NURS 5350 Inflammation, Immunity, and Wound Healing PDF

NURS 5350 Chapters 7-9: Inflammation, Immunity, and Wound Healing Innate Immunity ​ Types of Immunity: 1.​ Innate resistance: Natural barriers and inflammatory response. 2.​ Adaptive (acquired) immunity. ​ Lines of Defense: 1.​ First Line: Natural barriers (physical...

NURS 5350 Chapters 7-9: Inflammation, Immunity, and Wound Healing Innate Immunity ​ Types of Immunity: 1.​ Innate resistance: Natural barriers and inflammatory response. 2.​ Adaptive (acquired) immunity. ​ Lines of Defense: 1.​ First Line: Natural barriers (physical, mechanical, biochemical). 2.​ Second Line: Inflammation. 3.​ Third Line: Adaptive (acquired) immunity. First Line of Defense: Physical and Biochemical Barriers and Human Microbiome ​ Physical and Mechanical Barriers: ○​ Skin and low temperature/pH of skin. ○​ Linings of the gastrointestinal, genitourinary, and respiratory tracts. ​ Highly interconnected junctions. ​ Sloughing off of cells. ​ Coughing, sneezing, vomiting, urinating. ​ Mucus and cilia. ​ Biochemical Barriers: ○​ Synthesized substances trap or destroy microorganisms. ○​ Antibacterial peptides in mucus, perspiration, saliva, tears, and earwax. Second Line of Defense: Inflammation ​ Causes: ○​ Infection, mechanical damage, ischemia, nutrient deprivation, temperature extremes, radiation. ​ Functions: ○​ Prevent and limit infection. ○​ Limit/control inflammatory processes. ○​ Prepare the area for healing. ​ Characteristics: ○​ Rapid initiation and no memory cells. ​ Cardinal Signs: Redness, heat, swelling, pain, loss of function. ​ Vascular Response: ○​ Blood vessel dilation. ○​ Increased vascular permeability and leakage. ○​ WBC adherence to vessel walls and migration through vessels. Plasma Protein Systems in Inflammation ​ Complement System: ○​ Destroys pathogens directly (antibodies and antigens). ​ Clotting System: ○​ Forms a mesh to stop bleeding and prevents infection spread. ​ Kinin System:  ○​ Activates inflammatory cells, causing blood vessel dilation and increased permeability (bradykinin). Initial Cellular Responders in Inflammation ​ Cellular Mediators: ○​ Mast cells. ○​ Granulocytes (neutrophils, eosinophils, basophils). ○​ Monocytes, macrophages. ○​ Natural killer cells, lymphocytes. ○​ Cellular fragments (platelets). ​ Biochemical Mediators: ○​ Originate from destroyed cells. ○​ Modulate activity of other inflammatory cells. Cellular Receptors ​ Pattern Recognition Receptors (PRRs): Recognize pathogen-associated molecular patterns. ○​ Toll-like receptors (TLRs). ○​ Complement receptors. ○​ Scavenger receptors. ​ Inflammatory Response: Initiated by tissue injury. Mast Cells ​ Located in loose connective tissues near blood vessels. ​ Release biochemical mediators. ​ Activated by physical injury, chemical agents, immunologic processes, and TLRs. ​ Degranulation: Releases histamine and chemotactic factors. ○​ H1 receptor: Proinflammatory; induces bronchoconstriction. ○​ H2 receptor: Antiinflammatory; induces gastric acid secretion. Synthesis of Mediators by Mast Cells ​ Leukotrienes: Late inflammation stages. ​ Prostaglandins: Induce pain. ​ Platelet-Activating Factor: Activates platelets. Phagocytosis ​ Ingests and disposes of foreign material. ​ Key Cells: ○​ Neutrophils: Early responders; ingest bacteria, dead cells. ○​ Macrophages: Long-lived; important for tissue repair. ○​ Natural Killer Cells: Eliminate virus-infected and cancer cells. ○​ Eosinophils: Defend against parasites; regulate inflammation. Manifestations of Inflammation ​ Local Signs: Heat, redness, swelling, pain, loss of function. ​ Systemic Signs: Fever, leukocytosis, increased plasma protein synthesis. ​ Exudate Types: ○​ Serous: Watery; early inflammation. ○​ Fibrinous: Thick, clotted; advanced inflammation. ○​ Purulent: Pus; bacterial infection. ○​ Hemorrhagic: Contains blood; indicates bleeding. Chronic Inflammation ​ Lasts 2 weeks or longer. ​ Causes: ○​ Unsuccessful acute inflammatory response. ○​ Microorganisms, toxins, irritants. ​ Characteristics: ○​ Dense infiltration of macrophages and lymphocytes. ○​ Granuloma formation. Wound Healing ​ Stages: ○​ Inflammation: Cleans wound. ○​ Reconstruction: Begins 3-4 days post-injury; lasts 2 weeks. ○​ Remodeling: Scar formation over several weeks to years. ​ Types: ○​ Primary Intention: Minimal tissue loss. ○​ Secondary Intention: Significant tissue replacement; scar formation. ​ Dysfunctions: ○​ Causes: Ischemia, hemorrhage, hypovolemia, infection, malnutrition, medications. ○​ Results: Keloids, contractures, dehiscence. Adaptive Immunity ​ Characteristics: ○​ Recognizes foreign substances. ○​ Provides long-term protection. ○​ Has memory. ​ Key Components: ○​ T and B Cells: ​ T cells: Cellular immunity. ​ B cells: Humoral immunity. ○​ Antibodies (Immunoglobulins): ​ IgG: Most abundant; crosses placenta. ​ IgA: Found in body secretions. ​ IgM: First responder. ​ IgE: Involved in allergies and parasitic infections. Hypersensitivity Reactions 1.​ Type I: IgE-mediated (e.g., allergies, anaphylaxis). 2.​ Type II: Tissue-specific (e.g., Graves’ disease). 3.​ Type III: Immune complex-mediated (e.g., lupus). 4.​ Type IV: T-cell-mediated (e.g., contact dermatitis). Autoimmunity and Alloimmunity ​ Autoimmunity: Immune attack on self-antigens (e.g., lupus). ​ Alloimmunity: Reaction against beneficial foreign tissues (e.g., transplants, transfusions). Immune Deficiencies ​ Primary (Congenital): Genetic; includes SCID. ​ Secondary (Acquired): Caused by other diseases, conditions (e.g., HIV, malnutrition). Test Review Questions 1. What is often found with chronic inflammation? Chronic Inflammation: Inflammation that last 2 weeks or longer, often related to unsuccessful acute inflammatory response. Characteristics: 1.) Dense infiltration of lymphocytes and macrophages. 2. ) Granuloma formation-need rest for this. 3.) Epithelioid cell formation ​ Granuloma Formation is a characteristic feature of chronic inflammation. ​ Resolution Regeneration : Most favorable outcome of inflammation. It’s a process where damaged tissue is replaced with healthy tissue of the Original type. It’s not possible with extensive damage to tissue. ​ Repair: Refers to the replacement of destroyed tissue with scar tissue which has less stretch and give. 2. Functions of acute inflammation? ​ Prevents and limits infection and further damage. ​ Prepares the area of injury for healing. ​ Dilates toxins and carries plasma proteins and leukocytes to the injury site. ​ Carry plasma proteins and leukocytes to the injury site ​ Carry bacterial toxins and debris away from the site 3. What causes delayed wound healing? ​ Causes: Ischemia, hemorrhage, infection, hypovolemia, malnutrition, excessive scar formation, and medications (e.g., anti-inflammatory steroids), fibrous adhesions,  infection, foreign object, wound sepsis, hypoproteinemia, medications that cause vasoconstriction, dehiscence-usually 5-12 days after sure has too much pressure. 4. Active vs. passive immunity and examples of each. ​ Active Immunity/Acquired Immunity : Antibodies or T cells are produced after natural exposure to antigen or after immunization (e.g., vaccination). It is long lived ​ Passive Immunity: Preformed antibodies or T lymphocytes are transferred from a donor to a recipient (e.g., maternal antibodies to fetus).It can occur naturally or artificially. It is short lived (temporary) 5. Types of antibodies and their roles. ​ IgE: Allergies and parasitic infections. Are against environmental antigens (allergens). Cause the release of histamine from mast cells. Have H1 and H2 receptors that increase chemotactic activity. 1.) H1 S/S: Bronchial constriction, edema, and vasodilation. 2.) H2 S/S: Increased gastric secretions, and decreased histamine release from mast cells and basophils. ​ IgM: First responder in infections.It is the first antibody produced during the initial, or primary response to an antigen. ​ IgG: Provides long-term immunity; crosses placenta.( Most prevalent) ​ IgA: Found in secretions (e.g., saliva, tears, breast milk, respiratory secretions). 6. APC Antigen Presentation: ​ Antigen-Presenting Cells (APCs): Dendritic cells, macrophages, and B lymphocytes. For Processing and Presentation to Occur: Antigen must be the appropriate type, lymphocytes, must recognize presented antigen, and the antigen must be appropriately presented. Antigen processing : Is the process by which exogenous and endogenous cells are linked with the appropriate molecules, The cells help the antigen-driven maturation of B and T cells. ​ Function: Process and present antigens to T-helper cells to initiate immune response. 7. Types of hypersensitivity and examples: ​ Type I: IgE-mediated (e.g., anaphylaxis).IgE is against environmental antigens (allergens). Symptoms can include: itching, conjunctivitis, rhinitis, urticaria (itching), bronchospasm, angioedema, hypotension, GI cramps, malabsorption, dysrhythmias. ​ Type II: Tissue-specific (e.g., hemolytic anemia).: Cause target cell malfunction. They are immune reactions against a specific cell or tissue. Example: Antibody-dependent cell mediated cytotoxicity (ADCC). ​ Type III: Immune complex-mediated (e.g., lupus). Complexes are formed in the circulation and deposited later in vessel walls or tissue. It is not organ specific. Characterized by a variety of symptoms that have periods of remission and exacerbation. Example: Serum Sickness (Raynaud’s phenomenon) and Arthus reaction ​ Type IV: T-cell-mediated (e.g., contact dermatitis). Destruction of the tissue is caused by direct killing by toxins from cytotoxic T (Tc) cells. Example: Acute graft rejection, skin test for TB, contact allergic reaction, and some autoimmune diseases. 8. Anaphylaxis: ​ Severe allergic reaction caused by IgE cross linking. Severity depends on sensitivity. Possible reactions can come from bee sings, peanuts, eggs, shellfish, amongst others. ​ Symptoms: Itching, bronchoconstriction, laryngeal edema, vomiting, vascular collapse, erythema, headaches 9. Immune deficiency and clinical signs: ​ Recurrent, severe infections are the hallmark. ​ Primary Deficiency: Genetic; e.g., SCID. ​ Secondary Deficiency: Acquired; e.g., HIV/AIDS. 10. Autoimmunity vs. alloimmunity and examples: ​ Autoimmunity: Immune system attacks self (e.g., lupus). Autoimmunity is the breakdown of tolerance during which the body’s immune system begins to recognize self-antigens as foreign and attacks itself. Example is SLE: Chronic multisystem disease of autoantibodies. ​ Alloimmunity: Reaction to foreign tissues (e.g., transplant rejection). Individuals immune system reacting against antigens on the tissues of another human/species. Example: Rh system and Graft Reaction 11. Microbiome functions: ​ Prevents colonization by pathogens. ​ Maintains homeostasis by producing biochemical substances. ​ Consists of commensal bacteria and fungi. Cellular Biology, Fluid, and Electrolytes Test Review Test Review Questions 1. What are the differences between Prokaryotes and Eukaryotes? ​ Prokaryotes: ○​ Lack a distinct nucleus. ○​ Examples: Cyanobacteria, bacteria, Rickettsiae. ○​ Do not have membrane-bound organelles. ​ Eukaryotes: ○​ Contain a well-defined nucleus. ○​ Examples: Higher animals, plants, fungi, protozoa. ○​ Have membrane-bound organelles such as mitochondria, Golgi complex, and lysosomes. 2. What are the functions of cellular components? ​ Nucleus: Controls genetic information and is responsible for cell division. ​ Cytoplasm: Provides space for metabolic processes, waste transport, and storage. ​ Ribosomes: Responsible for protein synthesis. ​ Endoplasmic Reticulum (ER): ○​ Rough ER synthesizes proteins. ○​ Smooth ER synthesizes lipids and detoxifies substances. ​ Mitochondria: Generates energy in the form of ATP. ​ Golgi Complex: Processes and packages proteins for transport. ​ Lysosomes: Contain enzymes for digestion and nutrient signaling. ​ Peroxisomes: Utilize oxygen and assist in nerve cell myelination. ​ Cytoskeleton: Maintains cell shape and supports movement. ​ Plasma Membrane: Protects the cell, regulates transport, and facilitates communication. 3. Explain passive and active transport mechanisms. ​ Passive Transport: Being driven by osmosis, filtration (hydrostatic pressure), and osmosis ○​ Requires no energy. ○​ Examples: ​ Diffusion: Movement of solutes from high to low concentration. ​ Osmosis: Movement of water across a membrane. ​ Filtration (hydrostatic pressure): Movement of solutes and water due to pressure differences. ​ Active Transport: ○​ Requires energy (ATP). ○​ Examples:  ​ Na+/K+ Pump: Moves sodium out of and potassium into the cell against their concentration gradients. Uses ATPase ​ Endocytosis: Engulfing substances into the cell. ​ Exocytosis: Expelling substances out from the cell. 4. What are first and second messengers, and their roles? ​ First Messengers: Extracellular signals (e.g., hormones, neurotransmitters) that bind to receptors on the cell membrane. They signal one way. They convey instructions to the cell's interior. ​ Second Messengers: Intracellular signals triggered by first messengers. Examples include: ○​ Cyclic Adenosine monophosphate (cAMP): Activates specific enzymes within the cell. ○​ Calcium (Ca²⁺): Regulates cellular functions like muscle contraction and neurotransmitter release. 5. What are stem cells, their functions, and purposes? ​ Stem Cells: Undifferentiated cells capable of dividing and differentiating into specialized cell types. ​ Functions: ○​ Self-renewal: Ability to replicate while maintaining an undifferentiated state. ○​ Multipotency: Ability to differentiate into multiple cell types. ​ Purpose: Used in tissue repair, regeneration, and research for therapeutic applications. 6. What can alter cell environments and make them adapt? ​ Ischemia/Hypoxia: Low oxygen levels lead to cell injury or adaptation (e.g., atrophy).Also reduces blood flow. ​ Free Radicals: A molecule that has an unpaired electron that can pair with another molecule-double sided tape flapping and attaches to what is in the area. ​ Infections: Bring in macrophages and cause swelling and pressure. Trigger immune responses that may damage surrounding cells. ​ Chemical Agents: Changes the cytoplasm, transportation and signaling as changes in the environment where cells work-like nicotine and lung cells. ​ Nutritional Imbalances: Deficiencies hinder normal cellular functions (e.g., protein deficiency affects repair). ​ Physical Injury: Crush cells and cause swelling and temperature variation. ​ Immune reactions: Cells start attacking neighboring cells they see as a threat when they are not a threat. ​ Genetics: Cells are screwed up from the start, blame your mother as most are on X chromosome. ​ Infarction: Cell death as failure of blood supply. 7. Explain the Renin-Angiotensin-Aldosterone System (RAAS). ​ Activated in response to low blood pressure or sodium levels. ​ Steps: 1.​ The kidney releases renin. 2.​ Renin converts angiotensinogen (from the liver) into angiotensin I. 3.​ Angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II. 4.​ Angiotensin II increases blood pressure by: ​ Stimulating aldosterone release from the Adrenal Cortex (promotes sodium and water retention). ​ Causing vasoconstriction. 8. What are diseases and clinical signs of magnesium, calcium, potassium, and sodium imbalances? ​ Magnesium (Mg²⁺): Normal range: 1.5-3.0 mg/dL ○​ Hypomagnesemia: From Malabsorption ​ Neuromuscular irritability, tetany, convulsions, increased reflexes ​ Treatment: Magnesium sulfate replacement intravenously or orally. ○​ Hypermagnesemia: From Renal Failure ​ Muscle weakness, hypotension, respiratory depression, bradycardia ​ Treatment: Avoid magnesium intake; dialysis if severe. ​ Calcium (Ca²⁺): Normal range: 8.5-10 mg/dL ○​ Hypocalcemia: ○​ Cause: Inadequate calcium intake, ↓ in PTH and Vitamin D, blood transfusions. ​ Muscle spasms, Chvostek and Trousseau signs, tetany, neuromuscular excitability. ​ Treatment: Calcium gluconate intravenously or calcium replacement orally; reduce phosphate intake. ○​ Hypercalcemia: ○​ Cause: ↑PTH (hyperparathyroidism) and Vit D., bone metastasis, immobilization, acidosis, and sarcoidosis ​ Decreased neuromuscular excitability,Weakness, kidney stones, constipation. Kidney stones, constipation, and heart block. ​ Treatment: Hydration with IV saline, Oral phosphates, bisphosphonates, calcitonin, or corticosteroids, Denosumab ​ Potassium (K⁺): Normal Range: 3.5-5.0 mEq/L ○​ Hypokalemia: Decreased neuromuscular excitability, skeletal muscle weakness, cardiac dysrhythmias, smooth muscle atony, U wave on ECG. ​ Treatment: Potassium chloride orally or intravenously, dietary potassium supplementation. ○​ Hyperkalemia: Mild attack: tingling of lips and fingers, restlessness, intestinal cramping and diarrhea, T waves on ECG. Severe attack: Muscle weakness, loss of muscle tone, and paralysis. ​ Treatment: Calcium gluconate, insulin with glucose, sodium bicarbonate, or dialysis. ​ Sodium (Na⁺): Normal Range: 135-145 mEq/L ○​ Hyponatremia: (Free water excess): Compulsive water intoxication. S/S: Cerebral edema, pulmonary edema. ​ Treatment: Restriction of free water, hypertonic saline solution if severe. ○​ Hypernatremia: ○​ Cause: Related to sodium gain or water loss and H20 water movement form the ICF to the ECF (intracellular dehydration) ○​ Manifestation: Intracellular dehydration, seizures, muscle twitching, hyperreflexia ○​ Water deficit dehydration both sodium and water loss. ​ Manifestations: ↓BP, weak pulse and postural hypotension (20 systolic or 10 diastolic) or dizzy. ↑ Hematocrit and Sodium levels. Headache, dry skin, and dry mucous membranes. ​ Treatment: Oral or IV hypotonic fluids, careful correction to avoid cerebral edema. 9. Explain the four categories of acid-base imbalances and their causes. ​ Respiratory Acidosis: CO₂ retention from hypoventilation (e.g., COPD, brainstem trauma). Respiratory muscle paralysis, disorders of the chest wall (kyphoscoliosis, pickwickian syndrome, flail chest) ​ Respiratory Alkalosis: CO₂ loss from hyperventilation (e.g., anxiety, high altitudes). Early salicylate intoxication, anxiety or panic disorder, improper use of mechanical ventilators. ​ Metabolic Acidosis: Bicarbonate loss or acid gain (e.g., diarrhea, diabetic ketoacidosis). Lactic acidosis, renal failure, Diabetic ketoacidosis (DKA), diarrhea, starvation ​ Metabolic Alkalosis: Bicarbonate gain or acid loss (e.g., vomiting, diuretic use). Prolonged vomiting, gastric suctioning, excessive bicarbonate intake, diuretic therapy, hyperaldosteronism with hypokalemia. 10. What is the Carbonic Acid-Bicarbonate Buffering System? ​ The most important plasma buffering system is carbonic acid-bicarbonate system and Hemoglobin. They associate and dissociate very quickly (instantaneous). ​ Operates in the lungs and kidneys to maintain a pH of 7.35-7.45. ​ Mechanism: ○​ Lungs: Remove CO₂ to reduce carbonic acid levels. ○​ Kidneys: Reabsorb or excrete bicarbonate to balance pH, but do not act as fast as the lungs. ​ Compensation: ○​ Respiratory system adjusts ventilation to regulate CO₂. ○​ Renal system adjusts bicarbonate excretion or retention. 11. What triggers and stops ADH release? ​ Triggers: Increased plasma osmolality (high solute concentration) or decreased blood volume. ​ Function: Promotes water reabsorption in the kidneys. ​ Stops: Normalization of osmolality and blood volume. 12. What are the roles of buffering systems? ​ Carbonic Acid-Bicarbonate Buffering: Maintains pH balance through CO₂ and bicarbonate regulation. ​ Protein Buffering: Uses intracellular proteins (e.g., hemoglobin) to neutralize pH changes. ​ Respiratory Buffering: Adjusts ventilation to manage CO₂ levels. ​ Renal Buffering: Secretes hydrogen ions and reabsorbs bicarbonate in the kidneys. Cancer Test Review Test Review Questions 1. What is the difference between benign and malignant tumors? ​ Benign Tumors: ○​ Grow slowly. ○​ Well-defined capsule. ○​ Not invasive. ○​ Well-differentiated cells that resemble the tissue of origin. ○​ Do not metastasize. ​ Malignant Tumors: ○​ Grow rapidly. ○​ Lack a capsule and invade surrounding tissues. ○​ Poorly differentiated cells. ○​ Can spread distantly (metastasis). 2. What is carcinoma in situ (CIS)? ​ A pre-invasive epithelial tumor of glandular or squamous origin. ​ Characteristics: ○​ Has not invaded the basement membrane or surrounding stroma. ○​ Can remain stable, progress to invasive cancer, or regress and disappear. ○​ It is not malignant. ○​ Three prognosis: 1.) Can remain stable for a long time. 2.) Can progress to invasive and metastatic cancers. 3.) Can regress and disappear. 3. Explain genetic mechanisms for carcinogenesis. ​ Key Mechanisms: ○​ Activation of proto-oncogenes: Leads to oncogene formation, promoting uncontrolled cell growth. ○​ Mutation of tumor-suppressor genes: Reduces the ability to inhibit cell growth. ○​ Mutations preventing apoptosis: Allow tumor cells to survive and proliferate. ​ Caretaker Genes: Responsible for DNA repair. Loss of function increases mutation rates. ​ Epigenetic Silencing: Changes in gene expression without altering DNA sequence. ○​ 1.) Secretion of growth factors (autocrine stimulation). 2.) Mutation in the Ras intracellular signaling protein: That regulates cell growth.. 3.) Inactivation of retinoblastoma protein (Rb) tumor suppressor. 4.) Activation of protein  kinases that drive cell cycle. 5.) Mutation in the TP53 (tumor-suppressor gene)- Suppression of normal apoptosis. Chromosome Instability (CIN): Appears to be increased in malignant cells. Malfunction in chromosomal segregation at mitosis. Chromosomal loss can accelerate the loss of tumor suppressor genes and the overexpression of oncogenes. ​ Oncomirs: Are miRs that stimulate cancer development and progression. Chromosome instability: Increased in malignant cells causing high rate of chromosome loss, heterozygosity, and amplification. ​ Telomeres: Are protective caps on each chromosome that are held in place by a telomerase. Cancer cells can activate (“switch on”) telomeres, leading to continued division. 4. How does inflammation contribute to cancer? ​ Chronic inflammation promotes tumor development by: ○​ Stimulating cell proliferation. ○​ Increasing angiogenesis (blood vessel formation). ○​ Producing cytokines and growth factors. ○​ Cancer development and progression involve tissue microenvironment or stroma ​ Infiltration immune cells cause chronic inflammation, creating a permissive tumor-progressing environment. ​ Examples of inflammation-related cancers: ○​ Ulcerative colitis: Increased risk of colon cancer. ○​ H. pylori infection: Associated with stomach cancer. ○​ Susceptible organs are: GI, Thyroid gland, Liver, Prostate, urinary bladder Pleura, and skin ○​ Tumor-Associated Macrophage (TAM): Is the key cell that promotes tumor survival. a.) It blocks cytotoxic T cells and natural killer (NK) cell functions. b.) Produce cytokines that promote tumor growth and spread. c.) Secrete angiogenesis factor that promotes blood vessel creation and blood supply 5. What is the difference between active and passive immunotherapy? ​ Active Immunotherapy: ○​ Stimulates the body’s immune system to fight cancer. Active immunization with tumor antigens to elicit or enhance the immune response against a particular cancer. It uses vaccines or other treatments to trigger the immune system to attack cancer cells or pathogens. ○​ Example: Vaccination with tumor antigens (cancer vaccines), immune checkpoint inhibitors, oncolytic viruses. ​ Passive Immunotherapy: ○​ Uses external immune components like antibodies. Uses pre-formed antibodies or immune cells to fight disease. It DOES NOT generate  immunological memory- the immune system does not develop a memory of the disease. ○​ Example: Injection of monoclonal antibodies targeting tumor antigens, Cytokines, adoptive cell transfer 6. Which viruses are commonly associated with cancer? ​ Human Papillomavirus (HPV): Cervical, anal, and oropharyngeal cancers. ​ Epstein-Barr Virus (EBV): Nasopharyngeal cancer, Hodgkin lymphoma. ​ Hepatitis B and C Viruses (HBV and HCV): Liver cancer. ​ Kaposi Sarcoma Herpesvirus (KSHV): Kaposi sarcoma. 7. What are the clinical manifestations of cancer? ​ Paraneoplastic Syndromes: Symptoms caused by biological substances released from tumors (e.g., hormones) or immune responses. They can be life threatening ​ Cachexia: Severe malnutrition with symptoms including: ○​ Anorexia, weight loss, muscle wasting, anemia, and early satiety. ○​ Other S/S can include: Difficulty walking, swallowing (dysphagia), muscle wasting, slurred speech, memory loss, vision problems, sleep disturbances, dementia, seizures, sensory loss in limbs. 8. Explain cancer staging and what the stages mean. ​ Stages: 1.​ Stage 1: Cancer confined to its organ of origin. 2.​ Stage 2: Locally invasive. 3.​ Stage 3: Spread to regional structures, such as lymph nodes. 4.​ Stage 4: Spread to distant sites (metastasis). 9. Which lifestyle factors increase cancer risk? ​ Tobacco Use: Linked to lung, mouth, esophagus, pancreas, and other cancers. ​ Diet/Nutrition: High red and processed meat intake linked to colorectal cancer. ○​ Primary diet potential donors of DNA methylation include: a.) Folate b.) Choline. c.) B Vitamins. ○​ Dietary Factors: Altered micro-ribonucleic (miRNA) predisposes an individual to cancer. Suppressing cancer stem cell renewal decreases the risk of cancer. Consuming kiwi fruits, cooked carrots, or supplemental coenzyme Q10 improves DNA repair. It decreases the chance of cancer. ​ Obesity: Associated with breast, colorectal, and pancreatic cancers. ○​ Increases insulin-resistance-producing hyperinsulinemia. Insulin promotes insulin-like growth factor 1 (promotes normal growth of bones and tissues). Adipose tissue secretes adipokines. Circadian disruptions (body’s natural clock) may affect cancer growth ​ Alcohol Consumption: Increases the risk of oral, liver, and breast cancers.  ○​ A combination of cigarette smoking and alcohol consumption increases a person’s risk for malignant tumors. ​ Physical Inactivity: Physical activity Decreases the risk of cancer by Decreasing: ○​ a.) Insulin and insulin-like growth factors, ○​ b.) Obesity ○​ c.) Inflammatory mediators, ○​ d.) Circulating sex/metabolic hormones. It improves immune function. Physical activity reduces the risk for breast, colon, and endometrial cancers, independent of weight changes. After a cancer diagnosis, physical activity is associated with improved cancer-specific and overall survival with early stage breast, prostate, and colorectal cancers. ​ Air Pollution: Linked to lung cancer ​ ○​ Smog: Increases daily mortality. ○​ Particle Pollution: Causes pulmonary inflammation, oxidative stress and oxidation of DNA, nonfatal heart attacks, irregular heartbeat, and decreased lung function. ○​ Indoor Pollution (cigarette smoke, radon): Is considered worse than outdoor pollution. ​ Ionizing Radiation: Is emitted from X-ray machines, radioisotopes, etc. Associated with acute leukemias. They enter cells and deposit energy in tissues: Oncogene activation, tumor-suppressor genes deactivation, chromosomal aberrations and DNA damage, cell transformation, non-targeted/bystander effects ​ Ultraviolet Radiation ​ Electromagnetic Radiation ​ Infection: Is in an important contributor to cancer ○​ HPV: Cervical cancer ○​ Hep B and C: Liver cancer ○​ H. Pylori: Stomach cancers. ○​ Epstein-Barr Virus (EBV): Cancers of the nasopharynx and stomach, Hodgkin disease, and Non-Hodgkin lymphoma ○​ Herpes virus type : Kaposi sarcoma ○​ Human T-cell lymphotropic virus type 1: Leukemia and Lymphoma ​ Sexual and reproductive behaviors and HPV: HPV is the most common sexually transmitted virus. ​ Chemicals and Occupational Hazards: ○​ a.) Asbestos: Mesothelioma and lung cancer ○​ b.) Dyes, rubber, paint, aromatic amines: Bladder Cancer ○​ c.) Explosives, rubber cement, and dyeing industries: Leukemia ○​ d.) Heavy metals ○​ e.) Diesel exhaust In Utero: Conditions that increase susceptibility to cancer include: a.) Prenatal and early life exposure. b.) Parental exposure before conception. c.) Nutrition and Diethylstilboestrol (DES) exposure. d.) Gene and Environmental interactions: Avoid sun exposure during peak hours, cover the skin, increase physical exercise, and avoid high-risk sexual practices. 10. What are common cancers in children, and what are their characteristics? ​ Common Childhood Cancers: Leukemias, central nervous system tumors, lymphomas, and sarcomas. ​ Characteristics: ○​ Often fast-growing and diagnosed during peak growth periods and have metastasized before a diagnosis is made. Pedi tumors are more aggressive than in older adults. ○​ Originate from the mesodermal germ layer (connective tissue, bone, blood). ​ Causes: ○​ 1.) Genetic Factors: Oncogenes and tumor-suppressor genes. a.) Chromosome aberrations and single gene defects. Such as Down Syndrome (Trisomy 21) linked to Leukemia. Familial Risk: Wilms tumor, Retinoblastoma, WAGR syndrome ○​ 2.) Congenital Factors: a.) Chromosome alterations. b.) hereditary syndromes, c.) Immune deficiency disorders. d.) Congenital malformation syndromes. ○​ 3.) Environmental Factors: ​ a.) Prenatal Exposure:Prenatal Drug exposure: Diethylstilbestrol (DES) pesticides, environmental toxins. ​ b.) Childhood Exposure: Childhood exposure to drugs, ionizing radiation, viruses: Drugs like anabolic androgenic steroids, cytotoxic chemotherapy, immunosuppressive agents. Pesticides-linked to leukemias. Viruses: Epstein-Barr Virus, HIV Genetics Test Review Test Review Questions 1. What are DNA and RNA, and what are their roles? ​ DNA (Deoxyribonucleic Acid): ○​ Composed of a pentose sugar (deoxyribose), a phosphate group, and four nitrogenous bases: adenine (A), thymine (T), cytosine (C), and guanine (G). ○​ DNA is structured as a double helix and is the genetic material located in chromosomes. ○​ Function: Stores genetic information and provides the code for synthesizing proteins. ​ RNA (Ribonucleic Acid): ○​ Similar to DNA but single-stranded, with uracil (U) replacing thymine.  ○​ Types: Messenger RNA (mRNA), Transfer RNA (tRNA), and Ribosomal RNA (rRNA). ○​ Function: Facilitates protein synthesis through transcription (DNA to mRNA) and translation (mRNA to proteins). 2. What are common genetic disorders, their symptoms, and associated conditions? ​ Down Syndrome: ○​ Cause: Trisomy 21 (extra copy of chromosome 21). ○​ Symptoms: Mental challenges, low nasal bridge, epicanthal folds, protruding tongue, short stature, poor muscle tone. ○​ Associated Conditions: Congenital heart disease, respiratory infections, Alzheimer's disease, leukemia. ​ Turner Syndrome: ○​ Cause: Single X chromosome (45,X). ○​ Symptoms: Short stature, webbed neck, widely spaced nipples, absence of ovaries (sterile). ○​ Treatment: Estrogen therapy during adolescence. ​ Klinefelter Syndrome: ○​ Cause: Extra X chromosome(s) (e.g., 47,XXY). ○​ Symptoms: Male appearance, gynecomastia, small testes, sparse body hair. ○​ Associated with: Increased maternal age. 3. What is the difference between autosomal dominant and autosomal recessive inheritance? ​ Autosomal Dominant Inheritance: ○​ Characteristics: Disease is rare. ​ Affects males and females equally. Males and females are equally likely to pass the gene to his or her offspring. ​ No generational skipping. ​ Offspring of an affected parent have a 50% chance of inheriting the condition: One half of an affected heterozygous parent will express the condition (all or none of the children may have the condition. When one parent is affected by an autosomal dominant disease and the other is normal, the occurrence and recurrence risks for each child is one half. ○​ Examples: Huntington's disease, Marfan syndrome. ​ Autosomal Recessive Inheritance: ○​ Characteristics: ​ Appears in children, not parents. ​ Offspring of two carrier parents have a 25% chance of being affected. One quarter ¼ of the offspring are normal, and one-half are carriers.  ○​ Examples: Cystic fibrosis, sickle cell anemia. Cystic Fibrosis: Salt imbalance that results in abnormally thick, dehydrated mucus. The lungs and pancreas are affected; the person does not survive past 40 years old. 4. What genetic conditions should be considered during family history collection? ​ Common Genetic-Influenced Conditions: ○​ Cardiovascular diseases: Coronary artery disease (CAD), myocardial infarction (MI). ○​ Neurological disorders: Alzheimer's disease, schizophrenia. ○​ Cancers: Breast, colon, and prostate cancers. ○​ Metabolic diseases: Type 2 diabetes, obesity. 5. What are the types of epigenetic modifications, and how do they influence gene expression? ​ Epigenetics are chemical modifications of DNA sequences that alter the expression of genes, resulting in disease and phenotypic variations based on genetics. Types of Epigenetic Modifications: ​ DNA Methylation:Causes a gene to be inactive or silent ○​ Adds methyl groups to DNA, silencing genes. ○​ Example: Tumor suppressor gene silencing in cancer. ​ Histone Modification: Increases or decreases bond between DNA and histones. ○​ Alters the interaction between DNA and histones, affecting gene accessibility. ○​ Examples: Acetylation increases gene expression; deacetylation decreases it. ​ MicroRNAs (miRNAs):Changes signaling pathways. ○​ Regulate gene expression post-transcriptionally. ○​ Influence cancer progression and metabolic pathways. ​ Embryonic Stem cells: Can become any cell cell that is needed for development. It ensures that specific genes are expressed only in the cells and tissue types in which their gene products are needed. ○​ Helps determine the fate of each cell; that is, the type of cell it becomes, such as neuron, or fibroblast. 6. How do Prader-Willi and Angelman syndromes demonstrate genomic imprinting? ​ Genomic imprinting: Process of gene silencing, in which genes are predictably silenced. Transcriptionally silenced genes are usually heavily methylated. ​ Both syndromes involve a deletion of 4 million base pairs on chromosome 15. ​ Prader-Willi Syndrome: ○​ Cause: Deletion inherited from the father.  ○​ Symptoms: Obesity, hypotonia, small hands and feet, mild intellectual disability, short stature, mild-to moderate mental retardation, hypogonadism ​ Angelman Syndrome: ○​ Cause: Deletion inherited from the mother. ○​ Symptoms: Severe intellectual disability, ataxic gait, seizures. 7. What is the difference between incidence and prevalence? ​ Incidence: Number of new cases of a disease within a specific time period (typically 1 year) divided by the number of individuals in a population. ​ Prevalence: Proportion of the population affected by a disease at a specific point in time. 8. What are multifactorial inheritance traits, and what conditions follow this model? ​ Traits: Result from the combined effects of multiple genes and environmental factors. ​ Threshold Model: Disease manifests only when a certain genetic and environmental threshold is surpassed. ​ Examples: ○​ Congenital Conditions: Neural tube defects, cleft lip/palate, congenital heart disease. ○​ Adult-Onset Conditions: Hypertension, type 2 diabetes, cancer, Alzheimer’s disease. 9. How do genetic and environmental factors interact in obesity and Alzheimer’s disease? ​ Obesity: ○​ Genetic Factors: Leptin gene mutations, heritability estimates (60-80%). ○​ Environmental Factors: High-calorie diet, sedentary lifestyle. ○​ Study Evidence: Twin and adoption studies confirm genetic influence. ​ Alzheimer’s Disease: ○​ Genetic Factors: ​ Early-onset: Mutations in PS1, PS2, APP genes. ​ Late-onset: APOE-ε4 allele increases risk. ○​ Environmental Factors: Diet, physical activity, cognitive engagement. 10. What research methods help disentangle genetic and environmental effects? ​ Twin Studies: Compare monozygotic (identical) and dizygotic (fraternal) twins to assess heritability. ​ Adoption Studies: Examine traits in adopted individuals compared to biological and adoptive families. Multifactorial Disorders: Coronary Artery Disorder (CAD): Potential MI caused by atherosclerosis in the arteries. Potential CVA. ​ Risk Factors: a.) More affected relatives exist. b.) Females more at risk. c.) Age of onset younger than 55 years old. ​ Autosomal dominant familial hypercholesterolemia, high fat diet, lack of exercise, smoking, and obesity increase risk. Hypertension: Risk factor for heart disease, stroke, kidney disease. 20-40% of blood pressure variations are genetic, meaning environmental factors are important. ​ Environmental factors: Sodium intake, lack of exercise, stress, and obesity. ○​ Gene Involvement: RAAS system, nitric oxide, and kallikrein-kinin system Breast Cancer: Affects 12% of women who live to 85 years of age. ❖​ If a woman has a first-degree relative with breast cancer, her risk doubles (X2). Recurrence risk increases if the age of onset in the affected relative is early and if the cancer is bilateral. ❖​ An Autosomal dominant form (5-10%) has been linked to chromosomes BRCA2 and BRCA1. ​ This form causes 50-80% lifetime risk of developing breast cancer and increases the risk for Ovarian Cancer. Obesity: BMI >30. Substantial risk factor for heart disease, stroke, cancer, (prostate, breast, colon) and type 2 diabetes. Adoption Studies: Body weight of adopted people correlated with their natural parents BW. Genetics has an effect on body weight (BW). Gene for leptin and its receptors are related to obesity. Colorectal Cancer: The risk is 2-3X higher than the general population in those with an affected first-degree relative. Clusters in families. ​ Inherited adenomatous polyposis coli (APC) gene mutation plays a vital role in familial adenomatous polyposis. ​ Somatic mutations are involved in common colon cancers. ​ Environmental Factors: High fat and low fiber diet. Alzheimer Disease (AD): Results in progressive dementia and loss of memory. Produces amyloid plaques and neurofibrillary tangles.. ​ Risk Factor: First Degree relatives: Risk doubles. ​ Primary Cause: Presenilin 1 (PS1), Presenilin 2 (PS2) and amyloid-beta precursor protein (APP) gene. ​ Mutations for late onset AD: Allelic variation (E2,E3,and E4) in apolipoprotein E (APOE). Copy of the E3 allele: At least 2-5X at greater risk. Two copies of the E4 allele: at least 5-10X more likely to develop AD. Alcoholism : Risk is 3-5 times higher in the individual with an alcoholic parent ​ Adoption Studies: 1.) Alcoholic parent. Offsprings of an alcoholic parent, even when raised by nonalcoholic parents, have a 4 fold increased risk. Nonalcoholic parent:  Offspring of nonalcoholic parents, when raised by alcoholic parents, did not have an increased risk. ​ Genes: 1.) ALDH2*2- much LESS likely to become alcoholics. Allelic variation of gamma-aminobutyric acid (GABA) INCREASED risk. Bipolar Affective Disorder (Manic Depressive Disorder): ​ Risk Factor of First degree relative: Risk increases 5-10% as compared to risk of ½. ​ Twin and family studies show 60% of bipolar risk is due to genetic factors; 30% of the risk of unipolar disorder (major depression) is due to genetics. ​ Schizophrenia and bipolar disorder are heterogenous-reflect the influence of numerous genetic and environmental factors, making the phenotype hard to identify. Schizophrenia: Risk Factor: ​ One Affected Parent: Recurrence risk among offspring of one affected parent is 10 times higher than the general population. ​ One Affected Sibling and parent: Risk is 20%. ​ Two Affected Parents: 50% risk ​ Brain-expressed genes whose products interact with Glutamate receptors have been implicated