Cell Injury and Hypoxic Damage

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Questions and Answers

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:

Phospholipases = Degrade cell membranes Proteases = Catabolize structural proteins ATPases = Cause ATP depletion Endonucleases = Fragment DNA

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:

Vacuolization of mitochondria = Sign of irreversible injury Loss of cytoskeletal structure = Loss of ultrastructural features Blebbing of cell membrane = Formation of surface irregularities Whorled masses of phospholipids = Dead cell replacement Signup and view all the answers

Match the following components with their roles in cell injury:

Calcium influx = Activation of destructive enzymes Oxygen free radicals = Mediators of cell death Lipid breakdown products = Have detergent effects Inorganic phosphates = Accumulation during injury Signup and view all the answers

Match the following hypoxic effects with their outcomes:

Reduced intracellular ATP = Increased extracellular calcium Cytoplasmic eosinophilia = Decreased pH Glycogen depletion = Rapid lactic acid accumulation Reduced plasma membrane sodium pump = Sodium accumulation in cells Signup and view all the answers

Match the following phases of injury with their effects:

Reversible phase = Cellular swelling normalizes with oxygen Irreversible phase = Cellular structures are compromised Ischemic phase = Cell function decreases gradually Reperfusion phase = Calcium-mediated damage occurs Signup and view all the answers

Match the following types of radicals with their effects:

Toxic oxygen radicals = Release during ischemic injury Free radicals = Increase cellular damage Reactive oxygen species = Injury mediators post-reperfusion Lipid peroxides = Contribute to membrane damage Signup and view all the answers

Match the type of necrosis with its characteristic description:

Coagulative necrosis = Preservation of structural outlines of coagulated cells Liquefactive necrosis = Accumulation of white cells due to bacterial infection Gangrenous necrosis = Ischemic coagulative necrosis with superimposed infection Caseous necrosis = Cheesy appearance from tuberculous infection Signup and view all the answers

Match the cytoplasmic change with its description:

Eosinophilia = Cytoplasmic appearance due to acidosis Glassy appearance = Loss of glycogen in the cytoplasm Cytoplasmic vacuolation = Formation of vacuoles within the cytoplasm Calcification = Deposition of calcium salts in damaged tissue Signup and view all the answers

Match the nuclear change with its definition:

Karyolysis = Digestion of DNA leading to nucleus fading Pyknosis = Nuclear shrinkage and increased basophilia Karyorrhexis = Fragmentation of a pyknotic nucleus Condensed chromatin = Nuclear compaction often seen in necrosis Signup and view all the answers

Match the cellular alteration with its ultrastructural change:

Plasma membrane changes = Blebing and distortion of microvilli Mitochondrial swelling = Phospholipid-rich amorphous densities Endoplasmic reticulum dilation = Detachment of ribosomes Nuclear disaggregation = Loss of structural granular elements Signup and view all the answers

Match the necrosis type with its prime example:

Coagulative necrosis = Myocardial infarction Liquefactive necrosis = Brain hypoxic cell death Gangrenous necrosis = Wet gangrene from ischaemia Caseous necrosis = Tuberculosis infection Signup and view all the answers

Match the type of cell death process with its origin:

Autolysis = Enzymatic digestion from dead cells Heterolysis = Lysosomal activity from infiltrating leukocytes Necrosis = Irreversible cell death due to exogenous injury Apoptosis = Programmed cell death with nuclear changes Signup and view all the answers

Match the description of fatty change with its cause:

Steatosis = Fatty change in hypoxic injury Chemical injury = Damage from toxic substances Myocardial cells = Fatty change observed after hypoxia Liver change = Accumulation of fat droplets Signup and view all the answers

Match the term with its function in necrosis:

Enzymatic digestion = Breakdown of cellular components Denaturation = Structural alteration of proteins Phagocytosis = Removal of necrotic cells by immune cells Cytoplasmic vacuolation = Formation of fluid-filled spaces in cells Signup and view all the answers

Match the following terms with their descriptions:

Apoptosis = Programmed cell death in various conditions Fat necrosis = Focal areas of fat destruction due to pancreatic enzymes Intracellular Accumulations = Abnormal substances accumulating in cells Granulomatous inflammation = Chronic inflammatory response characterized by granuloma formation Signup and view all the answers

Match the following stimuli to the mechanisms initiating apoptosis:

Withdrawal of growth factors = Signals programmed cell death Engagement of specific receptors = Activates apoptotic pathways Injury by radiation = Causes cell death through DNA damage Intrinsic protease activation = Triggers internal cell death mechanisms Signup and view all the answers

Match the type of intracellular accumulation to its description:

Normal endogenous substance = Produced at an increased rate with slow metabolism Abnormal endogenous substance = Cannot be metabolized due to genetic defects Exogenous substance = Accumulated from outside sources like toxins Fatty change of liver = An example of normal substance accumulation in excess Signup and view all the answers

Match the stage of apoptosis to its characteristic feature:

Cell shrinkage = Initial morphological change during apoptosis Cytoplasmic budding = Formation of apoptotic bodies Nuclear chromatin condensation = Clumping of chromatin at the nuclear membrane Phagocytic recognition = Final clearance of apoptotic cells by immune cells Signup and view all the answers

Match the examples of apoptosis to their physiological contexts:

Embryogenesis = Programmed cell death during development Endometrial involution = Cell death during menstrual cycle Intestinal crypt epithelium = Deletion of cells in rapidly proliferating tissues Autoreactive T cells = Elimination of harmful immune cells in the thymus Signup and view all the answers

Match the pancreatic condition to their described outcome:

Activation of pancreatic enzymes = Leading to fat necrosis Hydrolysis of triglycerides = Causes peritoneal fat destruction Acute pancreatitis = Triggers fat necrosis in abdominal cavity Granulomatous inflammation = Typically not associated with fat necrosis Signup and view all the answers

Match the important players in apoptosis to their roles:

Calpain I = Type of intracellular protease Interleukin 1β converting enzyme = Protease involved in apoptosis FAS receptor = Engages apoptotic signaling pathways TNF = Triggers receptor-mediated apoptosis Signup and view all the answers

Match the type of cell death to its inflammatory response:

Apoptosis = Does not elicit inflammatory response Necrosis = Often associated with inflammation Fat necrosis = Related to cell injury with inflammation Granulomatous inflammation = Characterized by chronic immune response Signup and view all the answers

Match the following T cell types with their primary functions:

CD4+ = Helper T cells that activate B cells CD8+ = Cytotoxic cells that kill infected cells TH1 = Produces IL-2 and IFN-γ TH2 = Produces IL-4, IL-5, and IL-13 Signup and view all the answers

Match the following lymphocyte types with their characteristics:

B-Lymphocytes = 10-20% of circulating lymphocytes T-Lymphocytes = Require two signals for activation CD4+ T cells = Bind to class II MHC molecules CD8+ T cells = Bind to class I MHC molecules Signup and view all the answers

Match the following immunoglobulin classes with their features:

IgG = Main type of antibody in serum IgM = Present on the surface of B cells as BCR IgA = Found in mucosal areas IgE = Involved in allergic responses Signup and view all the answers

Match the following molecules with their roles in T cell activation:

TCR = Recognizes MHC-antigen complex CD28 = Interacts with CD80/CD86 on APC CD4 = Coreceptor for class II MHC CD8 = Coreceptor for class I MHC Signup and view all the answers

Match the following types of cytokines with their T cell subsets:

IL-2 = Secreted by TH1 cells IFN-γ = Secreted by TH1 cells IL-4 = Secreted by TH2 cells IL-5 = Secreted by TH2 cells Signup and view all the answers

Match the following roles of macrophages with their functions:

Antigen presentation = Present antigens to T-cells Cytokine production = Influence function of immune cells Toxic metabolite secretion = Lyses tumor cells Engulfment = Ingest pathogens and debris Signup and view all the answers

Match the following CD markers with their associated cells:

CD19 = Expressed on B cells CD20 = Expressed on B cells CD21 = Complement receptor and EBV binding CD40 = Interacts with CD154 on T cells Signup and view all the answers

Match the following immunoglobulin classes with their distribution:

IgG = Most abundant in blood IgM = First antibody produced in response IgA = Found in secretions like saliva IgD = Cell-bound on B cells Signup and view all the answers

Match the type of abnormal substance accumulation with its description:

Fatty Change = Abnormal accumulation of triglycerides within parenchymal cells. Cholesterol = Accumulation in macrophages of necrotic tissue leading to foamy cells. Glycogen = Vacuoles seen in abnormal metabolism of glucose or glycogen. Pathologic Calcification = Abnormal accumulation of calcium salts and other minerals. Signup and view all the answers

Match the cause of fatty change with its description:

Anoxia = Inhibits fatty acid oxidation. Alcohol = Alters mitochondrial and SER function. Obesity = Increases fatty acid mobilization from peripheral stores. Protein Malnutrition = Decreases synthesis of apoproteins. Signup and view all the answers

Match the type of cell involvement with its associated condition:

Macrophages = Become foamy from lipid debris. Smooth Muscle Cells = Filled with lipid vacuoles in atherosclerosis. Proximal Convoluted Tubules = Involved in proteinuria. Basal Cells = Involved in melanin accumulation causing freckles. Signup and view all the answers

Match the pigment accumulation with its specific type:

Hæmosiderin = Granular pigment derived from hemoglobin. Melanin = Colored substance resulting in freckles. Xanthomas = Fat accumulation in macrophages of connective tissues. Iron = Causes excess accumulation resulting in hæmosiderin. Signup and view all the answers

Match the organ with the condition associated with fatty change:

Liver = Most common site for fatty change. Heart = Possible site for fatty change. Skeletal Muscle = May have triglyceride accumulation. Kidney = Another potential site for fatty change. Signup and view all the answers

Match the clinical presentation with its definition:

Vacuoles = Small spaces seen in cytoplasm around the nucleus. Clear Spaces = Larger areas displacing the nucleus to the periphery. Yellow Liver = Liver grossly appears yellow in fatty change. Cellular Dysfunction = More severe fatty change may impair function. Signup and view all the answers

Match the condition with its characteristic feature:

Atherosclerosis = Presence of lipid vacuoles in smooth muscle cells. Fatty Change = Reversible accumulation mainly in liver. Proteinuria = Leads to protein accumulation in renal tubules. Xanthomas = White nodules due to fat accumulation in tissues. Signup and view all the answers

Match the type of cellular changes to their respective examples:

Foamy Cells = Result from macrophages taking up lipid. Triglyceride Accumulation = Seen in steatosis. Vacuolar Change = Observed in glycogen metabolism disorders. Calcium Accumulation = Characteristic of pathologic calcification. Signup and view all the answers

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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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.