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Learning outcomes
At the end of this lecture, students should be able to: Define injury and etiology of cellular injury Identify the role of cellular adaptation involve during injury. Differentiate between reversible and irreversible cell injury
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Cell injury; defined as a variety of stresses as a injury; 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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Cellular responses to injury may be as follows: i. Cellular adaptations ii. Reversible cell injury & Irreversible cell injury iii. Subcellular changes & Intracellular accumulations
ADAPTATIONS
ATROPHY, HYPERTROPHY, HYPERPLASIA, METAPLASIA, DYSPLASIA
Stress removed
CELL DEATH
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interaction .
Molecular interactions between cells; i. Cell adhesions molecules (CAMs) ii. Cytokines iii. Membrane receptors
i. Cell adhesions molecules (CAMs); these are (CAMs); chemicals which mediate the interaction between cells (cell-cell interaction) & between (cellcells and extracellular matrix (cell-ECM (cellinteraction).
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The ECM is the ground substances or matrix of connective tissue which provides environment to the cells such as collagen, elastin, elastin, (adhesion protein such as laminin and Molecules of proteoglycans & glycosaminoglycans such as hyaluronic acid. CAMs participate in tissue repair, homeostasis, cell death and inflammation. It can be detected on the surface and also free in circulation.
There are 5 groups of CAMs; celli. Integrins have a role in cell-ECM interactions & in leucocyte - endothelial cell interaction. ii. Cadherins these are calcium-dependent adhesion calciummolecules which bind adjacent cells. iii. Selectins movement of leucocytes and platelet and develop contact with endothelial cells. iv. Immunoglobulin superfamily have a major role in recognition & binding of immunocompetent cells. v. CD44 involved in leucocyte-endothelial interactions & leucocytecellcell-ECM interaction.
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system. 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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iii. Cell membrane receptor; molecules consists of receptor; proteins, proteins, glycoproteins or lipoproteins & may be located on the outer cell membrane, inside the cell membrane, or trans-membranous. 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 enzymes for metabolic & synthetic functions of cells)
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The causes of cell injury (reversible or irreversible) can be classified into 2 large groups; i. Genetic causes ii. Acquired causes
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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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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
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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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3.
Chemicals & Drugs; Drugs; Causes of chemicals & drugs are as below; i. chemical poisons ii. strong acids & alkalis iii. environmental pollutants iv. oxygen at high concentrations v. hypertonic glucose & salt
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4. Microbial agents Injury cause by microbes such as infection by bacteria, viruses, fungi.etc 5. Immunologic agents; agents; Causes of chemiclas & drugs are as below; i. hypersensitivity reactions ii. anaphylactic reactions iii. autoimmune diseases
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Causes of nutritional derangements are as below; i. nutritional deficiency e.g. starvation ii. nutritional excess e.g. heart disease
Causes of psychologic factors are as below; i. mental stress ii. overwork iii. frustration
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ASSESSMENT
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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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If the ischaemia or hypoxia is short duration, the duration, 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
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iii. Damage to plasma membrane sodium pump iv. Reduced protein synthesis v. Functional consequences vi. Ultrastructural changes
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Ischaemia & hypoxia both limit the supply of oxygen to the cells, thus causing defreased ATP generation from ADP. ADP. - In ischaemia, aerobic respiration as well as ischaemia, glucose availability are both compromised resulting in more severe effects of cell injury. injury. - In hypoxia, anaerobic glycolytic energy production continues and thus cell injury is less severe. severe.
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Due to low oxygen supply to the cell, aerobic respiration by mitochondria fails first. first. This is followed by switch to anaerobic glycolytic pathway for the energy requirement. requirement. This results in rapid depletion of glycogen and accumulation of lactic acid lowering the intracellular pH. pH.
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Normally, the energy-dependent sodium pump energyoperating 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 membranemembrane-regulated process. This result in intracellular accumulation of sodium and diffusion of potassium out of cell.
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Ribosomes are detached from granular endoplasmic, reticulum & polysomes are degraded to monosomes, thus causing reduced monosomes, protein synthesis. Functional consequences - reversible cell injury may result in functional disturbances.
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v. Functional consequences
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If the ischaemia or hypoxia is persistence, the persistence, effects are irreversible. irreversible. 2 essential phenomena always distinguish irreversible from reversible cell injury; i. mitochondrial dysfunction ii. disturbance in cell membrane function membrane damage.
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Following morphologic forms of reversible cell injury; injury; 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. sodium.
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i. Cellular swelling
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 nonlike the heart, skeletal muscle, kidneys and other organs.
iii. Mucoid change is a combination of proteins complexed with mucopolysaccharides, mucopolysaccharides, its chief constituent, normally produced by epithelial cells of mucous membranes and mucous glands .
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iv. Hyaline change iv. is a descriptive histologic term for glassy,homogenous, 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. extracellular.
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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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The pathologic processes involved in cell death are described below; i. autolysis ? ii. Necrosis ? iii. Apoptosis ? iv. Gangrene ?
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Cellular adaptation
The pathologic processes involved in cellular adaptation: i. Atrophy ? ii. Hypertrophy ? iii. Hyperplasia ? iv. Metaplasia ? v. Dysplasia ?
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Left Ventricle
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Caseous Tuberculosis
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"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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THANK YOU
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Question
Raudhah daughter has been diagnosed with hepatic ornithine transcarbamylase deficiency and has developed hepatic failure. The left lobe of an adult donor live is used as an orthotropic transplant. A year later, the size of each liver in donor and recipient is greater than at the time of transplantation. Based on the statement given, what is the cellular alteration occurred in this situation? ----? ----?
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Zainab suffered from chronic renal failure. She had blood pressure measurements in the range of 150/90 to 180/110 mm Hg. Laboratory studies showed her blood urea nitrogen was over 100 mg/dL. She required chronic dialysis mg/dL. and a few months later she died from heart failure. At autopsy, her heart weighed 540 gm. The size of her heart is most likely to be result of ------? ------?
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A 21 year old woman gives birth to her first child. She begin breast feeding the infant for almost a year. What is the cellular adaptation occurred in the breast that allowed her to nurse the infant for this period of time?
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