PATHO 370 MIDTERM EXAM REVIEW 2023 COMPLETE

PATHO 370 MIDTERM EXAM REVIEW 2023 COMPLETE. Stress: a state manifested by a specific syndrome of the body developed in response to any stimuli that made an intense demand on it. Influenced by genetics, socioeconomic status, prior susceptibilities, pre-existing health status, allostatic state and ability to manage stress General Adaptation Syndrome (GAS): Involves 3 STAGES: • Alarm stage: stimulation of the SNS, resulting in release of catecholamines & cortisol • Resistance stage: body selects the most effective and economic channels of defense; cortisol levels present in first stage drop b/c they are no longer needed • Exhaustion stage: resources are depleted & signs of “wear & tear” or systemic damage appear Acute versus Chronic Stress: • Acute stress: associated with the ANS, the fight or flight response; persons with preexisting heart disease can have complications with acute stress response that can lead to arrhythmias; in healthy individuals acute stress response can redirect attention from behaviors that promote health and interrupt compliance with medication regiments & exercise programs • Chronic stress: it has been linked to health disorders including diseases of the cardiovascular, gastrointestinal, immune, & neurological systems; sympathetic activity & cortisol are elevated Physiological stress & psychosocial stress: • Physiological stress: stress-induced changes in body functions; detected by body’s normal regulatory sensors; the body alters function to restore normal balance; when normal balance is restored, negative feedback stops the reaction • Psychosocial stress: Directly affects central nervous system; turns on the stress responses, even when the body’s internal sensors have not detected an imbalance Adaptation & Coping Mechanisms: Adaptation: the ability to respond to challenges of physical or psychological homeostasis & to return to a balanced state. • Influenced by previous learning, physiologic reserve, time, genetic endowment, age, health status & nutrition, sleep-wake cycles, & psychosocial factors. Coping Mechanisms: • Guided Imagery: scene visualization • Music therapy: listening to music to ease anxiety or stress • Massage therapy: manipulation of soft tissues to promote relaxation & relief of muscle tension • Biofeedback: technique in which individual leans to control physiologic functioning Catecholamines Epinephrine: Released from the adrenal medulla. • Increases heart rate, BP and cardiac output bronchodilation. • Increases glycogenolysis and elevates blood glucose levels • Supplementation and prolongation of fight or flight response, pupil dilation, dry mouth, increased blood coagulability. Norepinephrine: Released from postganglionic fibers. • Constricts blood vessels and raises blood pressure. • Reduces gastric secretions. • Increases night and far vision Adrenal Cortical hormones Cortisol: Primary glucocorticoid, found in adrenal cortex • Alteration in glucose, fat, and protein metabolism; • Suppression of inflammatory & immune responses Aldosterone: Primary mineralocorticoid • reabsorption of sodium and water • Increases blood pressure Chapter 4 Cell Injury, Aging, and Death Cellular response to Stress/Adaptation to stress: cells may adapt by undergoing changes in size, number, and type. These changes may lead to atrophy, hypertrophy, hyperplasia, metaplasia and dysplasia. Cellular stresses also include intracellular accumulations & storage of products in abnormal amounts. Reversible Cell Injury: Hydropic swelling: water accumulation. Malfunction of Na-K pump with accumulation of Na+ within the cell. Any injury that results in loss of energy (ATP) will also result in swelling. Generalized swelling of cells in organs can lead to increase in size and weight; “megaly” Intracellular Accumulations: Excess accumulations of substances in cells. Leads to cellular injury due to: toxicity, immune response and taking up cellular space. Ex. Fatty liver Cellular changes: Atrophy: decrease in cell size (cell shrinks). Cells that are atrophied reduce oxygen consumption and other cellular functions by decreasing the size and number of their organelles. ↓ functional demand. General causes: • Disuse: reduction in muscle use • Denervation: atrophy in muscles of paralyzed limbs • Loss of endocrine stimulation: in relationship with disuse atrophy • Inadequate nutrition and ischemia: cells decrease size and energy requirements due to inadequate nutrition and decreased oxygen. Hypertrophy: increase in cell size and with it an increase in the amount of functioning tissue mass. ↑ functional demand. Cause increased cell protein content • Pathogenic Hypertrophy: thickening of urinary bladder and myocardial hypertrophy. Hyperplasia: increase in the number of cells in an organ or tissue due to mitosis. Occurs in tissues such as epidermis, intestinal epithelium, and glandular tissue. Causes: usually in response to increased physiologic demands or hormonal stimulation, persistent cell injury, chronic irritation of epithelial cells. ↑ functional demand. Ex: • Breast and uterine enlargement during pregnancy • regeneration of the liver that occurs after partial hepatectomy • when removing a kidney, the other kidney with experience compensatory hyperplasia. Most forms on NONPHYSIOLOGICAL HYPERPLASIA are due to excessive hormonal or the effects of growth factors on target tissues. Metaplasia: a reversible change in which one adult cell type is replaced by another adult cell type. Usually occurs in response to irritation and inflammation. Fully reversible when injurious stimulation is removed. Dysplasia: A deranged cell growth of a specific tissue that results in cells that varies in size, shape, and organization. Strongly implicated as a precursor of cancer; reversible change. Cellular Injury: Reversible: Although impairing cell function, does not result in cell death. 2 patterns can be observed under microscope: • Cellular swelling: occurs with impairment of Na+/K+ pump, usually as a result of hypoxic cell injury • Fatty change: linked to intracellular accumulations of fat; reversible, usually indicates severe injury. Irreversible: Cell death or necrosis can occur in irreversibly damaged cells. Usually occurs as a consequence of ischemia or toxic injury. Necrosis: cell death and degradation; UNREGULATED death caused by injuries to cells; cell swells and ruptures; INFLAMMATION results.  It occurs when the injury is too severe or prolonged to allow adaptation. Usually from a disruption in blood supply  Cells may undergo liquefaction (brain), coagulation (heart), fat (pancreas), or caseous (lungs)  Local and systemic indicators of cell death: Pain, elevated serum enzyme levels, inflammation (fever, increased WBC, malaise), loss of function Gangrene: Large area of necrotic tissue. Results from interruption of blood supply to a particular part of the body. Types:  Dry gangrene: lack of arterial blood supply but venous flow can carry fluid OUT of tissue  Wet gangrene: lack of venous flow lets fluid ACCUMULATE in tissue  Gas gangrene: Clostridium infection produces toxins and bubbles.  Fournier’s gangrene: Affects perineal, perianal, genital areas Apoptosis (Programmed cell death): necessary death of cells; a form of cell death necessary to make way for new cells and to remove cells “worn out” cells; NORMAL PROCESS IN THE BODY  Cells TURN ON their own enzymes inside the cell, digest their own proteins and DNA is then destroyed by WBCs. Triggers intracellular cascades and activates a cellular suicide response  Does not cause inflammation Hypoxic and ischemic changes: -Hypoxia: an inadequate supply of oxygen to tissue that is below physiologic levels despite adequate perfusion of tissue by blood. Can result from inadequate amount of oxygen in air, respiratory disease, ischemia, anemia, edema, or inability of cells to use oxygen.  Causes ATP depletion or “POWER FAILURE”; when aerobic metabolism stops, less ATP is produced, Na+/K+ pump is impeded, cell swells up with water, lactic acid is produced as a result of ANAEROBIC metabolism.  Ischemic injury is reversible, but cell death occurs when plasma, mitochondrial, and lysosomal membranes are critically damaged.  Ischemia-reperfusion injury causes calcium overload, formation of free radicals, Subsequent inflammation. Ischemia: Decreased blood supply to a body organ or part usually due to functional constriction or actual obstruction of a blood vessel. In contrast to pure HYPOXIA, which depends on the oxygen content of the blood & affects ALL CELLS in the body, ISCHEMIA commonly depends on blood flow through limited numbers of blood vessels & produces LOCAL TISSUE injury Free Radicals: highly reactive chemical species with an unpaired electron in the outer orbit of the molecule.  ANTIOXIDANTS are natural and synthetic molecules that remove free radicals from the body Cellular Aging: - Replicative senescence: cells have limited capacity for replication -Genetic influence -Accumulation of Environmental & Genetic damage: cell life span may be determined by a balance between cellular damage resulting from metabolic events occurring within the cell and molecular responses that repair the damage -Syndromes of Premature aging (PROGERIA): usual aging but with much earlier ages of onset and more rapid rates of progression Chapter 7 Neoplasia Cancer-2nd leading cause of death in the developed world Oncology: the study or science of neoplasms Clinical oncology: deals with neoplastic disorders in the clinical setting; primarily in terms of diagnosis & treatment  Benign tumors usually are named by adding the suffix – oma to the tissue type from which the growth originated Neoplasm: an abnormal mass of tissue in which the growth exceeds and is uncoordinated with that of the normal tissues. (means new growth) • Malignant neoplasm = cancer • Benign growth is generally easily cured • Cancer is associated with altered expression of cellular genes Malignant vs Benign Malignant Tumor: Can kill host if untreated. Confirmed by invasive or metastasizing nature. No signals to “die” so achieve a kind of immortality in that they are capable of unlimited replication. Lose their differentiated features and contribute poorly or not at all to the function of their tissue (more undifferentiated = more malignant) • Tissue-specific differentiation (does not closely resemble tissue type of origin) • Increased anaplasia = aggressive malignancy • Grows rapidly, may initiate tumor vessel growth (angiogenesis) • Frequently necrotic and dysfunctional • Serve no useful purpose • Have cells that break loose and travel to distant sites to form metastases • Do not occur in response to an appropriate stimulus • Do not obey the laws of normal growth • “-carcinoma,” “-sarcoma” = malignant tumors • Exceptions (all the following are malignant): Lymphomas, Hepatomas, Melanomas Benign Tumor: Does not have potential to kill host, but may be life-threatening because of its location. Doesn’t invade adjacent tissue or spread to distant sites • Many are encapsulated and more closely resembles original tissue type • Grows more slowly with little vascularity • Rarely necrotic and often retains original function • “-oma” suffix = benign tumor (e.g., adenoma) Factors - Possible Causes linked to Cancer: The cause can be viewed from 2 perspectives genetic and external and more contextual factors: age, heredity, and environmental agents. Both mechanisms contribute to cancer and progress over time. • Multiple, not one disease • Heredity- Breast cancer is a good example • Hormones – Breast, ovarian, and endometrium cancer • Obesity- Breast, endometrial, and prostate cancers. May relate to increased sex hormone levels (androgens and estrogens) • Immune surveillance hypothesis- Impairment in immune system shows increased cancer risk • Chemicals- smoking, pollution, industrial waste, alcohol, fatty foods, fried foods, red meat. • Radiation- ionizing radiation, gamma radiation, even sun exposure (UV radiation does not penetrate very deep in body) • Viral/microbial agents- 4 in particular= HPV, Epstein-Barr, HBV, and human herpes virus 8 Genetic Mechanism of Cancer Carcinogen: Potential cancer-causing agent Proto-oncogene: Enhance growth-producing pathways • Normal cellular genes that can be transformed into oncogenes by activating (gain-offunction) mutations • Gain-of-function mutations code for: growth factors, receptors, cytoplasmic signaling molecules and nuclear transcription factors Oncogene: Proto-oncogene in its mutant overactive form Tumor suppressor gene: Inhibits cell proliferation. Cancers may arise when tumor suppressor gene function is lost or abnormally inhibited From Proto-Oncogene to Oncogene Proto-oncogenes become activated oncogenes when mutations alter their activity so that proliferation-promoting signals are generated inappropriately • Oncogenes introduced to host cell by retrovirus • Proto-oncogene within cell suffers a mutagenic event • DNA sequence may be lost/damaged and allows proto-oncogene to become abnormally active • Error in chromosome replication causes extra copies of proto-oncogene in the genome Tumor-Suppressor Genes Rb gene: Normally “master brake” for the cell cycle. • blocks/stops cell division • Binds transcription factors • Inhibits these factors from transcribing genes that initiate cell cycle • Normally can be induced to release transcription factors when sufficiently phosphorylated • An inactivating mutation of the Rb gene removes restraint on cell division and replication occurs P53 Gene: Most common tumor-suppressor gene defect identified in cancer cells • More than ½ of all types of human tumors lack functional p53 • inhibits cell cycling • Accumulates only after cellular (DNA) damage • Binds to damaged DNA and stalls division to allow DNA to repair itself • May direct cell to initiate apoptosis • Mutated or damaged p53 allows genetically damaged/unstable cells to survive and continue to replicate • Chemotherapy/radiation: Damages target/cancer cell to trigger p53-mediated cell death. Cancer cells that lack functional p53 may be resistant to chemotherapy/radiation BRCA1 and BRCA2 Genes: Tumor suppressor genes associated with breast cancer • Family history and inherited defect in BRCA1 increases risk of breast cancer Multistep Nature of Carcinogenesis Initiation: Genetic mutations: inappropriately activate proto-oncogenes; inactivate tumor suppressor genes • Proliferation: Required for cancer development (nonproliferating cells cannot cause cancer) • Each type of cancer has its own combination of mutations that lead to malignancy Promotion: Stage during which mutant cell proliferates • Activation of another oncogene • Inactivation of tumor suppressor gene • Nutritional factors and infection • Regulated by many hormonal growth factors • Cancer cells produce telomerase which allows immortality in cancer cells Progression: Mutant, proliferating cells begin to exhibit malignant behavior • Cells whose phenotype gives them a growth advantage proliferate more readily • Evolved tumor cells differ significantly from the normal tissue • Progress to malignant characteristics Metastasis: Process by which cancer cells leave their tissue of origin and initiate new colonies of cancer in distant sites • Specialized enzymes and receptors enable them to escape their tissue of origin and metastasize • Specialized enzymes and receptors allow them to replicate at new site Angiogenesis: Process by which cancer tumor forms new blood vessels in order to grow. Usually does not develop until late stages of development. Inhibition is important therapeutic goal. Grading and Staging: To predict clinical behavior of malignant tumor and guide therapeutic management Grading: histologic characterization of tumor cells. Greater degree of anaplasia = greater degree of malignant potential Staging: Location and patterns of spread within the host. Tumor size, extent of local growth, involvement and metastasis. Results of staging determine treatment modality TNM system most widely used  T-tumor  N-nodes involved  M-metastasis Clinical manifestations of cancer:  Anorexia and cachexia: overall weight loss due to increased metabolic rate, Nausea/vomiting and loss of appetite (anorexia)  Fatigue and sleep disorders: symptoms often remain for years after treatment  Paraneoplastic syndromes: manifestations of disease in sites not directly affected by cancer  Pain: May be due to metastasis (tissue destruction/inflammation)  Bone marrow suppression: leads to anemia, leukopenia, and thrombocytopenia, anemia CAUTION acronym for adults Change in bowel or bladder habits A sore that does not heal Unusual bleeding or discharge Thickening or lump in breast or elsewhere Indigestion or difficulty swallowing Obvious change in wart or mole Nagging cough or hoarseness CHILDREN acronym for children Continued, unexplained weight loss Headaches with vomiting in the morning Increased swelling/persistent pain in bones/joints Lump or mass in abdomen, neck, or elsewhere Development of whitish appearance in pupil Recurrent fevers not caused by infections Excessive bleeding or bruising Noticeable paleness or prolonged tiredness Screening for Cancer  The earlier the discovery, the better the curability  Physical exam  Laboratory tests (tumor markers help stage the cancer)  X-rays  Biopsy  Pap smears, mammography, PSA (used as a marker in prostate cancer), colorectal exams, self exams, etc. Cancer Management  Early detection best prognosis for cure  Mainstays of therapy: surgery, radiation therapy and drug therapy/chemotherapy  Emerging therapies: immunotherapy, targeted molecular therapies and stem cell transplantation Chapter 9 Inflammation and Immunity Normal immunity  Protective functions (against invasion of foreign substances, microorganisms and toxins)  Protects against proliferation of cancer cells, destroys abnormal/damaged cells  Healing process and inflammation  Has the ability to distinguish self from non-self. Mononuclear Phagocyte System - Composed of dendritic cells, monocytes and macrophages.  Monocytes migrate to organs to become macrophages (lung- Alveolar, brain- Microglial, Liver-Kupffer cells, neck- cervical lymph nodes, spleen- macrophages, kidneymesangeal phagocytes, joint- cynovial A cells. Blood- monocytes, lymph node- resident and recirculating macrophages, skin- Langerhans cells, precursors in bone marrow)  Macrophages and dendritic cells- First immune cells to encounter pathogen or foreign antigen. Secrete cytokines to communicate news of invasion to other cells.  Dendritic cells -Capture and present antigens. Located in subcutaneous and submucosal tissue.  Macrophages - Powerful phagocytes. Clean up dead neutrophils and inflammatory debris. Have a role in wound healing. Lymphoid System Primary organs: Bone marrow and Thymus gland where lymphocytes develop. Lymphocytes are produced from stem cells. T lymphocytes migrate to thymus to develop and B cells and NK cells stay in marrow to develop. NK cells function in innate immune responses, found mainly in the circulation and spleen. T and B lymphocytes, once mature migrate to secondary lymphoid organs for activation by antigens. Secondary organs: Lymph nodes, Spleen, Tonsils, Peyer patches in the intestine. Leukocytes (WBC): Primary cells of immune system. Formed from stem cells in bone marrow. Development is influenced by cytokines. Total WBC count 3500 to 10000 ul. Types: • Granulocytes: Neutrophils, Eosinophils, Basophils • Agranulocytes: Lymphocytes, Monocytes/macrophages