Key Terms

Chapter 19: Coagulation Disorders
Activated partial thromboplastin time (APTT) Laboratory measurement of the intrinsic and common coagulation pathways. The normal range is 26 to 42 seconds. Prolonged in hemophilia A and B. Used to guide heparin therapy. Antithrombin III A circulating anticoagulant that functions to inactivate thrombin. Arterial spiders Bright-red lesions with a pulsatile center and threadlike extensions radiating 5 to 10 mm in length. Bleeding time Laboratory procedure that tests both vascular status and platelet number and function, but does not differentiate between the two. A controlled puncture incision is made in the free-hanging earlobe (Duke method) or on the volar surface of the forearm (Ivy method). The length of time for bleeding to cease is recorded. Normal bleeding time is 3 to 7 minutes. Clotting factors Plasma proteins that circulate in the blood (except III and IV) as inactive molecules and complete the clotting process when activated to form a stable fibrin clot (secondary hemostasis). All are designated by a Roman numeral from I to XIII (there is no number VI). Components of the blood coagulation system (1) Blood vessels (contain the blood and constrict following injury to allow formation of the platelet plug); (2) platelets (adhere to the exposed collagen and form a temporary platelet plug [primary hemostasis]); and (3) the 12 clotting factors (complete the clotting process when activated to form a stable fibrin clot [secondary hemostasis]). Contact factors Factors including prekallikrein, high molecular weight kininogen (HMWK), and factors XII and XI; activated at the time of injury by contact with tissue surfaces; they also play a role in the dissolution of clots once they are formed. Disseminated intravascular coagulation (DIC or consumption coagulopathy) A complex syndrome characterized by diffuse thrombosis and occlusion of the microvasculature with an accompanying fibrinolysis. Patients with DIC clot and bleed simultaneously, and unless the underlying cause is removed, they continue to do so and may die. DIC is initiated by the release of tissue thromboplastin (tissue Factor III) secondary to tissue destruction (e.g., abruptio placentae, malignancies, chemotherapy, hemolytic transfusion reaction, burns, crushing injury) with an initiation of the extrinsic coagulation pathway. DIC can also be initiated by the intrinsic coagulation pathway, as in sepsis and shock. Diagnostic tests reveal prolonged PT, PTT, TT, and fibrin split products (FSP). Ecchymosis (bruise) An area of extravasated blood in the subcutaneous tissues and skin due to injury. Extrinsic coagulation pathway

Initiated by release of tissue thromboplastin (tissue factor III) from outside the blood vascular system, which in turn activates factor VII in the extrinsic path and then factors in the common pathway (X, V, II, I, XIII), resulting in the formation of a stable fibrin clot. Factor VIII A complex clotting factor with 3 distinct subunits: (1) the antihemophiliac factor (VIIIAHF), deficient in classic hemophilia A; (2) the von Willebrand factor (VIIIVWF), deficient in von Willebrand's disease; and (3) a subunit containing an antigenic site. Factor XII (Hageman factor) Plays a central role in linking three systems: (1) initiation of the intrinsic coagulation system; (2) acceleration of the activation of plasminogen to plasmin in the fibrinolytic system; and (3) change of kallikreinogen to kallikrein in the inflammatory system. This role ensures a balance between clot formation and digestion and ensures that clotting factors are localized at the site of inflammation or bleeding and not disseminated throughout the body. Fibrinolytic system A countermechanism to blood clotting, activated to dissolve the fibrin clot and restore blood vessel patency. The anticoagulant plasminogen circulates in the blood in the inactive form. Three major activators of the fibrinolytic system changing plasminogen to plasmin are: (1) tissue plasminogen activator (tPA), released from the endothelial cells in the presence of thrombin and fibrin; (2) urokinase, released from renal cells; and (3) streptokinase, released from streptococci if infection is present. Within the clot, plasmin (a proteolytic enzyme) digests fibrin, producing fibrin degradation (split) products (FSP or FDP) and also breaks down fibrinogen in the plasma. Plasminogen activator inhibitor (PAI-1) and alpha-macroglobulin inhibit tPA and limit plasmin activity to the level of the platelet plug. The Hageman factor (XII) accelerates activation of plasminogen to plasmin. Fibrin split (or degradation) products (FSP or FDP) Products of fibrin or fibrinogen degradation; elevated in DIC. Hemarthrosis Bleeding into a joint; suggests a factor VIII or IX deficiency. Hematoma A swelling or mass of blood confined to a space and caused by a break in a blood vessel. Hemophilia A (classic) An X-linked recessive disorder resulting in deficiency of anti-hemophilic factor VIII activity. Patients suffer joint and muscle hemorrhages and easy bruising. Patients have normal bleeding times (primary hemostasis is intact), normal prothrombin times (the extrinsic pathway clotting factors are normal), and prolonged partial thromboplastin time (because factor VIII is an intrinsic pathway clotting factor). Hemophilia B (Christmas disease) An X-linked recessive disorder caused by a deficiency of factor IX activity. Less common than hemophilia A and usually less severe. Heparin An anticoagulant that prevents conversion of prothrombin to thrombin and fibrinogen to fibrin by enhancing the inhibitory effects of antithrombin III.

Used for the acute treatment of deep venous thrombosis (DVT) or pulmonary embolism (PE) to keep the PTT 1.5 to 2.5 times the control value. International normalized ratio (INR) A method of standardizing the measurement of clotting activity, because the measurement of the PT may vary from laboratory to laboratory; reduces the risk of underdosing or overdosing patients on Coumadin therapy because of the changing sensitivity of tissue thromboplastins (used in the PT measurement) from one laboratory to another. Normal INR: 1.0 to 2.0; anticoagulated patients: 2.0 to 3.0; patients with mechanical heart valves or those who continue to have clotting problems: 2.5 to 3.5. Intrinsic coagulation pathway Includes factors XII, XI, IX, and VIII. The Hageman factor (XII) initiates the intrinsic coagulation pathway from inside the blood vessel when it comes in contact with subendothelial exposed collagen when the blood vessel is damaged. High molecular weight kininogen (HMWK) acts as a cofactor in the conversion of prekallikrein to kallikrein, which in turn augments the conversion of factor XII to XIIa. Once activated, XIIa in turn activates other factors in the intrinsic (XI, IX, VIII) and common pathway (X, V, II, I, XIII), with the result that a stable fibrin clot is formed. Compared to the extrinsic system, the intrinsic coagulation system is more sensitive, efficient, and powerful, because it can generate large amounts of fibrin using the principle of amplification. The intrinsic system is so powerful that there is enough clotting potential in 1 ml of blood to clot all the fibrinogen in the body in 10 to 15 seconds if it were not carefully coupled to the fibrinolytic system. Liver Site of the synthesis of all the clotting factors except factor VIII and possibly XI and XIII. Partial thromboplastin time (PTT) Screening test that measures the intrinsic and common pathway. Normal is 26 to 42 seconds. Prolonged in heparin therapy, hemophilia, DIC, vitamin K deficiency, and liver disease. Used to guide dosage in heparin therapy to decrease the risk of clotting, yet not cause hemorrhage. Petechiae Pinpoint hemorrhages (< 0.5 cm) into the dermis characteristic of platelet disorders, especially thrombocytopenia. Platelets (thrombocytes) Nonnucleated cell fragments (1-4 (m in diameter) from megakaryocytes, which stain light blue with red-purple granules. Platelets have a lifespan of 9 to 10 days; 80% circulate in the blood and 20% are sequestered in the spleen. Platelets play a vital role in primary hemostasis (temporary platelet plug), secondary hemostasis (formation of the stable fibrin clot), and in clot retraction; thus in thrombocytopenia all these functions are abnormal. The normal serum platelet count is 150,000 to 400,000/mm³. Protein C A circulating plasma anticoagulant that functions to inactivate factors Va and VIIIa. It is synthesized by the liver and is vitamin K-dependent. Protein S enhances the anticoagulant activity of protein C. Prothrombin time (PT) Screening test that measures the extrinsic and common pathway. Normal is 10 to 14 seconds. Prolonged in Coumadin therapy, liver disease, vitamin K

deficiency, and DIC. Used to monitor and adjust the dosage in Coumadin therapy. Purpura Patchy areas of bleeding (> 0.5 cm) into the skin, found especially in dependent body areas; may indicate platelet deficiency. Telangiectasia Dilation of capillaries and venules creating 2 to 3 mm, purple to red-purple macular spots that blanch with pressure and bleed with the slightest trauma. Thrombin time (TT) Laboratory test in which exogenous thrombin is added to citrated plasma, and clotting time is measured. Used to further delineate the missing clotting factors when both PT and PTT are abnormal. Thrombocytopenia A platelet count less than 100,000/mm³ of blood. Normal platelet count is 150,000 to 400,000/mm³. Patients with a platelet count of 100,000 would be expected to have prolonged bleeding after major surgery; under 50,000, prolonged bleeding and areas of ecchymoses occur after minor trauma; under 30,000, petechiae are a major manifestation; and under 20,000, spontaneous hemorrhage is possible. Thrombocytosis An increase in the platelet counts above 400,000/mm³, which causes both thrombosis and bleeding and may be primary or secondary. Vitamin K A fat-soluble vitamin that plays a crucial role in hemostasis (synthesis of clotting factors II, VII, IX, X, protein C, and protein S is vitamin Kdependent). Three major causes of vitamin K deficiency are: (1) inadequate dietary intake (after biliary tract surgery); (2) intestinal malabsorption (antibiotics, cephalosporin); and (3) loss of storage sites due to hepatocellular disease. Early laboratory measurements show prolonged PT (rapid fall in factor VII) and normal PTT; later, PTT is prolonged and vitamin K-dependent clotting factors are decreased. von Willebrand's disease (VWD) The most common inherited coagulation disorder, inherited as an autosomal dominant trait, occurring in men and women alike. In VWD there is decreased activity of both factor VIIIVWF and VIIIAHF. Depending on the subtype and severity of the disease, the spectrum of bleeding may be infrequent, mild-tomoderate mucocutaneous (skin and mucous membranes) bleeding, nosebleeds; bleeding secondary to trauma or surgery; or a life-threatening hemorrhage. Laboratory tests show increased PTT, increased bleeding time, decreased factor VIIIVWF and VIIIAHF activity, and normal PT. Mild cases are treated with vasopressin (DDAVP) and severe cases with cryoprecipitate. von Willebrand's factor (VIIIVWF) A subunit of clotting factor VIII. Besides being in plasma, vWF is present in endothelium and platelets. Its main purpose is to allow attachment of platelets to areas of endothelial injury, whereas in plasma it acts to stabilize and carry factor VIII. Warfarin (Coumadin) An anticoagulant used to reduce the risk of formation of blood clots (thrombi) in predisposed patients as in atrial fibrillation, mechanical heart valves, deep venous thrombosis, and pulmonary embolism. Coumarin acts by depressing

hepatic synthesis of vitamin K-dependent coagulation factors (II, VII, IX, X). The prothrombin time (PT) is used to adjust medication dosage to keep the coagulation time 1.5 to 2 times the normal value. Recently the international normalized ratio (INR) is used more frequently in place of the PT since it does not vary from one laboratory to another.

Chapter 15: Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS)
Acquired immunodeficiency syndrome (AIDS) The late stage of HIV disease. AIDS involves the loss of function of the immune system as CD4+ (T helper) cells are infected and destroyed, allowing the body to succumb to opportunistic infections (Pneumocystis carinii pneumonia, toxoplasmosis) that are generally not pathogenic in persons with intact immune systems. The CDC defines AIDS as the presence of at least one of several opportunistic infections or the presence of fewer than 200 CD4+ cells/mm3 in an HIV positive individual. Acute HIV infection phase An acute HIV syndrome experienced by more than half of patients 3 to 6 weeks after initial HIV infection, consisting of flu-like symptoms (fever, headache, sore throat, rash). These symptoms result from a cellular immune response that takes place before the immune system has had time to produce antibodies. During this phase antibody status changes from seronegative to seropositive. AIDS dementia complex Deterioration of intellectual faculties, emotional disturbance, and neuromuscular control as a result of HIV activity in the central nervous system. AIDS-related dementia typically affects people in the latter stages of the disease. Symptoms may include cognitive impairment (e.g., difficulty concentrating, memory loss), mood and personality changes, speech and vision difficulties, psychomotor dysfunction (e.g., lack of coordination, incontinence), and paralysis. Anergy The lack of an immune response to a foreign antigen. Anergy may indicate an inability to mount a normal allergic or immune reaction, and may be a sign of immunodeficiency. Patients with AIDS have cellular-mediated immunodeficiency, which may be demonstrated with delayed-type hypersensitivity skin tests (see Chapter 14). Antibody-dependent complement-mediated cytotoxicity (ADCC) An immune response in which antibodies bind to target cells and identify them for attack by natural killer (NK) cells and macrophages-a mechanism of removing HIV-infected CD4+ lymphocytes. Apoptosis A form of programmed cell death that is a normal mechanism for the elimination of effete cells in fetal organogenesis as well as in the cellular proliferation that occurs during a normal immune response. Apoptosis is

strictly dependent on cellular activation. It has been postulated that in HIV infection, sequential signals delivered to CD4+ T cells induce apoptosis. Asymptomatic phase A period of clinical latency, which may last for several years in a relatively intact immune system; however, continuous HIV replication occurs, predominately in the lymphoid tissues. Candidiasis A fungus infection, caused by a member of the genus Candida, especially in immunocompromised individuals. In the mouth, candidiasis is called thrush and shows up as white patches; in the vagina, it is called vulvovaginal candidiasis. Candidiasis can also attack the esophagus and lungs. Candidiasis is considered an AIDS-defining condition in the United States. Cervical dysplasia Abnormal growth of cells in the cervix that can lead to cervical cancer; associated with human papillomavirus. Cervical dysplasia is present in 40% of HIV-infected women, who should receive a Papanicolaou smear and colposcopic examination every 6 months for early detection of cervical cancer. Cluster of differentiation (CD) A marker protein embedded in the surface of cell membranes or interior of cells. CD molecules determine which other molecules can bind to a given cell (e.g., the CD4+ marker allows HIV to invade certain types of cells). The T helper cell has a CD4 marker on its surface, whereas the cytotoxic T cell has a CD8 marker. Colposcopy Examination of the cervix with a lighted microscope (colposcope) to identify abnormal cell growth and, if necessary, remove a tissue sample for biopsy. Coreceptors Different strains of HIV use two major coreceptors (CCR5 and CXCR4) along with CD4 to bind to, fuse with, and enter target cells. Individuals who inherit two defective copies of these coreceptors (homozygous) are resistant to the development of HIV infection despite repeated exposure to the HIV virus (about 1% of white Americans). Heterozygotes (one defective copy) for the CCR5 or CXCR4 coreceptors (about 18% of white Americans) are not protected from AIDS but may have a delayed onset. Enzyme-linked immunosorbent assay (ELISA) Generally the first screening test to detect HIV antibodies. If the test is positive, the test is repeated, and when both tests are positive, a more specific test, the Western Blot, is performed to confirm the diagnosis of HIV infection. False negative A negative test for a person who does in fact have the disease or condition being tested for. For example, an HIV-infected individual would have a negative ELISA or Western Blot test during the window period (antibodies to HIV generally appear in the circulation 2 to 12 weeks after infection but can take up to 1 year). False positive A positive test result for a person who does not in fact have the disease or condition being tested for. For example, an HIV antibody test (ELISA) on the newborn of a HIV-positive mother would test positive (because maternal HIV antibodies cross the placenta) when in fact the infant is not infected. Another

test, such as the p24 antigen capture assay or RNA PCR test, should be used to determine if the infant is infected. Gag The gene of the HIV that encodes the core proteins of the virus. Highly active antiretroviral therapy (HAART) A term for aggressive anti-HIV treatment, usually with two or more antiviral agents, such as protease inhibitors, nucleoside transcriptase inhibitors, and nonnucleoside transcriptase inhibitors. HAART therapy has greatly reduced mortality from AIDS in industrialized countries that have access to these drugs. HIV integrase A viral enzyme that aids in the insertion of the viral cDNA into the host nucleus. HIV protease A viral enzyme that cuts and assembles the virus protein into small segments that surround the viral RNA, forming the infectious virus particles that bud from the infected cell, thus essential to the HIV replication process. HIV RNA PCR A test to determine the blood serum viral load in HIV-infected patients, using polymerase chain reaction (PCR) as a technique. PCR amplifies cDNA generated from HIV viral RNA (see Polymerase Chain Reaction, below). Periodic assessment of the viral load is used to guide antiretroviral therapy and for prognostic purposes, whereas monitoring the CD4+ T cell count is used to assess the immune status. An HIV RNA count of 20,000 copies/ml is considered by most experts as an indication to begin antiretroviral drug therapy regardless of the CD4+ T cell count. Invasive cervical cancer A gynecologic malignancy associated with long-standing HIV disease, included in the case definition since 1993. Mycobacterium avium complex (MAC) A disease caused by Mycobacterium avium or Mycobacterium intracellulare (sometimes referred to as Mycobacterium avium-intracellulare or MAI), bacteria found in soil and water. In immunosuppressed persons, the bacteria can infect the lymph nodes, GI tract, liver, spleen, spinal fluid, and lungs. MAC is the most common bacterial infection in persons with advanced AIDS (usually with CD4+ T cell counts of < 50-75 cells/mm3). Symptoms include diarrhea, wasting, fever, night sweats, fatigue, and splenomegaly. Rifabutin is used as treatment and prophylaxis for MAC. MAC is considered an AIDSdefining condition in the United States. P24 antigen capture assay A test to detect the HIV p24 viral core protein in the blood of HIV-infected persons where it exists either as a free antigen or complexed to anti-p24 antibodies. Persistent glandular lymphadenopathy (PGL) A condition in which the lymph nodes are persistently swollen in one or more parts of the body; occurs during the early symptomatic phase of HIV infection. Pneumocystis carinii pneumonia (PCP) The most frequently diagnosed serious infection in patients with AIDS caused by a protozoan. PCP is a common infection that can cause severe illness in immunocompromised people (especially with CD4+ T cell counts less than

200 cells/mm³); it is a leading cause of death in persons with AIDS. Symptoms include dry cough, fever, chest tightness, and dyspnea. First-line treatment and prophylaxis is TMP-SMX (Bactrim, Septra); other drug treatment options include pentamidine or dapsone. PCP is an AIDS-defining condition in the United States. Polymerase chain reaction (PCR) A highly sensitive test that can detect small amounts of RNA or DNA in blood or tissue samples using an amplification technique that multiplies the existing RNA or DNA so that it can be detected more readily. Progressive multifocal leukoencephalopathy (PML) A rapidly progressing viral infection of the brain believed to be caused by the papovavirus. Symptoms include memory loss, loss of strength, coma, and death. PML is considered an AIDS-defining condition in the United States. Protease inhibitor A class of anti-HIV drug that prevents creation of an HIV-specific protease. Retroviruses Viruses that use ribonucleic acid (RNA) rather than deoxyribonucleic acid (DNA) as their genetic material. HIV are retroviruses and use reverse transcriptase to convert their genome RNA into double-stranded proviral DNA after they enter the host cell. Reverse transcriptase The enzyme, located in the HIV virion, that transcribes viral RNA into DNA after the virus enters the target cell. It is essential to HIV replication in the invaded target cell. Symptomatic phase of HIV infection The stage in which CD4+ cell counts have usually dropped below 300 cells/L. Symptoms indicating immunosuppression are present and continue until the person develops an AIDS-related condition-opportunistic infections, secondary neoplasms, and neurologic manifestations. Toxoplasmosis An opportunistic infection caused by Toxoplasma gondii, a protozoan found in undercooked meat and cat feces. A frequent manifestation of the disease is toxoplasmic encephalitis, characterized by cerebral edema, dementia, lethargy, seizures, and coma. Symptoms may include fever, severe headache and lymphadenopathy. Toxoplasmosis is considered an AIDS-defining condition in the United States. Western blot test Most common confirmatory test (detects anti-HIV antibodies) for HIV infection; less likely to give a false-positive or false-negative reading than ELISA.

hapter 10: Bronchial Asthma: Allergic and Otherwise
Acute phase asthmatic response In allergic asthma, this response begins within minutes of exposure to an inhaled antigen and resolves in approximately 1 hour. Consists of bronchoconstriction due to increased responsiveness of bronchial smooth muscle; hypersecretion of mucus leading to plugging of airways; and mucosal edema (owing to increased vascular permeability that leads to narrowing of airways. Mast cells in the bronchial epithelium also release leukotrienes and cytokines that cause the influx of leukocytes, neutrophils and monocytes, and especially eosinophils. Allergic (extrinsic; atopic) asthma Initiated by a type I hypersensitivity reaction induced by exposure to an extrinsic antigen, such as house dust mite, animal danders, feathers, pollens, molds, foods, food preservatives (sulfiting agents added to fruit and salads in restaurants). Asthma Clinically defined condition marked by recurrent episodes of reversible bronchial narrowing, often separated by periods of more normal ventilation. Classic triad of signs and symptoms in an acute asthmatic attack Dyspnea, cough, and prolonged wheezing respirations (at first more prominent during expiration but later evident both during expiration and inspiration). Common denominator underlying predisposition to asthmatic attacks Nonspecific hyperreactivity of the tracheobronchial tree. Asthmatic airways behave as if their beta-adrenergic receptors (which help preserve airway patency) are incompetent; bronchoconstrictor influences mediated by parasympathetic and alpha-adrenergic pathways are therefore predominant. Dyspnea Abnormal shortness of breath. Exercise-induced asthma (EIA) Asthmatic attack triggered by exercise, especially sprint running. FEV1.0 The maximum amount of air that can be exhaled as forcefully and as rapidly as possible during the first second after a maximum inspiration (normally, 83%). FEV1.0 is reduced in obstructive disorders, such as asthma. FEV1.0 is used to assess the severity and progression of the asthmatic episode and also to periodically assess the patient's response to treatment. Idiopathic (intrinsic) asthma Initiated by diverse nonimmunologic mechanisms, including ingestion of aspirin; respiratory infections; air pollutants (e.g., cigarette smoke, perfumes, aerosol sprays); inhalation of dry, cold air; and exercise. Late phase asthmatic response Begins several hours after exposure to an inhaled antigen but lasts much longer than the acute response; characterized by inflammation and inflammatory cells (PMNs, eosinophils, basophils), which can cause epithelial damage and airway constriction. Leukotrienes Extremely potent mediators that cause prolonged bronchoconstriction as well as increased vascular permeability and increased mucus production (formerly called slow reactive substance of anaphylaxis (SRS-A).

Status asthmaticus Severe asthma that has persisted for at least 24 hours and is not substantially managed by optimal doses of epinephrine and theophylline; may result in death from acute respiratory insufficiency.

Chapter 9: Familiar (IgE-Mediated) Allergic Disorders: Anaphylaxis and the Atopic Diseases
Allergen A substance (antigen) that can produce an allergic reaction in the body of sensitive individuals but is harmless to most people; for example, plant pollens, excreta of house dust mites, animal dander, feathers, certain foods. Allergic rhinitis A condition characterized by sneezing; rhinorrhea (runny nose); obstruction of the nasal passages; conjunctival and nasal itching; and lacrimation, all occurring in a temporal relationship to allergen exposure. It can be seasonal (hay fever) and commonly related to exposure to airborne plant pollens or perennial in an environment of chronic exposure (e.g., a research technician who handles animals every day and is exposed to animal danders to which he or she becomes sensitized). Allergy The capacity to react in an abnormal way to a specific substance acquired through prior contact with that substance. Three important aspects of allergy are (1) it is specific (reaction only to a specific antigen); (2) it is acquired rather than inherent; and (3) prior contact with the specific antigen is necessary to become sensitized (develop memory B or T lymphocytes). Anaphylactic kit Kit containing a tourniquet and preloaded syringes of epinephrine, and antihistamines for emergency self-treatment by individuals who are hypersensitive to insect venom and are at high risk of systemic anaphylaxis. Anaphylaxis An acute systemic hypersensitivity reaction to an antigen (usually injected) to which there has been prior sensitization, such as insect venom or penicillin. Type I hypersensitivity reaction is mediated by IgE attached to basophils and mast cells in smooth muscles of bronchioles and in connective tissue around blood vessels, resulting in the release of histamine and other vasoactive substances. Onset of symptoms is immediate (within minutes) after injection of the antigen and can be fatal. Manifested by respiratory distress (bronchospasm, laryngeal edema occluding airways) followed by vascular collapse or hypotensive shock. Cutaneous manifestations include intense itching and hives with or without angioedema. GI manifestations include nausea, vomiting, abdominal cramps, and diarrhea. Emergency treatment includes removing the offending substance (tourniquet proximal to injection site); establishing a patent airway (intubate if needed); administration of 0.3 ml 1:1000 epinephrine subcutaneously or IV; and support blood pressure by restoring plasma volume with IV normal saline. Angioedema

A well-demarcated, localized edema involving the deeper layers of the skin and subcutaneous tissue. Animal dander An allergen source from animals, including hair, epidermal scales, feathers, fur, silk, wool, saliva, lacrimal secretions, and even urine. Antihistamines Drugs commonly used for the symptomatic relief of allergies; mechanism of action involves competition with histamine for tissue receptors (unlike cromolyn sodium, antihistamines do not block the release of histamine from mast cells). Atopic diseases Term used to describe a group of hypersensitivity (allergic) diseases in which hereditary factors are known to be involved; it is the predisposition that is inherited and not sensitivity a particular allergen. About 75% of atopic individuals have elevated IgE levels. Atopic diseases include: (1) allergic seasonal and perennial rhinitis; (2) allergic (extrinsic) asthma; (3) atopic (eczematous) dermatitis; 4) urticaria (hives); and (5) angioedema. Dermatographism The appearance of a linear wheal at the site of a brisk stroke with a firm object; a type of physical urticaria. Eosinophil chemotactic factor of anaphylaxis (ECF-A) Chemical mediator that attracts eosinophils to an area of inflammation in type I hypersensitivity (allergic) reactions. Epinephrine Drug of choice for the emergency treatment of anaphylaxis. Hay fever Seasonal rhinitis, commonly associated with exposure to airborne allergens such as tree pollen, grasses, fungi, or ragweed pollen. IgE Immunoglobulin (antibody) involved in most type I allergic reactions. IgE is a cytophilic molecule whose Fc fragment (stem of the Y) is affixed to mast cells and basophils (IgE levels in the blood serum are low). When an allergen combines with the Fab site (tail fins of the Y) of IgE, IgE causes histamine and other vasoactive chemicals to be released from the mast cell or basophil, resulting in an inflammatory response. Immunotherapy (hyposensitization) Procedure involving subcutaneous injections of gradually increasing concentrations of extracts of a clearly known and documented allergen to which the patient is sensitive over prolonged periods. The goal is to relieve the symptoms to the specific allergen. The probable mechanism of hyposensitization is an increase in IgG which serves as a blocking antibody for IgE by competing with IgE for the allergen at mucosal surfaces; mast cells release less and less histamine as the patient is desensitized. The nurse or physician administering the treatment must keep an emergency dose of epinephrine on hand in the event of an anaphylactic reaction (this treatment could result in sensitizing rather than desensitizing the patient to the allergen). Laryngeal edema In a systemic anaphylactic reaction, edema of the vocal cords and epiglottis in mild cases may be experienced as a "lump in the throat", hoarseness, or stridor or may be severe enough to cause complete mechanical obstruction of the

airways, terminating in death. The edema is caused by the release of histamine and other vasoactive mediators from mast cells in the respiratory tract, resulting in increased permeability of blood vessels and exudation of fluid into the soft tissues of the upper airways. Mast cells Effector cells in type I hypersensitivity reactions; found throughout the body in loose connective tissue. Mast cells are covered with IgE receptors on their cell surface and filled with vesicles or granules containing chemical mediators, such as histamine, that produce inflammation when released; basophils in the blood have similar chemical mediators. Nasal polyps Edematous mucosal protrusions with variable degrees of infiltration by eosinophils commonly found in patients with perennial rhinitis; may cause obstruction of breathing through the nose. Pruritus Itching. Rhinitis medicamentosa A complication of improper self-medication (overuse) with sympathomimetic amines (e.g., Neo-Synephrine nose drops) resulting in rebound congestion of the nasal mucosa. Treatment involves withdrawal of the medication and substitution of a topical corticosteroid nasal spray for a few weeks. Rhinorrhea Watery discharge from the nose; excessive nasal secretion. Skin testing (for allergies) Two types of skin testing are used to test for potential allergens: (1) the epidermal (prick) test, which uses highly diluted allergen in a solvent and may be read in 15 minutes; and 2) the intracutaneous injection (0.02 ml) of the diluted allergen. A control site with the solvent only is also tested. Epinephrine must be kept on hand to use in case of an acute systemic anaphylactic reaction. Contrary to popular belief, a positive wheal and flare reaction provides no insurance that the patient's symptoms arise from exposure to the allergen in question. Individuals with atopy commonly react to numerous allergens used in skin testing but may not react to the same allergen when encountered in the environment. The value of allergen skin tests is to support or oppose impressions formed during clinical assessment. Type I immune disorders (anaphylactic, immediate hypersensitivity) Disorders that are usually mediated by IgE of the humoral immune system. Urticaria (hives) Well circumscribed wheals with erythematous borders and pale centers involving the superficial skin; distinctly pruritic but usually self-limited, lasting for 36 hours or less.

Chapter 8: Disturbances in Growth, Cellular Proliferation, and Differentiation
Adenocarcinoma A malignant neoplasm arising from the parenchyma of a gland. Adenoma

A benign neoplasm of glandular epithelial origin. Agenesis Phenomenon in which the embryonic rudiment of an organ never forms. Anaplasia "To form backwards"; lack of differentiation (like embryonic cells)-a hallmark of malignant neoplasms. Aplasia Phenomenon in which the embryonic rudiment of an organ fails to grow at all once it is formed. Apoptosis regulating genes Genes that regulate cell suicide or programmed cell death. The TP53 tumor suppressor gene (which codes for the p53 protein) can also trigger apoptosis. The p53 protein is the guardian of the G1-S checkpoint of the cell replication cycle. If there is DNA damage, p53 halts the cell replication and signals the DNA repair genes to correct the damage. If the damage is too great and cannot be repaired, then p53 induces apoptosis. Radiation and chemotherapy act by triggering apoptosis in response to DNA damage. Atrophic Organs that reach definitive size in the course of development and then shrink. Carcinogenesis The process of cancer development, classically consisting of three stages: (1) initiation, or the process involving a genetic mutation that becomes permanent in the DNA of the cell; (2) promotion, the stage during which the mutant cell proliferates; and (3) progression, the stage during which the clone of mutant cells acquires the characteristics of a malignant neoplasm. Carcinoma A malignant neoplasm arising from epithelium. Cervical intraepithelial neoplasia (CIN) Preneoplastic proliferation of atypical epithelial cells that occurs in the transformation zone of the cervix and is usually associated with human papillomavirus (HPV) infection; graded from CIN I to CIN III with increasing risk of development of carcinoma of the cervix (See Chapter 64). Chondroma A benign neoplasm of cartilage. Chondrosarcoma A malignant neoplasm arising from cartilage. Chromosomal rearrangements Translocation of one chromosome fragment onto another, or deletion of a fragment of a chromosome, which leads to a juxtapositioning of genes that are normally distant from each other. Differentiation The extent to which parenchymal cells resemble comparable normal cells both functionally and morphologically. Histologic assessment and grading of neoplasms allows prediction of likely tumor behavior. In general, benign neoplasms are well-differentiated. In contrast, malignant neoplasms range from well-differentiated to poorly differentiated (and thus more aggressive in growth pattern). A tumor grade is allocated on the basis of: (1) the degree of differentiation with reference to the tissue of origin; (2) the variation in the size and shape of the tumor's constituent cells (pleomorphism); and (3) the number of cells containing mitotic figures. Thus, a well-differentiated breast

carcinoma would be expected to show structures that resemble small ducts and glandular epithelium and the cells would show little variation in size and shape with few mitoses, whereas a poorly differentiated breast carcinoma would not show any attempt to form a glandular pattern and the cells would show much pleomorphism and a high density of mitoses. Grading generally ranges from I (well-differentiated) to IV (most anaplastic or lacking in differentiation). DNA repair genes Code for proteins that normally function to correct DNA replication errors during the cell cycle. Mutations in DNA repair genes can lead to failure in DNA repair which, in turn, allows subsequent mutations in protooncogenes and tumor suppressor genes to accumulate. Dysplasia An abnormality in the differentiation of proliferating cells, resulting in an abnormal degree of variation in the size, shape, and appearance of the cells and a disturbance in the usual arrangement of the cells that is potentially reversible. Dysplasia often arises in tissues that have been subject to chronic irritation (e.g., bronchial epithelium in a smoker). A sequence from dysplasia through in situ neoplasia to invasive neoplasia is now well recognized in several tissues. Fibroma A benign neoplasm of fibrous tissue. Fibrosarcoma A malignant neoplasm arising from fibrous tissue. Gene amplification A mechanism that causes the cell to acquire an increased number of copies of the protooncogene, causing overexpression of its protein products. Hyperplasia An increase in the absolute number of cells within a tissue, leading to an increase in the size of that tissue or organ. Hypertrophy An enlargement of a tissue or organ because of enlargement of individual cells (but not an increase in their number). Hypoplasia Phenomenon in which the embryonic rudiment forms and grows but never quite reaches definitive or adult size, yielding a dwarf organ. In situ neoplasia A stage of neoplasia prior to the development of local invasion; a very early stage of neoplasia showing cellular pleomorphism and increased mitotic activity. If left alone, such a neoplasm would progress to become invasive, whereas early detection and treatment are often completely curative. Lymphoma A neoplasm arising from lymphoid tissue. Medullary tumor A type of tumor that consists predominately of neoplastic cells with little stroma. Metaplasia A reversible change in which one adult cell type replaces another cell type not normally found in that area of the body. May be an adaptive substitution of cells better able to withstand an adverse environment, for example, change of

normal columnar epithelium in the respiratory tract to squamous epithelium in a chronic cigarette smoker. Metastasis (pl., metastases) A secondary malignant growth that originates from a primary tumor and is distant from the primary site. Cancer spread takes place through three routes: lymphatic system (most common); blood circulatory system; and seeding of body cavities and surfaces. A fourth potential route of spread is by direct implantation on surgical gloves or instruments used during surgery or biopsy. Neoplasm (tumor) An abnormal mass of proliferating cells. Oncogenes Cancer-causing genes derived from protooncogenes. Protooncogenes can be transformed into oncogenes by four basic mechanisms: a point mutation, gene amplification, chromosomal rearrangement, or insertion of a viral genome. Oncogenes produce abnormal oncoproteins that fail to regulate the cell replication cycle, resulting in excessive cell multiplication. Osteoma A benign neoplasm of bone. Osteosarcoma A malignant neoplasm arising from bone. Papanicolaou smear (exfoliative cytology) A cytologic test for malignant changes, mainly in the female genital tract (cervix, endometrium, vagina). Papilloma A growth projecting into the lumen of an organ in fingerlike projections. Point mutation A mechanism that involves a single base substitution in the DNA chain resulting in a miscoded protein that has one amino acid substituted for another. Poorly differentiated A situation in which the resemblance of neoplastic cells to comparable normal cells is slight, such that the tumor consists largely of primitive-appearing, unspecialized proliferating cells. Protooncogenes Cellular genes whose function is to promote the normal growth and differentiation of cells; they code for proteins involved in the regulation of the cell cycle. Sarcoma A malignant neoplasm derived from supporting tissue. Scirrhous tumor A type of tumor that contains an extremely dense fibrous stroma. Stroma Supporting framework. Telomerase An enzyme that repairs telomeres and may be the key to immortality. Embryonic stem cells and germ cells secrete telomerase, explaining their extensive ability to replicate, but somatic cells do not (explaining their finite lifespan). Cancer cells also secrete telomerase, which may be the key to their ability to divide indefinitely. Telomeres

The end caps on chromosomes, essential for chromosomal stability during cell replication. Telomeres shorten with each somatic cell replication until a critical length is reached and the cell is no longer able to replicate. Telomere shortening is believed to be the basis of aging (acts like a molecular clock keeping track of our lifespan). TNM staging system A method of staging a malignant tumor as an indication of how far it has spread. T refers to the size of the primary tumor and the number denotes its local extent and varies according to site; N refers to lymph node involvement, and a high number indicates an increasing extent of involvement; and M refers to the extent of distant metastases. The TNM system can be applied to many different types of tumor, although the criteria are different for each tumor site (e.g., the TNM criteria would be different for prostate and breast carcinoma). Tumor suppressor genes Genes that inhibit or "put the brakes on" the cell replication cycle in contrast to protooncogenes that encode proteins that promote cell growth. Mutation of tumor suppressor genes has the effect of removing the brakes in the regulation of the cell cycle resulting in a higher rate of uncontrolled growth-cancer. Most malignancies involve mutations in tumor suppressor genes and oncogenes. Well-differentiated A condition in which the resemblance of neoplastic cells to their normal ancestors is close.

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