Biochemistry of Free Radicals and Cell Injury

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Questions and Answers

Match the following types of injuries with their descriptions:

Chemical mediated injury = Involves binding to critical molecular components Radiation mediated injury = Caused by absorption of radiant energy Oxygen toxicity = Results from excessive reactive oxygen species Cellular aging = Associated with accumulated oxidative damage

Match the following free radicals with their formation processes:

Superoxide radicals (O2.-) = Generated during reduction-oxidation reactions Hydrogen peroxide (H2O2) = Intermediate product from oxygen reduction Hydroxyl radicals (OH.) = Produced in reactions involving metals Carbon trichloride (CCl3) = Created from metabolic conversion of CCl4

Match the following free radical reactions with their targets:

Lipid peroxidation = Affects plasma membranes DNA reaction = Involves thymine Protein cross-linking = Denatures and alters protein function Cellular swelling = Leads to vacuolar degeneration

Match the following enzymes with their roles in free radical generation:

Xanthine oxidase = Generates superoxide radicals P-450 oxidases = Converts non-toxic chemicals to toxic metabolites Catalase = Decomposes hydrogen peroxide Lipoxygenase = Catalyzes formation of leukotrienes Signup and view all the answers

Match the following consequences of free radical damage:

Swelling of SER = Leads to reduced lipid export Dissociation of ribosomes = Occurs after cell injury Membrane phospholipid peroxidation = Destroys cell membrane integrity Fatty liver change = Results from impaired hepatocyte function Signup and view all the answers

Match the following types of chemical injury with their mechanisms:

Inhibition of ATP transport = Mercury binding to sulfhydryl groups Accumulation of reactive metabolites = Conversion by P-450 oxidases Formation of toxic free radicals = Metabolizing inert chemicals Direct cellular damage = Binding to critical organelles or proteins Signup and view all the answers

Match the following elements with their roles in free radical chemistry:

Copper = Acts as an electron donor/acceptor Iron = Participates in Fenton reactions Oxygen = Primary substrate for radical formation Carbon = Involves in the metabolism of chemicals like CCl4 Signup and view all the answers

Match the following terms with their related concepts in free radical biology:

Hydropic changes = A form of reversible cell injury Oxidative stress = Caused by an imbalance in free radicals Autocatalytic peroxidation = Leads to rapid membrane damage Vacuolar degeneration = Results in cell swelling observable microscopically Signup and view all the answers

Match the following types of tumor-associated antigens with their corresponding cancer types:

Prostate-specific antigen (PSA) = Prostate cancer Alfa-fetoprotein (AFP) = Hepatocellular carcinoma Carcinoembryonic antigen (CEA) = Colorectal carcinoma Tumor-associated antigens = Shared by normal untransformed cells Signup and view all the answers

Match the following TNM staging components with their descriptions:

T = Tumor size N = Lymph node metastases M = Distant metastases Grading = Cytological differentiation of tumor cells Signup and view all the answers

Match the following components of the immune system with their function:

Natural killer (NK) cells = Kill virus-infected cells T-lymphocytes = Cell-mediated immunity B-lymphocytes = Humoral immunity Phagocytic cells = Engulf and digest pathogens Signup and view all the answers

Match the following terms related to immunity with their categories:

Innate immunity = Natural or native defense mechanisms Adaptive immunity = Specific defense mechanisms Cell-mediated immunity = Defense against intracellular microbes Humoral immunity = Defense against extracellular microbes Signup and view all the answers

Match the following elements of T-lymphocytes with their specific roles:

T cell receptor (TCR) = Antigen recognition CD3 complex = Signal transduction CD4 = Helper T cells CD8 = Cytotoxic T cells Signup and view all the answers

Match the following grades of tumor differentiation with their levels of anaplasia:

I = Well-differentiated II = Moderately differentiated III = Poorly differentiated IV = Undifferentiated or anaplastic Signup and view all the answers

Match the following characteristics of the immune response with their corresponding types:

Epithelial barriers = Innate immunity Trainee lymphocytes = Adaptive immunity Neutrophils = Innate immunity Antibodies = Humoral immunity Signup and view all the answers

Match the following types of cancer with their associated tumor markers:

Prostate cancer = Prostate-specific antigen (PSA) Hepatocellular carcinoma = Alfa-fetoprotein (AFP) Colorectal carcinoma = Carcinoembryonic antigen (CEA) Lung cancer = Not specified in the text Signup and view all the answers

Match the following conditions with their descriptions:

Fatty Change (Steatosis) = Abnormal accumulation of triglycerides within parenchymal cells Cholesterol Accumulation = Foamy cells in atherosclerosis filled with lipid vacuoles Glycogen Accumulation = Vacuoles seen in abnormal metabolism of glucose or glycogen Pathologic Calcification = Abnormal accumulation of calcium salts in tissues Signup and view all the answers

Match the following causes with the conditions they are associated with:

Anoxia = Inhibits fatty acid oxidation leading to fatty change Toxins (e.g., alcohol) = Alters mitochondrial and SER function Diabetes mellitus = Contributes to fatty change in the liver Starvation = Increases fatty acid mobilization from peripheral stores Signup and view all the answers

Match the following pigments with their sources:

Melanin = Accumulates in basal cells of the epidermis Hæmosiderin = Derived from excess hemoglobin and appears golden brown Cholesterol = Accumulates in macrophages in atherosclerosis Fatty acids = Component of triglycerides seen in fatty change Signup and view all the answers

Match the following cellular changes with their visibility under a light microscope:

Fatty Change = Small vacuoles coalesce to create clear spaces Glycogen Accumulation = Vacuoles in proximal convoluted tubules Cholesterol Accumulation = Foamy appearance in necrotic tissue Protein Accumulation = Seen in glomerular diseases with proteinuria Signup and view all the answers

Match the following diseases with their characteristic features:

Atherosclerosis = Lipid-filled smooth muscle cells and macrophages Cirrhosis = Can result from severe fatty change in the liver Obesity = Contributes to excessive triglyceride accumulation Hemochromatosis = Systemic excess iron leading to hæmosiderin accumulation Signup and view all the answers

Match the following conditions with the organs they most commonly affect:

Fatty Change = Liver Xanthomas = Subcutaneous connective tissues Proteinuria-related Accumulation = Kidney Pigment Accumulation = Dermal macrophages Signup and view all the answers

Match the following cytological features with their related substances:

Vesicles displacing the nucleus = Fatty change Foamy appearance in macrophages = Cholesterol esters Colored substances = Pigments Golden brown granules = Hæmosiderin Signup and view all the answers

Match the following metabolic disturbances with their effects:

Excess triglycerides = May transiently impair cellular function Defects in apoprotein synthesis = Increased fatty accumulation due to toxins Anoxia = Inhibition of fatty acid oxidation Starvation = Mobilization of fatty acids from stores Signup and view all the answers

Match the following processes with their descriptions:

Apoptosis = Programmed cell death that does not elicit an inflammatory response Fat necrosis = Focal areas of fat destruction due to pancreatic enzyme activation Intracellular accumulation = Abnormal substance buildup within cells under various circumstances Granulomatous inflammation = Formation of structureless amorphous granular debris Signup and view all the answers

Match the following triggers of apoptosis with their descriptions:

Withdrawal of growth factors = Reduction in survival signals leading to apoptosis Engagement of specific receptors = Activation of cell death pathways through receptor ligand interactions Injury by radiation = Cell damage due to ionizing radiation leading to apoptosis Intrinsic protease activation = Internal signals that trigger programmed cell death during development Signup and view all the answers

Match the following types of intracellular accumulation with their characteristics:

Normal endogenous substance = Produced at a normal rate but with inadequate metabolism Storage diseases = Genetic enzymatic defects preventing metabolization Abnormal exogenous substance = Accumulation of foreign substances within cells Dysfunctional metabolism = Impaired metabolic pathways leading to substance buildup Signup and view all the answers

Match the following apoptosis features with their descriptions:

Condensed chromatin = Nuclear chromatin aggregates to the periphery Cytoplasmic budding = Formation of bulges from the cytoplasm during cell shrinkage Apoptotic bodies = Membrane-bound fragments containing remnants of the dying cell Karyorrhexis = Fragmentation of the nucleus during apoptosis Signup and view all the answers

Match the following physiological conditions with their apoptotic processes:

Embryogenesis = Programmed cell death during development Endometrial involution = Hormonal changes resulting in cell death during the menstrual cycle Intestinal crypt epithelium = Cell deletion in rapidly proliferating tissues Thymus T cell deletion = Removal of autoreactive T cells to maintain immune tolerance Signup and view all the answers

Match the following pancreatic conditions with their consequences:

Acute pancreatitis = Release of activated enzymes leading to fat necrosis Focal fat destruction = Localized damage to adipose tissues due to enzymatic activity Vascular damage = Potentially results from increased lipase activity Peritoneal cavity changes = Alterations due to released triglyceride hydrolysis Signup and view all the answers

Match the following apoptosis initiators with their effects:

Growth factor withdrawal = Signals reduced cell survival Radiation damage = Causes cellular injury and may trigger apoptosis Toxins exposure = Induces programmed cell death through cellular stress Free radicals = Reactive species leading to oxidative stress in cells Signup and view all the answers

Match the following terms with their definitions:

Granulomatous inflammation = Type of inflammation marked by aggregates of macrophages Eosinophilic cytoplasm = Cytoplasmic staining characteristic during apoptosis Programmed cell death = Process of eliminating unwanted cells in a controlled manner Intracellular proteases = Enzymes that facilitate cellular breakdown during apoptosis Signup and view all the answers

Match the T cell subsets with their primary function:

TH1 = Facilitates macrophage activation TH2 = Aids in the activation of eosinophils CD8+ = Cytotoxic function to kill other cells CD4+ = Secretes cytokines primarily of the TH1 type Signup and view all the answers

Match the immunoglobulin types with their primary characteristics:

IgG = Majority plasma immunoglobulin IgA = Secreted in mucosal areas IgE = Present in trace amounts in serum IgD = Only cell-bound on B cells Signup and view all the answers

Match the cell surface markers with their corresponding cell types:

CD4 = Helper T cells CD8 = Cytotoxic T cells CD19 = B cells CD40 = Interactions with activated T-lymphocytes Signup and view all the answers

Match the antigen presenting functions with the respective cells:

B-Lymphocytes = Produce immunoglobulins after activation Macrophages = Present antigens to T-cells via MHC II 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 processes involved in T cell activation:

Engagement of TCR = Requires appropriate MHC-antigen complex Interaction of CD28 = Binds to CD80 or CD86 on APCs Anergic state = T cells become unreactive without proper signals Apoptosis = Occurs in absence of activation signals Signup and view all the answers

Match the cytokines with the T cell subsets they are primarily associated with:

IL-2 = Produced by TH1 cells IFN-γ = Secreted by TH1 cells IL-4 = Secreted by TH2 cells IL-13 = Produced by TH2 cells Signup and view all the answers

Match the functions of B-lymphocytes and macrophages:

B-Lymphocytes = Form germinal centers upon activation Macrophages = Produce cytokines influencing T and B cells Signup and view all the answers

Match the features of CD4 and CD8 T cells:

CD4+ = Facilitates delayed hypersensitivity CD8+ = Can secrete cytokines of the TH1 type Signup and view all the answers

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Study Notes

Free Radicals

Highly reactive chemical species with a single unpaired electron in their outer orbital.
Readily react with organic and inorganic chemicals.
Generated within cells through absorption of radiant energy, redox reactions, and enzymatic catabolism of oxygenous chemicals.
Contribute to chemical injury, radiation injury, oxygen toxicity, cellular aging, microbial killing, and inflammatory damage.

Chemical Injury

Two main mechanisms: combining with critical molecular components or being converted to reactive toxic metabolites by enzymes like P-450 oxidases.
Example: Carbon tetrachloride (CCl4) is converted to the toxic free radical CCl3. in the liver, leading to membrane peroxidation and damage to the endoplasmic reticulum.

Patterns of Acute Cell Injury

Reversible Cell Injury:
- Cell swelling (hydropic changes)
- Fatty change (accumulation of triglycerides)
- Microscopically, it is composed of structureless amorphous granular debris within granulomatous inflammation
Irreversible Cell Injury:
- Necrosis: characterized by cell death and breakdown.
- Apoptosis: programmed cell death, characterized by nuclear fragmentation and formation of apoptotic bodies.
- Fat Necrosis: focal areas of fat destruction often seen in acute pancreatitis

Apoptosis

Programmed cell death involved in physiological and pathological conditions.
Initiated by withdrawal of growth factors, engagement of specific receptors, injury by toxins and free radicals, and intrinsic protease activation.
Characterized by nuclear condensation and fragmentation, and the formation of apoptotic bodies.
No inflammatory response is elicited.

Intracellular Accumulations

Normal cells accumulate abnormal substances, either transiently or permanently.
Classified into three categories: normal endogenous substance, normal or abnormal endogenous substance that can't be metabolized due to genetic defects, and abnormal exogenous substances.
Examples: fatty change (steatosis), cholesterol and cholesterol esters, proteins, glycogen, and pigments.

Fatty Change (Steatosis)

Abnormal accumulation of triglycerides within parenchymal cells.
Most often seen in the liver, but can occur in the heart, skeletal muscle, kidney, and other organs.
Caused by toxins, diabetes mellitus, protein malnutrition, obesity, and anoxia.
May impair cellular function in severe cases.

Cholesterol and Cholesterol Esters

Macrophages in contact with lipid debris of necrotic cells can become filled with lipid, appearing as foamy cells.
Atherosclerosis involves smooth muscle cells and macrophages filled with cholesterol and cholesterol esters.
Xanthomas are accumulations of fat within macrophages of subcutaneous connective tissues.

Pathologic Calcification

Abnormal accumulation of calcium salts, often with smaller amounts of iron, magnesium, and other minerals.
Can be found in various conditions including:
- Atherosclerosis
- Tuberculosis
- Damaged heart valves

Tumor-Associated Antigens

Shared by normal and transformed cells.
Examples: prostate-specific antigen (PSA), alpha-fetoprotein (AFP), and carcinoembryonic (CEA) antigen.

Grading and Staging

Grading: based on the cytological differentiation of tumor cells and the number of mitoses.
Graded I, II, III, or IV in order of increasing anaplasia.
Staging: based on the size of the primary lesion, extent of spread to regional lymph nodes, and presence or absence of metastases.
TNM staging system: T (tumor size), N (lymph node metastases), M (distant metastases).

The Immune System

Innate Immunity: non-specific defense mechanisms present before infection.
- Includes epithelial barriers, phagocytic cells, NK cells, and complement system.
Adaptive Immunity: specific defense mechanisms that adapt to microbes.
- Includes cell-mediated immunity (T lymphocytes) and humoral immunity (B lymphocytes and antibodies).

Cells of the Immune System

T lymphocytes: make up 60-70% of circulating lymphocytes.
- Each T-cell has a specific TCR (T cell receptor) composed of alpha and beta polypeptide chains.
- CD4 and CD8 are expressed on different T-cell subsets and act as coreceptors.
- CD4+ T cells bind to Class II MHC molecules and help activate B cells.
- CD8+ T cells bind to Class I MHC molecules and kill cells infected with viruses or cancer cells.
B lymphocytes: constitute 10-20% of circulating lymphocytes.
- Transform into plasma cells that secrete antibodies after antigen stimulation.
- Express immunoglobulin receptors on their surface (BCR).
Macrophages: present antigens to T-cells, produce cytokines, and secrete toxic metabolites and proteolytic enzymes.
Other important cells of the immune system: NK cells (destroy virus-infected cells), neutrophils (phagocytize bacteria)

Activation of T lymphocytes

Activation requires two signals:
- Engagement of TCR by appropriate MHC-antigen complex with CD4 or CD8 coreceptors.
- Interaction of CD28 on T cells with CD80 or CD86 on antigen-presenting cells.
Absence of the second signal leads to apoptosis or anergy, preventing autoimmunity.

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