Cell Injury and Death Part II PDF

Cell Injury and Cell Death Part II PAMS-HIS Pathology Team  By the end of this session students should be able to: ◦ Differentiate between reversible and irreversible Session’s injury. ◦ Recognize cellular changes in the reve...

Cell Injury and Cell Death Part II PAMS-HIS Pathology Team  By the end of this session students should be able to: ◦ Differentiate between reversible and irreversible Session’s injury. ◦ Recognize cellular changes in the reversible and Objectives irreversible injury. ◦ Recognize types of cell death as a result of irreversible injury. Part II ◦ Identify necrosis (definition, morphology, types, and fate).  Effects of stresses on cells Stresses affect normal cell functions Continuous stress and ineffective adaptation Adaptive changes Cell Injury 1. Atrophy 2. Hypertrophy 3. Hyperplasia Reversible cell Irreversible cell 4. Metaplasia Injury Injury Apoptosis Necrosis  ◦ The changes which are produced in a cell in response to injury are still reversible if the cause of injury is removed. Reversible Cell ◦ Two main morphologic correlates of reversible cell Injury injury: ◦ Cellular swelling due to loss of Na+ K+ ATPase pump activity, so influx of water ◦ Fatty changes  Earliest changes on microscopy : ◦ Pinched off segments of ER, appear as small clear vacuoles within cytoplasm called as hydropic changes or vacuolar degeneration ◦ Appearance of lipid filled vacuoles in cytoplasm fatty changes. Commonly seen in Kidney, liver and heart as Reversible these organs are involved in fat metabolism (mainly in hypoxic & toxic injury). changes: Ultrastructural changes in reversible injury: structural ◦ Plasma membrane alteration: stretched, bulges, bleb formation but membrane remains intact. ◦ Mitochondrial changes: Water accumulation leads to swelling ◦ ER: Detachment of polysomes & dilatation. ◦ Nuclear alterations: Clumping of chromatin otherwise nuclei remain almost unchanged Reversible Cell Injury  Fatty changes Fatty change  ◦ Persistent and excessive severe cell injury in which cell can not restore normal functions. Irreversible cell ◦ Cell membrane rupture ◦ Mitochondria shows structural distortion, focal injury changes deposits of Ca+2 and loss of ribosomes and necrosis ◦ Lysosome rupture releases enzymes & auto- digestion ◦ Nuclear changes i.e. condensation is the most important indicator of irreversible injury  Irreversible Injury means CELL DEATH Apoptosis Necrosis Controlled cell death Uncontrolled cell death  ◦ Necrosis is type of cell death associated with loss of membrane integrity and leakage of Cell Death: cellular contents resulting from degradative Necrosis action of enzymes.  ◦ It is always pathological! ◦ Cell membrane rupture, so cell contents are leaked out and inflammatory response is seen in surrounding tissue. Necrosis ◦ Cell digestion is result of enzymes from dying cells lysosomes and lysosomes of inflammatory leucocytes Nuclear changes of cell death  Main morphological Types of Necrosis 1. Coagulative necrosis 2. Liquefactive necrosis Pattern of tissue ◦ Tissue specific Types necrosis ◦ Coagulative necrosis ◦ Liquefactive necrosis ◦ Gangrenous necrosis - wet/dry ◦ Caseous necrosis ◦ Fat necrosis Coagulative necrosis ◦ It implies preservation of the basic outline of the necrotic cells for several days. ◦ Cell components are dead but basic tissue architecture is preserved and firm ◦ This is due to denaturation of structural and enzymatic proteins, so proteolysis of the cells are blocked ◦ Ischemia leads to coagulative necrosis ◦ Everywhere except in brain where its Liquefactive necrosis ◦ Infarct: areas of ischemic necrosis in all solid organs Wedge-shaped infarct in the renal Pathogenesis and features: parenchyma Acidosis develops and denatures the enzymatic and structural proteins of the cell giving gross appearance of infarcted “wedge shaped area” (gross feature) and “tomb-stone appearance of cells” (microscopic finding) Coagulative necrosis in myocardial infarction Liquefactive necrosis A- Brain ◦ Necrosis with complete cell digestion and transformation of the tissue into a liquid viscous mass ◦ Ischemic Cerebral infarcts (brain/stroke) ◦ Infective foci (bacteria or fungi) cause abscess or pus formation (accumulation of phagocytes and enzymes of leukocytes that digest tissue) B- Abscess ◦ Pathogenesis and features: ◦ In cerebral infarct blood supply to parts of the brain is completely shut-off leading to necrosis but the high lipid content is enzymatically degraded. ◦ Loss of tissue architecture (cell features not identified) (gross/microscopic) In abscess: Debris and dead WBCs are accumulated in a walled-off space Liquefactive necrosis Necrosis characterized by liquefactive process resulting in complete digestion of the dead cells. ◦ Infarct/ Hypoxia in brain leads to liquefactive necrosis ◦ Focal bacterial and fungal infections in other tissues leading to abscess formation. Summary THANK YOU Summary