Cell injury, apoptosis & death II 2024 - Copy.pptx

Cell injury, apoptosis & death - II  Reversible and irreversible injury  Morphology of cell injury & necrosis  Apoptosis Learning outcomes  To differentiate between reversible and irreversible injury  To describe the morphology of cell injury and necrosis  To understand the concept and charact...

Cell injury, apoptosis & death - II  Reversible and irreversible injury  Morphology of cell injury & necrosis  Apoptosis Learning outcomes  To differentiate between reversible and irreversible injury  To describe the morphology of cell injury and necrosis  To understand the concept and characteristics of apoptosis Cell injury, apoptosis & death - II  Reversible and irreversible injury  Morphology of cell injury & necrosis  Apoptosis Sequence of events in cell injury Reversible Irreversible Cell death (necrosis) Early functional changes:  Decreased generation of ATP  Loss of cell membrane integrity  Defects in protein synthesis  Cytoskeletal damage and DNA damage Morphological changes of reversible injury  Cellular swelling (under light microscopy)  Ultrastructural changes: − Plasma membrane alterations: blebbing, blunting and distortion of microvilli − Mitochondrial swelling − Dilation of the endoplasmic reticulum − Nuclear alterations, with disaggregation of granular and fibrillar elements Irreversible injury Cell death (necrosis)        Extensive damage to all cellular membranes Swelling of lysosomes & vacuolization of mitochondria Extracellular calcium enters the cell Intracellular calcium (from stores) is released Activation of enzymes - catabolize membranes, proteins, ATP, and nucleic acids Continued loss of proteins, coenzymes, RNA from the hyperpermeable plasma membrane Nuclear Changes: pyknosis (shrink), karyorrhexis (fragmentation) and karyolysis (disintegration) Vacuolated mitochondria Cell injury, apoptosis & death - II  Reversible and irreversible injury  Morphology of cell injury & necrosis  Apoptosis Necrosis  Necrosis: Pathological cellular or tissue death in a living organism, irrespective of cause Refers to a spectrum of morphologic changes that follow cell death, largely resulting from the progressive degradative action of enzymes on the lethally injured cells  Different types of necrosis seen in different tissues - Coagulative necrosis - Liquefactive necrosis - Caseous necrosis - Fat necrosis Coagulative necrosis     Most common form of necrosis Characteristic of hypoxic death of cells in all tissues except the brain Cell maintains its architecture having lost its nucleus. Cytoplasm looks coagulated and stains pink with eosin Normal Myocardium Infarct Liquefactive/colliquative necrosis  Characteristic of focal bacterial infections (the accumulation of inflammatory cells)  Hypoxic death of cells in central nervous system  Complete digestion of the dead cells results in the transformation of the tissue into a liquid viscous mass  The material is frequently creamy yellow because of the presence of dead white cells and is called pus Kidney necrosis Coagulative Loss of nuclei and clumping of cytoplasm but with preservation of basic outlines of glomerular and tubular architecture Liquefactive The focus is filled with white cells and cellular debris, creating a renal abscess that obliterates the normal architecture Caseous necrosis    Most often in foci of tuberculous infection Cheesy white gross appearance The tissue architecture is completely obliterated A tuberculous lung with a large area of caseous necrosis; The caseous debris is yellow-white and cheesy Fat necrosis It is descriptive of focal areas of fat destruction, typically occurring in acute pancreatitis as a result of release of activated pancreatic lipases into the substance of the pancreas and the peritoneal cavity The areas of white chalky deposits represent calcium soap formation at sites of lipid breakdown Cell injury, apoptosis & death - II  Reversible and irreversible injury  Morphology of cell injury & necrosis  Apoptosis Apoptosis (Programmed Cell Death)  Individual cell deletion in physiological growth control and in disease  Activated or prevented by a variety of stimuli  Reduced apoptosis contributes to cell accumulation e.g. neoplasia  Increased apoptosis results in excessive cell loss e.g. atrophy Apoptosis (Programmed Cell Death)    Tightly regulated by intracellular program in which pro-apoptotic cells activate enzymes that degrade the cells' own DNA and proteins In normal situations, it serves to eliminate unwanted or potentially harmful cells In pathological events (radiation, viral infection), to eliminate irreversibly damaged cells especially when the damage affects the cell's DNA Characteristics of apoptotic cells       Degradation of the cytoskeletal framework Fragmentation of DNA Loss of mitochondrial function Nucleus shrinks (pyknosis) and fragmentation (karyorrhexis) Cell shrinks, but retains an intact plasma membrane, which rapidly induces phagocytosis Apoptotic bodies Sequential ultrastructural changes in necrosis and apoptosis Chromatin condensation & fragmentation Cytoplasmic budding Apoptotic bodies Enzymatic digestion Phagocytosis of apoptotic cells Leakage of Cellular contents Necrosis Apoptosis In lecture case study and questions A patient presents with symptoms of a stroke. A computed tomography (CT) scan shows a cerebral infarction. Ten days after the onset of symptoms, the patient dies and an autopsy is performed. What is the pathologist most likely to observe in the brain? a) b) c) d) e) Caseous necrosis Fatty change Fibrosis Liquefactive necrosis Normal appearances Summary     Cell injury: Reversible/Irreversible Cell death: Necrosis/Apoptosis Types of necrosis: (Refers to morphological changes) Coagulative (most common) Liquefactive; Caseous; Fat necrosis. Apoptosis (programmed cell death): Normal/pathological Features: DNA fragmentation; apoptotic bodies