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Questions and Answers
What is the primary consequence of irreversible cell injury?
What is the primary consequence of irreversible cell injury?
Which of the following is a common cause of necrosis?
Which of the following is a common cause of necrosis?
Which characteristic is associated with necrotic cells?
Which characteristic is associated with necrotic cells?
What type of necrosis is characterized by the preservation of tissue architecture for a few days?
What type of necrosis is characterized by the preservation of tissue architecture for a few days?
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How does liquefactive necrosis primarily affect tissue?
How does liquefactive necrosis primarily affect tissue?
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Which stage of gangrenous necrosis is commonly associated with the presence of pus?
Which stage of gangrenous necrosis is commonly associated with the presence of pus?
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What happens to cellular proteins during necrosis?
What happens to cellular proteins during necrosis?
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What is the role of pro-apoptotic proteins like BAX and BAK in the mitochondrial pathway of apoptosis?
What is the role of pro-apoptotic proteins like BAX and BAK in the mitochondrial pathway of apoptosis?
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Which step is critical in the initiation of the extrinsic pathway of apoptosis?
Which step is critical in the initiation of the extrinsic pathway of apoptosis?
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What is a key characteristic of apoptotic bodies in histological examination?
What is a key characteristic of apoptotic bodies in histological examination?
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Which proteins are considered anti-apoptotic members that help maintain mitochondrial integrity?
Which proteins are considered anti-apoptotic members that help maintain mitochondrial integrity?
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What is the primary purpose of phagocytosing apoptotic bodies by neighboring cells?
What is the primary purpose of phagocytosing apoptotic bodies by neighboring cells?
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What is the primary characteristic of caseous necrosis?
What is the primary characteristic of caseous necrosis?
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Which type of necrosis is primarily caused by the release of pancreatic lipases?
Which type of necrosis is primarily caused by the release of pancreatic lipases?
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What distinguishes apoptosis from necrosis?
What distinguishes apoptosis from necrosis?
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Which of the following best describes the outcome of necrotic tissue resorption in the brain?
Which of the following best describes the outcome of necrotic tissue resorption in the brain?
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What physiological role does apoptosis play during the menstrual cycle?
What physiological role does apoptosis play during the menstrual cycle?
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What is the first step in the process of apoptosis?
What is the first step in the process of apoptosis?
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In which pathological condition is apoptosis particularly critical to prevent cancerous transformation?
In which pathological condition is apoptosis particularly critical to prevent cancerous transformation?
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What microscopic feature is most distinctive of apoptosis?
What microscopic feature is most distinctive of apoptosis?
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Which of the following correctly describes the appearance of fibrinoid necrosis?
Which of the following correctly describes the appearance of fibrinoid necrosis?
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What outcome can occur as a result of dystrophic calcification in necrotic tissue?
What outcome can occur as a result of dystrophic calcification in necrotic tissue?
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Study Notes
Irreversible Cell Injury
- Irreversible cell injury results in cell death, which can occur in two primary forms: necrosis and apoptosis.
Necrosis
- Necrosis is a pathologic process that occurs due to severe cell injury.
- Causes include ischemia (loss of blood supply), toxin exposure, physical injury (burns), and conditions like pancreatitis.
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Characteristics:
- Denaturation of proteins results in a firm texture.
- Damaged membranes cause leakage of cellular contents, triggering local inflammation.
- Enzymatic digestion breaks down dead cells.
- Increased eosinophilia due to loss of RNA and protein accumulation.
- Nuclear changes:
- Karyolysis: Fading nucleus due to DNA degradation.
- Pyknosis: Nuclear shrinkage and increased basophilia.
- Karyorrhexis: Nuclear fragmentation.
Patterns of Tissue Necrosis
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Coagulative necrosis:
- Tissue architecture is preserved for several days.
- Firm texture with eosinophilic cells due to protein and enzyme denaturation.
- Commonly caused by ischemia, leading to tissue infarction.
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Liquefactive necrosis:
- Digests dead cells, transforming the tissue into a viscous liquid.
- Associated with bacterial or fungal infections and hypoxic brain death.
- Necrotic material often appears as pus due to leukocyte presence.
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Gangrenous necrosis:
- Clinical term describing tissue (often limb) undergoing necrosis due to loss of blood supply.
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Types:
- Dry gangrene: Coagulative necrosis affecting multiple levels of tissue.
- Wet gangrene: Bacterial infection superimposed on dry gangrene, leading to liquefactive necrosis.
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Caseous necrosis:
- Often seen in tuberculosis infections, characterized by cheese-like appearance.
- Microscopic appearance: Fragmented or lysed cells in a distinctive inflammatory border called a granuloma.
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Fat necrosis:
- Localized fat destruction, typically due to pancreatic lipases released during acute pancreatitis.
- Chalky-white areas are visible macroscopically, and histologically, necrotic fat cells show calcium deposits and an inflammatory reaction.
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Fibrinoid necrosis:
- Special form of necrosis occurring in immune reactions involving blood vessels.
- Antigen-antibody complexes and plasma proteins leak into the wall, creating a pink fibrin-like appearance on H&E stains.
Sequelae (Outcomes) of Necrosis
- Complete resolution: Some tissues, like the liver and kidney, can regenerate and repair fully.
- Repair by fibrous scarring: In organs like the heart, necrotic tissue is replaced by scar tissue.
- Resorption of necrotic tissue: In the brain, necrotic tissue is removed by macrophages leaving a fluid-filled cyst (pseudocyst).
- Calcification: Dystrophic calcification can occur in necrotic tissues, leading to calcium deposits.
Apoptosis
- Apoptosis is programmed cell death occurring when cells activate enzymes that degrade their DNA and proteins.
- It’s tightly regulated, essential for tissue homeostasis, and involves cell breakdown into membrane-bound fragments called apoptotic bodies.
- Membrane integrity remains intact, but surface alterations attract phagocytes.
- Rapid engulfment and digestion of the apoptotic body prevents inflammatory response.
Historical Context
- Apoptosis was first recognized in 1972, named after the Greek word for "falling off" due to the orderly nature of this cell death process.
Causes of Apoptosis
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Physiological situations:
- Developmental cell removal: Eliminates excess cells, involution of primordial structures, and remodeling maturing tissues.
- Involution of hormone-dependent tissues: Breakdown of endometrial cells during menstruation, ovarian follicular atresia during menopause, and regression of lactating breast after weaning.
- Cell turnover in proliferating populations: Maintains constant cell numbers in tissues with high turnover rates (e.g., lymphocytes, intestinal epithelial cells).
- Elimination of self-reactive lymphocytes: Prevents autoimmune reactions.
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Pathological conditions:
- DNA damage: Resulting from radiation, chemotherapy, or free radicals. Apoptosis prevents survival of mutation-carrying cells that could become cancerous.
- Accumulation of misfolded proteins: Misfolded proteins trigger ER stress, a defense mechanism against accumulation of harmful proteins.
- Infections: Induced by viral infections, directly by the virus or as a result of the host’s immune response.
- Pathologic atrophy: Contribute to atrophy after duct obstruction, causing cell loss and tissue shrinking.
Morphologic and Biochemical Changes in Apoptosis
- Cell shrinkage: Cell becomes smaller, with densely packed cytoplasm.
- Chromatin condensation: Distinctive feature of apoptosis, chromatin aggregates beneath the nuclear membrane.
- Nuclear fragmentation: Nucleus breaks into fragments as apoptosis progresses.
- Formation of cytoplasmic blebs and apoptotic bodies: Cell membrane forms blebs that break off into apoptotic bodies containing cytoplasmic and nuclear material. Eosinophilic appearance.
- Absence of inflammation: Rapid clearance of apoptotic bodies by phagocytes prevents the release of cell contents and prevents inflammation. Difficult to detect with light microscopy.
Mechanism of Apoptosis
- Apoptosis is orchestrated by caspases, activated through two main pathways:
- **Mitochondrial (intrinsic) pathway : **
- Initiated by increased permeability of the mitochondrial outer membrane.
- Cytochrome c released into the cytoplasm triggers apoptosis.
- Controlled by BCL2 family of proteins:
- Anti-apoptotic proteins: BCL2, BCL-XL, and MCL1 maintain membrane impermeability.
- Pro-apoptotic proteins: BAX and BAK increase membrane permeability when activated.
- Regulated apoptosis initiators: BAD, BIM, and BID initiate apoptosis when upregulated.
- **Death receptor (extrinsic) pathway: **
- Initiated by engagement of death receptors on the plasma membrane.
- Death receptors belong to the TNF receptor family with a cytoplasmic death domain.
- Key death receptors: TNFR1 and Fas (CD95).
- Fas ligand (FasL) expressed on T cells recognizes self-antigens and eliminates self-reactive lymphocytes.
- FasL is also expressed on cytotoxic T lymphocytes (CTLs).
- Upon binding of FasL to Fas, a binding site for the adaptor protein FADD is formed.
- FADD recruits inactive caspase-8, leading to its activation.
- Active caspase-8 initiates activation of executioner caspases.
- **Mitochondrial (intrinsic) pathway : **
Execution Phase of Apoptosis
- Both pathways lead to caspase cascade activation.
- Initiator caspases (caspase-9 for intrinsic, caspase-8 and caspase-10 for extrinsic) activate executioner caspases (caspase-3 and caspase-6).
Removal of Dead Cells
- Formation of cytoplasmic buds containing cell components.
- Formation of apoptotic bodies, encapsulating fragmented cellular contents.
- Phagocytosis of apoptotic bodies by neighboring cells or macrophages, ensuring safe and efficient removal and preventing inflammation.
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Description
This quiz explores aspects of irreversible cell injury, including necrosis and apoptosis. It covers the causes, characteristics, and patterns of tissue necrosis, detailing the various nuclear changes associated with cell death. Ideal for students studying pathology or related fields.
