Podcast
Questions and Answers
Match the following types of injuries with their characteristics:
Match the following types of injuries with their characteristics:
Reversible injury = Acute cellular swelling due to sodium influx Irreversible injury = Extensive damage of plasma membrane Hypoxic injury = Decreased ATP leading to anaerobic glycolysis Ischemic injury = Calcium-mediated injury during reperfusion
Match the following enzymes with their role in cell injury:
Match the following enzymes with their role in cell injury:
Phospholipases = Degrade cell membranes Proteases = Catabolize structural proteins ATPases = Cause ATP depletion Endonucleases = Fragment DNA
Match the following conditions with their consequences:
Match the following conditions with their consequences:
Decreased ATP = Increased anaerobic glycolysis Increased intracellular sodium = Acute cellular swelling Detachment of ribosomes = Reduced protein synthesis Accumulation of lactic acid = Decreased intracellular pH
Match the following cellular changes with their descriptions:
Match the following cellular changes with their descriptions:
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Match the following components with their roles in cell injury:
Match the following components with their roles in cell injury:
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Match the following hypoxic effects with their outcomes:
Match the following hypoxic effects with their outcomes:
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Match the following phases of injury with their effects:
Match the following phases of injury with their effects:
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Match the following types of radicals with their effects:
Match the following types of radicals with their effects:
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Match the type of necrosis with its characteristic description:
Match the type of necrosis with its characteristic description:
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Match the cytoplasmic change with its description:
Match the cytoplasmic change with its description:
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Match the nuclear change with its definition:
Match the nuclear change with its definition:
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Match the cellular alteration with its ultrastructural change:
Match the cellular alteration with its ultrastructural change:
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Match the necrosis type with its prime example:
Match the necrosis type with its prime example:
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Match the type of cell death process with its origin:
Match the type of cell death process with its origin:
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Match the description of fatty change with its cause:
Match the description of fatty change with its cause:
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Match the term with its function in necrosis:
Match the term with its function in necrosis:
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Match the following terms with their descriptions:
Match the following terms with their descriptions:
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Match the following stimuli to the mechanisms initiating apoptosis:
Match the following stimuli to the mechanisms initiating apoptosis:
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Match the type of intracellular accumulation to its description:
Match the type of intracellular accumulation to its description:
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Match the stage of apoptosis to its characteristic feature:
Match the stage of apoptosis to its characteristic feature:
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Match the examples of apoptosis to their physiological contexts:
Match the examples of apoptosis to their physiological contexts:
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Match the pancreatic condition to their described outcome:
Match the pancreatic condition to their described outcome:
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Match the important players in apoptosis to their roles:
Match the important players in apoptosis to their roles:
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Match the type of cell death to its inflammatory response:
Match the type of cell death to its inflammatory response:
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Match the following T cell types with their primary functions:
Match the following T cell types with their primary functions:
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Match the following lymphocyte types with their characteristics:
Match the following lymphocyte types with their characteristics:
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Match the following immunoglobulin classes with their features:
Match the following immunoglobulin classes with their features:
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Match the following molecules with their roles in T cell activation:
Match the following molecules with their roles in T cell activation:
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Match the following types of cytokines with their T cell subsets:
Match the following types of cytokines with their T cell subsets:
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Match the following roles of macrophages with their functions:
Match the following roles of macrophages with their functions:
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Match the following CD markers with their associated cells:
Match the following CD markers with their associated cells:
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Match the following immunoglobulin classes with their distribution:
Match the following immunoglobulin classes with their distribution:
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Match the type of abnormal substance accumulation with its description:
Match the type of abnormal substance accumulation with its description:
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Match the cause of fatty change with its description:
Match the cause of fatty change with its description:
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Match the type of cell involvement with its associated condition:
Match the type of cell involvement with its associated condition:
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Match the pigment accumulation with its specific type:
Match the pigment accumulation with its specific type:
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Match the organ with the condition associated with fatty change:
Match the organ with the condition associated with fatty change:
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Match the clinical presentation with its definition:
Match the clinical presentation with its definition:
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Match the condition with its characteristic feature:
Match the condition with its characteristic feature:
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Match the type of cellular changes to their respective examples:
Match the type of cellular changes to their respective examples:
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Study Notes
Cell Injury
- Ischemia or toxins trigger calcium influx from the extracellular space and the release of mitochondrial calcium
- This activates enzymes such as phospholipases, proteases, ATPases, and endonucleases, leading to cell damage
- Oxygen free radicals play a crucial role in cell death
Reversible Hypoxic Injury
- First effect: Reduced aerobic respiration (oxidative phosphorylation) by mitochondria, leading to decreased intracellular ATP
-
Consequences:
- Influx of extracellular calcium
- Reduced function of the plasma membrane sodium pump, leading to sodium accumulation and potassium loss
- Gain of isosmotic water, resulting in acute cellular swelling
-
Accumulation of:
- Inorganic phosphates
- Lactic acid
- Purine nucleotides
-
Increased rate of anaerobic glycolysis
- Glycogen depletion
- Lactic acid and inorganic phosphate accumulation
- Reduced intracellular pH
- Cytoplasmic eosinophilia (visible under a microscope)
-
Detachment of ribosomes from the endoplasmic reticulum
- Reduced protein synthesis
-
If hypoxia persists:
- Disappearance of the cytoskeleton
- Loss of ultrastructural features like microvilli
- Formation of cell surface blebs
Irreversible Injury
-
Indicators:
- Severe vacuolization of mitochondria and calcium build-up
- Extensive damage to the plasma membrane
- Lysosomal swelling
- Calcium-mediated injury due to reperfusion of oxygen
-
Continuing consequences:
- Loss of proteins, coenzymes, and RNA from the hyperpermeable membranes
- Leakage of lysosomal enzymes into the cytoplasm
- Activation of lysosomal enzymes due to reduced pH, leading to cytoplasmic component degradation
-
Cells may be replaced by:
- Whorled masses of phospholipids (myelin figures)
Mechanisms of Irreversible Injury
- Progressive loss of membrane phospholipids
-
Cytoskeletal abnormalities:
- Protease activation and increased calcium lead to cell membrane detachment
-
Toxic oxygen radicals:
- Generated after reperfusion of the ischemic area
- Released by neutrophils
-
Lipid breakdown products:
- Have detergent effects
Necrosis
- Definition: A sequence of morphologic changes following cell death in living tissue
-
Morphological appearances:
- Enzymatic digestion of the cell
- Denaturation of proteins
-
Hydrolytic enzymes:
- May derive from the dead cells themselves (autolysis)
- From lysosomes of infiltrating leukocytes (heterolysis)
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Cytoplasmic changes:
- Eosinophilia and glassy appearance due to glycogen loss
- Cytoplasmic vacuolation and calcification
-
Nuclear changes:
- Karyolysis: Digestion of DNA
- Pyknosis: Nuclear shrinkage and increased basophilia, mainly seen in apoptosis
- Karyorrhexis: Fragmentation of the pyknotic nucleus
Types of Necrosis
-
Coagulative necrosis:
- Preservation of the structural outlines of the coagulated cell or tissue for days
- Injury and acidosis denature enzymes, blocking cellular hydrolysis
- Example: Myocardial infarction
- Necrotic cells are removed by fragmentation and phagocytosis by leukocytes
- Characteristic of hypoxic death in all tissues except the brain
-
Liquefactive necrosis:
- Caused by focal bacterial or fungal infection with accumulation of white cells
- Hypoxic cell death in the CNS also results in liquefactive necrosis
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Gangrenous necrosis:
- Not a distinct pattern of necrosis but a clinical term
- Refers to ischemic coagulative necrosis with superimposed infection and liquefactive necrosis ("wet gangrene")
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Caseous necrosis:
- Seen in tuberculous infection
- Cheesy, white gross appearance of the central necrotic area
- Microscopically, it is composed of structureless amorphous granular debris within granulomatous inflammation
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Fat necrosis:
- Focal areas of fat destruction following acute pancreatitis
- Release of activated pancreatic enzymes hydrolyzes triglyceride esters within fat cells of the peritoneal cavity
Apoptosis
- Definition: Programmed cell death in physiologic and pathologic conditions
-
Role in:
- Programmed cell death during embryogenesis
- Hormone-dependent physiologic involution (e.g., the endometrium during the menstrual cycle)
- Cell deletion in proliferating populations (e.g., intestinal crypt epithelium)
- Deletion of autoreactive T cells in the thymus
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Morphological appearance:
- Round masses with intensely eosinophilic cytoplasm on H&E stained sections
- Condensed nuclear chromatin aggregating peripherally under the nuclear membrane
- Karyorrhexis occurs by the activation of endonucleases
- Cell shrinks, forms cytoplasmic buds, and fragments into apoptotic bodies
- Does not elicit an inflammatory response
Initiation of Apoptosis
- Withdrawal of growth factors or hormones
- Engagement of specific receptors (e.g., FAS, TNF)
- Injury by radiation, toxins, and free radicals
- Intrinsic protease activation (e.g., in embryogenesis)
Intracellular Accumulations
-
Normal cells may accumulate abnormal substances:
- Transiently or permanently
- May be harmful or injurious
- Locate in the cytoplasm or nucleus
- May be synthesized by the affected cell or produced elsewhere
-
Categorization:
- Normal endogenous substance: Produced at a normal or increased rate with inadequate metabolism (e.g., fatty change of the liver)
- Normal or abnormal endogenous substance: Cannot be metabolized due to genetic enzymatic defects (storage diseases)
- Abnormal exogenous substance: Deposit because the cell lacks the enzymatic machinery or ability to transport it elsewhere
Fatty Change (Steatosis)
- Definition: Abnormal accumulation of triglycerides within parenchymal cells
- Most often seen in the liver
- Reversible
- May also occur in the heart, skeletal muscle, kidney, and other organs
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Causes:
- Toxins
- Diabetes mellitus
- Protein malnutrition
- Obesity
- Anoxia
-
Excess accumulation of triglycerides:
- Defects at any step from fatty acid entry to lipoprotein synthesis
- Hepatotoxins like alcohol alter mitochondrial and SER function
- CCl4 and protein malnutrition decrease apoprotein synthesis
- Anoxia inhibits fatty acid oxidation
- Starvation increases fatty acid mobilization from peripheral stores
-
Effects:
- Mild changes may have no effect on cellular function
- Severe changes may transiently impair cellular function
-
Gross appearance:
- Liver enlarges and becomes progressively yellow
-
Microscopic appearance:
- Small vacuoles in the cytoplasm around the nucleus
- Vacuoles coalesce to create clear spaces, displacing the nucleus to the periphery
Cholesterol and Cholesterol Esters
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Macrophages in contact with lipid debris of necrotic cells:
- Become stuffed with lipid, appearing as foamy cells
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Atherosclerosis:
- Smooth muscle cells and macrophages filled with lipid vacuoles composed of cholesterol and cholesterol esters
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Xanthomas:
- Accumulation of fat within macrophages of subcutaneous connective tissues, appearing as white nodules
Proteins
- Less commonly seen
- Example: Accumulation in proximal convoluted tubules in glomerular diseases with proteinuria
Glycogen
- Seen in cases of abnormal metabolism of glucose or glycogen
- Appear as vacuoles under the light microscope
Pigments
- Colored substances, either exogenous or endogenous
- Melanin: Accumulates in basal cells of the epidermis, resulting in freckles or in dermal macrophages
-
Hemosiderin:
- A hemoglobin-derived granular pigment, golden brown
- Accumulates in tissues when there is local or systemic excess iron
Pathologic Calcification
-
Abnormal accumulation of calcium salts:
- With smaller amounts of iron, magnesium, and other minerals
Immune System Cells
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T lymphocytes (T cells): Responsible for cell-mediated immunity
- About 60% of T cells express CD4
- About 30% of T cells express CD8
- CD4:CD8 ratio is approximately 2:1
- CD4: Binds to class II MHC molecules expressed on antigen-presenting cells
- CD8: Binds to class I MHC molecules
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T-helper (TH) cells:
- TH1 subset: Synthesizes and secretes IL-2 and interferon-γ (IFN-γ), but not IL-4 or IL-5. Facilitates delayed hypersensitivity, macrophage activation, and synthesis of opsonizing and complement-fixing antibodies
- TH2 subset: Produces IL-4, IL-5, and IL-13, but not IL-2 or IFN-γ. Aids in the synthesis of other classes of antibodies and activation of eosinophils
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CD8+ T cells:
- Function mainly as cytotoxic cells to kill other cells
- Can secrete cytokines, primarily of the TH1 type
T Cell Activation
-
Requires two signals for complete activation:
- 1. Engagement of TCR: By appropriate MHC-antigen complex with CD4 and CD8 coreceptors
- 2. Interaction of CD28 on T cells: With CD80 or CD86 on antigen-presenting cells
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Absence of the second signal:
- T cells undergo apoptosis or become unresponsive (anergic), preventing autoimmunity
B Lymphocytes (B cells)
- Constitute 10-20% of circulating lymphocytes
-
Found in:
- Superficial cortex of lymph nodes
- White pulp of the spleen, forming lymphoid aggregates
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After activation:
- Transform into plasma cells that secrete immunoglobulins (IgG, IgM, IgA), comprising 95% of plasma immunoglobulins
- IgE and IgD: Occur in traces in the serum and are cell-bound to B cells, respectively
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Monomeric IgM:
- Present on the surface of all B cells
- Forms the B cell antigen receptor (BCR)
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Somatic rearrangement of immunoglobulin genes:
- Results in unique antigen specificity
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Other molecules expressed on B cells:
- CD19
- CD20
- CD21: Serves as a complement receptor and also binds to Epstein-Barr virus (EBV)
- CD40: Interacts with CD154 on activated T lymphocytes
Macrophages
-
Multiple roles in immune response:
- Present antigens to T cells: Through class II MHC molecules
- Produce cytokines: Influence the function of T and B cells, endothelial cells, and fibroblasts
- Secrete toxic metabolites and proteolytic enzymes: Lyse tumor cells
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Description
This quiz examines the mechanisms of cell injury, focusing on ischemia, toxin effects, and the role of oxygen free radicals. It also covers the consequences of reversible hypoxic injury and the resultant cellular changes. test your understanding of these critical concepts in cell biology.