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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:
Match the following components with their roles in cell injury:
Match the following components with their roles in cell injury:
Match the following hypoxic effects with their outcomes:
Match the following hypoxic effects with their outcomes:
Match the following phases of injury with their effects:
Match the following phases of injury with their effects:
Match the following types of radicals with their effects:
Match the following types of radicals with their effects:
Match the type of necrosis with its characteristic description:
Match the type of necrosis with its characteristic description:
Match the cytoplasmic change with its description:
Match the cytoplasmic change with its description:
Match the nuclear change with its definition:
Match the nuclear change with its definition:
Match the cellular alteration with its ultrastructural change:
Match the cellular alteration with its ultrastructural change:
Match the necrosis type with its prime example:
Match the necrosis type with its prime example:
Match the type of cell death process with its origin:
Match the type of cell death process with its origin:
Match the description of fatty change with its cause:
Match the description of fatty change with its cause:
Match the term with its function in necrosis:
Match the term with its function in necrosis:
Match the following terms with their descriptions:
Match the following terms with their descriptions:
Match the following stimuli to the mechanisms initiating apoptosis:
Match the following stimuli to the mechanisms initiating apoptosis:
Match the type of intracellular accumulation to its description:
Match the type of intracellular accumulation to its description:
Match the stage of apoptosis to its characteristic feature:
Match the stage of apoptosis to its characteristic feature:
Match the examples of apoptosis to their physiological contexts:
Match the examples of apoptosis to their physiological contexts:
Match the pancreatic condition to their described outcome:
Match the pancreatic condition to their described outcome:
Match the important players in apoptosis to their roles:
Match the important players in apoptosis to their roles:
Match the type of cell death to its inflammatory response:
Match the type of cell death to its inflammatory response:
Match the following T cell types with their primary functions:
Match the following T cell types with their primary functions:
Match the following lymphocyte types with their characteristics:
Match the following lymphocyte types with their characteristics:
Match the following immunoglobulin classes with their features:
Match the following immunoglobulin classes with their features:
Match the following molecules with their roles in T cell activation:
Match the following molecules with their roles in T cell activation:
Match the following types of cytokines with their T cell subsets:
Match the following types of cytokines with their T cell subsets:
Match the following roles of macrophages with their functions:
Match the following roles of macrophages with their functions:
Match the following CD markers with their associated cells:
Match the following CD markers with their associated cells:
Match the following immunoglobulin classes with their distribution:
Match the following immunoglobulin classes with their distribution:
Match the type of abnormal substance accumulation with its description:
Match the type of abnormal substance accumulation with its description:
Match the cause of fatty change with its description:
Match the cause of fatty change with its description:
Match the type of cell involvement with its associated condition:
Match the type of cell involvement with its associated condition:
Match the pigment accumulation with its specific type:
Match the pigment accumulation with its specific type:
Match the organ with the condition associated with fatty change:
Match the organ with the condition associated with fatty change:
Match the clinical presentation with its definition:
Match the clinical presentation with its definition:
Match the condition with its characteristic feature:
Match the condition with its characteristic feature:
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)
- 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
- 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")
- 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
- 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
- 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
- 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
- Macrophages in contact with lipid debris of necrotic cells:
- Become stuffed with lipid, appearing as foamy cells
- Atherosclerosis:
- Smooth muscle cells and macrophages filled with lipid vacuoles composed of cholesterol and cholesterol esters
- 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
- 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
- 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
- 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
- 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
- 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
- Monomeric IgM:
- Present on the surface of all B cells
- Forms the B cell antigen receptor (BCR)
- Somatic rearrangement of immunoglobulin genes:
- Results in unique antigen specificity
- 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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