Med 2 Exam #4 Immune and Cancer

Immunity

the body’ ability to resist disease

-serves 3 functions

1. defense: protect against invasions by microorganisms and prevent development of infection by attacking foerign antigens and pathogens

2. Homeostasis: damaged cellular substances are digested and removed

3. Surveillance: mutations continually arise, they are recognized as foregin and destroyed

antigen

substance that elicits an immune response

-all body’s cells have antigens on their surface, they are unique to that person and enable the body to recognize itself

Innate immunity

present at birth

-primary role is first-line defense against pathogens

-neutrophils and monocytes are primary white blood cells involved

-not antigen specific; respond within minuts to an invading pathogen w/o prior exposure to that antigen

Active acquired immunity

results from the invasion of the body by foreign substances and the subsequent development of antibodies and sensitized lymphocytes

-w/ each reinvasion the body responds more rapidly and vigorously to fight off the invader

-may result naturally from a disease or artificially through immunization

Passive acquired immunity

host receives antibodies to an antigen rather than making them

-may take place naturally through transfer of immunoglobulins across the placental membrane from mother to fetus

-may occur through injection w/ gamma globulin

-short lived bc the person does not make the antibodies and memory cells for the antigen

Types of acquired immunity

Active natural:

-natural contact w/ antigen through actual infection

Active artificial:

-immunization w/ antigen = vaccines

Passive natural:

-transplacental and colostrum transfer from mother to child

Passive artificial:

-injection of serum with antibodies from 1 person to another person who does not have antibodies

lymphoid organs

-central lymphoid organs are the thymus gland and the bone marrow

-peripheral lymphoid organs are the lymph nodes, tonsils, spleen, and gut-,bronchial-, and skin-associated lymph tissues

-make lymphocytes in bone marrow

-thymus is involved in the differentiation and maturation of T lymphocytes

• essential for a cell-mediated immune response

• by age 75 thymus is little more than fatty tissue and make few T lymphocytes

-antigens interact w/ B and T lymphocytes and macrophages in the lymph nodes

-2 major function of lymph nodes

• filtration of foreign material brought to site

• circulation of lymphocytes

-tonsils are example of lymphoid tissue

-spleen is important as primary site for filtering foreign antigens from the blood

-lymphoid tissue in the submucosa of the GI, genitourinary, and respiratory tracts protects the body from external microorganisms

-skin associated lymph tissue consists primarily of lymphocytes and Langerhans cells

• when Langerhans cells are depleted, the skin cannot initiate an immune response

• delayed hypersensitivity reaction does not occur

Mononuclear phagocytes

includes monocytes in blood and macrophages found throughout body

-have a critical role in the immune system = responsible for capturing, processing, and presenting the antigen to the lymphocytes

• capturing is accomplished through phagocytosis

-antigen is presented to circulating T or B lymphocytes and thus triggers an immune response

B lymphocytes

differentiate into plasma cells when activated

-plasma cells make antibodies (immunoglobulins)

IgG:

-most abundant antibody

-found in plasma and interstitial fluid

-only immunoglobulin that crosses placenta

-responsible for secondary immune response

IgA:

-found in body secretions including tears, saliva, breast milk, and colostrum

-lines mucous membranes and protects body surfaces

IgM:

-found in plasma

-responsible for primary immune response

-forms antibodies to ABO blood antigens

-”miserable” = infection is CURRENT

IgD:

-found in plasma

-does not cross placenta

-present on lymphocyte surface

-aids in differentiation of B lymphocytes

IgE:

-found in plasma and interstitial fluids

-causes symptoms of allergic reactions

-fixes to mast cells and basophils

-aids in defense against parasitic infection

T lymphocytes

mainly responsible for immunity to intracellular viruses, tumor cells, and fungi

-can live from a few months to the lifespan of a person

-account for long-term immunity

T cytotoxic cells:

-involved in attacking antigens on the cell membrane of foreign pathogens and releasing cytolytic substances that destroy the pathogen

-have antigen specificity and are sensitized by exposure to the antigen

-some remain as memory cells

T helper cells:

-involved in regulating cell-mediated immunity and the humoral antibody response

-differentiate into subsets of cells that make distinct types of cytokines

T dendritic cells:

-have atypical shape w/ extensive dendritic processes that form and retract

-found in many places on the body including the skin, lining of the lungs/nose/stomach/intestine

-function primarily to capture antigens at site of contact w/ external environment and then transport the antigen until it meets a T cell w/ specificity to that antigen

Natural killer cells (NK cells)

involved in cell-mediated immunity

-not T or B cells but are large lymphocytes w/ many granules in their cytoplasm

-do not need prior sensitization for their generation

-engage in recognition and killing of virus-infected cells, tumor cells, and transplanted grafts

-vital role in immune surveillance for malignant cell changes

Cytokines

-soluble factors secreted by WBCs and a variety of other cells in the body

-act as messengers among the cell types

-instruct cells to alter their proliferation, differentiation, secretion or activity

-have a beneficial role in hematopoiesis and immune function

-can have detrimental affects s/a those seen in chronic inflammation, autoimmune diseases, and sepsis

-types include

• colony stimulating 

• interferons

• interleukins

Interleukins

act as immunomodulatory factors

IL-1:

-proinflammatory mediator

-promotes proliferation of B cells; activates T cells, NK cells, and macrophages

IL-2:

-activates T cells, NK cells, and macrophages

-stimulates release of other cytokines

IL-3:

-hematopoietic growth factor for hematopoietic precursor cells

IL-4:

-anti-inflammatory mediator

-B cell growth and differentiation

-includes differentiation into TH2 cells

-stimulates growth of mast cells

IL-5:

-B cell growth and differentiation

-promotes growth and differentiation of eosinophils

IL-6:

-proinflammatory mediator

-T and B cells growth factor, promotes differentiation of B cells into plasma cells and stimulates antibody secretion

-induces fever

-synergistic effects w/ IL-1 and TNF

Tumor necrosis factor (TNF):

-proinflammatory mediator

-activates macrophages and granulocytes

-promotes immune and inflammatory responses

-kills tumor cells

-responsible for weight loss w/ chronic inflammation in cancer

Interferons

antiviral and immunomodulatory

alpha and beta INF:

-inhibits viral replication

-activates NK cells and macrophages

-antiproliferative effects on tumor cells

y INF:

-proinflammatory mediator

-activates macrophages, neutrophils, and NK cells

-promotes B-cell differentiation

-inhibits viral replication

Humoral immunity

antibody-mediated immunity

• antibodies are made by plasma cells (B cells) and are found in plasma

-B cells recognizes the antigen bc it has receptors on its cell surface specific for that antigen

-when the antigen comes in contact w/ the cell surface receptor, the B cell becomes activated, and most B cells differentiate into plasma cells

-mature plasma cells secrete immunoglobulins, some stimulated cells remain memory cells

-primary immune response becomes evident 4-8 days after first exposure to antigen

• IgM is first antibody formed = intravascular space

• as immune response progresses we make IgG = can move from intravascular space to extravascular space

-when person is exposed to antigen a second time, a secondary response occurs

• occurs faster (1-3 days), is stronger, and lasts for a longer time than primary response

• IgG is primary antibody found in secondary immune response

Cell-mediated immunity

immune responses that we initiate through specific antigen recognition by T cells

-cells involves include T cells, macrophages, and NK cells

-of primary importance in

• immunity against pathogens that survive inside of cells including, viruses and some bacteria

• fungal infections

• rejection of transplanted tissues

• contact hypersensitivity reactions

• tumor immunity

Aging and Immune system

-increased incidence of tumors

-greater susceptibility to infection

-increase autoantibodies

-decreased cell-mediated immunity

-thymic shrinkage

-decreased delayed hypersensitivity reaction

-↓ IL-1 and IL-2 synthesis

-↓ expression of IL-2 receptors

-↓ proliferation response of T and B cells

-↓ primary and secondary antibody responses

Hypersensitivity reactions

-immune response is overreactive against foreign antigens or reacts against its own tissues

-results in damage

-classified according to

• source of antigen

• time sequence

• immunologic mechanism causing injury

-4 types

• type I, II, and III = immediate, humoral immunity

• type IV = delayed, cell-mediated immunity

Type I: IgE mediated reactions

-occur only in susceptible people who are highly sensitized to specific allergens

-on first exposure to antigen, IgE antibodies are made and bind to mast cells and basophils

-on any subsequent exposures the allergen links w/ IgE and triggers degranulation of the cells and the release of chemical mediators from the granules

• mediators that are released attack target tissues, causing clinical symptoms of an allergic response = smooth muscle contraction, increased vascular permeability, vasodilation, hypotension, increased secretion of mucus, and itching

-systemic reaction leads to anaphylaxis

-localized reaction may lead to cutaneous reaction = wheel and flare reaction

• pale wheal containing edematous fluid surrounded by a red flare from hyperemia. Ex: mosquito bite

• occurs in minutes or hrs and usually not dangerous

Anaphylaxis

can occur when mediators are released systemically

-occurs w/i minutes and can be life-threatening due to bronchial constriction and vascular collapse

-initial symptoms:

• edema, itching at site of exposure

-shock can occur rapidly

• rapid, weak pulse; hypotension; dilated pupils; dyspnea; and possibly cyanosis

-bronchial edema and angioedema

-death w/o emergency treatment

-drugs = leading cause of anaphylaxis-related deaths

Atopic reactions

around 20% of population has inherited tendency to become sensitive to environmental allergens

-atopic disease that can result include allergic rhinitis, asthma, atopic dermatitis, and angioedema

Allergic rhinitis:

-most common type I hypersensitivity reaction

-year round or seasonal

-airborne substances s/a pollens, dust and molds are primary cause

-target areas effected = conjunctiva and mucosa of upper respiratory tract

-symptoms = nasal discharge; sneezing; tearing; mucosal swelling w/ airway obstruction; and itching of eyes, nose, and throat

Asthma:

-many pts have an allergic component to this disease

-mediators cause bronchial smooth muscle constriction, excess secretion of thick mucus, edema of mucus membranes of the bronchi, and decreasing lung compliance

-results in dyspnea, wheezing, coughing, tightness in chest, and thick sputum

Atopic dermatitis:

-chronic inherited skin disorder characterized by exacerbations and remissions

-allergens often hard to identify

-have high IgE levels and positive skin tests; skin lesions are more generalized and involve blood vessel vasodilation

-results in interstitial edema w/ vesicle formation

Urticaria:

-cutaneous reaction against systemic allergens

-transient wheals (pink, raised, edematous, itchy areas) that vary in size and shape

-hives develop rapidly after exposure to an allergen and may last minutes or hours

-histamine cause localized vasodilation, transudation of fluid, and flaring. Also causes itching 

Angioedema:

-similar to hives but involving deeper layers of skin and submucosa

-principle areas involved = eyelids, lips, tongue, larynx, hands, feet, GI tract, and genitalia

-swelling usually begins in face then progresses to airways and other parts of body

-outer skin appears normal or has reddish hue; lesions may burn, sting, or itch

-acute abdominal pain if in the GI tract

-swelling may occur suddenly or over hours; usually lasts 24hrs

Allergens causing anaphylactic shock

-Animal sera

• diptheria anitoxin

• rabies antitoxin

• snake venom antitoxin

• tetanus antitoxin

-Drugs

• aspirin

• cephalosporins

• chemotherapy drugs

• insulins

• local anesthetics

• NSAIDs

• penicillins

• sulfonamides

• tetracycline

-Foods

• eggs, milk, nuts, peanuts, shellfish, fish, chocolate, strawberries

-Insect venoms

• wasps, hornets, yellow jackets, bumblebees, ants

Treatments:

-allergy extracts used in immunotherapy

-blood products (whole blood and components)

-Iodine-contrast media for CT scan or other radiologic procedures

Type II reactions (cytotoxic and cytolytic reactions)

-involve the direct binding of IgG or IgM antibodies to an antigen on the cell surface

-activate the complement system, whuc mediates the reaction

-cellular tissue is either destroyed by

• activation of the complement system resulting in cytolysis

• enhanced phagycytosis

-traget cells often destroyed often RBCs, WBCs, and platelets

• antigens involved are the ABO blood group, Rh factor, and drugs

-disorder characteristic of type II reactions =

• ABO incompatibility transfusion rxn

• Rh incompatibility transfusion rxn

• autoimmune and drug-related hemolytic anemias, leukopenia, thrombocytopenia, erythroblastosis fetalis

• Good posture syndrome

Types of type II reactions

Hemolytic transfusion reactions:

-ABO incompatible blood transfusion

-agglutination occurs = clumping of cells due to antibodies coating the foreign RBC

• blocks small blood vessles

• uses and depletes existing clotting factors

• leads to bleeding

-neutrophils and macrophages phagocytize the agglutinated cells

-complement system is activated resulting in cell lysis

-vascular spasm in the kidney causes blockage of the renal tubules and can lead to acute kidney injury

Goodpasture syndrome:

-disorder involving lungs and kidneys

-antibody-mediated autoimmune rxn occurs involving glomerular and alveolar basement membranes

-deposists of IgG form along cell basement membranes which may result in pulmonary hemorrhage and glomerulonephritis

Type III reaction (Immune-complex reactions)

-tissue damage rsults from antigen-antibody complexes

-soluble antigens combine w/ IgG and IgM to form complexes that are too small for mononuclear phagocyte system to effectively remove them

• complexes deposit in the tissue or small blood vessels

• release of chemostatic factors that lead to inflammation and destruction of involved tissue

-may be local or systemic and immediate or delayed

-common sites = kidneys, skin, joints, blood vessles, and lungs

-sever rxns are associated w/ autoimmune disorders s/a SLE, acute glomerulonephritis, and rheumatoid arthritis

Type IV reaction (Delayed hypersensitivity reactions)

-cell-mediated immune response

-tissue damage occurs in these reactions, although these are usually protective mechanisms

• sensitized T cells attack or release cytokines

• some of these cytokines attract macrophages

• macrophages and enzymes they release cause most of tissue destruction

-takes 24-48hrs for response to occur

Contact dermatitis:

-reaction occurs when the skin is exposed to substances that easily penetrate the skin to combine w/ epidermal proteins

-on subsequent exposure to the substance eczematous skin lesions develop w/i 48hrs

-most antigenic substances = metal compounds; rubber compunds; poison ivy, oak, and poison sumac; cosmetics; and some dyes

-ina cute episodes skin lesions appear red and swollen and are covered w/ papules, vesicles, and bullae. Area itches and may burn or sting

-when becomes chronic the lesions resemble atopic dermatitis = thickened, scaly, and lichenified

Microbial hypersensitivity reactions:

-classic example is body’s defense against the tubercle bacillus

-organism itself does not directly cause damage to lung tissue; however antigenic material released from organism reacts w/ T cells, initiating cell-meidated immune response

• resulting response causes extensive caseous necrosis of lung

-subsequent contact w/ tubercle bacillus or and extract of purified protein from organism causes a delayed hypersensiticity rxn

• this is basis for PPD tuberculosis skin test

Allergic disorders assessment/diagnostics

Subjective data:

-family hx = atopic reactions, specific disorder, manifestations, treatment

-past and present allergies

• time of year rxn occurs, medications used to treat, manifestations, course of rxn

-social and environmental factors

• pets, trees, plants

• pollutants, floor coverings, houseplants, cooling and heating systems

• food diary

• lifestyle and stress level associated w/ allergic symptoms

Objective data:

-integument focused assessment on site of allergic manifestations

-EENT

-respiratory

Diagnostics:

-CBC w/ differential

• absolute lymphocyte and eosinophil count

• immunodeficiency if < 1200/microliter

-T and B cell quantification can diagnose specific immunodeficiency syndromes

-serum IgE level

-pulmonary function tests; skin testing

-Radioallergosorbent tests (RAST) blood test and ELISA blood test

• if client using a drug that interferes w/ skin test results, cannot tolerate many needle scratches of skin testing, or has skin disorder

Skin tests

can identify specific allergens that are causing the allergy symptoms

-has become common to omit skin testing in pts w/ allergic rhinitis

-cannot do skin testing on pts who cannot stop taking drugs that suppress the histamine response or pts w/ food allergies

• blood testing is used in these cases

Procedure:

-3 diff methods; usually done in arms and back

• allergens are applied to the skin in rows w/ a corresponding control site opposite the test site

• saline or other dilutant applied to control site

-scratch test = drop of allergen is placed on skin then pricking device used so allergen can enter skin

-intradermal test = allergen extract is injected under skin

-patch test = allergen is applied to a patch that is placed on the skin

Results:

-in scratch and dermal test results in 5-10 min

-patches must be worn for 48-72 hrs

-if hypersensitive rxn will occur w/i minutes and may last 8-12 hrs

• size of positive rxn does not always correlate to severity of allergy symptoms

• negative results do not always mean person does not have allergic disorder; positive results does not always mean allergen was causing manifestations

Precautions:

-highly sensitive person always at risk for developing anaphylactic rxn = never leave pt during testing period

-if severe rxn occurs

• extract is immediately removed

• apply anti-inflammatory topical cream

• if intradermal testing used, apply tourniquet to arm

• pt may need sub-q injection of epinephrine

Emergency management of anaphylactic shock

Cause: injection of, inhalation or, ingestion of, or topical exposure to substance that produces profound allergic response

Interventions:

-ensure patent airway. Intubation if evidence of impending obstruction

-remove insect stinger if present

-establish IV access

-give epinephrine IM or IV preferably in mid-out thigh. Repeat every 5-10 min

• pts taking B-bloskers may be resistent to epinephrine and develop refractory hypotension and bradycardia = should be given glucagon instead

-give high flow O2 (8-10mL) via face mask

-nebulized albuterol for bronchospasm resistant to epinephrine

-IV diphenhydramine for hives and itching

-IV corticosteroids

- if hypotension develops

• place recumbent and elavate legs

• IV normal saline rapid bolus of 1-2L

• maintain BP w/ fluids, volume expanders, vasopressors

Ongoing monitoring:

-monitor vital signs, respiratory effort, O2 saturation, LOC, heart rhythm, and urine output

-anticipate intubation w/ severe respiratory distress

-anticipate criothyrotomy or tracheostomy w/ severe laryngeal edema

Nursing management chronic allergies

Allergen recognition and control:

-lifestyle adjustments so that there is minmal exposure to the allergens

-pt will never be completely desensitized or completely symptom free

-plan a stress management program

-practice relaxation techniques when coming in for immunotherapy

-changing an occupation, moving to a diff climate, or giving up a favorite pet may be necessary

-sleeping in air-conditioned room, damp dusting daily, covering mattresses and pillows w/ hypoallergenic covers, and wearing a mask outdoors may be helpful

-if allergen is a drug have pt avoid drug

-wear a medical alert bracelet

-for pt allergic to insects have commercial kits containing automatic injectable epinephrine and insect-sting kit whenever going outdoors

Drug Therapy:

includes antihistamines, sympathomimetic/decongestant drugs, corticosteroids, antipruritic drugs, and mast cell -stabilizing drugs

Chronic allergy drug therapy

Antihistamines:

-diphenhydramine, loratadine, cetrizine, fexofenadine, levocitrizine

-best drugs for allergic rhinits, itching, and hives

-less effective for severe allergic rxns and do not prevent bronchoconstriction

-block the effect of histamine

-best if they are taken as soon as allergy appears

Sympathomimetic/decongestant drugs:

-major drug is epinephrine

-acts directly on mast cells to stabilize them against further degranultaions

-lasts only a few minutes

-minor sympathomimetics = drugs containing phenylephrine and pseudoephedrine

• taken orally or nasally

• last several hrs

• mainly treat allergic rhinits

Antipruritic drugs:

-provide relife from itching and protect skin

-most effective when applied topically to intact skin

-common OTC drugs = calamine lotion, coal tar solutions, and camphor

-menthol and phenol may be added to other lotions to relive itching

Coticosteroids:

-budesonide, fluticasone, mometasone

-effective in reliving symptoms of allergic rhinits

-brief course of oral corticosteroids can be used in manifestations that are truly incapacitating

Mast-cell stabilizing drugs:

-cromolyn

-inhibits release of histamines, leukotrines, and other agents from mast cells after IgE interaction

-inhalant nebulizer solution or nasal spray

-used in management of allergic rhinits

Leukotrine receptor antagonists:

-block leukotriene

-taken orally

-used to treat allergic rhinitis and asthma

Immunotherapy

recommended treatment for control of allergic symptoms when allergen cannot be avoided, and drug therpay is not effective

-definitively indicated for those w/ anaphylactic rxns to insect venom

-involves giving small titers of an allergen extract in increasing strengths until hyposensitivity to specific allergen is achieved

• avoid offending allergen whenever possible bc complete desensitization is impossible

-food allergies cannot be safely treated w/ this therapy

-eczema may worsen w/ immunotherapy

MOA:

-allergens mor readily combine w/ IgG

-administration of allergen will stimulate increased IgG levels

-IgG binds to allergen-reactive sites

• interferes w/ allergen binding to mast cell bound IgE

• prevents mast cell degranulation

-goal is to keep IgG levels high to maintain “blocking” action

Subcutaneous therapy:

-sub-q injection of titrated amounts of allergen extracts biweekly or weekly

-often takes 1-2 years to reach maximal therapeutic effects

-therpy may continue for 5 years

-severe allergies or sensitivity to insect stings may continue maintenance therapy indefinitely

Sublingual therapy:

-allergen extracts taken under tongue

• Oralair, Grastek, Ragwitek

-usually take once daily at home

-some pts have local application site rxns = oral pruritis, throat irritation, tongue swelling

-has advantage of being conveint, self-administerted oral therapy

Nursing management:

-always carries risk for severe anaphylactic rxn

-HCP, emergecy equipment, and essnetial drugs should be available whenever injections are given

-early manifestations of systemic rxn = itching, hives, sneezing, laryngeal edema, and hypotension

• begin measures for anaphylactic shock

-describe any local rxns according to degree of redness, swelling at injection site, if area is greater than the size of a quarter in an adult report reaction to HCP

-always give allergen extract in extremity away from joint so you can apply torniquet for severe rxn

-rotate injection sites

-observe pt for 20-30 min after injection

-teach pt that delayed rxn can occur up to 24hrs later

Latex allergy

-increased coincides w/ sharp increase in glove use

-more frequent and prolonged exposure to latex, ther greater the risk for developing allergy

-latex proteins become aerosolized through power on gloves and can result in serious rxns when inhaled by sensitized persons

Type IV rxns:

-contact dermatitis is caused by the chemicals used in manufacturing latex gloves

-delayed rxn that occurs w/i 6-48hrs

-first has dryness, itching, fissuring, and cracking of the skin followed by redness, swelling, and crusting at 24-48hrs

-chronic exposure can lead to lichenification, scaling, and hyperpeigmentation

Type I rxn:

-a response to the natural rubber latex proteins

-occurs w/i minutes of contact

-manifestations can vary from skin redness, hives, rhinitis, conjunctivitis, or asthma to full-blown anaphylactic shock

Latex-food syndrome:

-some food may cause allergic rxn in people w/ latex allergy

-banana. avacado, chestnut, kiwi, tomato, water chestnut, guava, hazelnut, potato, peach, grape, and apricot

• most people allergic to at least 1 related food

Nursing management:

-obtain thorough health hx

-greatest risk factor is long-term multiple exposures to latex products

• other risk factors = pt hx of rhinits, asthma, and allergies to those latex-related foods

-use latex precaution protocols

• use non latex gloves for activities not not likely to involve contact w/ infectious materials

• if you choose latex gloves, use powder-free gloves

• do not use oil-based hand creams or lotions when wearing latex gloves

• frequently clean work areas that are contaminated w/ latex-containing dust

• frequently change ventilation filters and vacuum bags used in latex contaminated areas

• learn to recognize symptoms of latex allergy = skin rash; hives; flushing; itching; nasal, eye, or sinus symptoms; asthma

• if symptoms of allergy develop, avoid direct contact with glloves and products

• wear medic alert bracelet and carry epipen

Multiple chemical sensitivity

subjective illness marked by recurrent, vague, nonspecific symptoms attributed to low levels of chemical, biologic, or physical agents

-commonly accused substances = smoke, pesticides, plastics, synthetic fabrics, scented products, petroleum products, and paint fumes

-wide range of non-specific symptoms

• headache, fatigue, dizziness, nausea, congestion, itching, sneezing, sore throat, chest pain, breathing problems, muscle pain or stiffness, skin rash, diarrhea, bloating, gas, confusion, difficulty concentrating, memory problems, and mood changes

-diagnosis made on pts health hx

-psychotherapy recommended

-in pts unwilling to undergo psychotherapy SSRIs and drugs for anxiety and sleep have been used

Autoimmunity

immune response against self in which the immune system no longer differentiates self from non-self

-antibodies and autosensitized T cells cause tissue damage

-cause is unknown but main factors in development include

• inheritance of susceptibility genes

• initiation of autoreactivity by triggers s/a infections

-autoimmune disease tend to cluster

-viruses may be involved in the development of diseases s/a type 1 diabetes

• rheumatic fever and rheumatic heart disease are autoimmune responses triggered by strep infection

-drugs can be precipitating factors in autoimmune disease

-gender and hormones have role in autoimmune disease

• more women than men have autoimmune diseases

-often group diseases according to organ specific and systemic diseases

- SLE classic example of autoimmune disease characterized by damage to multiple organs

Aphresis

procedure to separate components of blood followed by the removal of 1 or more of these components

-effective treatment for several autoimmune diseases

-plateletpherisis is removal of platelets

-leukocytapheresis is removal of WBCs

-apheresis is used in hematopoietic stem cell transplantation to collect stem cells from peripheral blood

Plasmapheresis:

-removal of plasma containing components causing or thought to cause disease

-involves removing whole blood then circulating the blood through and apheresis machine

• plasma is replaced w/ normal saline, lactated ringers, fresh frozen plasma, plasma protein fractions, or albumin

-has been used to treat autoimmune diseases s/a SLE, glomerulonephritis, Goodpasture syndrome, myasthenia gravis, rheumatoid arthritis, and Guillain-Barre syndrome

-reason for perfroming is to remove pathologic substances present in plsma

-may remove inflammatory mediators that cause tissue damage

-most common complications are hypotension and citrate toxicity

• citrate, used as anticoaguant, may cause hypocalcemia → headache, parsethesias, and dizziness

Immunodeficiency disorders

involve an impairment of 1 or more immune mechanisms which include =

• phagocytosis

• humoral response

• cell-mediated response

• complement

• combined humoral and cell-mediated deficiency

-primary if immune cells are improperly developed or absent

-secondary is an illness or treatment causes the deficiency

Secondary immunodeficiency disorders:

-causes

• age (infant, older)

• AIDS, burns, cancers, CKD, cirrhosis, diabetes, Hodgkin lymphoma, severe infection, SLE, trauma

• chemotherapy drugs, corticosteroids

• cachexia, dietary deficiency

• chronic stress, trauma (physical or emotional)

• antsthesia, radiation, surgery

-drug immunosuppression is most common

• immunosuppression is a serious side effect of drugs used in chemotherapy

-secondary infections common in immunosuppressed pts

-malnutrition alters cell-mediated response

• protein deficiency increases infection susceptibility

-viruses may cause immunodeficicency by direct cytotoxic damage to lymphoid cells

-radiation can destroy lymphocytes either directly of through depletion of stem cells

-splenectomy in children is especially dangerous

-stress may alter immune response

Human leukocyte antigen system (HLA)

major histocompatiblity antigens = responsible for rejection of genetically unlike tissues

-present on all nucleated cells and platelets

-primarily used to match organs and tissues for transplantation

• primarily use A, B, and DR genes for compatibility matching

-many of HLA-associted disease are autoimmune disorders

-those that have these allelles have a greater relative risk of developing the disease. Ex:

• HLA-B27 and ankylosing spondolytis

• HLA-DR2, HLA-DR3 and SLE

• HLA-DR3, HLA-DR4 and diabetes mellitus

Organ transplantation

-common tissue transplants include

• corneas, skin, bone marrow, heart valves, bone, and connective tissues

-transplanted organs currently come from many diff body systems and include

• heart, lung, liver, kidney, pancreas, and intestine

-multiple organs can be transplanted together

-some organs cen be trnasplanted in parts or segments instead of transplanting an entire organ

-organ donations come from either deceased or living donors. most currently com from deceased

• on either death or imminent death, the person’s legal next of kin may need to consent to the donations regardless of the donor’s wishes

-organs in highest demand are kidneys, hearts, and livers = also the most transplanted

-pts are matched to available donors based on several factors

• ABO blood and HLA typing, medical urgency, time on waitlist, and geogrpahic location

• donor and recipient do not need to share same Rh factor

Tissue typing

-donor and recipient do not have to share same Rh factor

HLA typing:

-only A, B, and DR anitgens are clinically significant for tranplantation

-antigen matches of 5 and 6 antigens and some 4-antigen matches have better clinical outcomes

• means pt less likely to reject transplanted organ

-degree of HLA typing needed for suitable successful transplanation depends on type of organ and degree of acceptable risk

• in kidney and bone marrow transplantation, HLA typing is very important since these transplants are at high risk for graft rejection

• hard to get good HLA matches for liver, lung, and heart transplants

Panel of reactive antibodies:

-shows the recipients sensitivity to various HLAs before receving a transplant

-allows us to determine whether a recipient is of high or low reactivity to potential donors

• pts awaiting tranplantation usually have done on regular basis

-a high PRA means that the person has many cytotoxic antibodies and is highly sensitized; there will be a poor chance of finding a cross-match negative donor

-plasmapheresis and IV immunoglubulin are options to lower the # of antibodies

Crossmatch:

-done to determine existance of antibodies against the potential donor

-can be used as a screening tests when possible living donors are being considered or once a cadaver is chosen

-negative crossmatch means that no performed antibodies are present, and it is safe to go ahead w/ transplantation

• positive crossmatch is absolute contraindication in living-donor transplants; may be done if no other living donor exists = plasmapheresis and IV immunoglobulin can remove antibodies 

-not always possible to complete crossmatch prior to transplantation

-prospective crossmatch is especially important for kidney transplants

• not an option for lung, liver, and heart transplants

Transplant rejection

-occurs as a normal response to foreign tissue

-immunosuppression therapy, ABO and HLA matching, and ensuring crossmatch is negative reduces chance for rejection

• perfect match is nearly impoossible unless tissue is from self, identical twin, or sibling

Hyperacute rejection:

-occurs w/i 24 hrs after transplantation

-occurs bc person has preeixsting antibodies against transplanted tissue or organ

-no treatment

-must remove transplanted organ

-rare event

Acute rejection:

-most often occurs w/i first 6 months after transplantation

-usually cell-mediated immune response by recipients lymphocytes

-also occurs when recipient develops antibodies to trnaplanted organ (humoral rejection)

-common to have at least one rejection episode, especially w/ organs from deceased donors

-usually reversible w/ additional immunosuppressive therapy

• increased corticosteroid doses or polyclonal or monoclonal antibodies

-need lifelong use of immunosuppression therpay

Chronic rejection:

-occurs over months to years

-irreversible

-can occur from unknown reasons or from repeated episodes of acute rejection

• T and B cells infiltrate the transplanted organ, w/ ongoing, low-grade, immune mediated injury → fibrosis and scarring

-no definitive treatment, primarialy supportive

-hard to manage and does not have optimistic prognosis

Immunosuppressive therapy

requires lifelong balance btwn rejection and infection

-many drugs have significant side effects

-risk for toxicity continues for the rest of their lives

-major agents include

• calcineurin inhibitors

• corticosteroids

• purine synthesis antagonists

• sirolimus

-most pts typically initially on triple therapy

-standard triple therapy includes = calcineurin inhibitor, corticosteroid, and mycophenolate mofetil

-doses are reduced over time after transplant

• minimal corticosteroids used due to their side effects

Calcineurin inhibitors

cyclosporine, tacrolimus

-foundation of most immunosuppression regimens

-prevent cell-meidated attack against the transplanted organ

-do not cause bone marrow suppression or alterations oof normal inflammatory response

-generally used in combo w/ corticosteroids, mycophenolate mofetil, and sirolimus

*do not take w/ grapefruit or grapefruit juice

SE:

Cytotoxic drugs

Sirolimus:

-approved for renal transplant pts

-used in combo w/ coricosteroids and cyclosporine or w/ tacrolimus

-SE:

Mycophenolate mofetil:

-lymphocyte-specific inhibitor of purne synthesis

-most effective when taken w/ tacrolimus or cyclosporine

-decrease the indcidence of late graft loss

-can cause GI toxicity

-reconstitute w/ D5W; IV admin over 2 or more hrs

-SE:

Monoclonal antibodies

alemtuzumab, basiliximab

-prevent and treat acute rejection episodes

-Muromonab = first used

• binds w/ CD3 receptors on T cells causing cell lysis and inhibits function of cytotoxic T cels

• causes flu like symptoms during first few days of therapy - fever, rigors, headache, myalgias, GI distrubances

• co-admin of acetaminophen, diphenhydramine, and IV methylpredinisone can reduce these side effects

-newer gen drugs have fewer side effects

• daclizumab, basiliximab

Polyclonal antibodies

horse antithymocyte globulin (atgam), rabbit antithymocyte globulin

-used as induction therapy or to treat acute rejection

-induction therapy causes severe immunosuppression immediately after transplantation to prevent early rejection

-horses are immunized w/ human lymphocyted then the antibodies are obtained, purufied, and administered via IV

-recipient can have allergic reactions to foreign proteins

• fever, arthralgis, and tachycardia

-administer over 4-6hrs, premediacting w/ acetaminophen, diphenhyrdamine, and methylpredinisone can decrease rxns

-primary toxicities include lymphopenia and thrombocytopenia

Graft-versus-host disease (GVHD)

occurs when an immunodeficient pt receives immunocompetent cells

-the grafts (donated tissue) rejects the host (recipient) tissue

-most common in hematopoietic cell transplants

-may begin 7-30 days after transplantation

-involves donor T cells attacking and destroying vulnerable host cells

-target organs include skin, liver, and GI tract

-skin

• maculopapular rash w/ pruritis or pain

• initially on palms and soles

• can progress to generalized eythema and bollus formation and desquamation

-liver

• range from mild jaundice w/ elevated liver enzymes to hepatic coma

-GI tract

• mild to moderate diarrhea, severe abdominal pain, GI bleeding, and malabsoprtion

-biggest problem w/ disease is infection, w/ diff types of infection seen in diff periods

-no adequate treatment once established

• corticosteroids often used but enhance susceptibility to infection

• immunosuppressive agents most effective as preventative measure rather than treatment

• Ibrutinib is an option for some pts w/ chronic GVHD

cancer

a group of diseases characterized by uncontrolled and unregulated cell growth

-majority of cases are diagnosed in those over age 55, however occurs in people of all ages

-both incidence and mortality rates have been declining

-overall incidence is higher in men than women

-second most common cause of death in U.S.

-leading cause of death in people 40-79 years of age

-two major dysfunctions present in the process of development

• defective cell proliferation (growth)

• defective cell differentiation

-development is usually an orderly process that occurs over time

• 3 stages = initiation, promotion, and progression

Cancer gender considerations

Men:

-more die from cancer-related deaths each year

-have a higher mortality rate from lung cancer

-prostate cancer has the highest incidence among men

-more likely to develop liver cancer

-more likely to be diagnosed w/ invasive cancer over their lifetime

Women:

-lung cancer has highest death rate among women

-Breast cancer has highest incidence among women

-thyroid cancer is more prevalent in women

-cancer incidence is higher in females during early adulthood (ages 20-49)

Initiation (cancer development)

cancer cells arise from normal cells because of changes in genes

-involves mutation in the cell’s genetic structure 

• mutation = any change in usual DNA sequence

• can be inherited or acquired 

-most cancers are acquired from damaged genes during ones lifetime

-if cell death or repair does not occur before cell division, the cell will replicate into daughter cells, each w/ the same genetic alteration

Carcinogens:

-cancer causing agents capable of producing cell alterations = can enter cell’s nucleus and alter DNA

-may be chemical, radiation or viral

Chemical carcinogens:

-benzene, arsenic, formaldehyde

-people exposed to these chemicals over time have a greater incidence of certain cancers

-long latency period makes it hard to identify cancer-causing chemicals

Radiation carcinogens:

-can cause cancer in almost any body tissue

-higher incidence of cancer may occur in people exposed to radiation in certain occupations

• radiologists, radiation chemists, aircrews, and uranium miners

-UV radiation has long been associated w/ melanoma and squamous and basal cell skin cancers

• most common type of cancer among whites

• sunlight exposure is main source of UV radiation, can also be exposed from tanning beds

Viral carcinogens:

-oncogenic viruses can alter the cells they infect and induce malignant transformation

-identified as causative agents of cancer in animals and humans

• Epstein-Barr virus

• HIV

• Hepatitis B

• HPV

Promotion (cancer developement)

second stage in cancer development

-characterized by the reversible proliferation of the altered cells

-an increase in the altered cell population increases the likelihood of more mutations

-activity of promoters is reversible

-promoting factors include agents s/a = obesity, cigarette smoking, and alcohol use

-lifestyle changes to modify these risk factors can reduce the chance of cancer development

• cancers caused by obesity, alcohol use, unhealthy diet, smoking, and physical activity are avoidable

-several promoting agents have activity against specific body tissues

• cigarette smoking is a promoting agent in lung cancer

• cigarette smoking and alcohol use promotes esophageal and bladder cancers

-complete carcinogens are capable of initiating AND promoting cancer development

• ex: cigarette smoke

-time btwn first genetic alteration and actual clinical evidence of cancer = latent period. Includes initiation and promotion stages

• this process is years or decades in length for most cancers

-for disease to be clinically significant tumor must reach a critical mass that can be detected

• 0.4 inch is detectable on palpation

• 0.5cm is smallest size that can be detected w/ current diagnostic measures s/a MRI

Progression (cancer development)

third and last stage of cancer development

-increased growth rate of the tumor, increased invasiveness, and metastasis

-some cancers have affinity for a particular tissue or organ for site of metastasis

• most common sites of metastasis = lungs, liver, bone, and brain/cerebrospinal fluid

Metastasis:

-begins w/ rapid growth of primary tumor, as it grows develops its own blood supply

• process of forming blood vessels w/i tumor itself = angiogenesis

-tumor cells can detach from primary tumor, invade tissue surrounding tumor, and penetrate the walls of lymph or vascular vessels for metastasis to distant sites

-tumor cells often travel to distant sites via hematogenous or lymphatic routes

Hematogenous metastasis:

-begins w/ primary tumor cells penetrating blood vessels

-tumor cells then enter the circulation, travel through the body, and adhere to and penetrate small blood vessels of distant organs

Lymphatic metastasis:

-tumor cells can be “trapped” in the first lymph node to which cancer cells are most likely to spread from a tumor = sentinel lymph node

-sentinel lymph node biopsy (SLNB) can help determine the extent of the cancer

• positive biopsy means cancer is present in sentinel node and may have spread to other lymph nodes and organs

-tumor cells may bypass local lymph nodes and travel to distant lymph nodes = skip metastasis

-vascularization is critical to the supply of nutrients to the metastatic tumor and the removal of waste products

Immune system in cancer

-cancer cells may have altered cell-surface antigens bc of malignant transformation = tumor-associated antigens (TAAs)

-immune system responds to TAAs through immunologic surveillance

• lymphocytes continuously check cell-surface antigens = detect and destroy cells w/ abnormal or altered cell-surface antigens

-immune response to cancer involves cytotoxic T cells, NK cells, macrophages, and B cells

-cytotoxic T cells kills tumor cells directly and produce cytokines

-NK cells and activated macrophages can lyse tumor cells

-B cells produce antibodies that bind to tumor cells

Immunologic escape:

-process by which cancer cells evade the immune system

-possible mechanisms include…

• suppression of factors that stimulate T cells to react to cancer cells

• weak surface antigens allowing cancer cells to “sneak through”

• immune system develops tolerance to some antigens

• suppression of immune system by products secreted by cancer cells

• induction of suppressor T cells by tumor

• blocking antibodies that bind TAAs

Oncofetal antigens

-type of tumor antigen found on the surfaces and the inside of cells and fetal cells

-examples include CEA and AFP

-can be used as tumor markers that may be clinically useful to monitor the effect of therapy and indicate tumor recurrence

• not 100% effective for tumor recurrence

Benign vs malignant neoplasms

Benign:

-well differentiated

-usually encapsulated

-metastasis is absent

-recurrence is rare

-have slight vascularity

-have expansive mode of growth

-cells are fairly normal, like parent cells

Malignant:

-range from well-differentiated to undifferentiated

-rarely encapsulated

-capable of metastasis

-recurrence is possible

-have moderate to marked vascularity

-have infiltrative and expansive mode of growth

-cells are abnormal, become more unlike parent cells

Anatomic site classification (cancer)

-tumor is identified by the tissue of origin, anatomic site, and behavior of the tumor

-carcinomas originate from the skin and glands (ectoderm) and mucous membrane linings of the respiratory tract, GI tract, and genitourinary tract (endoderm)

-sarcomas originate from connective tissue, muscle, bone, and fat (mesoderm)

-lymphomas and leukemias originate from the hematopoietic system

Histologic classification

-grading is based on the degree to which the cells resemble the tissue of origin

• poorly differentiated tumors have a poorer prognosis than those that are closer in appearance to the normal tissue of origin

• 4 grades

-Grade I: cells differ slightly from normal cells (mild dysplasia) and are well-differentiated (low-grade)

-Grade II: cells are more abnormal (moderate dysplasia) and moderately differentiated (intermediate grade)

-Grade III: cells are very abnormal (severe dysplasia) and poorly differentiated (high-grade)

-Grade IV: cells are immature, primitive (anaplasia), and undifferentiated. Cell origin is hard to determine (high-grade)

-Grade V: grade cannot be assessed

Clinical staging classifications

-staging involves classifying extent and spread of disease

-can be done initially and at several points

-can guide treatment selection

-clinical staging determines the anatomic extent of the cancer

• Stage 0: cancer in situ

• Stage I: tumor limited to the tissue of origin; localized tumor growth

• Stage II: limited local spread

• Stage III: extensive local and regional spread

• Stage IV: metastasis

-carcinoma in situ (CIS) refers to a cancer whose cells are localized and show no tendency to invade or metastasize to other tissues

TNM classification

-used to determine th anatomic extent of cancer involvement

-3 parameters = tumor size and invasiveness (T), presence or absence of regional spread to the lymph nodes (N), and metstasis to distant organs (M)

-do not use this staging w/ all cancers

• do not stage leukemias w/ this system since they are not solid tumors

-latest cancer staging guidelines for some cancers add non-anatomic factors when making the final determination of stage

• staging still based on TNM but it adds grade and hormone receptor expression, also includes genomic profile results

-allows for a more accurate determination of prognosis and better guide therapy

-surgical staging determines extent of disease by surgical excision, exploration, and/or lymph node sampling

• margins of any masses may be marked w/ metal clips for use during radiation therapy

-if pt needs more treatment, if tratment fails = restaging is done to determine the extent of the disease before retreatement

-”restaging-classification (rTNM) is distinguished from the stage at diagnosis since the clinical signifcance may be diff

-staging cannot decrease, but stage can increase

• ex can progress from stage 3 lung cancer to stage 4

-can use other rating scales to describe and document the pts status at the time of diagnosis, treatment, retreatment, and at each follow-up appointment

• Kanofsky Performance Scale

• Katz Index of Independence in Activities of Daily Living

7 warning signs of cancer

C.A.U.T.I.O.N

-changes in bowel or bladder habits

-a sore that does not heal

-unusual bleeding or discharge from any body orifice

-thickening of a lump in the breast or elsewhere

-indigestion or difficulty in swallowing

-obvious change in a wart or mole

-nagging cough or hoarseness

Diagnoses of cancer

-help coordinate care among multiple specialties

-explain the purpose of required tests and any special preparation needed

-actively listen to pt concerns

-learn to manage own discomfort during difficult conversations

-avoid conversation that hinders exploration of feelings and meaning

-give clear, understandable explanations and reinforce them as needed; avoid using overly technical language

-diagnostic plan includes a health hx, identifying risk factors, the physical assessment, and specific diagnostic studies

-concentrate on risk factors for cancer

-assess factors that may call for additional supportive care during therapy s/a alcohol or drug use, living situation, social support, and coping strategies for perceived stressors

Diagnostic studies:

-cytology studies

-CXR

-CBC, chemistry profile

-liver function studies

-endoscopic examinations

-radiographic studies

-radioisotope scans

-PET scan

-tumor markers

-genetic markers

-molecular receptor status

-bone marrow examination

Biopsy

the removal of a tissue sample for pathologic analysis

-Percutaneous biopsy = done for tissue that can be safely reached through the skin

-endoscopic biopsy = may be used for lung or intraluminal lesions

-when a tumor is not easily accessible, surgery may be done to obtain a piece of the tumor tissue

-radiographic techniques may be used to improve tissue localization

• CT, MRI, ultrasound-guided biopsy, and stereotactic biopsy

-fine needle aspiration (FNA) = may be done w/ small gauge aspiration needle that provides cells from the mass or cytologic examination

-large-core biopsy = cutting needles deliver an actual piece of tissue for analysis

-excisional biopsy = surgical removal of the entire lesion, lymph node, nodule, or mass

• therapeutic as well as diagnostic

-incisional biopsy = partial excision that may be done w/ scalpal or dermal punch

-pathologic evaluation of a tissue sample is only definitive way to diagnose cancer

• pathologist examines tissue to determine = benign or malignant, origin, and histologic grade

Prevention and detection of cancer

-prevention is key

-war on cancer will not be won w/ drugs or radiation therapy

-a stronger emphasis on prevention is needed

Lifestyle habits to reduce risks:

-practice recommended cancer screenings

-practice self-examination

-know seven warnings signs of cancer

-seek medical care if cancer is suspected

-avoid or reduce exposure to known or suspected carcinogens

• cigarette smoke, excessive sun exposure

-eat a balanced diet

-limit alcohol intake

-exercise regularly

-have a regular health exam

Cancer Treatment goals

cure, control, and palliation

-main factors that determine the therapy plan are tumor histology and staging outcomes

• other crucial factors are pts psychologic status, physiologic status, and personal desires

-many pts receive 2 or more treatment modalities = has benefit of being more effective

• takes advantage of more than 1 mechanism of action at the expense of greater toxicity

Cure:

-expect treatment to have greatest chance of eradicating the cancer

-therapy differs by type of cancer

-may involve local therapies alone or in combination w/ or w/o adjunctive system therapy

-no benchmark that ensures “cure” for most cancers

-risk for recurrent disease is highest after treatment completion

• gradually decreases the longer the pt is cancer free after treatment

-cancer w/ a higher mitotic rate are more likely to recur than cancers w/ lower mitotic rate

-timeframe to consider person “cured” differs depending on the tumor and its characteristics

Control:

-goal of treatment for cancers that we cannot completely eradicate but are responsive to anticancer therapies

-pts may receive an initial course of treatment followed by maintenance therapy for as long as the disease is responding

-monitored closely for early signs and symptoms of cancer recurrence or progression and the cumulative effects of therapy

Palliation:

-goal of treatment when the goals are symptom control or relief and maintaining a satisfactory quality of life

-palliative care and treatment can take place concurrently

-example of palliation goal includes using radiation therapy to reduce tumor size and relive subsequent symptoms

Personalized cancer medicine

-involves using the pts genetic information to guide decisions about cancer prevention, diagnosis, and treatment

-have found that genetic differences in people and their tumors explain some of the diff treatment responses

-next gen sequencing, or massive parallel sequencing can determine if a pts cancer is caused by a hereditary cancer syndrome or if its sporadic

• results guide which specific drugs target a pts mutation and help identify clinical trials specific to the genetic mutation

-targeted therapy targets a cancer’s specific genes or proteins that contribute to cancer growth and survival

• treatment depends on assessing whether tumor has specific target

-not all types of cancer have personalized treatment options

-some personalized treatments, s/a targeted treatments can be expensive

• many insurance companies do not cover the costs of genetic testing needed for these treatments

Surgical therapy (cancer)

oldest form of cancer treatment

-can eliminate or reduce the risk for cancer development

-prophylatic removal of nonvital organs has been successful in reducing risk for some cancers

• total colostomy to prevent colon cancer

• prophylactic mastectomy

Cure or control:

-when the goal is cure or control, the objective is to remove all or as much resectable tumor as possible while sparing normal tissue

• trend is toward less radical surgeries

-pt must undergo a debulking or cytoreductive procedure if tumor cannot be completely removed

-debulking = as much tumor as possible if removed, pt then rececives chemotherpay and/or radiation therapy

-pt may need to receive neoadjuvant (treatment before surgery) chemotherapy or radiation to reduce tumor size and improve surgical outcome

Supportive and Palliative Care:

-surgical procedures can be part of supportive care that maximizes bodily function or facilitates cancer treatment

• insertion of gastric feeding tube

• placement of central venous access device

• prophylactic surgical fixation of bones at risk for pathologic fracture

-effects of treatment or symptoms from metastatic cancer may require surgical intervention for palliation

Chemotherapy

use of chemicals as a systemic therapy for cancer

-can offer cure for some cancers, control other cancer for long periods, and in some cases, offer palliative relief of symptoms when cure or control is no longer possible

Effect on cells:

-goal of chemotherapy is to eliminate or reduce the number of cancer cells in the primary and metastatic tumor sites

-2 major categories of drugs

• cell cycle phase non-specific = have their effect on the cells during all phases of the cell cycle

• cell cycle phase specific = have their greatest effects during specific phases of cell cycle

-giving drugs together maximizes their effectiveness by using drugs that act in diff ways and throughout cell cycle

-most chemotherapy drugs are only effective against actively dividing cells (not those in the resting or inactive phase)

Preparation:

-only persons specifically trained in chemotherapy handling techniques should be involved in preparation and administration of cancer drugs

-may pose a health hazard to persons who do not follow safe handling guidelines

-may be some risk in handling the body fluids and excretions of people during the first 48hrs after they receive chemotherapy

Methods of admin:

-IV route is most common

• major concerns are venous access device problems or catheter related infection and extravasation

• can be given through central access device = allow frequent, continuous, or intermittent admin of chemotherapy, immunotherapy, targeted therapy, and other products

-w/ advances in drug formulation techniques more oral chemotherapy drugs are available

Extravasation (chemotherapy)

the infiltration of drugs into tissues surrounding the infusion site, causing local tissue damage

Irritants:

-damage the intima of the vein, causing phlebitis an sclerosis and limiting future peripheral venous access

-will NOT cause tissue damage if infiltrated

Vesicants:

-if infiltrated may cause severe local tissue breakdown and necrosis

-very important to monitor for and take prompt action if extravasation of vesicant occurs

Regional chemotherapy

involves delivery of the drug directly to the tumor site

-can deliver higher concentrations of the drug to the tumor w/ less systemic toxicity

Intraarterial chemotherapy:

-delivers the drug to the tumor through the arteries supplying the tumor

Intraperitoneal chemotherapy:

-delivery of chemotherapy to the peritoneal cavity

chemotherapy is usually infused into the peritoneum in 1-2L of fluid and allowed to dwell in peritoneum for 1-4 hrs

• after dwell time fluid is drained

Intrathecal or Intraventricular chemotherapy:

-involves a lumbar puncture and injection of chemotherapy into the subarachnoid space

-may have an ommaya reservoir inserted = soft, plastic, dome-shaped disk w/ extension catheter

Intravesical bladder chemotherapy:

-involves instilling chemotherapy into the bladder

-solution is retained for 1-3 hrs

Chemotherapy effects

Effects on normal tissues:

-drugs cannot selectively distinguish btwn normal cells and cancer cells

-chemotherapy induced side effects result from the destruction of normal cells, espeically those that are rapidly proliferating

• cells in bone marrow, lining of GI tract, and integument

-acute toxicicty occurs during and right after drug administration

• anaphylactic and hypersensitivity rxns, extravasation or flare rxns, anticipatory N/V, dysrhythmias

-delayed effects are numerous

• delayed N/V, mucosistis, alopecia, skin rashes, bone marrow suppression, altered bowel function, and various cummulative neurotoxicities

-chronic toxicities involve damage to organs s/a heart, liver, kidneys, and lungs

Treatment plan:

-most common treatment plans combine drugs in multidrug regimens = target more than one signaling pathway

• can have increase in toxicities

-chemotherapy most effective when tumor burden is low, therapy is not interrrupted, and the pt receives the intended dose

-mutation of cancer cells w/i the tumor can result in cells that are resistant to chemotherapy

Radiation therapy (cancer)

uses high energy beams or waves that when absorbed into tissue, produce ions in the cells

-acts to break the chemical bonds in DNA

-the DNA is damaged causing cell death

-low energy beams penetrate only a short distance

• clinically useful in treating superficial skin lesions

-high energy beams have greater depth of penetration, not reaching full intensity until they reach a certain depth

• suitable for delivering optimal doses to internal targets while sparing skin

-radiation to surrounding tissue must be limited to the “maximal tolerated dose” for that specific tissue

-radiation doses are expressed in units called a gray (Gy) or centigray (cGy)

• 100 centigray - 1 gray

• once total dose to be delivered is determined the dose is divided into daily fractions

• doses btwn 180 and 200 cGy/day are considered standard fractionation

-typically delivered once a day Mon-Fri for a period of 2-8 weeks

-radiosensitivity is the relative responsiveness of cells and tissues to the effects of radiation

-radiation is used to treat a carefully defined area of the body

• not appropriate as the main treatment for systemic disease

• may be used by itself, in combo w/ chemo or surgery to treat primary tumors, or for palliation of metastatic lesions

Simulation:

-a process by which radiation treatment fields are defined, filmed, and marked out on skin

-radiation oncologist specifies dose and volume of area to be treated

-marks placed on skin to outline treatment field

Radiation methods

radiation is used to treat a defined area of the body

External radiation:

-most common form of raiation delivery

-pt is exposed to radiation from a megavoltage treatment machine

-a linear accelerator is the most commonly used machine for delivering external beam radiation

-gamma knife technology = used to deliver highly accurate stereotactic treatment to a localized treatment volume. Uses cobalt source

Internal radiation:

-brachytherapy = consists of implantation or insertion of radioactive materials directly into the tumor or near the tumor

-allows for direct delivery of radiation to the target w/ minimal exposure to surrounding healthy tissues

-may be primary or adjuvant therapy

-sources of radiation include temporary sealed sources and permanent sealed sources supplied in the form of seeds or ribbons

-w/ a temporary implant the source may be placed into a special catheter or metal tube that has been inserted into the tumor area

-permanent implants involve the insertion of radioactive seeds directly into the tumor tissue, where they stay permanently

-pts are not considered radioactive, however, some initial radiation precautions may be recommended

-overtime radioisotopes that are used decay and are no longer radioactive

-radioactive drugs or radiopharmeceuticals are used to treat same cancer systemically

-pts w/ temporary implants are only radioactive while the source is in place; radioactive exposure to the outside and other is low

-follow principles of ALARA (as low as reasonably achieveable and time, distance, and shielding) 

• vital to safety when caring for person w/ internal radiation

• do not deliver care w/o wearing film badge to show cumulative exposure

Bone marrow suppression (side effects of radiation and chemotherapy)

-myelosuppression is one of the most common effects of chemotherapy

-can result in life-threatening and distressing effects

• hemorrhage, infection, and overwhelming fatigue

-radiation only affects bone marrow w/i the treatment feild

-chemo affects bone marrow function throughout the body

• WBCs are affected first (w/i 1-2 weeks), then platelets in 2-3 weeks, and RBCs later

-radiation to a large marrow containing regions of the body cause more clinicaly significant myelosuppression

• most of the active marrow is in the pelvis and thoracic and lumbar vertebrae

-monitor the CBC, pts often have lowest blood cell counts btwn 7 and 10 days after starting therpay

-neutropenia is mor common in pts receiving chemo. Is is a serious risk factor for life-threatening infection and sepsis

• hand hygiene is mainstay of pt safety

• monitor temp routinely = fever in presence of neutropenia is a medical emergency

-WBC growth factors are used as prophylactic measure to prevent neutropenia when highly suppressive chemotherpay drugs are used

-thrombocytopenia can result in spontaneous bleeding or major hemorrhage

• avoid activities that place them at risk for injury or bleeding

-Anemia is common in pts undergoing either radiation or chemo

• generally has later onset

• may receive RBC growth factors

• in extreme circumstances may need RBC transfusions, in general we avoid RBC transfusions

Fatigue (side effect of radiation and chemo)

-persistent sense of tiredness that inteferes w/ usual day-to-day function

-many describe fatigue as most disturbing of treatment-related side effects

-anemia is one cause of fatigue

-other causes related to

• toxic substances left in the body from cells killed by cancer treatment

• need for extra energy to repair and heal body tissue damaged by treatment

• lack of sleep caused by some chemo drugs or steroids

-assess for reversible causes of fatigue = anemia, hypothyroidism, depression, insomnia, dehydration, infection

identify days or times during the day when pts typically feel better and encourage them to be more active during those periods

-rest before activity and have others to w/ work or home tasks

-maintain exercise and activity w/ tolerable limits

-encourage use of walking programs

GI effects (side effects of radiation and chemo)

-problems include N/V, diarrhea, mucosistis, and anorexia

-radiation to treatment feilds that contain GI structures and selected chemo drugs cause direct injury to GI epithelial cells

Nausea and vomitting:

-chemotherapy induced N/V may occur w/i 1 hr of chemo admin

-vomiting may start a few hrs after radiation therapy to the chest or abdomen

-administer antiemetics

• dexmethason given w/ other antiemetics helps manage acute and delayed CINV

-anticipatory N/V can develop if pt had poorly controlled N/V w/ prior chemo admin

• preventing N/V w/ first cycle lowers risk

• giving prophylactic antiemetic and antianxiety meds 1hrs before treatment helps

• eating light meal of nonirritating food before treatment is helpful

-delayed N/V can develop 24hrs to a week after treatment

• treatment includes antiemetic drugs, diet adjustments, and nondrug interventions

Diarrhea:

-best managed w/ diet adjustments, antidiarrheals, antimotility drugs, and antispasmodics

-diet low in fiber ad residue

-limiting foods high in roughage = fresh fruits, veggies, seeds, nuts

-avoid fried, fatty, and highly seasoned foods

-may need hydration and electrolyte supplements

Mucosistis:

-irritation, inflammation, and/or ulceration of the mucosa

-pts who receive radiation for head and neck cancer are at high risk

-meticulous oral care during and after treatment reduces risk for cavities

-saliva supplements may help w/ xerostomia

-dysgeusia (taste loss) may develop; dysphagia further impedes eating

-pts w/ odynophagia (painful swallowing) may need analgesics before meals

-teach pt to use soft-bristled tooth brush

-treat mucositis of pain in throat w/ systemic and topical analgesics and antibiotics if infection present 

Anorexia:

-important to have dietician involved before cancer treatment starts 

-seems to peek around 4 weeks of treatment, resolves more quickly than fatigue

-monitor to ensure weight loss does not become excessive 

Skin reactions

Radiation:

-skin changes are local, occuring only in the treatment field

-erythema may develop 1-24hrs after a single treatement

-generally occurs progressively as the treatment dose accumulates

-espically evident in areas of skin folds or where skin is subjected to pressure

• behind the ear, in gluteal folds, on the perinueam, breast or collar line, and bony prominences

-goal is to prevent infection and promote wound healing

-protect raidated skin from temp extremes

-avoid constricting garments, rubbing harsh chemicals and deodarants since they may traumatize skin

-dry rxns are uncomfortable and cause pururuits

• calendula ointment, topical hyaluronic acid cream, aloe vera gel

-wet desquamation generally causes pain, drainage and increased risk for infection

• keep tissues clean w/ normal saline compresses of modified Burow’s solution soaks

• moisture vapor-permeable dressings or vaseline petroleum gauze

Chemotherpay:

-erythrodysesthesia syndrome (hand-foot syndrome) = causes mild redness and tingling of the palms and soles

• may also cause painful moist desquamation, ulceration, blistering, and pain

-alopecia

• w/ radiation is local

• w/ chemotherapy hair loss is throughout body system

-alopecia from chemo is usually reversible

• hair does not grow back until 3-4 weeks after the end of therapy

Cardiopulmonary effects (side effects of radiation and chemo)

Pulmonary effects:

-both radiation and chemo have potential to cause irreversible and progressive lung damage

-acute effects may mimic symptoms that lead to cancer diagnosis

-pneumonitis is a delayed acute inflammatory rxn that may occur w/i 1-3 months after completing thoracic radiation

• increase in cough, fever, and night sweats may occur

-most common toxicities from chemo include pulmonary edema, hypersensitivity pneumonitis, interstitial fibrosis, and pneumonitis

Cardiac effects:

-radiation to the thorax can damage the pericardium, myocardium, valves, and coronary blood vessels

-pericarditis and pericardial effusion are key problems

-anthracyclines cause cardiotoxicity

-acute cardiotoxicities may cause ECG changes

-late effects cause left ventricular dysfunction and heart failure

Cognitive effects (side effects radiation and chemo)

“chemo brain”

-mental cloudiness or fog

-can have thinking and memory problems

-can last short time or years 

-can be so severe that pts may be unable to be involved in any activities that need mental effort including school, work, or social activities 

Reproductive effects (side effects chemo and radiation)

-inform pt of expected sexual side effects

-use appropriate shielding

-encourage discussion of issues related to reporduction and sexuality

-refer to counseling if needed

Late effects of radiation and chemo

-acute radiation effects generally manifest as transient inflammatory changes in highly proliferative cells

-late radiation effects occur most often in post-mitotic cells

• late effects may be progressive and generally permanent

-long term effects of chemotherapy include cardiac toxicity, cataracts, arthralgia, endocrine problems, renal insufficiency, hepatitis, osteoporosis, and neurocognitive problems

-cancer survivor may be at risk for secondary cancers including = leukemia, angiosarcoma, and skin cancer

-potential risk for developing secondary cancer does not contraindicate having cancer treatment

Immunotherpay and targeted therapy 

Immunotherapy:

-uses immune system to fight cancer

-some types called biologic therapy

-boost or manipulate the immune system and create an environement that is conducive for cancer cells to grow

-attack cancer cells directly

-types include cytokines, vaccines, and monoclonal antibodies

• monoclonal antibodies are very successful immunotherapy

Targeted therapy:

-interferes w/ cancer growth by targeting specific cell receptors and pathways that are important in tumor growth

• does less damage to normal cells

• agents that target specific oncogenes are being 

• key class of therapy is tyrosine kinase inhibitors

Side effects:

-flulike symptoms

-anorexia/ weight loss

-fatigue, malaise, weakness, 

-N/V

-photosensitivity

-tachycardia and orthostatic hypotension are common

-CNS effects

-hepatotoxicity

-renal system side effects

Nursing management:

-side effects occur more acutely and are dose limited

-can influence pt decision to continue therapy

-may not be reported for fear treatment may be stopped

Hormone therapy

-sex hormones when given as cancer treatment can block effects of the hormone and stop growth of cancer cells

-corticosteroids used in combo w/ drug regimens to help curb side effects

-surgical interventipns can be used to remove the effects of the hormone on cancer growth

Hematopoietic growth factors

-CSFs stimulate production, maturation, regulation, and activation of cells of the hematologic system

-erythropoiesis-stimulating agents (ESAs) can be used to treat anemia from chemotherapy that is not intended to cure

• can cause potential harm and increase the risk of death

• give the lowest dose that will gradually increase Hgb to the lowest level sufficient to avoid the need for blood transfusion

Hematopoietic stem cell transplant

-includes peripheral stem cell transplantation

-both allow for the safe use of very high doses of chemotherapy in pts whose tumors have developed resistance or did not respond to standard doses of chemotherapy and radiation

-drawback is that pts have long-term or delayed complications that can affect their quality of life

-approach is to eradictae diseased tmor cells and/or clear the bone marrow of its components to make way for engraftment of the transplanted, healthy stem cells

-life threatening consequences from pancytopenia and other adverse effects can result

-after chemotherapy and radiation therapy are over, healthy cells are infused

-intensive procedure w/ many risks

Allogenic transplantation:

-stem cells are acquired from a donor who has been determined to be HLA matched to the recipient

• common indications for allogenic transplantation are certain leukemias, multiple myeloma, and lymphoma

Syngeneic transplatation:

-involves obtaining stem cells from one identical twin and infusing them into the other

Autologous transplanatation:

-pts receive their own stem cells back after myeloablative chemo

HSCT procedures

Harvest procedures:

-stem cells are harvested from a donor or the recipient via 2 methods

1. harvesting stem cells via bone marrow is done in operating room and requires multiple bone marrow aspirations

• post harvest donor may have pain at collection site that lasts up to 7 days

• can be treated w/ mild analgesics

2. peripheral stem cell transplants are obtained from peripheral blood in outpatient procedures

• cell separator automatically separtates stem cells from the blood circualting through the machine

• often takes more than 1 procedure to obtain enough stem cells

• growth factors may be given to increase stem cell production for collection = stem cells will be harvested 4-5 days after they are given

-after collection stem cells are used immediately or bagged w/ preservatives for cryopreservation and stored until they are needed

-umbilical cord blood is rich in stem cells

• disadvantage is the risk of insufficient # of stem cells to allow a transplant to adults

Preparative regimens and stem cell infusions:

-Total body irradiation (TBI) can be used for immunosuppression or to treat the disease = conditioning regimen

-stem cell infusions given IV

-usually takes 2-4 weeks for transplanted marrow to start making hematopoeitic blood cells; during this period pt has pancytopenia

Complications:

-bacterial, viral, and fungal infections are common after HSCT

-potentially serioud complication after allogenic transplant is graft-vs-host disease

-hematologic recovery period in PSCT is shorter, and fewer, less severe complications occur

Gene therapy

experimental therapy that involves introducing genetic material into a person’s cells to fight disease

Complications of cancer

Malnutrition:

-pt may have protein and calorie malnutrition w/ fat and muscle depletion

-teach pt to avoid extremes of temp, tobacco, alcohol, spicy or rough foods, and other irritants. Use nutrition supplements in place of milk when cooking or baking

-weigh pt at least 2x a week to monitor for weight loss

-referral for diet counseling to the pt or HCP as soon as 5% weight loss is noted or if the pt has the potential for protein and calorie malnutrition

• once a 10lb weight loss occurs, it may be hard to maintain the pts nutrition status

Altered taste sensation (dysgeusia):

-physiologic basis of altered taste is unknown

-teach pt to

• avoid food that they dislike

• experiment w/ spices and seasonings to mask alterations

Cancer cahexia:

-characterized by anorexia and/or unintended loss of weight and appetite

-accompanied by generalized tissue wasting, skeletal muscle atrophy, immune dysfunction, and metabolic problems

-best way to manage is to treat cancer

-second option is to increase intake, but this does not completely reverse the wasting from cachexia

-third option is to use megestrol acetate which stimulates appetite in pts w/ cachexia

Infection:

-primary cause of death

-usual sites of infection = lungs, genitourinary tract, mouth, rectum, peritoneal cavity, blood

-occurs due to ulceration, compression of vital organs by tumor

-neutropenia caused by disease or treatment

Oncologic emergencies

life-threatening emergencies that occur due to cancer or cancer treatment

-obstructive emergencies are mainly caused by a tumor obstruction of an organ or blood vessel

• superior vena cava syndrome, spinal cord suppression syndrome, third space syndrome, and intestinal obstruction

-metabolic emergencies are cause by production of ectopic hormones directly from the tumor or from metabolic problems caused by the cancer or cancer treatment

• SIADH, hypercalcemia, tumor lysis syndrome, septic shock, and DIC

-infiltrative emergencies occur when cancer infiltrates major organs or from cancer treatment

• cardiac tamponade and carotid artery rupture

cancer pain

-pain management for the cancer pt must address both persistent and breakthrugh components of pain

-drug therapy including NSAIDs, opioids, and adjuvant pain medications should be used and selected based on the character and cause of pain

-drug dosages are adjusted to control pain w/ the fewest side effects

-corticosteroids are involved many drug regimens

-radioactive drugs may help pts w/ diffuse pain

-nonpharamcologic interventions including relaxation therapy and imagery, can be used effectively

coping with cancer and treatment

Nursing assessment and support are key

-pervasive anxiety and fear

• fears of dependency

• loss of control

• family relationship stress

• financial burden

• fear of death

Gerontologic cancer considerations

-clinical manifestations may be mistaken for age-related changes

-more vulnerable to complications of cancer and cancer therapy

-functional status should be considered when a treatment plan is selected

Cancer survivorship

-cancer survivors continue to increase due to

• aging and growth of population

• improvement in early detection and treatment

-be aware of the late and long term effects of cancer

• secondary cancer

• cognitive changes

• cardiovascular/sexual dysfunction

• psychosocial effects