1. TISSUE RESPONSE TO INJURY
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2. OBJECTIVES
• Highlight the basic concepts & principles of
tissue response to injury.
• Differentiate between normal tissue &
pathologic tissue.
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3. CONTENTS
3.1: Definitions & Concepts of Tissue Response To
Injury
3.2: Etiology of Cell Injury
3.3: Pathogenesis of Cell Injury
3.4: Morphology of Reversible & Irreversible Cell
Injury
3.5: Aging
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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
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5. • Cellular responses to injury may be as follows:
i. Cellular adaptations
ii. Reversible cell injury & Irreversible cell injury
iii. Subcellular changes & Intracellular
accumulations
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6. • Molecular interactions between cells;
i. Cell adhesions molecules (CAMs)
ii. Cytokines
iii. Membrane receptors
i. Cell adhesions molecules (CAMs); these are
chemicals which mediate the interaction
between cells (cell-cell interaction) & between
cells and extracellular matrix (cell-ECM
interaction).
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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)
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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.
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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
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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)
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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
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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
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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. anaemia
2. 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
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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 & salt
4. Microbial agents
5. Immunologic agents;
• Causes of chemiclas & drugs are as below;
i. hypersensitivity reactions
ii. anaphylactic reactions
iii. autoimmune diseases
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15. 6. Nutritional derangements;
• Causes of nutritional derangements are as below;
i. nutritional deficiency e.g. starvation
ii. nutritional excess e.g. heart disease
7. Psychologic factors;
• Causes of psychologic factors are as below;
i. mental stress
ii. overwork
iii. frustration
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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
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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
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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.
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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.
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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.
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21. iv. Reduced protein synthesis
• Ribosomes are detached from granular
endoplasmic, reticulum & polysomes are
degraded to monosomes, thus causing
reduced protein synthesis.
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22. v. Functional consequences
• reversible cell injury may result in functional
disturbances.
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23. vi. Ultrastructural changes
• - Endoplasmic reticulum
• - Mitochondria
• - Plasma membrane
• - Myelin figures
• - Nucleolus
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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
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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.
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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 .
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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.
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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
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29. • Cerebral
atrophy -
Alzheimer
s
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30. • Heart hypertrophy
in hypertension
Left Ventricle
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31. • Muscle ischemic atrophy
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32. • Extensive Caseous
Necrosis Tuberculosis
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33. • Caseous Tuberculosis
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34. • Gangrene – Amputated diabetic foot
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35. • Gangrene Intestine - Thrombosis
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36. • Stroke – Liquifactive necrosis
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37. • Renal Infarction - Coagulative
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38. • Splenic Infarction – Coagulative necrosis
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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
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40. Cellular mechanisms of aging
i. Cross linking proteins & DNA
ii. Accumulation of toxic by products
iii. Aging genes
iv. Loss of repair mechanism
v. Free radical injury
vi. Telomerase shortening
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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.
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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.
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44. • Organ changes in aging;
i. Cardiovascular system
ii. Nervous system
iii. Musculoskeletal system
iv. Eyes
v. Hearing
vi. Immune system
vii. Skin
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45. • Pathology of
elderly
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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
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47. "No matter how dark things seem to
be or actually are, raise your sights
and see the possibilities – always
see them, for they're always there.“
Norman Vincent Peale
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48. THANK YOU
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