Childhood Immunizations
Immunizations
• Purpose is to protect against infectious diseases
• Most effective method is to create a highly immune population
• Universal vaccine is the goal
• Vaccines carry risk, but risks of disease are much greater
General Considerations – Definitions
• Vaccine: Whole or fractionated microorganisms
• Killed vaccines versus live vaccines
• Toxoid: Bacterial toxin that has been changed to a nontoxic form
• Vaccination: Any vaccine or toxoid
General Considerations – Immunization
• Active: Response to infection or to administration of a vaccine or toxoid.
• Passive: Conferred by giving a patient preformed antibodies (immune globulins). Unlike
active immunity, passive immunity protects immediately but persists only as long as the
antibodies remain in the body.
General Considerations - Specific Immune Globulins
• Preparations contain a high concentration of antibodies directed against a specific antigen
(eg, hepatitis B virus)
• Administration provides immediate passive immunity
• Preparations are made from donated blood
General Considerations - Reporting Vaccine-Preventable Diseases
• Determine whether an outbreak is occurring
• Evaluate prevention and control strategies
• Evaluate the impact of national immunization policies and practices
General Considerations - Immunization Records
• National Childhood Vaccine Act of 1986 requires a permanent record of each mandated
vaccination
o Date of vaccination
o Route and site of vaccination
o Vaccine type, manufacturer, lot number, expiration date
o Name, address, title of person administering the vaccine
• Reason for record
o To ensure appropriate vaccination
o To avoid overvaccination
General Considerations - Adverse Effects of Immunization
• Immunocompromised children are at special risk from live vaccines
o Congenital immunodeficiency
o Human immunodeficiency virus (HIV) infection
o Leukemia
o Lymphoma
o Generalized malignancy
o Therapy with radiation
o Cytotoxic anticancer drugs
o High-dose glucocorticoids
Target Diseases
• Measles
• Mumps
• Rubella
• Diphtheria
• Tetanus (lockjaw)
• Pertussis (whooping cough)
• Poliomyelitis (polio, or infantile paralysis)
• Haemophilus influenzae type b
• Varicella (chickenpox)
• Hepatitis B
• Hepatitis A
• Pneumococcal infection
• Meningococcal infection
• Influenza
• Rotavirus gastroenteritis
• Genital human papillomavirus infection
• Respiratory syncytial virus
Specific Vaccines and Toxoids – MMR
• Measles, mumps, and rubella virus vaccine (MMR)
o Adverse reactions
§ Hemorrhage
§ Anaphylaxis
o No causal link between MMR and development of autism, Crohn’s disease, or any
other serious long-term illness
o Precautions and contraindications
§ Not given in pregnancy
§ Children w/history of bleeding disorder or analphylaxis
o Injection: Subcutaneous to outer upper arm
o Schedule: 2 shots
§ Between 12-15 months
§ Between 4-6 years old
§ If 2nd dose is missed: Between 7-18 years old
Specific Vaccines and Toxoids DTaP
• Diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP)
o Full series and booster shots
§ Full series in childhood
§ Boosters Q10years
o Adverse effects: (rare) Encephalopathy w/long term neuro defects
o Precautions and contraindications
§ Do not give to child with moderate/severe fever
§ Prior vaccine produced anaphylaxis or encephalopathy
§ Give with caution or avoid giving to children with h/o shock, high fever
48 hrs after vaccine, inconsolable crying 3+ hours, seizures
o Injection: IM deltoid muscle or thigh
o Schedule: 5 shots + Q10yr boosters
§ 2 months
§ 4 months
§ 6 months
§ Between 15-18 months
§ Between 4-6 years
§ Td every 10 years for life
Specific Vaccines and Toxoids – Polio
• Poliovirus vaccine
o Inactivated poliovirus vaccine (IPV, Salk vaccine)
o Adverse effects: no serious effects
§ Use with caution in children with allergy to streptomycin, neomycin, and
bacitracin (antibiotics)
o Injection: Subcutaneous at anterolateral thigh
o Schedule: 4 shots
§ 2 months
§ 4 months
§ 6-18 months
§ 4-6 years
o NOTE: Oral polio vaccine has been taken off the market.
Specific Vaccines and Toxoids – Hib
• H. influenzae type b conjugate (Hib) vaccine
o Adverse effects: no serious effects
o Injection: IM to midthigh or outer upper arm
o Schedule: 4 doses
§ 2 months
§ 4 months
§ 6 months
§ 12-15 months
§ Note: If Pedvax HIB was given first two times, can skip 6 month dose
Specific Vaccines and Toxoids – Varicella
• Varicella live-attenuated virus vaccine
o Live, attenuated varicella viruses
o Adverse effects
§ None to the vaccinated
§ Temporarily avoid close contact with susceptible, high-risk individuals
(e.g., neonates, pregnant women, immunocompromised people).
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o Injection: subcut into the outer aspect of the upper arm or into the anterolateral
thigh
o Schedule: 2 shots
§ Never had chickenpox:
• 12-15 months
• 4-6 years
§ Never had chickenpox and > 12 years old: 2 doses 28 days apart
Why temporarily avoid close contact with susceptible, high-risk individuals (e.g.,
neonates, pregnant women, immunocompromised people)? Because the disease can be
transmitted to these weaker people.
Specific Vaccines and Toxoids Hepatitis A vaccine
• Recommended for
o all children 12 - 23 months old,
o children >23 months who live in areas where vaccination programs target older
children.
o HepA is also recommended for people in communities that have frequent
outbreaks of hepatitis A
• Adverse effects: rare
• Injection: IM into the deltoid muscle
• Schedule: 2 shots
o 2 shots 6 months apart
o First dose can be given at 12 months
Specific Vaccines and Toxoids - Hep B
• Hepatitis B vaccine
o Hepatitis B surface antigen (HBsAg), the primary antigenic protein in the viral
envelope
o Promotes synthesis of specific antibodies directed against hepatitis B virus
o Viral component, not live virus; cannot cause disease
o Adverse effects: Avoid giving if prior analphylactic reaction to HepB vaccine or
baker’s yeast
o Injection: IM anterolateral thigh (infants) or deltoid (adults)
o Schedule: 3 shots
§ Within 12 hours of birth
§ 1-2 months
§ 6 months
§ ADULT/OLDER CHILD: immediately, 1 month later, 6 months later
Specific Vaccines and Toxoids Pneumococcal conjugate vaccine
• Pneumococcal conjugate vaccine: Prevention of invasive pneumococcal disease in infants
and children
• Types
o PCV13: for infants and children
o PCV23: adults (does not work in children < 2 yrs old)
• Adverse effects: none
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Injection: IM anterolateral thigh or deltoid
Schedule: Depends on when the 1st dose is given
o 2months: 2,4,6, and 12-15 months (4 shots)
o 7-11months: 1st two shots 4 weeks apart, 3rd is 8weeks later (3 shots)
o 12-23months: 2 doses 8 weeks apart (2 shots)
Specific Vaccines and Toxoids MCV4 vaccine
• Meningococcal conjugate vaccine (MCV4)
o Concerns that MCV4 might cause Guillain-Barré syndrome appear to be
unfounded
o Side effects: pain, HA, fatigue
o Who should get it:
§ 2 months to 55 years old (MPSV4 is for > 55 year old)
§ People living in close quarters or having other high risk
o Injection: IM to the deltoid
o Schedule: Depends on age & risk group
§ 11-18 y/o: 11-12 y/o + 16 y/o (2 shots)
§ 11-18 w/HIV: 2 dose series 2 months apart + 1 at 16y/o (3 shots)
§ 2-55 y/o w/reduced or no spleen: 2 dose series 2 months apart + booster
every 5 years (3+ shots)
Specific Vaccines and Toxoids Influenza vaccine
• Influenza vaccine:
o Annual vaccination against influenza, including the H1N1 subtype, is now
recommended for all children between 6 months and 18 years of age & adults
o Four different kinds of vaccines
o Injection: IM to the deltoid
o Schedule: every year around September to November
Specific Vaccines and Toxoids - HPV
• Human papillomavirus vaccine: Gardasil and Cervarix
o Prevents genital warts and anal cancer in men and women
o Prevents cervical cancer, vulvular cancer, and vaginal cancer
o Very safe
o Who should be vaccinated?
§ Girls and boys 11-12 years old
§ Females and males 13-21 years old never vaccinated
o Contraindications: pregnant patients [breast feeding = OK]
o Injection: IM deltoid or anterolateral thigh
o Schedule: 3 doses over 6 months (initial, 1 month later, 6 months later) = 3 shots
Cytokines are chemical messengers
Responsible for activating other cells and regulating inflammatory response.
Cytokines are a broad and loose category of small proteins important in cell signaling.
Cytokines are peptides and cannot cross the lipid bilayer of cells to enter them.
Chemokines
• Synthesized by many cells (macrophages, fibroblasts, endothelial cells) in response to
proinflammatory cytokines
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Induces chemotaxis to promote phagocytosis and wound healing
Examples:
o Monocyte/macrophage chemotactic proteins
o Macrophage inflammatory proteins
o Neutrophils
Interleukins (IL)
• Produced primarily by macrophages and lymphocytes
• Many types - Examples:
o IL-1 is proinflammatory
o IL-10 is anti-inflammatory
Tumor necrosis factor-alpha
• Secreted by macrophages
o Induces fever by acting as an endogenous pyrogen
o Increases synthesis of inflammatory serum proteins
o Causes muscle wasting (cachexia) and intravascular thrombosis
Interferon (IFN)
• Protects against viral infections
• Produced and released by virally infected host cells in response to viral double-stranded
RNA: Protects neighboring healthy cells
• Types:
o IFN-α and IFN-β: Induce production of antiviral proteins
o IFN-g: Increases microbiocidal activity of macrophages
Mast Cells and Basophils
• Mast cells are cellular bags of granules located in the loose connective tissues close to
blood vessels
o Located: Skin, digestive lining, and respiratory tract
o Contain: histamine, cytokines, and chemotaxic factors
• Basophils are found in blood and probably function in same way as mast cells
• Chemical release in 2 ways
o Degranulation: The release of the contents of mast cell granules
o Synthesis: Production and release of new mediators in response to a stimulus
Immunoglobulin G (IgG)
• Most abundant class (80%-85%)
• Accounts for most of the protective activity against infections
• Transported across the placenta.
Immunoglobulin A (IgA)
• Two classes:
o IgA molecules are found predominantly in the blood
Immunoglobulin M (IgM)
• Largest of the immunoglobulins
• Pentamer stabilized by a J chain
• First antibody produced during the primary response to an antigen
• Synthesized early in neonatal life
Immunoglobulin D (IgD)
• Low concentration in the blood
• Function as one type of B cell antigen receptor
Immunoglobulin E (IgE)
• Least concentrated of the immunoglobulin classes in the circulation
• Mediator of many common allergic responses
• Defender against parasites
IgE Function
• Provides protection from large parasites
o Initiates an inflammatory reaction to attract eosinophils
• When produced against innocuous environmental antigens, they are a common cause of
allergies
o Fc portions of IgEs are bound to mast cells
T Helper Lymphocytes
• “Help” the antigen-driven maturation of B and T cells
• Facilitate and magnify the interaction between APCs and immunocompetent lymphocytes
• Subsets
o Th1 cells provide help in developing cell-mediated immunity.
o Th2 cells provide help in developing humoral immunity.
o Differences based on cytokine production.
HIV basically turns healthy human cells into viral replication factories.
Which person(s) should the nurse anticipate will be diagnosed as having AIDS?
A. Viral load of 103 with CD4 count of 1,000
B. Viral load of 500 with CD4 count of 950
C. Diagnosis of Kaposi’s Sarcoma
D. Diagnosis of Influenza
E. Viral load of 105 with CD4 count of 50
ANSWER:
C: emergence of opportunistic infection
E: CD4 count < 200
The complement system consists of proteins that complement the work of antibodies by
fascilitating many of their actions.
Notice the differences in SHAPE of the antibodies.
• IgM is the largest.
• IgG is the smallest – it can cross the placenta.
• IgE is responsible for allergic reactions – because it attaches to Mast Cells which releast
histamine when activated.
• IgA is found in mucous and breast millk.
Corticosteroids reduce inflammation and swelling.
NonSteroidal Anti-Inflammatory Drugs (NSAIDS) reduce inflammation by inhibiting
cyclooxygenase (COX), which is the enzyme that converts arachidonic acid to prostaglandins
(substances that cause pain).
Acetaminophen is NOT an NSAID. It is a pain reliever and an antipyretic (fever reducer).
Cyclooxygenase (COX) Inhibitors
Uses
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Suppress inflammation
Relieve pain
Reduce fever
Adverse effects
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Gastric ulceration
Bleeding
Renal impairment
Mechanism of action: Inhibit cyclooxygenase (COX), the enzyme that converts arachidonic acid
into prostanoids (prostaglandins and related compounds)
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Inhibition of COX-1 ("good COX")
o Gastric ulceration
o Bleeding
o Renal impairment
Inhibition of COX-1 [Beneficial effects]: Protection against myocardial infarction (MI)
and stroke
Inhibition of COX-2 ("bad COX"): Largely beneficial effects:
o Suppression of inflammation
o Alleviation of pain and reduction of
o Protection against colorectal cancer
Drugs with anti-inflammatory properties: Nonsteroidal anti-inflammatory drugs (NSAIDs)
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Aspirin
celecoxib
ibuprofen
naproxen
Drugs without anti-inflammatory properties: Acetaminophen
AHA Statement about COX Inhibitors
Most COX inhibitors, especially COX-2 inhibitors, increase the risk for MI and stroke.
First Generation NSAIDS
Inhibit COX-1 and COX-2
Used to treat inflammatory disorders (rheumatoid arthritis, osteoarthritis, bursitis)
Non-Aspirin First Generation NSAIDS
Aspirin-like drugs with fewer GI, renal, and hemorrhagic effects than aspirin
20+ nonaspirin NSAIDs available (all similar, but for unknown reasons, patients tend to do
better on one drug or another)
Inhibits COX-1 and COX-2: Inhibition is reversible (unlike with aspirin)
Principal indications: Rheumatoid arthritis, bursitis, and osteoarthritis
Does not protect against MI and stroke
Side effect of 1st gene NSAIDS:
Anticholinergic effects: Weak atropine-like effects (dry mouth, blurred vision, dry eyes,
constipation, urinary retention, dizziness due to drop in blood pressure on standing up
[postural hypotension], congnitive problems [confusion], heart rhythm disturbance)
EXAMPLES: Asprin, Ibruphen
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2nd generation NSAIDS:
Examples:
Fexofenadine [Allegra, Allegra Allergy, Allegra ODT]
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Uses: Oral therapy of seasonal allergic rhinitis and for chronic idiopathic urticaria
Of second-generation antihistamines, offers best combination of efficacy and safety
Use with caution in patients with renal impairment
Do not take with fruit juice
Cetirizine [Zyrtec]
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Uses: Allergic rhinitis and chronic idiopathic urticaria
Food delays absorption
More sedating than other second-generation antihistamines but less sedating than firstgeneration drugs
Levocetirizine [Xyzal]
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Uses: Allergic rhinitis and chronic idiopathic urticaria
More sedating than other second-generation antihistamines but less sedating than firstgeneration agents
Most common side effects: Drowsiness, fatigue, muscle weakness, dry mouth
Avoid alcohol and other CNS depressants
Loratadine [Claritin] (prototype drug)
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Use: Seasonal allergic rhinitis
Generally, well tolerated
Food delays absorption
Use with caution in patients with significant hepatic and renal impairment
Desloratadine [Clarinex]
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Uses: Seasonal allergic rhinitis, perennial allergic rhinitis, and chronic idiopathic urticaria
Azelastine [Optivar] (prototype drug)
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Uses:
Nasal spray: allergic rhinitis
Eye drops: allergic conjunctivitis
By mouth: asthma, skin rashes
Corticosteroids, glucocorticoids, and mineralcorticoids
There are two major types of corticosteroids
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Glucocorticoids
o Primary glucocorticoid: Cortisol
o Affect blood glucose concentration
• Mineralcorticoids
o Primary mineralcorticoid: Aldosterone
o Affects extracellular electrolytes (or minerals) - especially sodium & potassium
• PROTOTYPE Drugs:
• Hydrocortisone
• Prednisone
• Methylprednisolone
Pharmacology of Glucocorticoids: Introduction
Molecular mechanisms of action are different from those of other drugs
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Glucocorticoid receptors are inside the cell
Glucocorticoids modulate the production of regulatory proteins rather than signaling
pathways.
Effects on metabolism and electrolytes
Anti-inflammatory and immunosuppressant effects: Major clinical applications of the
glucocorticoids stem from their ability to suppress immune responses and inflammation
Therapeutic uses in nonendocrine disorders
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Rheumatoid arthritis
Systemic lupus erythematosus
Inflammatory bowel disease
Miscellaneous inflammatory disorders
Allergic conditions
Asthma
Dermatologic disorders
Neoplasms
Suppression of allograft rejection
Prevention of respiratory distress syndrome in preterm infants
Adverse Effects of Glucocorticoids:
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Cataracts and glaucoma: Long-term glucocorticoid therapy
Peptic ulcer disease: Corticosteroids
o inhibit prostaglandin synthesis
o augment secretion of gastric acid and pepsin
o inhibit production of cytoprotective mucus
o reduce gastric mucosal blood flow
Iatrogenic Cushing's syndrome: Hyperglycemia, glycosuria, fluid and electrolyte
disturbances, osteoporosis, muscle weakness,cutaneous striations, lowered resistance to
infection; redistribution of fat produces a "potbelly,""moon face," and "buffalo hump"
Use in pregnancy and lactation
Pharmacology of Glucocorticoids: Special Precautions
Contraindications and precautions
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Patients with systemic fungal infections
Those receiving live virus vaccines
Use with caution in pediatric patients and in pregnancy/breast-feeding
Adrenal suppression: High risk with long term glucocorticoid use
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Why it can develop: Exogenous drug inhibited the production of endogenous
glucocorticoid
Adrenal suppression and physiologic stress: Addisonian Crisis
Taper dosage over 7 days
Switch from multiple doses to single doses
Taper dosage to 50% of physiologic values
Monitor for signs of insufficiency
(Addisonian Crisis or Acute adrenal crisis is a life-threatening state caused by insufficient
levels of cortisol,
which is a hormone produced and released by the adrenal gland.
Prototype: Hydrocortisone
3 forms with brand names:
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Hydrocortisone (Rx) (hy-droh-kor′tih-sone): Cortef, Colocort, Cortena
Hydrocortisone acetate (Rx): Anucort, Anusol, Cortifoam, Hemril, Protocort, Rectasol
Hydrocortisone sodium succinate (Rx): A-hydroCort, Solu-Cortef
Drug class: Short-acting glucocorticoid
Pregnancy category C
Action: Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and
fibroblasts and reversing increased capillary permeability and lysosomal stabilization (systemic);
antipruritic, antiinflammatory (topical)
Therapeutic outcome: Decreased inflammation
Nursing considerations
Assessment
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Adrenal insufficiency (cushingoid symptoms)
o Nausea, anorexia, shortness of breath, moon face, fatigue, dizziness, weakness,
o joint pain before and during treatment; monitor plasma cortisol levels during
long-term therapy;
o check adrenal function periodically for hypothalamic-pituitary-adrenal axis
suppression
Prototype drug: Prednisone
Prednisone (Rx) (pred′ni-sone): Winpreo
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Drug class: Corticosteroid, Intermediate-acting glucocorticoid
Pregnancy category C
Action: Decreases inflammation by increasing capillary permeability and lysosomal
stabilization, minimal mineralocorticoid activity
Therapeutic outcome: Decreased inflammation, decreased adrenal insufficiency
Prototype Drug: Methylprednisolone
Methylprednisolone (Rx) (meth-ill-pred-niss′oh-lone): A-Methapred, Depo-Medrol, Medrol,
Solu-Medrol
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Drug class: Synthetic corticosteroid, immediate-acting glucocorticoid
Pregnancy category C
Action: Decreases inflammation by suppression of migration of polymorphonuclear
leukocytes, fibroblasts; reverses increased capillary permeability and lysosomal
stabilization
Therapeutic outcome: Decreased inflammation
Immunization is active artificial adaptive immunity.
Adaptive immunity is also called acquired immunity. It is distict from innate immunity in that
one is not born with it.
Immunizations: Using your immune system to build protection against illness WITHOUT
having to have the illness
Purpose is to protect against infectious diseases
Most effective method is to create a highly immune population (why everyone should
get vaccinated)
• Universal vaccine is the goal
• Vaccines carry risk, but risks of disease are much greater
Immunization with vaccines promotes active adaptive (or acquired) artificial immunity.
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Mechanism of action: Vaccines
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Vaccines promote synthesis of antibodies directed against bacteria and viruses
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Toxoids promote synthesis of antibodies directed against toxins that bacteria produce,
but not against the bacteria themselves.
Killed vaccines are composed of whole killed microbes or isolated microbial
components
Live virus vaccines are composed of live microbes that have been weakened
(attentuated) or rendered completely avirulent.
Benefits of widespread vaccination
5 Vaccine-Preventable Diseases (VPDs) are virtually gone from the US
o Diphtheria
o Small pox
o Poliomyelitis
o Rubella
o Measles
• measles & wild-type polio are gone from the Western hemisphere
• smallpox is gone from the planet
• The incidence of several other VPDs has been greatly reduced.
Cancer
• Diseases in which abnormal cells divide without control and are able to invade other
tissues
• Derived from Greek word for crab, karkinoma
• Tumor
o Also referred to as a neoplasm—new growth
What does DIFFERENTIATED mean?
Normal differentiation
˜ A stem cell is undifferentiated
˜ A normal cell with a specific identity is differentiated
Classification and Nomenclature
Benign tumors
• Named according to the tissues from which they arise
• Includes the suffix “-oma”
o Lipoma
o Leiomyoma
o Meningioma
• May progress to cancer
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Malignant tumors
• Named according to the tissues from which they arise
o Carcinoma: Epithelial tissue
o Adenocarcinoma: From ductal or glandular tissue
o Sarcoma: Mesenchymal tissue
o Lymphoma: Lymphatic tissue
o Leukemia: Blood-forming cells
Sustained Proliferative Signaling
• Proto-oncogenes
o Normal genes that direct protein synthesis and cellular growth
• Oncogenes
o Mutant genes
• Tumor-suppressor genes
o Encode proteins that in their normal state negatively regulate proliferation
o Also referred to as anti-oncogenes
• Oncogene activation
o Point mutation in RAS gene converts from regulated to unregulated
o Translocations
§ Burkitt lymphomas
§ Chronic myeloid leukemia
§ Gene amplification
What is a RAS gene?
A family of genes that make proteins involved in cell signaling pathways that control cell growth
and cell death. Mutated (changed) forms of the RAS gene may be found in some types of cancer.
These changes may cause cancer cells to grow and spread in the body.
Telomeres and Immortality
• Body cells are not immortal and can only divide a limited number of times (senescence)
• Telomeres are protective caps on each chromosome and are held in place by telomerase
o They block cell division and prevent immortality
• Telomeres become smaller and smaller with each cell division
• Cancer cells can activate telomerase and cause unlimited division and proliferation
(cellular immortality)
Angiogenesis
• Growth of new vessels
• Advanced cancers can secrete angiogenic factors (VEGF)
o Vascular endothelial GF
o Platelet-derived GF
o Basic fibroblast GF
• Those factors promote the creation of new blood vessels around the tumor
• Steals resources from the body à weight loss
Resisting Apoptotic Cell Death
• Apoptosis is programmed cell death
o Self-destruction
• Defects in intrinsic or extrinsic pathways provide resistance to apoptotic cell death
Inflammation and Cancer
• Chronic inflammation is an important factor in the development of cancer
o Cytokine release from inflammatory cells
• Helicobacter pylori
o Chronic inflammation associated with:
§ Peptic ulcer disease
§ Stomach carcinoma
§ Mucosa-associated lymphoid tissue lymphomas
Metastasis
• Spread of cancer from a primary site of origin to a distant site
• Direct invasion of contiguous organs is known as local spread
• Metastases to distant organs by the lymph system and in blood
• Requires great efficiency
• Usually occurs in late stages
Clinical Manifestations - Cachexia Syndrome
• Most severe form of malnutrition
• Includes anorexia, early satiety, weight loss, anemia, asthenia, taste alterations, and
altered protein, lipid, and carbohydrate metabolism
Clinical Manifestations - Blood-Related
Anemia
• A decrease of hemoglobin in the blood
• Mechanisms:
o Chronic bleeding resulting in iron deficiency
o Severe malnutrition
o Medical therapies
o Malignancy in blood-forming organs
Leukopenia and thrombocytopenia
• Direct tumor invasion to the bone marrow causes leukopenia (low White Blood Cell
count) and thrombocytopenia (low platelets)
• Chemotherapy drugs are toxic to the bone marrow
Infection: Risk increases when the absolute neutrophil and lymphocyte counts fall
Clinical Manifestations - GI & Skin
Gastrointestinal manifestations
• Oral ulcers caused by reduced cell turnover from chemotherapy and radiation
• Malabsorption
• Diarrhea
• Therapy-induced nausea
Hair and skin manifestations
• Alopecia from chemotherapy: Usually temporary
• Skin breakdown and dryness
Diagnosis
• Manifestations based on site, tumor size
• Diagnostic testing: Biopsy
o Magnetic Resonance Imaging (MRI)
o Computed Tomography (CT) scan
Cancer Staging
• Microscopic analysis for staging—based on presence of metastasis
o Stage I: No metastasis
o Stage II: Local invasion
o Stage III: Spread to regional structures
o Stage IV: Distant metastasis
Tumor Markers
• Tumor cell markers (biologic markers) are substances produced by cancer cells that are
found on or in tumor cells, in the blood, CSF, or urine
o Hormones
o Enzymes
o Genes
o Antigens
o Antibodies
• Tumor markers are used to:
o Screen and identify individuals at high risk for cancer
o Diagnose specific types of tumors
o Observe clinical course of cancer
o Problem: false positives and negatives
Growth Fraction and Its Relationship to Chemotherapy
• Cell cycle
o Four major phases
• Growth fraction
o Growth fraction is the percentage of actively dividing cells at any point in time.
o Impact of tissue growth fraction on responsiveness to chemotherapy
o Chemotherapeutic drugs are much more toxic to tissues with a high growth
fraction than to tissues with a low growth fraction
Tissue Growth and Chemotherapy
• Chemotherapeutic drugs are more toxic to tissue with a high growth fraction:
o Bone marrow
o Skin
o Hair follicles
o Sperm
o Gastrointestinal tract
• High growth fraction = cells that rapidly replicate
Major Toxicities of Cancer Chemotherapy
Myelosuppression (bone marrow suppression)
• Reduces the number of circulating neutrophils, platelets, and erythrocytes
• Loss of these cells has 3 major consequences:
o Infection (from loss of neutrophils)
o Bleeding (from loss of platelets)
o Anemia (from loss of erythrocytes)
Neutropenia
• Reduction in circulating neutrophils
• Incidence and severity of infection are increased
• Nadir (trough), occurs between days 10 and 14
Thrombocytopenia
• Reduction of circulating platelets, which increases the risk of serious bleeding
• Patient care
o Use caution w/procedures that promote bleeding
o Avoid IM injections
Anemia
• Reduction of circulating red blood cells
• Treatment: Transfusion of erythropoietin (hormone that promotes red blood cell
production)
Digestive tract injury
• Stomatitis (inflammation of the oral mucosa)
o Treatment of mild stomatitis: Mouthwash containing a topical anesthetic (eg,
lidocaine) plus an antihistamine (eg, diphenhydramine)
o Treatment of severe stomatitis: Systemic opioid
• Diarrhea
o Treatment: Oral loperamide
• Nausea and vomiting
o Stimulation of the CTZ (Chemoreceptor Trigger Zone)
o Treatment: Premedicate w/antiemetics
o Antiemetic combinations are more effective
o Aprepitant, dexamethasone, and a serotonin antagonist, such as ondansetron
Other Toxic Effects
• Alopecia – hair loss
• Hyperuricemia: Prophylaxis with allopurinol
• Reproductive toxicity - sterility
• Local injury from extravasation of vesicants
• Unique toxicities
o Daunorubicin: Can cause serious injury to the heart
o Cisplatin: Can injure the kidneys
o Vincristine: Can injure peripheral nerves
• Carcinogenesis
Making the Decision to Treat
• Karnofsky Performance Scale
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Benefits of treatment must outweigh risks
Patient must be given some idea of benefits of proposed therapy
One of these three should be possible:
o Cure
o Prolongation of life
o Palliation