TYPES OF NECROSIS by 70eaO6

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									General pathology
   Introduction to                  Cellular
    pathology                         Adaptations


   Mechanisms of                    Necrosis and
    Cell Injury                       Apoptosis



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 Introduction to pathology
 Scientific study of structural and functional
  changes in cells tissues and organs
  underlying disease.
 Basically subdivided into these core
  aspects
     Aetiology
     Pathogenesis
     Morphological changes
     Complications and clinical significance

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Cellular Adaptations
 Normal cell are in homeostasis
 Reactions to severe stress or injury will
  cause cellular adaptations
 The Adaptations are
       Hyperplasia
       Hypertrophy
       Metaplasia
       Atrophy
       Hypoplasia
       Fatty
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                change   Babatunde J Olasode   3
Thyroid Enlargement




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Mechanisms of Injury
 Depends on type severity and nature
 Ability to recover depends on cell’s
  nutrition, blood supply and metabolism
 Targets of injury are
     Aerobic  respiration
     Cellular membrane
     Protein synthesis
     Cytoskeleton
     Genetic apparatus
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Necrosis and Apoptosis
   Necrosis
       Coagulative   necrosis
       Liquifarctive necrosis
       Caseous necrosis
       Putrefactive necrosis
       Fat necrosis




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            TYPES OF NECROSIS




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            TYPES OF NECROSIS




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Morphology of Necrosis
 Cellular Swelling
 Mitochondrial changes
 Nuclear changes
       Pyknosis
       Karyolysis
       Karyorrhexis




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Causes of Cellular Injury
 Oxygen lack
 Physical Agents
 Chemical Agents
 Infectious Biologic Agents
 Immunologic Reactions
 Genetic Defects
 Nutritional imbalance


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Apoptosis
   Physiological                      Pathological
    Apoptosis                           Apoptosis
       During embryogenesis              Injurious   stimuli like
       Hormone induced                    radiation
       Lymphocyte selection              Viral diseases

       Lining epithelium                 Duct obstuction
                                          Tumor growth
                                           regression



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            Activation of cell cycle




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            Inhibition of cell cycle




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            Biochemical features

Protein Cleavage
Protein Crosslinking
DNA Breakdown
Phagocytic Recognition




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            Activation of Apoptosis




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            Types of Apoptosis

Tumor Necrosis factor Induced Apoptosis
Fas – Fas mediated induced Apoptosis
Cytotoxic T Lymphocyte stimulated
Growth deprivation induced Apotosis
DNA damaged induced Apoptosis


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            p53 control of apoptosis




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               Regulators

Bcl2 Superfamily
Caspases
Transglutamases
Endonucleases
Cytochrome C


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        P53 mutant prevents arrest




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            Disorders with dysregulated
                    Apoptosis
Cancers with p53 mutations
Hormone dependent tumors
Autoimmune Disorders
Neurodegenerative Disorders
Myocardial Infarction
Virus induced lymphocyte depletion-AIDS


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   Cell Cycle; Pathologic Calcifications;
    Calcium Homeostasis Intracellular
    Accumulation – lipids, Pigments, Protein,
    Glycogen

   Free Radical Injury, Cellular Aging,
    Signaling Mechanisms, Adhesion
    Molecules, Cytokines, ECM and cell-
    matrix interactions;


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Pathologic
Calcifications
   Dystrophic                           Metastatic
    Calcification                         Calcification
       Normal  serum calcium               Abnormal  calcium
       Normal calcium                       metabolism
        metabolism                          Occurs in
       Focal and occurs in                  hypercalceamia
        necrotic tissue                     Occurs in the kidneys
       Atheroma, fat necrosis               lungs and stomach
        etc


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Intracellular Accumulation – lipids,
Pigments, Protein, Glycogen

   Lipids, proteins and             Pigments
    glycogen                            Exogenous
    accumulations are                           Anthracosis
    storage disorders eg                        Coal workers
                                                tattoos
    xanthomas, Russel
                                        Endogenous    or
    bodies in plasma cells
                                            Haemoglobin derived
    and inborn errors of                        Lipofuscin
    metabolism                                  Melanin, homogentisic acid
                                                Haemosiderin, haemozoin


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Free Radical Injury
   Produced in                      Causes
    metabolic respiration               Radiations
   Oxygen reactive                     Metabolism   of drugs
    species                             In many REDOX
                                         reactions
   Occurs in imbalance
                                        Metabolism with
    between production
                                         transition metals
    and removal
                                        Nitric oxide




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Free Radical Injury
   Inactivation of free
    radicals is by
       Antioxidants
       Catalase
       Superoxide       dismutase
       Glutathione
            peroxidase




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Signaling Mechanisms
   Primary Messenger                   Autocrine
   Secondary                           Paracrine
    Messenger                           Endocrine
        cyclic AMP pathway             Growth factors
       kinase pathway
                                        Cytokines
       IP3 pathway
       JAK/STAT pathway
                                        G protein receptors



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Adhesion Molecules, Cytokines,
ECM and cell-matrix interactions;
   Important in
    inflammation and
    repair.




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Cellular Aging
   Environmental Insults            Genetic factors




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