Lec 1 - Pathology - PDF

11/15/2015 Basic Tremonology  Pathology: is the study of the disease  Pathologists: Diagnostic Performing necropsy Surgical Performing biopsy Toxicologic Evaluate the effect and safety...

11/15/2015 Basic Tremonology  Pathology: is the study of the disease  Pathologists: Diagnostic Performing necropsy Surgical Performing biopsy Toxicologic Evaluate the effect and safety 1  11/15/2015 Clinical Performing tests Study the tissue, cellular, Experimental molecular mechanisms of diseases Pathogenesis Is the mechanism of how the disease develops from its initiation to its molecular and cellular manifestations 2  11/15/2015 How to diagnose a diseases Case history Symptoms Clinical signs Blood Analysis Body fluids Biopsy Postmortem examination “Gross Necropsy lesions – Macroscopic lesions” 3  11/15/2015 Microscopic lesions Histopathology Ultra structural changes Isolation Etiologic Identification identification Deferential diagnosis Treatment The expected outcome Prognosis of the disease Prevention Hygienic measures and control Vaccination 4  11/15/2015 What is the disease ? Any deviation from or interruption of the normal structure or function of any part, organ or system (or combination thereof ) of the body that is manifested by a characteristic set of symptoms and sings and whose etiology, pathology, and prognosis may be known or unknown Type of Diagnosis 1. Clinical diagnosis  case history  Clinical signs  Physical examination 5  11/15/2015 2. Clinical pathologic diagnosis “Based on changes that observed in the chemistry of fluids and hematology, structure, and function of cells collected from the living patient” 3. Morphological diagnosis or lesion diagnosis  Macroscopic “gross” or Microscopic “histologic”  Describe Severity Duration Distribution Degenerative Location Inflammatory Nature Neoplastic 6  11/15/2015 4. Etiological diagnosis “Is more definitive and names the specific cause of the disease” Type of Prognosis The expected outcome of the disease  Excellent  Good  Guarded  Grave 7  11/15/2015 How to detect and evaluate the morphologic changes?  Gross examination  Microscopic examination  Advanced techniques Gross examination  Physical examination of living animal  Postmortem examination of dead animal 8  11/15/2015 Microscopic examination Light microscope H&E Special stains Immunohistochemistry PAS In situ hybridization Toluidine blue Giemsa stain Microscopic examination Electron microscopy Transmission Scanning 9  11/15/2015 Advanced techniques  Specialized microscopes (dark field, contrast, fluorescence)  Laser capture microdissection “ capture tumor cells”  DNA microarrays  proteomics The normal cell 10  11/15/2015 Causes of cell injury 1. Oxygen deficiency 2. Physical agents 3. Infectious agents 4. Nutritional deficiency and imbalance 5. Genetic derangement 6. Workload imbalance 7. Chemical, drugs, and toxins 8. Immunologic dysfunction 9. Aging Cell injury Cells or tissues respond to injury or stress in three ways: 1- Adaptation (with or without accumulation or degenerative changes) 2- Reversible cell injury ( with or without subcellular changes) Necrosis 3- Irreversible cell injury (Death) Apoptosis 11  11/15/2015 Normal cell Reversible Cell Homeostasis Injury Stress Injurious stimuli Mild Transient Adaptation Cell Injury Inability to Sever adapt Progressive Irreversible Cell Injury Necrosis Cell Death Apoptosis Reversible cell injury Acute cell swelling - Hydropic degeneration CNS ------- Cytotoxic Edema Epidermis --- Ballooning degeneration 12  11/15/2015 Reversible cell injury Definition hydropic degeneration is manifested as increased cell size and volume resulting from an overloud of water caused by a failure of the cell to maintain normal homeostasis and regulate the ingress and excretion of water. Reversible cell injury Differential Diagnosis Hypertrophy: cell enlargement that is caused by an increase of cell organelles. 13  11/15/2015 Reversible cell injury Normal homeostasis + + ATP Energy control the Na -K ion pump within the cell membrane + One molecule of Na + Normal homeostasis + K ATP Na K + Na + Normal osmotic pressure Osmosis Moves passively across the cell membrane Controlled by + proteins & Na H2O Reversible cell injury Mechanism of hydropic degeneration (Hypoxia) + + Hypoxia ATP Energy disruption of the Na -K ion pump K + Na + ATP Cell + K + Na + swelling Na Osmotic pressure Moves passively across the cell membrane H2O 14  11/15/2015 The sequence of events in acute cell swelling caused by hypoxia 1. Hypoxia 2. Decrease of oxidative phosphorylation and ATP (aerobic glycolysis) 3. Activation of phosphofructokinase – anaerobic gycolysis- increase intracellular lactate and inorganic phosphate and depletion of glycogen stores + + 4. Failure of Na -K ion pump 5. Influx of Na+, Ca+, H2O with loss of intracellular K +and Mg2+ 6. Swelling of mitochondria and cytocavitary network 7. Detachment of ribosomes, clumping of nuclear chromatin, loss of microvilli, vesiculation of ER, formation of membrane whorls (myelin figures) 8. Sever disruption of cell membrane, influx of Ca into mitochondria and cytosol, overall cell enlargement, clearing of cytosol 9. Irreversable cell injury – cell death (necrosis) 15  11/15/2015 Reversible cell injury Mechanism of hydropic degeneration (Cell membranes injury) Cell membranes injury destroy the selective permeability barrier K + Na + Cell + K + Na proteins + swelling Na Osmotic pressure Moves passively across the cell membrane H2O Cell membranes injury Hepatotoxicities Carbon tetrachloride CCL4 Chloroform CHCL3 Tricholoromethyl radical Phosgen COCL2 Progressive lipid peroxidation of unsaturated fatty acids of cellular membranes Destruction of cell selective permeability barriers 16  11/15/2015 Examples of cell membranes injury in nature Hemolysin of streptococci Form channels in cell membranes Implantation of hollow NK cells proteins in cell membranes Morphology of acute cell swelling Gross appearance 1. Pale 2. Swelled 3. Rounded edges 4. Decreased specific gravity 5. Bulged when incised 17