Downloaded 39 times
![• A series of enzymes acts as free radical-
scavenging systems
▫ Catalase, present in peroxisomes, which
decomposes H2O2 (2 H202 -> O2 + 2 H20).
▫ Superoxide dismutases are found in many cell
types and convert superoxide to H2O2 (2 02 + 2 H
->H202 + O2 ).
▫ Glutathione peroxidase also protects against
injury by catalyzing free radical breakdown (H
202 + 2 GSH ->GSSG [glutathione homodimer] +
2 H 2O2 or 2 OH +2 GSH —> GSSG + 2 H2O).](https://image.slidesharecdn.com/mechanismofcellinjury-191115061954/85/Mechanism-of-cell-injury-17-320.jpg)
![Mechanisms of Hypertrophy.
• The genes that are induced during hypertrophy
include those encoding
• Transcription factors
• Growth factors (TGF-β, insulin-like growth
factor-1 [IGF-1], fibroblast growth factor); and
• Vasoactive agents (α-adrenergic agonists,
endothelin-1, and angiotensin II)](https://image.slidesharecdn.com/mechanismofcellinjury-191115061954/85/Mechanism-of-cell-injury-30-320.jpg)
![• A series of enzymes acts as free radical-
scavenging systems
▫ Catalase, present in peroxisomes, which
decomposes H2O2 (2 H202 -> O2 + 2 H20).
▫ Superoxide dismutases are found in many cell
types and convert superoxide to H2O2 (2 02 + 2 H
->H202 + O2 ).
▫ Glutathione peroxidase also protects against
injury by catalyzing free radical breakdown (H
202 + 2 GSH ->GSSG [glutathione homodimer] +
2 H 2O2 or 2 OH +2 GSH —> GSSG + 2 H2O).](https://image.slidesharecdn.com/mechanismofcellinjury-191115061954/75/Mechanism-of-cell-injury-17-2048.jpg)
![Mechanisms of Hypertrophy.
• The genes that are induced during hypertrophy
include those encoding
• Transcription factors
• Growth factors (TGF-β, insulin-like growth
factor-1 [IGF-1], fibroblast growth factor); and
• Vasoactive agents (α-adrenergic agonists,
endothelin-1, and angiotensin II)](https://image.slidesharecdn.com/mechanismofcellinjury-191115061954/75/Mechanism-of-cell-injury-30-2048.jpg)
More Related Content
Similar to Mechanism of cell injury
Mechanism of cell injury
- 1. Mechanism of cellinjury and cellular adaptation to injury By Dr Ajish M Saji Deparment of Oral Pathology Malabar Dental College Edappal
- 2. Contents • Mechanisms ofcell injury • Principles • Depletion of ATP • Mitochondrial damage • Influx Of Intracellular Calcium And Loss Of Calcium Homeostasis • Accumulation Of Oxygen-derived Free Radicals (Oxidative Stress)
- 3. • Defects inmembrane permiability • Ischemic and hypoxic injury • Ishcemic and reperfusion injury • Cellular adaptations to injury • Hyperplasia • Hypertrophy • Atrophy • Metaplasia • Summary • References
- 4. Mechanisms of cellinjury • Principles • The cellular response to injurious stimuli depends on the type of injury, its duration, and its severity. • The consequences of cell injury depend on the type, state , and adaptability of the injured cell.
- 5. • Cell injuryresults from functional and biochemical abnormalities in one or more of several essential cellular components. • (1) aerobic respiration involving mitochondrial oxidative phosphorylation and production of ATP. • (2)the integrity of cell membranes, on which the ionic and osmotic homeostasis of the cell and its organelles depends; • (3) protein synthesis; • (4) the cytoskeleton • (5) the integrity of the genetic apparatus of the cell.
- 7. DEPLETION OF ATP •ATP depletion and decreased ATP synthesis are frequently associated with both hypoxic and chemical (toxic) injury.
- 8. • Depletion ofATP to <5% to 10% of normal levels has widespread effects on many critical cellular systems: • The activity of the plasma membrane energy- dependent sodium pump (ouabain-sensitive Na+ , K +-ATPase) is reduced. • Cellular energy metabolism is altered. • Failure of the Ca2+ pump leads to influx of Ca2+. • Reduction in protein synthesis. • Unfolded protein response.
- 9. MITOCHONDRIAL DAMAGE • Failureof oxidative phosphorylation and progressive depletion of ATP. • Death by apoptosis
- 10. INFLUX OF INTRACELLULARCALCIUM AND LOSS OF CALCIUM HOMEOSTASIS • Increased cytosolic Ca2+ activates a number of enzymes; • Phospholipases-cause membrane damage • Proteases-break down both membrane and cytoskeletal proteins. • Endonucleases-are responsible for DNA and chromatin fragmentation • Adenosine triphosphatases- thereby hastening ATP depletion.
- 11. ACCUMULATION OF OXYGEN-DERIVED FREERADICALS (OXIDATIVE STRESS) • Free radicals are chemical species that have a single unpaired electron in an outer orbit. • Free radicals may be initiated within cells in several ways; • Absorption of radiant energy. • Enzymatic metabolism of exogenous chemicals or drugs. • The reduction-oxidation reactions that occur during normal metabolic processes.
- 12. • Transition metalssuch as iron and copper donate or accept free electrons during intracellular reactions and catalyze free radical formation. • Nitric oxide (NO).
- 14. • Reactions relevantfor cell injury are; ▫ Lipid peroxidation of membranes. Double bonds in membrane polyunsaturated lipids are vulnerable to attack by oxygen-derived free radicals. ▫ Cross-linking of proteins. Free radicals promote sulfhydryl-mediated protein cross-linking, resulting in enhanced degradation or loss of enzymatic activity. ▫ DNA fragmentation. Free-radical reactions with thymine in nuclear and mitochondrial DNA produce single-strand breaks.
- 16. • Mechanisms toremove free radicals and minimize injury. • Antioxidants either block the initiation of free radical formation or inactivate free radicals and terminate radical damage. • Iron and copper can catalyze the formation of reactive oxygen species.
- 17. • A seriesof enzymes acts as free radical- scavenging systems ▫ Catalase, present in peroxisomes, which decomposes H2O2 (2 H202 -> O2 + 2 H20). ▫ Superoxide dismutases are found in many cell types and convert superoxide to H2O2 (2 02 + 2 H ->H202 + O2 ). ▫ Glutathione peroxidase also protects against injury by catalyzing free radical breakdown (H 202 + 2 GSH ->GSSG [glutathione homodimer] + 2 H 2O2 or 2 OH +2 GSH —> GSSG + 2 H2O).
- 18. DEFECTS IN MEMBRANE PERMEABILITY •Mitochondrial dysfunction. • Loss of membrane phospholipids. • Cytoskeletal abnormalities. • Reactive oxygen species • Lipid breakdown products.
- 20. Ischemic and HypoxicInjury • Ischemia, or diminished blood flow to a tissue, is the most common cause of cell injury. • In hypoxia energy generation by anaerobic glycolysis can continue.
- 21. • loss ofATP leads to the failure of many energy- dependent cellular systems; • Ion pumps. • depletion of glycogen stores. • reduction in protein synthesis.
- 22. Ischemia-Reperfusion Injury • Therestoration of blood flow to ischemic but otherwise viable tissues results, paradoxically, in exacerbated and accelerated injury.
- 23. Cellular Adaptations toInjury • Cells respond to increased demand and external stimulation by hyperplasia or hypertrophy. • They respond to reduced supply of nutrients and growth factors by atrophy. • Cells change from one type to another, a process called metaplasia.
- 25. HYPERPLASIA • Hyperplasia isan increase in the number of cells in an organ or tissue, usually resulting in increased volume of the organ or tissue. • Hyperplasia can be physiologic or pathologic.
- 26. Physiologic Hyperplasia • Physiologichyperplasia can be divided into: • (1) hormonal hyperplasia, which increases the functional capacity of a tissue when needed. • (2) compensatory hyperplasia, which increases tissue mass after damage or partial resection.
- 27. Mechanisms of Hyperplasia •Increased local production of growth factors. • Increased levels of growth factor receptors on the responding cells. • Activation of particular intracellular signaling pathways.
- 28. Pathologic Hyperplasia • Excessivehormonal stimulation or growth factors acting on target cells. • Endometrial hyperplasia is an example of abnormal hormone-induced hyperplasia. • Pathologic hyperplasia, however, constitutes a fertile soil in which cancerous proliferation may eventually arise.
- 29. HYPERTROPHY • Hypertrophy refersto an increase in the size of cells, resulting in an increase in the size of the organ. • The increased size of the cells is due to the synthesis of more structural components. • Nuclei in hypertrophied cells will have a higher DNA content. • Hypertrophy can be physiologic or pathologic.
- 30. Mechanisms of Hypertrophy. •The genes that are induced during hypertrophy include those encoding • Transcription factors • Growth factors (TGF-β, insulin-like growth factor-1 [IGF-1], fibroblast growth factor); and • Vasoactive agents (α-adrenergic agonists, endothelin-1, and angiotensin II)
- 31. • In theheart, there are two groups of signals: • Mechanical triggers, such as stretch, • Trophic triggers, such as polypeptide growth factors (IGF-1) and vasoactive agents (angiotensin II, a-adrenergic agonists).
- 32. ATROPHY • Shrinkage inthe size of the cell by loss of cell substance. • Atrophy can be physiologic or pathologic. • The common causes of atrophy are I. Decreased workload (atrophy of disuse). II. Loss of innervation (denervation atrophy). III. Diminished blood supply
- 33. IV. Inadequate nutrition. V.Loss of endocrine stimulation. VI. Aging (senile atrophy) VII.Pressure. • Although atrophic cells may have diminished function, they are not dead
- 34. METAPLASIA • Metaplasia isa reversible change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type. • The influences that predispose to metaplasia, if persistent, may induce malignant transformation in metaplastic epithelium.
- 35. Mechanisms of Metaplasia •It is the result of a reprogramming of stem cells that are known to exist in normal tissues, or of undifferentiated mesenchymal cells present in connective tissue. • The differentiation of stem cells to a particular lineage is brought about by signals generated by cytokines, growth factors, and extracellular matrix components in the cell's environment.
- 36. SUMMARY • ATP depletion:failure of energy-dependent functions → reversible injury → necrosis • Mitochondrial damage: ATP depletion → failure of energy-dependent cellular functions → ultimately, necrosis; under some conditions, leakage of proteins that cause apoptosis • Influx of calcium: activation of enzymes that damage cellular components and may also trigger apoptosis
- 37. • Accumulation ofreactive oxygen species: covalent modification of cellular proteins, lipids, nucleic acids. • Increased permeability of cellular membranes: may affect plasma membrane, lysosomal membranes, mitochondrial membranes; typically culminates in necrosis. • Accumulation of damaged DNA and misfolded proteins: triggers apoptosis.
- 38. • Hypertrophy: increasedcell and organ size, often in response to increased workload; induced by mechanical stress and by growth factors; occurs in tissues incapable of cell division • Hyperplasia: increased cell numbers in response to hormones and other growth factors; occurs in tissues whose cells are able to divide.
- 39. • Atrophy: decreasedcell and organ size, as a result of decreased nutrient supply or disuse; associated with decreased synthesis and increased proteolytic breakdown of cellular organelles. • Metaplasia: change in phenotype of differentiated cells, often a response to chronic irritation that makes cells better able to withstand the stress; usually induced by altered differentiation pathway of tissue stem cells; may result in reduced functions or increased propensity for malignant transformation.
- 40. References • 1)Kumar ,Abbas,Fasusto ,Robbins And Cotran ,Pathologic Basics Of Diseases ,Elsevier, Seventh Edition,5-18. • 2)Harsh Mohan, Essential Pathology For Dental Students, Jaypee, Second Edition ,6-11. • J P Cobb , R S Hotchkiss , I E Karl , and T G Buchman ; Mechanism of cell injury and death ; British journal of Anesthesia 1996 ; 77 : 3-10.
- 41.