Downloaded 155 times
![The Cell and the Environment
StimuliStimuli [[Causes of Cell Injury]
Cell
AdaptationAdaptation
Cell Injury
Reversible
Irreversible (cell death)
apoptosis necrosis](https://image.slidesharecdn.com/cellinjuryadaptationclass-1-170910051006/75/Cell-injury-adaptation-class-1-3-2048.jpg)
![The Cell and the Environment
StimuliStimuli [Causes of Cell Injury]
Cell
AdaptationAdaptation
Achieving a new steady state and preserving viability](https://image.slidesharecdn.com/cellinjuryadaptationclass-1-170910051006/75/Cell-injury-adaptation-class-1-14-2048.jpg)
More Related Content
Similar to Cell injury adaptation class 1
Cell injury adaptation class 1
- 1.
- 2. Cellular adaptation • Cellsare the structural and functional units of tissues and organs. They are capable of adjusting their structure and functions in response to various physiological and pathological conditions. This capability is called cellular adaptation. • Cellular adaptations include: – Atrophy--shrinkage of cells – Hypertrophy--increase in the size of cells which results in enlargement of the organs – Hyperplasia--increased number of cells in an organ or tissue – Metaplasia--transformation or replacement of one adult cell type with another
- 3. The Cell andthe Environment StimuliStimuli [[Causes of Cell Injury] Cell AdaptationAdaptation Cell Injury Reversible Irreversible (cell death) apoptosis necrosis
- 4.
- 5.
- 7. Cell injury • Ifthe cells fail to adapt under stress, they undergo certain changes called cell injury. The affected cells may recover from the injury (reversible) or may die (irreversible).
- 8. Causes of CellInjury 1.1. Hypoxia:Hypoxia: (Oxygen deficiency) Mainly due to: ischemia (impaired blood supply) most commonmost common inadequate oxygenation of blood (cardio-respiratory failure) loss of oxygen carrying capacity (anaemia) Carbon monoxide poisoning 1.1. Physical AgentsPhysical Agents Trauma, radiation, extremes of temperatures, electric shock 1.1. Chemicals and DrugsChemicals and Drugs Wide variety 1. Microbiologic Agents Viruses, worms, bacteria ….. 1. Immunologic Reactions Allergic reactions, autoimmune diseases 1. Genetic Defects Obvious congenital malformations (Down syndrome) Subtle single amino acid substitution (hemoglobin S of sickle cell anemia) 1. Nutritional Imbalances Deficiency of nutrients/ or excess 1. Aging
- 9. Morphology of cellinjury • Reversible: – Cellular swelling and vacuole formation (Hydropic changes) – Changes at this stage are better appreciated by EM that may show blebbing of the plasma membrane, swelling of mitochondria and dilatation of ER – Fatty changes
- 10. Hydropic change isone of the early signs of cellular degeneration in response to injury. refers to the accumulation of water in the cell. This is clearly seen in this slide. The accumulation of water in the tubular cells is usually due to hypoxia of the tissue with a resultant decrease in aerobic respiration in the mitochondria and a decreased production ATP. Hydropic Change
- 11. Fatty changes • Thisliver is slightly enlarged and has a pale yellow appearance, seen both on the capsule and cut surface. This uniform change is consistent with fatty metamorphosis (fatty change).
- 12. Morphology of cellinjury • Irreversible/Necrosis – The changes are produced by enzymatic digestion of dead cellular elements, denatunation of proteins and autolysis (by lysosomal enzymes) – Cytoplasm - increased eosinophilia – Nucleus - nonspecific breakdown of DNA leading to • pyknosis (shrinkage), • karyolysis (fading) and • karyorrhexis (fragmentation
- 14. The Cell andthe Environment StimuliStimuli [Causes of Cell Injury] Cell AdaptationAdaptation Achieving a new steady state and preserving viability
- 15. IMPORTANT TARGETS OFCELL INJURY • Aerobic respiration – – ATP depletion or decreased synthesis. • Cell membranes - plasma membranes, mitochondrial, lysosomal and other organelle membranes. • Protein synthesis. • Cytoskeleton. • Genetic apparatus.
- 16. ADAPTATION 1. Atrophy: decrease insize or number of cells leading to reduction in tissue mass 2. Hypertrophy: increase in size of cells leading to increase in size of organ 1. Hyperplasia: increase in number of cells leading to increase size of organ 2. Metaplasia: Is the replacement of one type of cells by another
- 17. ADAPTATION Atrophy: causes Decreased workload Loss of innervation Diminished blood supply Inadequate nutrition Loss of endocrine stimulation Aging
- 20. Reduction in structuralcomponents of cell
- 21. 1.Atrophy of thymusgland 2.thyroglossal duct after birth 3.atrophy of ovaries & uterus after menopause 4.Atrophy of uterus following child birth PHYSIOLOGICAL TYPES OF ATROPHY
- 22. 1. Starvation PATHOLOGICAL 3. Senileatrophy : in old age 2.Neuropathic atrophy: due to loss of innervation
- 23. 4.Pressure atrophy: dueto long continued pressure on a tissue leading to decrease in its blood supply with atrophy of its cells e.g. amyloidosis of the liver 6.Decreased work load: e.g. immobilized limb 5.Ischemic atrophy: due to decrease of blood supply e.g. atherosclerosis
- 24. How To AvoidAtrophy? 1.eating a healthy diet 2.getting regular, moderate exercise 3.avoiding smoking or quitting 4.Do not stay in one position for too long
- 25. ADAPTATION Hypertrophy: increase insize of cells leading to increase in size of organ Increased functional demand skeletal muscle in exercise myocardium in hypertension Specific hormonal stimulation uterus in pregnancy
- 26. Heart, left ventricularhypertrophy Heart, normal
- 27. TYPES • Physiological Hypertrophy Increasein size due to increased work load or exercise. The common examples includes: I- Muscular hypertrophy: increase in bulk of skeletal muscles that occurs in response to strength training exercise II- Ventricular hypertrophy: Increase in size of ventricular muscles of the heart-good if it occurs in response to exercise
- 28. Continued…. • Pathological Hypertrophy Increasein cell size in response to pathological changes Example: Ventricular hypertrophy that occurs due to pathological conditions such as high blood pressure where the work load of ventricles increases
- 29. Continued… • Compensatory Hypertrophy Increasein size of cell of an organ that occurs in order to compensate the loss or dysfunction of another organ of same type Examples: Hypertrophy of one kidney when the other kidney stops functioning Increase in muscular strength of an arm when other arm is lost or dysfunction
- 31. ADAPTATION Hyperplasia: increase innumber of cells leading to increase size of organ Physiologic Hormonal (breast during pregnancy) Compensatory (partial hepatectomy) Pathologic Excessive hormonal / growth factor absolute or relative increase in estrogen over progesterone--endometrial hyperplasia Benign Prosthetic hyperplasia (androgens)
- 32. Hyperplasia: Mechanism • Cellproliferation • via increased production of TRANSCRIPTION FACTORS due to * Increased production of GF * Increased levels of GF receptors * Activation of intracellular signaling • Results in larger organ
- 34.
- 35.
- 36. ADAPTATION Metaplasia: • Isthe replacement of one type of cells by another TYPES: Physiological metaplasia: Replacement of cells in normal conditions Examples: transformation of cartilage into bones and transformation of monocytes into macrophages Pathological Metaplasia: Irrevesible replacement of cells due to constant exposure to harmful stimului Example: Chronic smoking results in transformation of normal mucus secreting ciliated columnar epithilial cells into non mucus secreting non ciliated squamous epithilial cells which become cancerous cells if stimulus (smoking) is prolonged Squamous Metaplasia Intestinal Metaplasia Lower esophageal epithelium chronic gastric reflux
- 37. Metaplasia: Mechanism • Reprogramming 1.of stem cells present in normal tissues 2. of undifferentiated mesenchymal cells in connective tissue • Mediated by signals from cytokines, Growth Factor Leading to induction of specific transcription factors
- 38. Photomicrograph of thetrachea from a smoker. Note that the columnar ciliated epithelium has been replaced by squamous epithelium.
- 39.
- 40. Dysplasia Cellular dysplasia refersto an alteration(abnormality) in the size, shape and organization of the cellular components of a tissue. It is established that dysplasia is a preneoplastic lesion, in the sence that, it is a necessary stage in the multi-step cellular evolution to cancer.
- 41.
- 42. Aplasia • Defective development resultingin the absence of all or part of an organ or tissue Aplasia Cutis Congenita
- 43. Hypoplasia • Incomplete orarrested development of an organ or a part • It may be hereditary or acquired. Enamel hypoplasia
- 44. The Cell andthe Environment StimuliStimuli Cell AdaptationAdaptation Cell Injury Reversible Irreversible (cell death) apoptosis necrosis Atrophy Hypertrophy Hyperplasia metaplasia Reduced oxidative phosphorylation, adenosine triphosphate (ATP) depletion water influx ---Cellular swelling
- 46. Mechanisms of cellinjury
- 47. Depletion of ATP •Usually in hypoxic and chemical injuries. • Sources : oxidative phosphorylation of ADP in the mitochondria and Glycolytic pathway using Glucose. • The major causes of ATP depletion are reduced supply of oxygen and nutrients, mitochondrial damage and the actions of some toxins (Cyanide).
- 49. ATP depletion continued…. •Tissues with a greater glycolytic capacity (liver) are more able to survive loss of oxygen and decreased oxidative phosphorylation better than are tissues with limited capacity for glycolysis (brain). • Low oxygen situation results in misfolding of proteins which trigger a cellular response called the unfolded protein response that may lead to cell death (Activation of apoptosis).
- 50. Mitochondrial damage • SuppliesATP (energy) to the cell. • Damaged by Calcium influx, reactive oxygen species, radiation, oxygen deprivation, toxins and mutations in mitochondrial genes. • Consequences of mitochondrial damage: Formation of mitochondrial permeability transition pore which leads to loss of membrane potential, failure of phosphorylation and ATP depletion and then necrosis. • Release of cytochrome c into the cytosol that activate apoptosis (death). Failure of oxidative phosphorylation leads to ATP depletion and formation of reactive oxygen species(ROS).
- 52. • Depleting extracellularCa protects the cell from injury and delays it. • Cytosolic Ca concentration is very low and is present intracellularly in mitochondria and ER. • Injury will lead to increase cytosolic Ca. • Consequences of Ca increase: opening of mitochondrial permeability transition pore, and activation of a number of enzymes (phospholipases, proteases, endonucleases & ATPases) • Induction of apoptosis by direct activation of caspases and increasing mitochondrial permeability Influx of calcium and loss of calcium homeostasis
- 54. • It isimportant in chemical and radiation injuries, ischemia-reperfusion injury, cellular aging and microbial killing by phagocytosis. • Free radicals: chemical species that have a single unpaired electron in the outer orbital. • Unstable atoms, react with inorganic and organic chemicals (proteins, lipids, carbohyd.) • Initiate autocatalytic reactions..... Creation of more radicals (propagation). Accumulation of oxygen derived free radicals
- 56. • One ofthe oxygen derived free radicals. • Produced normally in small amounts and removed by defence mechanisms. • Once the ROS amount increases this will lead to what so called oxidative stress. • Oxidative stress : cell injury, cancer, aging and some degenerative diseases like Alzheimer. Also ROS are produced by leukocytes and macrophages in inflammation. Reactive oxygen species (ROS)
- 57. • Decay spontaneously. •Antioxidants: Vitamin E and A, ascorbic acid and glutathione in the cytosol. • Binding proteins. • Enzymes: Catalase-----H2O2 ----- O2 and H2O, Superoxide dismutase-(SOD)----- superoxide anion ----H2O2, Glutathione peroxidase---- H2O2 ---H2O or OH------ H2O. Reduced Glutathione level is important in cell safety. Removal of free radicals
- 58. Pathological applications offree radicals • Lipid peroxidation in membranes. Oxidative damage of the double bonds in the polyunsaturated fatty acids resulting in formation of peroxides which are unstable and lead to membrane damage. • Oxidative modification of proteins. Damage the active sites on enzymes, change the structures of proteins and enhance proteosomal degradation of unfolded proteins. • Lesions in DNA. Single and double strand breaks in DNA. Oxidative DNA damage has been implicated in cell aging and in malignant transformation of cells. • Radicals are involved in both necrosis and apoptosis.
- 60. Accumulation of Oxygen-DerivedFree Radicals (Oxidative Stress)
- 61. Patterns of AcuteCell Injury • Apoptosis (a falling away from) Apoptosis is programmed cell death. It is a pathway of cell death that is induced by a tightly regulated intracellular program in which cells destined to die activate their own enzymes to degrade their own nuclear DNA, nuclear proteins and cytoplasmic proteins. The cell's plasma membrane remains intact, but its structure is altered in such a way that the apoptotic cell sends signal to macrophages to phagocytose it.
- 62. Apoptosis – Involves singlecells – Eosinophilia, condensed chromatin with peripheral aggregation – karyorrhexis
- 63. Regulation of apoptosis •It is mediated by a number of genes and their products : • - bcl-2 gene inhibits apoptosis • - bax genes facilitates apoptosis • - p53 facilitates apoptosis by inhibiting bcl2 and promoting bax genes.
- 64. Two types ofcell death Necrosis • Large No. of cells • Invariably (always ) pathologic • Disrupted Plasma membrane • Inflammation Apoptosis • Single cells or small clusters • Often physiologic; may be pathologic • Intact Plasma membrane • No inflammation , • phagocytes to eleminate it
- 65. The Cell andthe Environment StimuliStimuli Cell AdaptationAdaptation Cell Injury Reversible Irreversible (cell death) apoptosis necrosis Atrophy Hypertrophy Hyperplasia metaplasia
- 66.
- 67. Intracellular Accumulations – Endogenous •normal substance produced at normal or increased rate/rate of metabolism inadequate for removal (fatty liver) • normal or abnormal substance cannot be metabolized (storage diseases) – Exogenous – cell cannot degrade substance (carbon)
- 68. Intracellular Accumulations • FattyChange (Steatosis) • Any abnormal accumulation of triglycerides within parenchymal cells. • It is most often seen in the liver, since this is the major organ involved in fat metabolism, but it may also occur in heart, skeletal muscle, kidney, and other organs. • Alcohol abuse and diabetes associated with obesity are the most common causes of fatty change in the liver (fatty liver) in industrialized nations.
- 69. Intracellular Accumulations • FattyChange (Steatosis) – Liver • increased weight, yellow color
- 70. fat vacuoles within cytoplasmof hepatocytes
- 71. Intracellular Accumulations • ExogenousPigments – Carbon (anthracosis) • When inhaled, it is phagocytosed by alveolar macrophages and transported by lymphatics to lymph nodes • mild accumulations usually are of no consequence-- heavy accumulations may induce a fibroblastic response
- 73. Intracellular Accumulations • EndogenousPigments – Lipofuscin (“wear and tear pigment) • insoluble brownish-yellow granular intracellular material that accumulates in a variety of tissues (particularly the heart, liver, and brain) as a function of age or atrophy. • It is not injurious to the cell but is important as a marker of past free-radical injury.
- 74. Intracellular Accumulations • EndogenousPigments – Melanin • brown-black pigment produced in melanocytes • It is synthesized exclusively by melanocytes located in the epidermis and acts as a screen against harmful ultraviolet radiation
- 75. Intracellular Accumulations • EndogenousPigments – Hemosiderin • iron containing golden-yellow pigmen • Local or systemic • Local excesses of iron and hemosiderin result from hemorrhages or vascular congestion, eg hemosiderosis is the common bruise. With lysis of the erythrocytes, the hemoglobin eventually undergoes transformation to hemosiderin.
- 76. hemosiderin • hemosiderosis • systemicoverload of iron, hemosiderin is deposited in many organs and tissues [ liver, bone marrow, spleen, and lymph nodes • occurs in 1. increased absorption of dietary iron, 2. impaired utilization of iron, 3. hemolytic anemias, 4. transfusions • hemochromatosis • hereditary more extensive accumulations of iron with tissue injury including liver fibrosis, heart failure, and diabetes mellitus.
- 77. PATHOLOGIC CALCIFICATION • dystrophiccalcification • deposition occurs in dead or dying tissues, • normal serum levels of calcium. • metastatic calcification • deposition in normal tissues • almost always reflects some derangement in calcium metabolism (hypercalcemia).