result in a new but altered state that preserves the viability of the cell Adaptations are reversible responses to physiologic stress and pathologic stimuli ; Takes several formsA.ATROPHY -Decrease in cell size and number, leading to decrease in size of tissue/organ; Shrinkage in the size of the cell by loss of cell integrity and substance (mitochondria, myofilaments, ER) -Mechanism: result from decrease in protein synthesis as result of a decrease in metabolic activity and increase in protein degradation via ubuquitin-proteosome pathway Ubiquitin ligase ubiquitin attaches to cellular protein degradation Atrophy may also be accompanied by increased AUTOPHAGY (self eating) wherein a starved cell eats its o wn components to survive. -Causes: 1)Decrease workload (disuse atrophy) –immobilization -Immobilized fractured bone or complete bed rest cause skeletal muscle atrophy; reversible once activity is resumed -Skeletal muscle fibers decrease in cell size and number which can lead to increased bone resorption then to osteoporosis 2)Loss of innervations muscle atrophy (paralyzed patients) 3)Decrease blood supply (ex. arteriosclerosis of the BV supplying the brain cerebral ischemia cerebral atrophy) 4)Inadequate nutrition -Marasmus (profound protein-calorie malnutrition) is associated with the use of skeletal muscle as a source of energy after other reserves have been depleted resulting in muscle wasting (Cachexia) 5)Loss of endocrine stimulation -A) Postmenopause: Lo ss of estrogen stimul ation after menopause results in physiologic atrophy of the endometrium/vaginal epithelium and breast (atrophy of the lining epithelium of the uterus = becomes thin and shiny); B) Aging 6)Pressure atrophy -Tissue compression for any given time -Ex. Benign tumors can cause atrophy in the surrounding ATHEROSCLEROTIC CEREBROVASCU LAR DISEASE resulting in reduced blood supply; Loss of brain substance narrows the gyri and widens the sulci Physiologic Atrophy: Occurs during normal development; Ex. Atrophy of notochord during fetal development B.HYPERTROPHY -Increase in the size of cells that results to increased organ size -Mechanism: results of increased production of cellular proteins (structural components) -New cells are not present, only larger ones -Hypertrop hy can be accompanied by hyperplasi a among normally dividing cells; But non-dividing cells undergoes HYPERTROPHY when stressed. 1)PHYSIOLOGIC HYPERTROPHY 1.Hormonal stimulation Ex. Increase in uterine size during pregnancy due to estrogenic hormones; breast and sex organs during puberty 2.Increased functional demand Ex. Exercise 2)PATHOLOGIC HYPERTROPHY 1.Abnormal hormone levels Ex. Enlargement of thyroid gland, due excessive levels of T3 and T4 (Goiter) 2.Increased functional Demand Ex. Chronic hemodynamic overload in left ventricular hypertrophy as seen in hypertension and valvular disease ADDITIONAL: The most common stimulus for muscle hypertrophy is an increase in workload. Mechanisms of Hypertrophy: -The coordinated actions of mechanical sensors, growth factors (GFs) and vasoactive agents increase the synthesis of muscle proteins responsible for hypertrophy. -Hypertrophy can also be associated with the “switch of contractile protein from adult to fetal or neonatal forms (Kumar, A bbas, Fausto, & Aster, 2009, p. 7).” -Occurs in non-dividing cells like myocardial and skeletal muscle fibers C.HYPERPLASIA -Increase in the number of cells in an organ/tissue resulting to increase mass of organ/tissue-Mechanism: due to the growth factor-driven proliferation of mature cells and sometimes by increased output of new cells from tissue stem cells-↑local production of growth factors, ↑levels of growth factor receptors on the responding cells, or activation of particular intracellular signaling pathways that leads to production of transcription factors that turn on many cellular genes (encoding growth factors, receptors for growth factors, and cell cycle regulators) and the net result is cellular proliferation-Occurs if the cell population is capable of dividing1)PHYSIOLOGIC HYPERPLASIA a)Hormonal–pregnant uterus; proliferation of glandular epithelium of breast at puberty or pregnancy which is usually accompanied by hypertrophy
