Cell Injury - PDF

 DR SHEREEN FATHY (MD) PROF. OF PATHOLOGY  Causes of cellular injury: 1. Living infectious irritant 2. Non-living 3. Hypoxia 4. Hypersensitivity 5. Nutritional disturbances 6. Genetic disorders 7. Enzymatic disorders  Causes of cell injury: 1- Hypoxia: (Decrease oxygen s...

 DR SHEREEN FATHY (MD) PROF. OF PATHOLOGY  Causes of cellular injury: 1. Living infectious irritant 2. Non-living 3. Hypoxia 4. Hypersensitivity 5. Nutritional disturbances 6. Genetic disorders 7. Enzymatic disorders  Causes of cell injury: 1- Hypoxia: (Decrease oxygen supply)is caused by: a. Ischemia e.g. arterial occlusion and atherosclerosis b. Inadequate oxygenation e.g. cardiac and pulmonary disease c. Decreased oxygen carrying capacity of the blood e.g. anaemia and carbon monoxide poisoning. 2-Infectious agents:Viruses, bacteria, fungi and parasites. 3- Physical agents: Trauma, heat, cold, irradiation and electric shock. 4- Chemical agents & Drugs:Acids, alkalies, animal and plant poisons, certain therapeutic drugs. 5-Immunological reactions:Autoimmune diseases. 6-Nutritional disturbances. 7-Genetic & Enzymatic disorders. File:Animal cell structure en.svg 4 intracellular systems vulnerable to cell injury: Aerobic respiration Maintenance of And cell membrane generation of ATP Synthesis of enzymes and the genetic apparatus structural proteins  EFFECTS OF CELL INJURY 1. ATP depletion 2. Altered membrane permeability 3. Increased intracellular Ca 4. Formation of intracellular toxic compounds Mechanisms of cellular injury:  Mechanisms of cell injury Increases intracellular calcium: The source of Ca2+ is influx from plasma membrane or release from mitochondria and endoplasmic reticulum. Increased cytosolic Ca2+ activates a number of enzymes: A- Phospholipases degrade membrane phospholipids B- Proteases break down both membrane and cytoskeletal proteins C- Endonucleases DNA and chromatin fragmentation D- ATPases thereby hastening ATP depletion Effect of injury depends on: 1. Type of injured cells 2. Duration 3. Severity of irritant  Injurious Agent (Hypoxia, Ischemia) Mitochondria (-Oxidative Phosphorylation) ATP Depletion ATP decreases Pathogenesis ---Na K Pump Na & H20 enter cell Cellular Swelling End result of injury : 1. Inflammation 2. Reversible injury (Degeneration) 3. Irreversible injury ( Necrosis //Apoptosis) 4. Intracellular accumulation (water, Fat……) 5. Extracellular accumulation (calcification, amylodosis) 6. Vascular disturbances (Thrombosis and odema) 7. Disturbance of cell growth (dysplasia, neoplasia) End result of injury : IRREVERSIBLE (CELL DEATH) Necrosis Apoptosis REVERSIBLE (DEGENERATION) Cloudy swelling Water Accumulation Hydropic swelling Parenchymal Fat Accumulation Mesenchymal  Cloudy swelling: Pathological accumulation of water. Reversible cell injury characterized morphologically by swelling of the cells (due to water accumulation) and granularity of the cytoplasm.  CLOUDY SWELLING Def.: Pathogenesis: HYPOXIA Inhibition of oxidative phosphorylation ATP depletion 1. Failure of sodium and potassium pump 2. Increase intracellular osmotic load 3. Swelling and beading of the mitochondria Gross Picture: Rounded pale borders Tense Heavy capsule Enlarged Liver, Bulging cut Kidney section , Heart Gross picture: Increased weight and pale color Microscopic picture: Cytomegaly and pale eosinophilic granular cytoplasm Examples: A. Renal tubules (nephritis ) albuminurea B. Cardiac muscles Weak contractility C. Liver Microscopic picture Cells :Swollen Cytoplasm: Fine red granules Nucleus: Normal Capillaries between cells: Compressed.  If the injury stops If the injury → Reversible (cell Fate: continues → returns to Hydropic swelling normal).  Hydropic swelling Definition: Reversible cell injury characterized morphologically by swelling of the cells and vacuoles in the cytoplasm (due to excess water accumulation). The lesion is more advanced than cloudy swelling Pathogenesis: Similar to cloudy swelling  Hydropic degeneration Pathogenesis: same as cloudy swelling but with more water accumulation Gross picture: Microscopic picture: -Viral hepatitis - Diabetes mellitus (B cells) Examples: - Epidermal cells in burns - Renal tubules (K defficiency)  Fatty change Definition: Pathological accumulation of excess neutral fat in parenchymatous cells  Fatty change (fatty degeneration) Def.: Lipid accumulation in the parenchymal cells Pathogenesis: Suppression of enzymes involved in lipid metabolism Liver Affected organs.: Other Causes in liver: 1- Hypoxia 2- Excessive fat intake 3- Deficiency of lipotropic factors 4. Hepatotoxins 5. Hepatitis Gross: Organomegaly, Tense capsule, Soft greasy in consistency, Yellowish Liver Diffuse ( as in severe alcoholic hepatitis) Spoty (Patchy) (as in CVC) Nutmeg liver HEART Diffuse (as in diphtheritic toxic myocarditits) Spoty (Patchy) (as in hypoxia) Tabby cat heart = tiger heart Microscopic Signet ring appearance Diagnostic microscopic sign Special stain: Sudan III (orange), Osmic acid (black) Nutmeg liver File:Non-alcoholic fatty liver disease1.jpg *  Causes: 1- Hypoxia 2- Bacterial toxins of acute and chronic infections 3- Chemicals as alcohol, phosphorous and carbon tetrachloride File:Stage of liver damage.JPG Effects End result of injury : IRREVERSIBLE (CELL DEATH) Necrosis Apoptosis REVERSIBLE (DEGENERATION) Cloudy swelling Water Accumulation Hydropic swelling Parenchymal Fat Accumulation Mesenchymal Def.: Local death of a large groups of cells. Gross picture: Opaque yellow surrounded by red area  Microscopic picture: CELLULAR CHANGES: ARCHITECURAL CHANGES NUCLEAR Structurless CYTOPLASMIC (Autolysis) Structure Pyknosis Indistinct CM ghost (Coagulation) Karyorrhexis Cytomegaly Karyolysis Eosinophilia Ca++ File:Necrotic leg wound.png 220px-Tissue_necrosis_following_bite_from_Bothrops_asper_PLoS_Medicine Types of necrosis: 1. Coagulative Necrosis Structure ghost ALL organs except CNS Denaturation > Lysis 2. Liquefactive Necrosis Structurless CNS and abscess Lysis > Denaturation 3. Caseous Necrosis Chessy necrosis = yellowish white T.B Causes: ** Ischemic (End arteritis oblitrans) ** Allergic inflammation ** Bacilli  4. Fat Necrosis a) Enzymatic: - as in acute hemorrhagic pancreatitis - Caused by digestion of peritoneal fat by lipase and protease enz. - Grossly: Hard chalky white patches b) Traumatic - Due to breast trauma - caused by auto-digestion and ruptured fat cells - hard mass - clinically : misdiagnosed as carcinoma  Other types of necrosis 5. Gummatous 6. Haemorrhagic 7. Fibrinoid Apoptosis Introduction on apoptosis : *Apoptosis is programmed cell death involved in development, elimination of damaged cells, and maintenance of cell homeostasis. I. Physiological Apoptosis: - During embryogenesis - hormone dependent - normal turn over of cells II. Pathological Apoptosis: - Organ rejection - Viral hepatitis (Councilman bodies) - malignant tumors - mild radiation and mild thermal injury Morphology of apoptotic cells: File:Apoptosis.png Morphology of apoptotic cells: !. Shrinkage of cell size 2. Nuclear Condensation and DNA fragmentation 3. Formation of apoptotic bodies 4. Not surrounded by inflammation File:Apoptosis multi mouseliver.jpg Comparison between the necrosis and apoptosis: Feature Necrosis Apoptosis Cell size Enlarged (swelling) Reduced (shrinkage) Nucleus Pyknosis → karyorrhexis Fragmentation into → karyolysis nucleosome-size fragments Plasma Disrupted Intact; membrane Cellular contents Enzymatic digestion; may Intact; leak out of cell inflammation Frequent No Cause Invariably pathologic Often physiologic