Cell Death Mechanisms in Pathology
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Questions and Answers

What is the primary morphologic hallmark of cell death?

  • Cell swelling and lysis
  • Loss of cellular membrane integrity
  • Disruption of the cytoplasm
  • Loss of the nucleus (correct)

    • Which type of necrosis is characterized by the preservation of cell shape and organ structure?

  • Liquefactive necrosis
  • Gangrenous necrosis
  • Caseous necrosis
  • Coagulative necrosis (correct)

    • Which of the following conditions is associated with liquefactive necrosis?

  • Brain infarction (correct)
  • Chronic ischemia
  • Dry gangrene
  • Fibrosis

    • Dry gangrene is best described as which kind of necrosis?

    <p>Coagulative necrosis</p> Signup and view all the answers

    Which mechanism is primarily responsible for the formation of caseous necrosis?

    <p>Tuberculous infection</p> Signup and view all the answers

    What type of necrosis occurs with inflammation and is often seen post-infarction of solid organs?

    <p>Coagulative necrosis</p> Signup and view all the answers

    What characteristic feature distinguishes wet gangrene from dry gangrene?

    <p>Presence of superimposed infection</p> Signup and view all the answers

    What defines the histological appearance of liquefactive necrosis?

    <p>Soft and friable necrotic tissue</p> Signup and view all the answers

    What is the primary characteristic appearance of fat necrosis?

    <p>Chalky-white appearance due to calcium deposition</p> Signup and view all the answers

    Which condition is NOT typically associated with fat necrosis?

    <p>Chronic kidney disease</p> Signup and view all the answers

    What process describes the joining of fatty acids with calcium in fat necrosis?

    <p>Saponification</p> Signup and view all the answers

    In the context of necrosis, what distinguishes dystrophic calcification from metastatic calcification?

    <p>Dystrophic is associated with normal serum calcium levels, while metastatic is linked to high levels.</p> Signup and view all the answers

    Fibrinoid necrosis is characterized by damage to which part of the body?

    <p>Blood vessel walls</p> Signup and view all the answers

    What type of staining is typically seen microscopically in the case of fibrinoid necrosis?

    <p>Bright pink staining due to protein leakage</p> Signup and view all the answers

    Which condition is associated with fibrinoid necrosis?

    <p>Malignant hypertension</p> Signup and view all the answers

    What occurs in metastatic calcification according to serum levels?

    <p>High serum calcium or phosphate levels</p> Signup and view all the answers

    Which phenomenon is characterized by the organized fragmentation of the nucleus and the removal of apoptotic bodies by macrophages?

    <p>Apoptosis</p> Signup and view all the answers

    What initiates the intrinsic mitochondrial pathway of apoptosis?

    <p>Inactivation of Bcl2</p> Signup and view all the answers

    Which of the following statements is true regarding the morphology of apoptotic cells?

    <p>The cytoplasm becomes eosinophilic and the nucleus condenses.</p> Signup and view all the answers

    How is apoptosis mediated at the molecular level?

    <p>Through caspases activating proteases and endonucleases</p> Signup and view all the answers

    Which pathway involves FAS ligand binding to FAS death receptor to induce apoptosis?

    <p>Extrinsic receptor-ligand pathway</p> Signup and view all the answers

    What is the primary role of granzyme in the cytotoxic CD8+ T cell-mediated apoptosis?

    <p>To activate caspases after entering through pores</p> Signup and view all the answers

    In what case would you observe apoptosis during the menstrual cycle?

    <p>During endometrial shedding</p> Signup and view all the answers

    What happens when CD8+ T cells mediate apoptosis of virally infected cells?

    <p>They employ perforins and granzymes to induce cell death.</p> Signup and view all the answers

    What chemical species is characterized by having an unpaired electron in its outer orbit?

    <p>Free radicals</p> Signup and view all the answers

    Which of the following processes is responsible for physiologic generation of free radicals?

    <p>Oxidative phosphorylation</p> Signup and view all the answers

    What type of free radical is primarily generated during inflammation by NADPH oxidase?

    <p>Superoxide ions</p> Signup and view all the answers

    Which mechanism is NOT involved in the elimination of free radicals?

    <p>Macrophage phagocytosis</p> Signup and view all the answers

    Which enzyme converts superoxide into hydrogen peroxide?

    <p>Superoxide dismutase</p> Signup and view all the answers

    What cellular injury is primarily associated with carbon tetrachloride (CCl4) exposure?

    <p>Protein synthesis impairment</p> Signup and view all the answers

    What is one consequence of reperfusion injury after blood supply returns to ischemic tissue?

    <p>Higher levels of cardiac enzymes</p> Signup and view all the answers

    Which of the following metals is associated with the generation of hydroxyl free radicals through the Fenton reaction?

    <p>Iron</p> Signup and view all the answers

    Apoptosis is always followed by significant inflammation.

    <p>False</p> Signup and view all the answers

    Caspases are only activated by the intrinsic mitochondrial pathway.

    <p>False</p> Signup and view all the answers

    The process of endonuclease action during apoptosis results in the fragmentation of DNA.

    <p>True</p> Signup and view all the answers

    During apoptosis, the nucleus condenses and fragments in a disorganized manner.

    <p>False</p> Signup and view all the answers

    FAS ligand binding to its receptor can trigger apoptosis in target cells.

    <p>True</p> Signup and view all the answers

    Granzyme from CD8+ T cells enters the target cell to initiate apoptosis via membrane pores.

    <p>True</p> Signup and view all the answers

    Bcl2 is a protein that promotes apoptosis under physiological conditions.

    <p>False</p> Signup and view all the answers

    Dying cells during apoptosis typically swell and become more basophilic.

    <p>False</p> Signup and view all the answers

    Fat necrosis is characterized by a necrotic appearance resembling bright pink staining due to protein leakage.

    <p>False</p> Signup and view all the answers

    Dystrophic calcification occurs in states of high serum calcium levels leading to calcium deposition in normal tissues.

    <p>False</p> Signup and view all the answers

    Fibrinoid necrosis is typically associated with conditions like malignant hypertension and vasculitis.

    <p>True</p> Signup and view all the answers

    Metastatic calcification occurs in dead tissues and acts as a nidus for calcification.

    <p>False</p> Signup and view all the answers

    Saponification is a process associated with the release of fatty acids during pancreatitis that involves calcium deposition.

    <p>True</p> Signup and view all the answers

    Apoptosis is characterized by the disorganization and rupture of the cell membrane.

    <p>False</p> Signup and view all the answers

    Necrotic adipose tissue has a chalky-white appearance due to the process of metaplasia.

    <p>False</p> Signup and view all the answers

    Apoptosis is a process that can lead to inflammation in surrounding tissues.

    <p>False</p> Signup and view all the answers

    The hallmark of cell death includes the loss of the nucleus through pyknosis, karyorrhexis, and karyolysis.

    <p>True</p> Signup and view all the answers

    Coagulative necrosis is typically associated with brain infarction.

    <p>False</p> Signup and view all the answers

    Liquefactive necrosis can occur in conditions such as brain infarction and pancreatitis.

    <p>True</p> Signup and view all the answers

    Gangrenous necrosis describes tissue that has become liquefied due to enzymatic activity.

    <p>False</p> Signup and view all the answers

    Caseous necrosis is characterized by a 'cottage cheese-like' appearance and is associated with tuberculosis.

    <p>True</p> Signup and view all the answers

    Red infarction occurs when blood re-enters necrotic tissue that was previously poorly organized.

    <p>True</p> Signup and view all the answers

    Pyknosis refers to the fragmentation of the nucleus during cell death.

    <p>False</p> Signup and view all the answers

    Wet gangrene arises from coagulative necrosis that has become superinfected.

    <p>True</p> Signup and view all the answers

    Free radicals can cause cellular injury through the peroxidation of lipids and oxidation of proteins.

    <p>True</p> Signup and view all the answers

    The Fenton reaction involves the conversion of hydrogen peroxide to superoxide.

    <p>False</p> Signup and view all the answers

    Antioxidants like glutathione and vitamin C are ineffective in eliminating free radicals.

    <p>False</p> Signup and view all the answers

    Ionizing radiation can lead to the generation of hydroxyl free radicals through the hydrolysis of water.

    <p>True</p> Signup and view all the answers

    The enzyme superoxide dismutase converts hydrogen peroxide into oxygen and water.

    <p>False</p> Signup and view all the answers

    Reperfusion injury occurs when blood supply is restored to ischemic tissues, resulting in further oxidative damage.

    <p>True</p> Signup and view all the answers

    Copper and iron are examples of metals that can indirectly generate free radicals through reactions in the body.

    <p>True</p> Signup and view all the answers

    Hydrogen peroxide is primarily generated during oxidative phosphorylation as a byproduct.

    <p>True</p> Signup and view all the answers

    What is the appearance of necrotic adipose tissue in fat necrosis?

    <p>Chalky-white due to calcium deposition.</p> Signup and view all the answers

    Which condition is commonly associated with the necrotic damage to blood vessel walls seen in fibrinoid necrosis?

    <p>Malignant hypertension.</p> Signup and view all the answers

    What biochemical process involves the binding of fatty acids to calcium in fat necrosis?

    <p>Saponification.</p> Signup and view all the answers

    In the context of necrosis, what differentiates dystrophic calcification from metastatic calcification?

    <p>Dystrophic calcification occurs in normal calcium levels, while metastatic occurs in high serum calcium levels.</p> Signup and view all the answers

    What is a characteristic histological feature observed in the case of fibrinoid necrosis?

    <p>Bright pink staining of the vessel wall.</p> Signup and view all the answers

    What type of necrosis is particularly associated with trauma to fat, especially in the breast?

    <p>Fat necrosis.</p> Signup and view all the answers

    What types of conditions might lead to the development of metastatic calcification?

    <p>Conditions with elevated serum calcium or phosphate levels, like hyperparathyroidism.</p> Signup and view all the answers

    What cellular process is typically associated with the death of cells in fat necrosis due to pancreatitis?

    <p>Release of lipase resulting in saponification.</p> Signup and view all the answers

    What is a characteristic feature of coagulative necrosis that differentiates it from liquefactive necrosis?

    <p>In coagulative necrosis, the tissue remains firm and cell shape is preserved, whereas in liquefactive necrosis, the tissue becomes liquefied.</p> Signup and view all the answers

    How does gangrenous necrosis differ from caseous necrosis in terms of tissue appearance?

    <p>Gangrenous necrosis appears mummified or dry, while caseous necrosis has a soft, friable texture resembling cottage cheese.</p> Signup and view all the answers

    What role do proteolytic enzymes play in liquefactive necrosis?

    <p>Proteolytic enzymes lead to the enzymatic lysis of cells and proteins, resulting in the liquefaction of the necrotic tissue.</p> Signup and view all the answers

    What type of necrosis is characterized by a 'cottage cheese-like' appearance and what conditions most commonly cause it?

    <p>Caseous necrosis is characterized by a 'cottage cheese-like' appearance and is commonly caused by tuberculosis or fungal infections.</p> Signup and view all the answers

    What distinguishes red infarction from pale infarction in the context of coagulative necrosis?

    <p>Red infarction occurs when blood re-enters previously ischemic tissue, resulting in hemorrhage, while pale infarction features a lack of blood supply due to vascular occlusion.</p> Signup and view all the answers

    Under what circumstances would wet gangrene develop from dry gangrene?

    <p>Wet gangrene develops from dry gangrene when there is a superimposed infection of the necrotic tissue.</p> Signup and view all the answers

    Identify two major types of cell death and briefly describe their defining characteristics.

    <p>The two major types are necrosis, which involves the death of large groups of cells with inflammation, and apoptosis, which is a regulated process of programmed cell death without inflammation.</p> Signup and view all the answers

    What morphologic changes occur in the nucleus during cell death, specifically in apoptosis?

    <p>In apoptosis, the nucleus undergoes condensation (pyknosis), fragmentation (karyorrhexis), and dissolution (karyolysis).</p> Signup and view all the answers

    What are the main processes involved in the apoptosis of cells mediated by cytotoxic CD8+ T cells?

    <p>Cytotoxic CD8+ T cells secrete perforins that create membrane pores, allowing granzyme to enter and activate caspases.</p> Signup and view all the answers

    Describe the morphology of a dying cell during apoptosis.

    <p>A dying cell shrinks, leading to eosinophilic cytoplasm, and its nucleus condenses and fragments in an organized manner.</p> Signup and view all the answers

    How does the intrinsic pathway of apoptosis get activated?

    <p>Inactivation of Bcl2 allows cytochrome c to leak from mitochondria, activating caspases.</p> Signup and view all the answers

    What role do caspases play in apoptosis?

    <p>Caspases activate proteases and endonucleases that break down the cytoskeleton and DNA.</p> Signup and view all the answers

    What is the fate of apoptotic bodies after cell death?

    <p>Apoptotic bodies are removed by macrophages, preventing subsequent inflammation.</p> Signup and view all the answers

    Explain the extrinsic receptor-ligand pathway of apoptosis.

    <p>It involves FAS ligand binding to the FAS death receptor, activating caspases in the target cell.</p> Signup and view all the answers

    What initiates the process of endonuclease action during apoptosis?

    <p>Caspase activation leads to the action of endonucleases, resulting in DNA fragmentation.</p> Signup and view all the answers

    What physiological event exemplifies apoptosis during the menstrual cycle?

    <p>The shedding of the endometrium is a physiological example of apoptosis during the menstrual cycle.</p> Signup and view all the answers

    Describe the role of cytochrome c oxidase in the generation of free radicals during oxidative phosphorylation.

    <p>Cytochrome c oxidase transfers electrons to oxygen, resulting in the partial reduction of O2 and the production of superoxide, hydrogen peroxide, and hydroxyl radicals.</p> Signup and view all the answers

    How does ionizing radiation lead to the formation of free radicals in biological systems?

    <p>Ionizing radiation hydrolyzes water molecules, producing hydroxyl free radicals which can cause cellular damage.</p> Signup and view all the answers

    Explain how NADPH oxidase contributes to free radical production during inflammation.

    <p>NADPH oxidase generates superoxide ions as part of the respiratory burst in neutrophils, aiding in the destruction of pathogens.</p> Signup and view all the answers

    What is the Fenton reaction, and which metal is primarily involved in this process?

    <p>The Fenton reaction involves the conversion of Fe2+ to generate hydroxyl free radicals, leading to oxidative damage.</p> Signup and view all the answers

    Discuss the implications of free radical-induced lipid peroxidation on cellular structures.

    <p>Lipid peroxidation damages cellular membranes, leading to loss of integrity and function, which can contribute to cell death.</p> Signup and view all the answers

    Identify the mechanisms by which antioxidants can eliminate free radicals in biological systems.

    <p>Antioxidants such as glutathione neutralize free radicals either directly or via enzymatic reactions, helping to mitigate oxidative stress.</p> Signup and view all the answers

    What cellular consequences arise from the exposure to carbon tetrachloride (CCl4)?

    <p>CCl4 leads to the generation of CCl3 free radicals, causing swelling of the rough endoplasmic reticulum and detachment of ribosomes, impairing protein synthesis.</p> Signup and view all the answers

    Explain how reperfusion injury contributes to oxidative damage in ischemic tissues.

    <p>Reperfusion injury increases the production of O2-derived free radicals, which exacerbate tissue damage following ischemia.</p> Signup and view all the answers

    Fat necrosis involves necrotic adipose tissue with a ______ appearance due to calcium deposition.

    <p>chalky-white</p> Signup and view all the answers

    Saponification is an example of ______ calcification in which calcium deposits occur on dead tissues.

    <p>dystrophic</p> Signup and view all the answers

    Metastatic calcification occurs when there are ______ serum calcium or phosphate levels.

    <p>high</p> Signup and view all the answers

    Fibrinoid necrosis is characterized by necrotic damage to blood vessel ______.

    <p>walls</p> Signup and view all the answers

    Fibrinoid necrosis results in bright pink staining of the vessel wall microscopically due to the leakage of ______.

    <p>proteins</p> Signup and view all the answers

    Characteristic conditions for fibrinoid necrosis include malignant hypertension and ______.

    <p>vasculitis</p> Signup and view all the answers

    Fatty acids released by trauma or lipase combine with calcium via a process called ______.

    <p>saponification</p> Signup and view all the answers

    In dystrophic calcification, the necrotic tissue acts as a ______ for calcification.

    <p>nidus</p> Signup and view all the answers

    The two mechanisms of cell death are necrosis and ______.

    <p>apoptosis</p> Signup and view all the answers

    Coagulative necrosis is characteristic of ischemic infarction of any organ except the ______.

    <p>brain</p> Signup and view all the answers

    Liquefactive necrosis involves the ______ of necrotic tissue due to enzymatic actions.

    <p>liquefaction</p> Signup and view all the answers

    Gangrenous necrosis can present as dry gangrene, which resembles ______ tissue.

    <p>mummified</p> Signup and view all the answers

    Caseous necrosis has a soft and friable appearance, often described as ______ cheese-like.

    <p>cottage</p> Signup and view all the answers

    In necrosis, large groups of cells die and are followed by acute ______.

    <p>inflammation</p> Signup and view all the answers

    Red infarction occurs if blood re-enters a loosely organized ______.

    <p>tissue</p> Signup and view all the answers

    Necrosis is never a ______ process but always due to underlying pathology.

    <p>physiologic</p> Signup and view all the answers

    Apoptosis is a ______-dependent, genetically programmed cell death.

    <p>ATP</p> Signup and view all the answers

    During apoptosis, the nucleus ______ and fragments in an organized manner.

    <p>condenses</p> Signup and view all the answers

    Apoptosis is mediated by ______ that activate proteases and endonucleases.

    <p>caspases</p> Signup and view all the answers

    The intrinsic mitochondrial pathway involves the inactivation of ______ to activate apoptosis.

    <p>Bcl2</p> Signup and view all the answers

    FAS ligand binds FAS death receptor (CD95) on the target cell, activating ______.

    <p>caspases</p> Signup and view all the answers

    CD8+ T cells utilize ______ to create pores in the membrane of target cells during apoptosis.

    <p>perforins</p> Signup and view all the answers

    Apoptotic bodies are removed by ______ after the cell has undergone programmed cell death.

    <p>macrophages</p> Signup and view all the answers

    During the process of apoptosis, the dying cell becomes more ______ as it shrinks.

    <p>eosinophilic</p> Signup and view all the answers

    Free radicals are chemical species with an unpaired electron in their outer ______.

    <p>orbit</p> Signup and view all the answers

    During oxidative phosphorylation, complex IV transfers electrons to ______.

    <p>oxygen</p> Signup and view all the answers

    NADPH oxidase generates superoxide ions during oxygen-dependent killing by ______.

    <p>neutrophils</p> Signup and view all the answers

    The P450 system of the liver metabolizes drugs such as ______, generating free radicals.

    <p>acetaminophen</p> Signup and view all the answers

    The elimination of free radicals occurs via multiple mechanisms, including ______ such as vitamins A, C, and E.

    <p>antioxidants</p> Signup and view all the answers

    Carbon tetrachloride (CCl4) exposure can result in swelling of the ______ endoplasmic reticulum.

    <p>rough</p> Signup and view all the answers

    Reperfusion injury produces O2-derived free radicals that further damage ______ tissue.

    <p>ischemic</p> Signup and view all the answers

    Hydroxyl free radicals are generated from the reaction of Fe2+ through the ______ reaction.

    <p>Fenton</p> Signup and view all the answers

    Match the type of necrosis with its defining characteristic:

    <p>Fat necrosis = Necrotic adipose tissue with chalky-white appearance due to calcium deposition Fibrinoid necrosis = Necrotic damage to blood vessel walls with bright pink staining Dystrophic calcification = Calcium deposits on dead tissues with normal serum levels Metastatic calcification = Calcium deposition in normal tissues due to high serum calcium levels</p> Signup and view all the answers

    Match the type of calcification with its occurrence:

    <p>Dystrophic calcification = Occurs in necrotic tissues regardless of serum calcium levels Metastatic calcification = Occurs in organs like kidneys during hyperparathyroidism Saponification = Involves joining of fatty acids with calcium after trauma Chalky-white appearance = Characteristic of necrotic adipose tissue in fat necrosis</p> Signup and view all the answers

    Match the type of necrosis with its associated condition:

    <p>Fat necrosis = Associated with trauma to fat or pancreatitis Fibrinoid necrosis = Characteristic of malignant hypertension and vasculitis Dystrophic calcification = Seen in necrotic tissues of individuals with normal serum levels Metastatic calcification = Linked to hyperparathyroidism affecting various tissues</p> Signup and view all the answers

    Match the types of necrosis with their characteristics:

    <p>Coagulative necrosis = Preservation of cell shape and organ structure Liquefactive necrosis = Conversion of tissue into a liquid mass Gangrenous necrosis = Resembles mummified tissue Caseous necrosis = Soft, friable tissue with a 'cottage cheese-like' appearance</p> Signup and view all the answers

    Match the necrosis type with its associated condition:

    <p>Coagulative necrosis = Ischemic infarction of the heart Liquefactive necrosis = Brain infarction Gangrenous necrosis = Ischemia of lower limb Caseous necrosis = Tuberculous infection</p> Signup and view all the answers

    Match the process with its description:

    <p>Saponification = The process involving fatty acids and calcium after tissue injury Dystrophic calcification = Calcium deposits occurring in dead tissues with normal serum levels Fibrinoid necrosis = Bright pink staining from protein leakage into blood vessel walls Fat necrosis = Necrosis characterized by calcification in damaged adipose tissue</p> Signup and view all the answers

    Match the description with the type of necrosis:

    <p>Liquefactive necrosis = Enzymatic lysis leading to liquefaction Gangrenous necrosis = Infection leads to liquefaction of dead tissue Caseous necrosis = Combination of coagulative and liquefactive features Coagulative necrosis = Nucleus disappears, proteins coagulate</p> Signup and view all the answers

    Match the type of necrosis with its features:

    <p>Metastatic calcification = Deposition of calcium in normal tissues due to high serum levels Fat necrosis = Chalky-white appearance and necrotic adipose tissue Fibrinoid necrosis = Necrotic vessel wall with bright pink coloration Dystrophic calcification = Calcium deposition in areas of necrosis with normal serum levels</p> Signup and view all the answers

    Match the necrosis type with its gross pattern characteristics:

    <p>Coagulative necrosis = Wedge-shaped pale infarcted area Liquefactive necrosis = Occurs with brain or abscess formation Gangrenous necrosis = Can be classified into dry and wet forms Caseous necrosis = Associated with granulomatous inflammation</p> Signup and view all the answers

    Match the necrosis process with its specific characteristic:

    <p>Fibrinoid necrosis = Leakage of fibrin and proteins into blood vessel walls Saponification = Process linking fatty acids and calcium in necrotic fat Dystrophic calcification = Calcification of dead tissue though serum levels are normal Metastatic calcification = Calcium accumulation in normal tissues from high serum calcium</p> Signup and view all the answers

    Match the type of necrosis with its diagnostic clues:

    <p>Fat necrosis = Associated with deposition of calcium and necrotic fat tissue Fibrinoid necrosis = Results in bright pink staining of the involved blood vessel walls Dystrophic calcification = Occurs in necrotic tissues with normal serum calcium and phosphate Metastatic calcification = Leads to calcium deposition in normal tissues during hypercalcemia</p> Signup and view all the answers

    Match the type of necrosis with its pathophysiological basis:

    <p>Coagulative necrosis = Underlying ischemia leading to necrosis Liquefactive necrosis = Presence of proteolytic enzymes Gangrenous necrosis = Ischemia with possible superimposed infection Caseous necrosis = Fungal or tuberculous infection</p> Signup and view all the answers

    Match the definitions to the types of necrosis:

    <p>Coagulative necrosis = Firm necrotic tissue with preserving architecture Liquefactive necrosis = Necrosis involving tissue liquefaction Gangrenous necrosis = Seen as mummified or mummified-like tissue Caseous necrosis = Necrosis resembling cottage cheese</p> Signup and view all the answers

    Match the term with its related definition:

    <p>Fibrinoid necrosis = Necrosis linked to malignant hypertension and vasculitis Saponification = Dystrophic calcification involving fatty acids and calcium Fat necrosis = Necrotic fat with a distinctive chalky-white appearance Metastatic calcification = Involves high serum levels of calcium leading to deposition in healthy tissues</p> Signup and view all the answers

    Match the necrosis type with examples of conditions it could describe:

    <p>Coagulative necrosis = Ischemic conditions in solid organs Liquefactive necrosis = Neutrophil response in abscess Gangrenous necrosis = Infarction of lower limbs Caseous necrosis = Pulmonary tuberculosis</p> Signup and view all the answers

    Match the mechanisms of cellular death with their descriptions:

    <p>Necrosis = Pathological death with inflammation Apoptosis = Programmed cell death without inflammation Coagulative necrosis = Protein denaturation preserves architecture Liquefactive necrosis = Release of proteolytic enzymes from cells</p> Signup and view all the answers

    Match the examples of apoptosis with their respective descriptions:

    <p>Removal of cells during embryogenesis = Developmental function for proper structure formation CD8 + T cell-mediated killing of virally infected cells = Immune response to eliminate infected cells Caspases activating proteases = Molecular mechanism in apoptosis execution Endometrial shedding during menstrual cycle = Physiological process of tissue remodeling</p> Signup and view all the answers

    Match the components of the intrinsic mitochondrial pathway of apoptosis with their roles:

    <p>Bcl2 = Inhibits apoptosis when active Cytochrome c = Leaked into cytoplasm to activate caspases Caspases = Proteolytic enzymes that execute apoptosis Decreased hormonal stimulation = Triggers the intrinsic pathway by inactivating Bcl2</p> Signup and view all the answers

    Match the properties of apoptotic cells with their respective morphological changes:

    <p>Dying cell shrinks = Cytoplasm becoming more eosinophilic Nucleus condenses and fragments = Organized nuclear disassembly Apoptotic bodies formed = Phagocytosed by macrophages Absence of inflammation = Contrast to necrosis effects</p> Signup and view all the answers

    Match the apoptosis induction pathways with their respective triggers:

    <p>Extrinsic receptor-ligand pathway = Involves death receptors like FAS Cytotoxic CD8+ T cell-mediated pathway = Involves perforins and granzyme FAS ligand binding = Initiates caspase activation in target cells TNF receptor binding = Activates downstream caspases</p> Signup and view all the answers

    Match the terms associated with necrosis to their relevant characteristics:

    <p>Fat necrosis = Appearance resembling bright pink staining Fibrinoid necrosis = Associated with malignant hypertension Metastatic calcification = Calcium deposits in necrotic tissues Dystrophic calcification = Deposits in normal tissues despite normal calcium levels</p> Signup and view all the answers

    Match the terms relating to free radical injury with their descriptions:

    <p>Hydroxyl free radicals = Generated by reactions involving metals like iron NADPH oxidase = Enzyme producing superoxide during inflammation Superoxide dismutase = Enzyme converting superoxide into hydrogen peroxide Reactive oxygen species = Chemical species with unpaired electrons causing cellular damage</p> Signup and view all the answers

    Match the apoptotic pathways with their regulatory components:

    <p>Intrinsic pathway = Regulated by Bcl family proteins Extrinsic pathway = Involves receptor-ligand interactions Caspase activation = Essential for executing the apoptotic process Cytotoxic pathway = Relies on CD8+ T cells to eliminate infected cells</p> Signup and view all the answers

    Match the types of cell death with their notable characteristics:

    <p>Apoptosis = Programmed cell death without inflammation Necrosis = Uncontrolled cell death often leading to inflammation Autophagy = Self-degradation of cellular components Pyroptosis = Inflammatory form of programmed cell death</p> Signup and view all the answers

    Match the following free radical generation mechanisms with their sources:

    <p>Ionizing radiation = Hydroxyl free radical from water hydrolysis NADPH oxidase = Superoxide ions during inflammation P450 system = Free radical generation from drug metabolism Fenton reaction = Hydroxyl free radicals from Iron</p> Signup and view all the answers

    Match the following free radicals with their descriptions:

    <p>Superoxide (O2ꜙ) = Produced from partial reduction of oxygen Hydrogen peroxide (H2O2) = Formed by dismutation of superoxide Hydroxyl radical (˙OH) = Generated via Fenton reaction Carbon trichloride radical (CCl3) = Derived from CCl4 metabolism</p> Signup and view all the answers

    Match the following enzymes with their functions in free radical elimination:

    <p>Superoxide dismutase = Converts superoxide to hydrogen peroxide Glutathione peroxidase = Reduces free radicals using glutathione Catalase = Decomposes hydrogen peroxide to water and oxygen NADPH oxidase = Produces superoxide during immune response</p> Signup and view all the answers

    Match the following free radical-related injuries with their causes:

    <p>Carbon tetrachloride (CCl4) = Organic solvent causing hepatocyte injury Reperfusion injury = O2-derived free radicals after ischemia Inflammation = Superoxide production via NADPH oxidase Drug metabolism = Free radical generation by P450 system</p> Signup and view all the answers

    Match the following antioxidants with their sources:

    <p>Vitamin A = Fat-soluble antioxidant Vitamin C = Water-soluble antioxidant Glutathione = Non-enzymatic antioxidant in cells Vitamin E = Protects lipids from peroxidation</p> Signup and view all the answers

    Match the following steps in lipid peroxidation with their consequences:

    <p>Initiation = Formation of free radicals from lipids Propagation = Reaction of free radicals with polyunsaturated fatty acids Termination = Deactivation of free radicals Damage = Cellular injury from oxidized lipids</p> Signup and view all the answers

    Match the following radicals with their effects on biological molecules:

    <p>Hydroxyl radical (˙OH) = Causes DNA damage Superoxide (O2ꜙ) = Leads to lipid peroxidation Hydrogen peroxide (H2O2) = Induces protein oxidation Carbon trichloride radical (CCl3) = Impairment of protein synthesis in liver</p> Signup and view all the answers

    Match the following free radical elimination strategies with their mechanisms:

    <p>Antioxidants = Neutralize free radicals chemically Enzymes = Catalyze reactions to detoxify free radicals Metal carrier proteins = Bind to metals and prevent radical generation Phagocytic cells = Ingest and eliminate radical-generating pathogens</p> Signup and view all the answers

    Study Notes

    Cell Death Mechanisms

    • Necrosis: Group cell death due to underlying pathology, never physiologic.
      • Coagulative Necrosis: Tissue remains firm, cell shape preserved, nucleus disappears.
        • Occurs in ischemic infarction of most organs, excluding the brain.
        • Area of infarction is usually wedge-shaped, pointing to the vascular occlusion.
        • Red infarction can occur when blood re-enters loosely organized tissue.
      • Liquefactive Necrosis: Tissue liquefies due to enzymatic lysis.
        • Characteristic of brain infarction, abscess, and pancreatitis.
      • Gangrenous Necrosis: Coagulative necrosis resembling mummified tissue (dry gangrene).
        • Occurs in ischemia of the lower limb and GI tract.
        • Wet gangrene results with superimposed infection.
      • Caseous Necrosis: Soft and friable necrotic tissue with a 'cottage cheese-like' appearance.
        • Combination of coagulative and liquefactive necrosis.
        • Characteristic of granulomatous inflammation due to TB or fungal infection.
      • Fat Necrosis: Necrotic adipose tissue with a chalky white appearance due to calcium deposition.
        • Occurs in trauma to fat or pancreatitis.
        • Fatty acids released by trauma or lipase join with calcium, a process called saponification.
        • Saponification is an example of dystrophic calcification, where calcium deposits on dead tissue despite normal serum calcium and phosphate.
        • Metastatic calcification, in contrast, occurs when high serum calcium or phosphate levels cause calcium deposition in normal tissues.
      • Fibrinoid Necrosis: Necrotic damage to blood vessel walls.
        • Proteins, including fibrin, leak into the vessel wall, resulting in a bright pink stain microscopically.
        • Occurs in malignant hypertension and vasculitis.
    • Apoptosis: Energy-dependent, genetically programmed cell death involving single cells or small groups.
      • Examples: Endometrial shedding, removal of cells during embryogenesis, CD8+ T cell-mediated killing of infected cells.
      • Morphology
        • Dying cell shrinks, making the cytoplasm more eosinophilic (pink).
        • Nucleus condenses and fragments in an organized manner.
        • Apoptotic bodies are removed by macrophages, no inflammation.
      • Caspases activate proteases and endonucleases.
        • Proteases break down cytoskeleton.
        • Endonucleases break down DNA.
      • Caspase activation pathways:
        • Intrinsic pathway: Cellular injury, DNA damage, or decreased hormonal stimulation leads to Bcl2 inactivation.
          • Cytochrome c leaks from the mitochondria, activating caspases.
        • Extrinsic pathway: FAS ligand binds FAS death receptor (CD95) on the target cell, activating caspases.
          • Tumor necrosis factor (TNF) binds TNF receptor, activating caspases.
        • Cytotoxic CD8+ T cell-mediated pathway:
          • Perforins secreted by CD8+ T cells create pores in the target cell membrane.
          • Granzyme enters the pores and activates caspases.
      • Example: CD8+ T cell killing of virally infected cells.

    Free Radical Injury

    • Free radicals: Chemical species with an unpaired electron in their outer orbit.
    • Physiologic generation: Occurs during oxidative phosphorylation.
      • Cytochrome c oxidase transfers electrons to oxygen, sometimes incompletely.
      • Partial reduction of O2 produces superoxide, hydrogen peroxide, and hydroxyl radicals.
    • Pathologic generation:
      • Ionizing radiation: Water hydrolyzed to hydroxyl radical.
      • Inflammation: NADPH oxidase generates superoxide ions during neutrophil killing.
      • Metals (copper and iron): Fe2+ produces hydroxyl radicals.
      • Drugs and chemicals: Liver P450 system metabolizes drugs, producing free radicals.
    • Damage:
      • Peroxidation of lipids, oxidation of DNA and proteins.
      • DNA damage contributes to aging and cancer development.
    • Elimination:
      • Antioxidants: Glutathione, vitamins A, C, and E.
      • Enzymes:
        • Superoxide dismutase: Converts superoxide to hydrogen peroxide.
        • Glutathione peroxidase: Reduces free radicals with the help of glutathione.
        • Catalase: Breaks down hydrogen peroxide.
      • Metal carrier proteins: Transferrin and ceruloplasmin.

    Examples of Free Radical Injury

    • Carbon tetrachloride (CCl4):
      • Used in dry cleaning.
      • Converted to CCl3 free radical by liver P450 system.
      • Causes cell injury: Swelling of the endoplasmic reticulum, detachment of ribosomes, impaired protein synthesis.
      • Decreased apolipoproteins lead to fatty change in the liver.
    • Reperfusion injury:
      • Blood return to ischemic tissue results in increased production of O2-derived free radicals, further damaging the tissue.
      • Leads to a continuing rise in cardiac enzymes after reperfusion of infarcted tissue.

    Cell Death

    • Necrosis refers to the death of a large group of cells, followed by an acute inflammatory response.

      • Coagulative Necrosis: Necrotic tissue remains firm, with cells maintaining their shape but losing their nucleus.

        • Often observed in ischemic infarction of organs (except the brain).
        • Infarcted areas are wedge-shaped, pointing towards the point of vascular occlusion.
        • Red infarction occurs when blood re-enters loosely organized tissues, adding a red hue.

      • Liquefactive Necrosis: Necrotic tissue is liquefied due to enzymatic lysis of cells and proteins.

        • Characteristic of brain infarction, abscesses, and pancreatitis.

      • Gangrenous Necrosis: Coagulative necrosis that resembles mummified tissue (dry gangrene).

        • Typically observed in ischemic lower limbs or the gastrointestinal tract.
        • Wet gangrene ensues if infection occurs in the dead tissues.

      • Caseous Necrosis: Necrotic tissue becomes soft, friable, and "cottage cheese-like."

        • A combination of coagulative and liquefactive necrosis.
        • Characteristically seen in granulomatous inflammation caused by tuberculosis or fungi.

      • Fat Necrosis: Necrotic adipose tissue with a chalky-white appearance due to calcium deposition.

        • Occurs in trauma to fat (e.g., breast) or pancreatitis-mediated damage of peripancreatic fat.
        • Calcium joins released fatty acids in a process called saponification.

      • Fibrinoid Necrosis: Necrotic damage to the blood vessel wall.

        • Leakage of proteins (including fibrin) into the vessel wall causes a bright pink staining microscopically.
        • Found in malignant hypertension and vasculitis.

    • Apoptosis is a genetically programmed, energy-dependent process of cell death that involves single cells or small groups of cells.

      • Examples include endometrial shedding during menstruation, cell removal during embryogenesis, and CD8+ T cell-mediated killing of infected cells.
      • Characterized by cell shrinkage, increased eosinophilia (pink staining), nuclear condensation and fragmentation, with the formation of apoptotic bodies that are removed by macrophages without inflammation.
      • Caspases, which activate proteases and endonucleases, are key mediators of apoptosis.
        • Proteases break down the cytoskeleton.
        • Endonucleases break down DNA.
      • Caspases are activated via various pathways:

        • Intrinsic Mitochondrial Pathway: Cellular injury, DNA damage, or decreased hormonal stimulation leads to the inactivation of the Bcl2 protein. This allows cytochrome c to leak from the mitochondria into the cytoplasm and activate caspases.

        • Extrinsic Receptor-Ligand Pathway: FAS ligand binds to the FAS death receptor (CD95) on the target cell, activating caspases. An example is the negative selection of thymocytes in the thymus. Tumor necrosis factor (TNF) can also bind to its receptor on the target cell, activating caspases.

        • Cytotoxic CD8+ T Cell-mediated Pathway: Perforins secreted by CD8+ T cells create pores in the target cell membrane, allowing granzyme to enter and activate caspases. Killing of virally infected cells is an example.

    Free Radical Injury

    • Free radicals are chemical species with an unpaired electron in their outer orbit.

    • Physiological Generation of Free Radicals occurs during oxidative phosphorylation.

      • Cytochrome c oxidase (complex IV) transfers electrons to oxygen.
      • Partial reduction of O2 produces superoxide (O2-), hydrogen peroxide (H2O2), and hydroxyl radicals (•OH).

    • Pathologic Generation of Free Radicals arises from:

      • Ionizing radiation: water hydrolyzed to hydroxyl free radicals.
      • Inflammation: NADPH oxidase generates superoxide ions during oxygen-dependent killing by neutrophils.
      • Metals (e.g., copper and iron): Fe2+ generates hydroxyl free radicals.
      • Drugs and chemicals (e.g., acetaminophen): The P450 system of the liver metabolizes these substances, producing free radicals.

    • Free Radical Injury occurs through peroxidation of lipids and oxidation of DNA and proteins.

      • DNA damage is implicated in aging and oncogenesis.

    • Elimination of Free Radicals is achieved through:

      • Antioxidants (e.g., glutathione and vitamins A, C, and E)
      • Enzymes:
        • Superoxide dismutase (in mitochondria): Converts superoxide (O2-) to H2O2.
        • Glutathione peroxidase (in mitochondria): Detoxifies free radicals using glutathione (GSH).
        • Catalase (in peroxisomes): Converts H2O2 to O2 and H2O.
      • Metal carrier proteins (e.g., transferrin and ceruloplasmin)

    Examples of Free Radical Injury

    • Carbon Tetrachloride (CCl4): An organic solvent used in dry cleaning.
      • Converted to CCl3 free radicals by the P450 system of hepatocytes.
      • Leads to cell injury with swelling of the endoplasmic reticulum, detachment of ribosomes, impairment of protein synthesis, and reduced apolipoproteins, resulting in fatty liver change.
    • Reperfusion Injury: The return of blood to ischemic tissue results in the production of oxygen-derived free radicals, causing further damage.
      • Results in a continued rise in cardiac enzymes after reperfusion of infarcted myocardial tissue.

    Cell Death

    • Necrosis is the death of a group of cells due to an underlying pathological process.

      • Coagulative necrosis is characterized by the preservation of cell shape, causing an area of infarcted tissue to appear wedge-shaped. This is often seen in ischemic infarction of organs except the brain.
      • Liquefactive necrosis results in the liquefaction of necrotic tissue by enzymatic lysis of cells and protein. This is seen in brain infarction, abscesses, and pancreatitis.
      • Gangrenous necrosis resembles mummified tissue (dry gangrene) and is characteristic of ischemia in the lower limb and GI tract. If infection occurs, it can lead to wet gangrene.
      • Caseous necrosis is a combination of coagulative and liquefactive necrosis, leading to soft and friable necrotic tissue often seen in granulomatous inflammation due to tuberculosis or fungal infection.
      • Fat necrosis is characterized by the formation of chalky-white necrotic adipose tissue due to calcium deposition. This can be seen in trauma to fat and pancreatitis.
      • Fibrinoid necrosis is characterized by damage to the blood vessel wall, resulting in leakage of proteins like fibrin into the vessel wall. It is often seen in malignant hypertension and vasculitis.

    • Apoptosis is a genetically programmed cell death involving single cells or small groups of cells. It is an energy-dependent process.

      • Examples of apoptosis include endometrial shedding during the menstrual cycle, removal of cells during embryogenesis, and CD8+ T cell-mediated killing of virally infected cells.
      • Morphology: the dying cell shrinks, the nucleus condenses and fragments, and apoptotic bodies are removed by macrophages without inflammation.
      • Caspases are activated by multiple pathways to mediate the process:
        • Intrinsic mitochondrial pathway: Cellular injury, DNA damage, or decreased hormonal stimulation leads to inactivation of Bcl2, causing cytochrome c to leak from the mitochondria and activate caspases.
        • Extrinsic receptor-ligand pathway: FAS ligand binds to the target cell's FAS death receptor (CD95), activating caspases. Tumor necrosis factor (TNF) can also bind to its receptor and activate caspases.
        • Cytotoxic CD8+ T cell-mediated pathway: Perforins create pores in the target cell's membrane, allowing granzyme from CD8+ T cells to enter and activate caspases. This is an example of CD8+ T cell killing of virally infected cells.

    Free Radical Injury

    • Free radicals are chemical species with an unpaired electron in their outer orbit.

      • Physiologic generation: occurs during oxidative phosphorylation, yielding superoxide, hydrogen peroxide, and hydroxyl radicals.
      • Pathologic generation: occurs due to ionizing radiation, inflammation, metals, and drugs/chemicals like acetaminophen.
      • Cellular injury: free radicals cause peroxidation of lipids and oxidation of DNA and proteins, which is implicated in aging and oncogenesis.
      • Elimination: occurs through antioxidants (glutathione and vitamins A, C, and E), enzymes (superoxide dismutase, glutathione peroxidase, and catalase), and metal carrier proteins (transferrin and ceruloplasmin).

    • Examples of Free Radical Injury:

      • Carbon tetrachloride (CCl4): This organic solvent is converted to a free radical by the liver's P450 system, leading to cell injury, swelling of the RER, and impaired protein synthesis. This can result in fatty change in the liver.
      • Reperfusion injury: Returning blood to ischemic tissue can produce oxygen-derived free radicals, further damaging the tissue. This can lead to a continued rise in cardiac enzymes even after reperfusion of infarcted myocardial tissue.

    Cell Death

    • Morphologic Hallmark of cell death: Loss of nucleus, which is observed as nuclear condensation (pyknosis), fragmentation (karyorrhexis), dissolution (karyolysis).
    • Two mechanisms of cell death: Necrosis and Apoptosis.

    Necrosis

    • Necrosis is the death of a large group of cells followed by acute inflammation.
    • Causes: Underlying pathologic processes.
    • Physiological? Never physiological.
    • Types of Necrosis: Divided into several types based on gross features.

    Gross Patterns of Necrosis

    • Coagulative Necrosis:
      • Necrotic tissue remains firm.
      • Cell shape and organ structure are preserved by protein coagulation, but the nucleus disappears.
      • Seen in ischemic infarction of any organ except the brain.
      • Area of infarcted tissue is usually wedge-shaped.
      • Red Infarction: occurs when blood re-enters loosely organized tissue (e.g. pulmonary or testicular infarction).
    • Liquefactive Necrosis:
      • Necrotic tissue is liquefied.
      • Enzymatic lysis of cells and proteins results in liquefaction.
      • Characteristic of:
        • Brain Infarction: Proteolytic enzymes from microglia liquefy brain tissue.
        • Abscess: Proteolytic enzymes from neutrophils liquefy tissue.
        • Pancreatitis: Proteolytic enzymes from the pancreas liquefy parenchyma.
    • Gangrenous Necrosis:
      • Coagulative necrosis resembling mummified tissue (dry gangrene).
      • Seen in ischemia of the lower limb and GI tract.
      • If a superimposed infection occurs, liquefactive necrosis ensues (wet gangrene).
    • Caseous Necrosis:
      • Soft, friable necrotic tissue with a "cottage cheese-like" appearance.
      • Combination of coagulative and liquefactive necrosis.
      • Characteristic of granulomatous inflammation due to tuberculous or fungal infection.
    • Fat Necrosis:
      • Necrotic adipose tissue with a chalky-white appearance due to calcium deposition.
      • Seen in trauma to fat (e.g., breast) and pancreatitis-mediated damage to peripancreatic fat.
      • Mechanism: Fatty acids released from trauma or lipase join with calcium (saponification).
        • Saponification represents dystrophic calcification.
          • Dystrophic calcification occurs in necrotic tissue with normal serum calcium and phosphate levels.
        • Metastatic Calcification: Occurs with high serum calcium or phosphate levels leading to calcium deposition in normal tissues (e.g. hyperparathyroidism leading to nephrocalcinosis).
    • Fibrinoid Necrosis:
      • Necrotic damage to the blood vessel wall.
      • Leaking of proteins (including fibrin) into the vessel wall results in bright pink staining of the wall microscopically.
      • Seen in malignant hypertension and vasculitis.

    Apoptosis

    • Definition: Energy (ATP)-dependent, genetically programmed cell death involving single cells or small groups of cells.
    • Examples:
      • Endometrial shedding during the menstrual cycle
      • Removal of cells during embryogenesis
      • CD8+ T cell-mediated killing of virally infected cells
    • Morphology:
      • Dying cell shrinks, leading to a more eosinophilic cytoplasm (pink).
      • Nucleus condenses and fragments in an organized manner.
      • Apoptotic bodies are removed by macrophages; apoptosis does not trigger inflammation.
    • Mediation
      • Caspases: Activate proteases and endonucleases.
        • Proteases: Break down the cystoskeleton.
        • Endonucleases: Break down DNA.
    • Caspase Activation Pathways:
      • Intrinsic Mitochondrial Pathway:
        • Cellular injury, DNA damage, or decreased hormonal stimulation leads to inactivation of Bcl2.
        • Lack of Bcl2 allows cytochrome c to leak out of the inner mitochondrial matrix, activating caspases.
      • Extrinsic Receptor-Ligand Pathway:
        • FAS ligand binds FAS death receptor (CD95) on the target cell, activating caspases (e.g. negative selection of thymocytes in the thymus).
        • TNF binds TNF receptor on the target cell, activating caspases.
      • Cytotoxic CD8+ T Cell-Mediated Pathway:
        • Perforins secreted by CD8+ T cells create pores in the membrane of the target cell.
        • Granzyme from CD8+ T cells enters the pores and activates caspases.
        • Example: CD8+ T cell killing of virally infected cells.

    Free Radical Injury

    • Definition: Free radicals are chemical species with an unpaired electron in their outer orbit.
    • Physiological Generation: Free radical generation occurs during oxidative phosphorylation.
      • Cytochrome c oxidase (complex IV) transfers electrons to oxygen.
      • Partial reduction of O2 yields superoxide (O2-), hydrogen peroxide (H2O2), and hydroxyl radicals (˙OH).
    • Pathological Generation:
      • Ionizing Radiation: Water is hydrolyzed to a hydroxyl free radical.
      • Inflammation: NADPH oxidase generates superoxide ions during oxygen-dependent killing by neutrophils.
      • Metals: Fe2+ generates hydroxyl free radicals (Fenton reaction).
      • Drugs & Chemicals: P450 system of the liver metabolizes drugs, generating free radicals.
    • Cellular Damage: Free radicals cause injury via lipid peroxidation and oxidation of DNA and proteins; DNA damage contributes to aging and oncogenesis.
    • Elimination Mechanisms:
      • Antioxidants: (e.g., glutathione, vitamins A, C, E)
      • Enzymes:
        • Superoxide Dismutase: (Mitochondria) Superoxide (O2-) → H2O2
        • Glutathione Peroxidase: (Mitochondria) 2GSH + free radical → GS-SG and H2O
        • Catalase: (Peroxisomes) H2O2 → O2 and H2O
      • Metal Carrier Proteins: (e.g., transferrin, ceruloplasmin)

    Examples of Free Radical Injury

    • Carbon Tetrachloride (CCl4):
      • Organic solvent used in the dry cleaning industry.
      • Converted to CCl3 free radical by the P450 system of hepatocytes.
      • Results in cell injury with swelling of the RER; ribosomes detach, impairing protein synthesis.
      • Decreased apolipoproteins lead to fatty change in the liver.
    • Reperfusion Injury:
      • Return of blood to ischemic tissue results in production of O2-derived free radicals, causing further tissue damage.
      • Leads to a continued rise in cardiac enzymes (e.g., troponin) after reperfusion of infarcted myocardial tissue.

    Cell Death

    • Necrosis is a form of cell death involving large groups of cells and causing acute inflammation. It is always a consequence of underlying pathology and never a physiological process.
    • Apoptosis is a genetically programmed, energy-dependent cell death involving single cells or small groups. It is not followed by inflammation and can be physiological or pathological.

    Types of Necrosis

    • Coagulative necrosis: Characterized by preservation of cell shape and tissue structure due to protein coagulation, but the nucleus disappears. It is commonly observed in ischemic infarction of organs except the brain.
    • Liquefactive necrosis: Necrotic tissue becomes liquefied due to enzymatic lysis of cells and proteins. It is characteristic of brain infarction, abscess, and pancreatitis.
    • Gangrenous necrosis: It resembles mummified tissue (dry gangrene) and occurs due to ischemia of lower limb and GI tract. If infection superimposes, it progresses to liquefactive necrosis (wet gangrene).
    • Caseous necrosis: Necrotic tissue exhibits a soft, friable, “cottage cheese-like” appearance, resulting from a combination of coagulative and liquefactive necrosis. Typically found in granulomatous inflammation caused by infection.
    • Fat necrosis: Characterized by chalky-white necrotic adipose tissue due to calcium deposition. It is associated with trauma to fat (e.g., breast) and pancreatitis-mediated damage to peripancreatic fat.
    • Fibrinoid necrosis: Necrotic damage to blood vessel walls, resulting in leakage of proteins, including fibrin, into the vessel wall. Microscopic examination reveals bright pink staining. It is characteristic of malignant hypertension and vasculitis.

    Apoptosis

    • Morphological features of apoptosis include cell shrinkage with increased cytoplasmic eosinophilia, nuclear condensation and fragmentation, and the formation of apoptotic bodies that are removed by macrophages.

    Mechanisms of Apoptosis

    • Caspase activation is central to apoptosis, triggering protease and endonuclease activity.
      • Proteases degrade the cytoskeleton.
      • Endonucleases fragment DNA.
    • Intrinsic mitochondrial pathway: Cellular injury, DNA damage, or decreased hormonal stimulation inactivates Bcl2, leading to cytochrome c release from mitochondria into the cytoplasm, which activates caspases.
    • Extrinsic receptor-ligand pathway: FAS ligand binds to the FAS death receptor (CD95) on the target cell, activating caspases. Similarly, tumor necrosis factor (TNF) binding to its receptor triggers caspase activation.
    • Cytotoxic CD8+ T cell-mediated pathway: Perforins secreted by CD8+ T cells create pores in the target cell membrane, allowing granzyme to enter and activate caspases.

    Free Radical Injury

    • Free radicals are chemical species with an unpaired electron in their outer orbit.
    • Physiologic generation: Occurs during oxidative phosphorylation in the electron transport chain where partial reduction of oxygen yields superoxide, hydrogen peroxide, and hydroxyl radicals.
    • Pathologic generation:
      • Ionizing radiation: Hydrolyzes water to generate hydroxyl free radicals.
      • Inflammation: NADPH oxidase generates superoxide ions during oxygen-dependent killing by neutrophils.
      • Metals (copper, iron): Fe2+ generates hydroxyl free radicals via the Fenton reaction.
      • Drugs and chemicals: The P450 system in the liver metabolizes drugs, generating free radicals.
    • Damage mechanisms: Free radicals cause cellular injury by lipid peroxidation, DNA oxidation, and protein oxidation.
    • Elimination mechanisms:
      • Antioxidants (glutathione, vitamins A, C, E)
      • Enzymes (superoxide dismutase, glutathione peroxidase, catalase)
      • Metal carrier proteins (transferrin, ceruloplasmin)

    Examples of Free Radical Injury

    • Carbon tetrachloride (CCl4): Used in dry cleaning, it is metabolized to CCl3 free radicals by the P450 system, leading to cell injury, swelling of the endoplasmic reticulum, ribosome detachment, and impaired protein synthesis. These events result in decreased apolipoproteins and fatty change in the liver.
    • Reperfusion injury: Restoration of blood flow to ischemic tissue leads to increased production of oxygen-derived free radicals, further damaging the already compromised tissue. This explains the continued elevation of cardiac enzymes after reperfusion of infarcted myocardial tissue.

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    Pathoma 2023 PDF- Cellular Injury and Cell Death

    Description

    This quiz covers various mechanisms of cell death, including necrosis and its subtypes such as coagulative, liquefactive, gangrenous, and caseous necrosis. Understand the characteristics and clinical implications of each type, including their occurrences in different organ systems. Test your knowledge of how these processes manifest in pathological conditions.

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