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Tissue Response to Injury


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Tissue Response to Injury

  2. 2. OBJECTIVES• Highlight the basic concepts & principles of tissue response to injury.• Differentiate between normal tissue & pathologic tissue. 2
  3. 3. CONTENTS3.1: Definitions & Concepts of Tissue Response To Injury3.2: Etiology of Cell Injury3.3: Pathogenesis of Cell Injury3.4: Morphology of Reversible & Irreversible Cell Injury3.5: Aging 3
  4. 4. 3.1 Definitions & Concepts of Tissue Response To Injury• Cell injury; defined as a variety of stresses as a result of changes in internal & external environment.• All cells of the body have inbuilt mechanism to deal with changes in environment.• The cellular response to stress varies & depends on: i. Type of cell & tissue involved ii. Type of cell injury 4
  5. 5. • Cellular responses to injury may be as follows: i. Cellular adaptations ii. Reversible cell injury & Irreversible cell injury iii. Subcellular changes & Intracellular accumulations 5
  6. 6. • Molecular interactions between cells; i. Cell adhesions molecules (CAMs) ii. Cytokines iii. Membrane receptorsi. Cell adhesions molecules (CAMs); these are chemicals which mediate the interaction between cells (cell-cell interaction) & between cells and extracellular matrix (cell-ECM interaction). 6
  7. 7. • The ECM is the ground substances or matrix of connective tissue which provides environment to the cells & consists of 3 components; i. Fibrillar structural proteins (collagen, elastin) ii. Adhesion proteins (fibronectin, laminin) iii. Molecules of proteoglycans & glycosaminoglycans (heparan sulphate, hyaluronic acid) 7
  8. 8. • There are 5 groups of CAMs; i. Integrins – have a role in cell-ECM interactions & in leucocyte - endothelial cell interaction. ii. Cadherins – these are calcium-dependent adhesion molecules which bind adjacent cells. iii. Selectins – which bind to glycoproteins & glycolipids on the cell surface. iv. Immunoglobulin superfamily – have a major role in recognition binding of immunocompetent cells. v. CD44 – involved in leucocyte-leucocyte-endothelial interactions & cell-ECM interaction. 8
  9. 9. ii. Cytokines; main role is in activation of immune system.• 6 categories of cytokines; i. Interferons (IFN) ii. Interleukins (IL) iii. Tumor necrosis factor (TNF) iv. Transforming growth factor (TGF) v. Colony stimulating factor (CSF) vi. Growth factors 9
  10. 10. iii. Cell membrane receptor; molecules consists of proteins, glycoproteins or lipoproteins & may be located on the outer cell membrane, inside the cell or trans-membranous.• There are 3 main types of receptors; i. Enzymed - linked receptors (involved in control of cell growth) ii. Ion channels (for ion exchange) iii. G-protein receptors (activate phosphorylating enzymes for metabolic & synthetic functions of cells) 10
  11. 11. 3.2 Etiology of Cell Injury• The causes of cell injury (reversible or irreversible) can be classified into 2 large groups; i. Genetic causes (Down’s syndrome) ii. Acquired causes 11
  12. 12. • Acquired causes of cell injury can be further categorised as follows; i. Hypoxia & Ischaemia ii. Physical agents iii. Chemical agents & drugs iv. Microbial agents v. Immunologic agents vi. Nutritional derangements vii. Psychological factors 12
  13. 13. 1.Hypoxia (deficiency of oxygen) & Ischaemia• Hypoxia is the most common cause of cell injury• Causes of hypoxia are as below; i. by reduced blood supply to cells e.g. ischaemia ii. oxygen deprivation of tissues e.g. anaemia2. Physical agents• Causes of physical agents are as below; i. mechanical trauma e.g. road accidents ii. thermal trauma e.g. heat or cold iii. electricity iv. radiation e.g. ultraviolet v. rapid changes in atmospheric pressure 13
  14. 14. 3. Chemicals & Drugs;• Causes of chemicals & drugs are as below; i. chemical poisons ii. strong acids & alkalis iii. environmental pollutants iv. insecticides & pesticides v. oxygen at high concentrations vi. hypertonic glucose & salt4. Microbial agents5. Immunologic agents;• Causes of chemiclas & drugs are as below; i. hypersensitivity reactions ii. anaphylactic reactions iii. autoimmune diseases 14
  15. 15. 6. Nutritional derangements;• Causes of nutritional derangements are as below; i. nutritional deficiency e.g. starvation ii. nutritional excess e.g. heart disease7. Psychologic factors;• Causes of psychologic factors are as below; i. mental stress ii. overwork iii. frustration 15
  16. 16. 3.3 Pathogenesis of Cell Injury• In general, the following principles apply in pathogenesis of most forms of cell injury by various agents; i. Type, duration & severity of injurious agent ii. Type, status & adaptability of target cell iii. Underlying intracellular phenomena iv. Morphologic consequences 16
  17. 17. Reversible Cell Injury• If the ischaemia or hypoxia is short duration, the effects are reversible e.g. coronary artery occlusion, myocardial contractility.• The sequential changes in reversible cell injury are as under; i. Decreased generation of cellular ATP ii. Reduced intracellular pH iii. Damage to plasma membrane sodium pump iv. Reduced protein synthesis v. Functional consequences vi. Ultrastructural changes 17
  18. 18. i. Decreased generation of cellular ATP• - Ischaemia & hypoxia both limit the supply of oxygen to the cells, thus causing decreased ATP generation from ADP.• - In ischaemia, aerobic respiration as well as glucose availability are both compromised resulting in more severe effects of cell injury.• - In hypoxia, anaerobic glycolytic energy production continues and thus cell injury is less severe. 18
  19. 19. ii. Reduced intracellular pH• Due to low oxygen supply to the cell, aerobic respiration by mitochondria fails first.• This is followed by switch to anaerobic glycolytic pathway for the energy requirement.• This results in rapid depletion of glycogen and accumulation of lactic acid lowering the intracellular pH. 19
  20. 20. iii. Damage to plasma membrane sodium pump• Normally, the energy-dependent sodium pump operating at the plasma membrane allows active transport of sodium out of the cell and diffusion of potassium into the cell.• Lowered ATP in the cell and consequent increased ATPase activity interfere with this membrane-regulated process.• This result in intracellular accumulation of sodium and diffusion of potassium out of cell. 20
  21. 21. iv. Reduced protein synthesis• Ribosomes are detached from granular endoplasmic, reticulum & polysomes are degraded to monosomes, thus causing reduced protein synthesis. 21
  22. 22. v. Functional consequences• reversible cell injury may result in functional disturbances. 22
  23. 23. vi. Ultrastructural changes• - Endoplasmic reticulum• - Mitochondria• - Plasma membrane• - Myelin figures• - Nucleolus 23
  24. 24. Irreversible Cell Injury• If the ischaemia or hypoxia is persistence, the effects are irreversible.• 2 essential phenomena always distinguish irreversible from reversible cell injury; i. mitochondrial dysfunction ii. disturbance in cell membrane function 24
  25. 25. 3.4 Morphology of Reversible & Irreversible Cell Injury Reversible Cell Injury• Following morphologic forms of reversible cell injury; i. Cellular swelling =the commonest & earliest form of cell injury from almost all causes, common cause of cellular swelling include bacterial toxins, chemicals, poisons, burns, high fever, intravenous administration of hypertonic glucose or saline, cloudy swelling results from impaired regulation of cellular volume especially for sodium.• ii. Fatty change =the intracellular accumulation of neutral fat within parenchymal cells, especially common in the liver but may occur in other non-fatty tissues like the heart, skeletal muscle, kidneys and other organs. 25
  26. 26. • iii. Hyaline change =is a descriptive histologic term for glassy,homogenous, eosinophilic appearance of material in H & E stained sections and does not refer to any specific substance, hyaline change is associated with heterogenous pathologic conditions and may be intracellular or extracellular. iv. Mucoid change =is a combination of proteins complexed with mucopolysaccharides, it’s chief constituent, normally produced by epithelial cells of mucous membranes and mucous glands . 26
  27. 27. Irreversible Cell Injury• Cell death is a state of irreversible injury• It may occur in the living body as a local or focal change e.g. autolysis, necrosis & apoptosis & the changes that follow it e.g. gangrene. 27
  28. 28. • The pathologic processes involved in cell death are described below; i. autolysis ii. necrosis iii. apoptosis iv. gangrene v. atrophy vi. hypertrophy vii. hyperplasia viii. metaplasia ix. dysplasia 28
  29. 29. • Cerebral atrophy - Alzheimer s 29
  30. 30. • Heart hypertrophy in hypertension Left Ventricle 30
  31. 31. • Muscle ischemic atrophy 31
  32. 32. • Extensive Caseous Necrosis Tuberculosis 32
  33. 33. • Caseous Tuberculosis 33
  34. 34. • Gangrene – Amputated diabetic foot 34
  35. 35. • Gangrene Intestine - Thrombosis 35
  36. 36. • Stroke – Liquifactive necrosis 36
  37. 37. • Renal Infarction - Coagulative 37
  38. 38. • Splenic Infarction – Coagulative necrosis 38
  39. 39. 3.5 Aging• In general, the life expectancy of an individual depends upon the following factors; i. intrinsic genetic process ii. environmental factors iii. lifestyle of the individual iv. age-related diseases 39
  40. 40. Cellular mechanisms of agingi. Cross linking proteins & DNAii. Accumulation of toxic by productsiii. Aging genesiv. Loss of repair mechanismv. Free radical injuryvi. Telomerase shortening 40
  41. 41. • Experimental cellular senescene with every cell division, there is progressive shortening of telomerase present at the tips of chromosomes which is normal cell is repaired by the presence of RNA enzyme, telomerase. However, due to aging, due to inadequate presence of telomerase enzyme, lost telomerase is not repaired resulting in interference in viability of cell• Genetic control in invertebrates-clock genes responsible for controlling the rate and time of aging that slowing metabolic function. 41
  42. 42. • Disease of accelerated aging : aging is under genetic control in human beings supported by the observation of high concordance in lifespan.• Oxidative stress hypothesis : aging is partly caused by progressive and reversible molecular oxidative damage due to persistent oxidative stress on the human cell. 42
  43. 43. 43
  44. 44. • Organ changes in aging; i. Cardiovascular system ii. Nervous system iii. Musculoskeletal system iv. Eyes v. Hearing vi. Immune system vii. Skin 44
  45. 45. • Pathology of elderly 45
  46. 46. • Factors affecting aging; o Diminished stress o Stress response o Infections o Diminished immune o Diseases response o Malnutrition o Good health o Accidents 46
  47. 47. "No matter how dark things seem to be or actually are, raise your sights and see the possibilities – always see them, for theyre always there.“ Norman Vincent Peale 47
  48. 48. THANK YOU 48