Exam 2: Immunity, Immunization, Immune Disorders

• Colonization occurs when microorganisms inhabit a specific body site (ie: skin) but do not cause signs and symptoms of infection.
• They have the potential to cause infection if they spread to a different site or person (ie: from skin to urinary tract

• Interferes with cellular metabolism
• Produce toxins
• Ability to multiply in host, some rapidly reproduce
• Virulence - # of microorganisms required to kill a host

• Direct contact

• Inhalation
• Ingestion
• Bite

• Thru lymph and blood for invasion

• Pathogens try to outsmart the body
• Some bacteria produce thick capsules – impairs phagocytosis
• Some produce toxins that kill neutrophils
• Some pathogens may overwhelm the body before a sufficient immune response is mounted. Ex:

• Capsular coating – protects from phagocytes
• Produce exotoxins: Proteins released during growth

• Produce endotoxins

• Usually produced by Gram Neg. bacteria

• E coli
• Pseudomonas. etc

• Endotoxin release → vasodilation → ↓ BP → ↓ oxygen delivery and subsequent shock
• Diagnosed with blood cultures

• ID the organism
• Drug sensitivity to the organism

• Status of host

• First choice: Drug with greatest efficacy, lowest toxicity and narrowest spectrum

• What are some reasons not to employ the first choice?- allergies, present diseases & toxicity

• Prior to completion of or without lab tests/cultures
• MUST obtain cultures prior to giving first dose of antibiotics, otherwise the drug will alter or suppress microbial growth
• When you can’t wait:

• Gram stain – ID of infecting organism

• Most useful samples are from direct aspirate from the site of infection

• Sensitivity “S”: The ability of the antibiotic to inhibit growth

• Resistance “R”: When the antibiotic does not inhibit growth. Occurs when bacteria alter their genetic code

• Intermediate or inconclusive growth: Seen as “I” on lab report

• Purpose of C&S: Ensure client is receiving the correct antibiotic for a particular infection

• Especially important for drugs thought to be resistant
• Can establish:

• MIC – Minimum Inhibitory Concentration: Lowest concentration of an antibiotic that inhibits growth

• Host defenses

• Phagocytic cells
• Goal is not to outright kill infecting organism, but to suppress growth until immune system can take over

• Site of infection

• Age: Reduced ability to metabolize and eliminate

• Pregnancy and lactation: Drugs that cross placental barrier and breast milk (Tetracycline)

• Allergies: Consider type of reaction and only if NO other drug available
• Risk of toxicities

• Dosage should be = or > MIC.
• Drug levels of 4 to 8 times MIC are often desirable: ex: if 10 mg inhibits growth, usually 40 mg given

• Prior to some surgeries
• Congenital heart dx., prosthetic heart valves (bacterial endocarditis)
• Neutropenia
• Severe trauma, protruding organs or bones

• Cultures till sterile
• Serum drug levels

• CBC

• An infection occurring during antimicrobial therapy for another infection. Results in overgrowth of nonsusceptible organisms
• Example: Thrush – Candida Albicans
• Teach: Ingest yogurt, buttermilk, douche with yogurt

• AAPMC (Antibiotic associated pseudomembranous colitis)
• Suprainfection of the bowel. Usually with staphylococci or Clostridium Difficile. Produces severe diarrhea, can be life threatening.
• Ask about _____BMs________!!!!!

• Bactericidal
• Mech. of Action: Disruption of the cell wall

• Kill a wide variety of gram (+) and some gram (-)
• Most effective against cells undergoing active growth and division
• Generally considered least toxic of all antimicrobials. Widely prescribed

• Allergic reactions to penicillins are thought to be the most common type of drug allergy
• Often manifested by:

• Overall rather safe side effect profile

• Penicillin G – inactivated in GI tract, given parenterally
• Penicillin V  (Pen VK) – stable in stomach acid, used for oral therapy
• Least toxic of all antibiotics and considered one of the safest meds

Pencillinase – enzyme produced by some bacteria that inactivates penicillin and promotes resistance

• Nafcillin (IV)
• Oxacillin (IV)
• Dicloxacillin (PO)

• Ampicillin (Principen)

• Ampicillin/Sulbactam (Unasyn)

• Amoxicillin (Amoxil, Trimox)

• Amoxicillin/Clavulanate (Augmentin)

• Carbenicillin indanyl (Geocillin): PO

• Ticarcillin (Ticar): IV

• Ticarcillin/clavulante (Timentin): IV

• Piperacillin: IV

• Piperacillin/tazobactam (Zosyn): IV, Newest extended spectrum

• Oral absorption limited by the presence of food and gastric acid

• Cross sensitivity to Cephalosporins
• Cautious use:

• Medic Alert bracelet
• Inactivates aminoglycosides – do not mix in same IV
• Refrigerate liquid forms

• Chemically altered derivatives of a fungus, have the same mech. of action as penicillins and exhibit a similar bacterial spectrum
• Bactericidal
• Beta-lactam antibiotics: Cell nucleus contains a beta-lactam ring that is required for antibiotic activity

• Widely used for Gram (-) infections

• Similar to penicillins
• Peudomembraeous enterocolitis
• Bleeding tendencies

• Grouped according to:

• In general as you progress from first generation agents to fourth you see:

• First Generation

• Second Generation

• Third Generation

• Fourth Generation

• Teach about cross-sensitivity to PCN

• Use Xylocaine for IM and give deep IM
• Refrigerate suspensions
  

• Inhibits cell wall synthesis
• Potentially toxic drug used only for serious infections
• DOC for MRSA infections
• IV or oral (for local GI effect, not absorbed from GI tract)
• Cubicin – newer

• Red neck or Red man’s Syndrome

• Ototoxicity, Nephrotoxicity

• Infuse over 60 minutes/IV pump
• Monitor BUN and Creat.
• Monitor peak and trough
• Monitor for tinnitus
• Caution in elderly, pregnant/lactating women and neonates

• First member of new class – Oxazolidinones
• Bacteriostatic
• PO, IV
• Generally mild SE, well tolerated
• Important because it has activity against multidrug-resistant gram (+) pathogens including MRSA and Vanc resistant

• Bactericidal
• Mech. of Action – disrupt bacterial protein synthesis resulting in cell death
• Are not absorbed from the GI tract, do not enter the CSF, and are rapidly excreted from kidneys
• Potent narrow-spectrum antibiotics capable of serious side effects
• Generally reserved for serious gram (-) infections
• Resistance due to production of bacterial enzymes that inactivate aminoglycoside

• Nephrotoxicity
• Ototoxicity
• Suprainfections
• N/V/D
• Hypersensitivity reaction

• Gentamicin
• Tobramycin
• Neomycin :**Given orally to decontaminate the GI tract

• Amikacin: Develops the least resistance

• Monitor BUN and Creat
• Peak and trough
• Baseline hearing test
• Many drug/drug interactions
• Increase fluids 1500-2000 ml/day
• Monitor for tinnitus

• Bacteriostatic
• Mech. of Action – inhibit protein synthesis
• DOC for Chlamydia, Mycoplasma Pneu., Rickettsial dxs. (Rocky mtn. & typhus fever)
• Unique in that they have other uses, specifically:

• Also useful for:

• Strong affinity to calcium
• Multiple causes for resistance

• Binds to calcium

• Hepatotoxicity
• Phototoxicity
• Suprainfections
• N/V/D

• Vibramycin (Doxycycline): Only one that can be administered with meals

• Sumycin: Least expensive most widely used drug in this class

• Avoid foods high in calcium
• Take on an empty stomach, Except Doxycycline

• Do not administer with antacids
• Avoid sunlight or use sunscreen
• Do not administer during pregnancy, lactation or < 8 yrs

• Bactericidal
• Mech. of Action – inhibits DNA replication
• Mild SE, resistance develops slowly
• Excellent oral absorption, Exception Norfloxacin

• N/V/D
• Suprainfections
• Photosensitivity
• Contraindicated in Peds except with anthrax exposure and UTI’s caused by E. coli

• Antacids interfere with absorption
• Incompatible with most IV solutions
• Monitor I & O, BUN, Creat

• Bacteriostatic
• Inhibit bacterial protein synthesis
• Generally very safe
• Used when allergic to PCNs or Cephalosporins
• Unique effect of causing GI irritability causing the secretion of motilin which increases gastric motility

• GI disturbances
• Increased liver function tests with prolonged use
• Suprainfections of the bowel
• Small risk for QT prolongation and sudden cardiac death associated with Erythromycin

• Bacteriostatic
• Mech. of Action – inhibit synthesis of folic acid
• Inexpensive
• Only a few still remain on the market, as newer antibiotics have been introduced

Cancer is a group of many diseases of multiple causes that can arise in any cell of the body capable of evading regulatory controls over:

• 1. Cellular Proliferation, and/or
• 2. Cellular Differentiation

In the normal cell cycle cellular proliferation occurs so that the # cells dividing = # cells dying

• State of equilibrium: cellular proliferation = cellular degeneration

• In neoplasm's, cells continue to grow at the expense of the host

the process whereby proliferating cells are transformed into different and more specialized cell types.  As cells mature, they differentiate to perform the specific functions of the tissue they constitute

• In normal growth and development, cells become more specialized or "committed” to a particular pathway of differentiation.
• As cells mature, they differentiate to perform the specific functions of the tissue they constitute.
• The more differentiated: the less ability to replicate

• Autonomy =  (altered function) cancer cells independent from normal cellular controls
• Anaplasia =  (altered structure) loss of differentiation; “without form”. As cancer cell becomes less differentiated you have more replication.

• Undifferentiated cells (stem cells) are not totally committed to a specific function

-Every cell carries a set of coded instructions for every function it performs. Different genes are active in different cells, which is why a brain cell caries out many different activities from a muscle cell.

-The growth and division of normal cells is tightly controlled by the activity of genes.

-Normally genes help to prevent Cancer, but when genes are faulty or become damaged they can cause growth and division of cells that is out of normal cellular control

• Initiation: Initiators alter the DNA causing permanent mutation changes

• Promotion: After initiation, promoting factors stimulate replication of the DNA-damaged cells

• Progression: ↑ malignant behavior, invade and metastasize

Viruses

Exposure to sun, radiation

Environmental:  asbestos, tobacco

Accidental transplantation during surgery (a cell or 2 may get loose)

Diet:  colorectal cancer (high protein & high fat diet)

Genetics/Heredity

Chemicals

• Leukemia:  a chronic or acute disease of unregulated  proliferation of the stem cells of the blood-forming tissues. These cells are unable to mature normally. Can be myeloid or lymphoid
• Lymphoma (Hodgkin’s Disease):  Solid tumor of the lymphoreticular system that can have its origin in any lymphoid tissue, usually begins in the lymph nodes.
• Multiple Myeloma:  A neoplastic disease characterized by the infiltration of bone and bone marrow by myeloma cells. It is a B cell cancer

-Begins when an immature blood cell in the bone marrow (Progenitor cell), becomes cancerous. It divides uncontrollably and override the body’s normal restrictions on cell division.

-Over time the marrow becomes crowded with cancerous cells, all of them descendants of the first abnormal cell. The malignant cells accumulate in the patient’s lymph nodes, spleen and elsewhere

-In people with leukemia, the bone marrow produces a large number of abnormal white blood cells, which don't function properly

Acute vs Chronic

• Acute – proliferation of primitive WBCs with rapid development of the disease
• Chronic – proliferation of more mature WBCs

Lymphocytic vs Myelogenous

• Lymphocytic – arise from lymphocytes
• Myelogenous – arise from myeloid tissue (granulocytes, myelocytes, myeloblasts)

Diverse group of malignant neoplasms that develop from the proliferation of lymphocytes, histiocytes, and their precursor in the lymphoid tissue

One of the most curable forms of CA

2 classes:

-Hodgkins Disease

-Non-Hodkins Disease

-Arises in a single node of a chain of nodes and spreads

-Staged I – IV

-Reed-Sternberg (RS) cells are the distinguishing feature of HD, they represent malignant transformed cells (giant, multinucleated cells)

-Higher in M than F

-Higher in whites than blacks

-On the decline, currently accounts for only 1% of all cancers

-Enlarged painless lymph node(s) in neck cervical, axillary, inguinal and/or retroperitoneal nodes

-Possible asymptomatic mediastinal mass on Xray

-Intermittent fever without infection, drenching night sweats

-Weight loss

-Anemia

-Generic term for a wide spectrum of disorders characterized by the malignant transformation of B and T cells and the lymphoid system

-Does not have RS cells

-Seen with increasing frequency in persons with AIDS, with subsequent poor diagnosis

-Clinical manifestations – may be local or generalized lymphadenopathy, similar to HD

-Most common manifestation – painless, superficial lymphadenopathy of head/neck region

-In general, poorer prognosis than Hodgkin’s lymphoma. Dependent on Stage

-B lymphocytes (such as hematopoietic stem cells in the bone marrow) are the origin of myeloma

-Characterized by multiple malignant tumor masses of plasma cells scattered throughout the skeletal system and in the soft tissue

-Higher incidence in blacks than whites

Evidence of diffuse destructive bone lesions

Bones affected in ↓ order:

• Vertebrae, ribs, skull, pelvis, femur, clavicle and scapula
• c/o back pain

Destroys cortical bone

• Pain, pathological fxs.

Hypercalcemia

• Confusion, lethargy, weakness

Repeated Infections

• D/T suppressed humoral immune response

Renal insufficiency and failure

New, abnormal cell growths (tumors) can be categorized as benign or malignant- “new formation” Refers to altered cell differentiation and growth: abnormal mass of proliferating cells. Often used interchangeably with the word "tumor"

-Encapsulated by connective tissue

-Well Differentiated

-Slow-growing

-May cause problems depending on site

-Examples:

Wart, mole

Brain tumor

Invasive

• Local invasion

Poorly Differentiated

• Not like the normal cell of origin

Often rapid growing and metastatic

As a general rule, malignant tumors have the potential to kill the host if left untreated

Tumors spread by:

• 1) Invasion - the growth of the PRIMARY tumor into surrounding tissues
• 2) Metastasis - the dissemination or spread of malignant cells from the primary site to other parts of the body.
• 50% of diagnosed tumors already have mets by the time they are clinically detectable
• 75% of pts. who die have mets to the liver
  

-Vascular channels: spread throught the blood stream

-spread through the blood stream, the cells escape the basement membrane of the tissue of origin, move thru the extracellular space, & penetrate the basement of the vessel

In early stages, growth is exponential (tumor takes a constant amount of time to double in size) and depends on 3 factors:

• number of cells actively dividing
• duration of cell cycle
• number of cells lost compared to new cells
  

-GF Defined:  ratio of dividing cells to resting cells

-Doubling Time defined:  time it takes for the total mass of cells in a tumor to divide

-During early phase, large portion of tumor cells actively dividing = growth fraction

Note:  As GF >, doubling time <

Grading – classification of tumor cell; refers to cell differentation

Staging - the progression and degree of organ involvement; size of tumor and presence of mets(clinical spread of disease)

• TNM system (tumor, nodes, metastasis)

Grade I - well differentiated

Grade II - moderately well-differentiated

Grade III - poorly to very poorly differentiated

Grade IV - very poorly differentiated

Poorly differentiated tumors are less responsive to treatment

T – primary tumor/tumor spread

• T0 – no evidence of primary tumor, in sutu

• T1,2,3,4 - Progressive increase in tumor size or involvement

N – extent of node involvement

• N0 – regional lymph nodes normal
• Progressive # means increasing degrees of abnormalities of regional lymph nodes

M – presence of distant metastasis

• M0 – no known mets
• M 1,2,3,4 - Extent of metastasis to distant sites

-Benign growth can be trivial or lethal:  Brain vs GI tract

-Malignant growth can be the same but usually more aggressive, destructive

-Cancer cells are known to secrete substances that suppress the immune system

-Pain is usually due to invasion of metastatic cells into organs or bones

-Leukopenia d/t malignant invasion of bone marrow, or chemotherapy

-infection, hemorrhage, & organ failure are primary causes of CA death

-failure of CA ridden organs results in loss of life-sustaining functions

Radiology/imaging/endoscopic examinations

Pap smear

Tissue biopsy

Tumor markers:  antigens that are expressed on the surface of tumor cells or substances released from normal cells in response to the presence of tumor:  used for prognosis, treatment and detection.

CA-125 = tumor marker for detection, extent of disease and tx. of ovarian cancer

PSA = prostrate-specific antigen

• increased in benign prostatic hypertrophy and prostatic cancer; used along with rectal exam
• must be collected before rectal exam (which can cause it to elevate)

CEA = carcinoembryonic antigen

• used to aid diagnosis (not diagnostic alone) for colon & GI cancer; more for monitoring treatment; may be elevated for many other reasons

T-cells recognize cancer cells and stimulate the production of Killer T-cells and other cytotoxins

The immune system recognizes the foreign molecules of cancer as

• Tumor specific antigens (TSAs) or
• Tumor-associated antigens (TAAs)

• Both of these are expressed by cancer cells, not normal cells

Interferon is the body’s natural anti-viral. It has anti-tumor characteristics

• Cure
• Control the growth of cancer cells
• Palliation:  comfort and relief of symptoms

Surgery

Immunotherapy - involves stimulating the host

Hormone and Antihormone Therapy

Radiation - to eradicate cells or for palliative treatment

• Adverse effects are dose specific (anorexia, N/V, bone marrow depression)

Chemotherapy - palliative, primary, or to decrease tumor size

Others

Local treatment, success dependent on:

• Can the cancer be completely removed
• Can a border of healthy tissue be removed with the cancer
• Has the cancer already spread at the time of surgery

Generally the main lymphatic vessels and lymph nodes nearest to the cancer or organ are removed.

Risk for micrometastases

• Why physicians often prescribe adjuvant therapy after surgery or neo-adjuvant (before surgery)

-Also called Biological Response Modifier Therapy. Given to a patient with cancer to stimulate their immune systems to more effectively recognize and attack CA cells.

-Hematopoietic Growth Factors – for chemotherapy induced anemia – Epoetin alfa **Not approved for pts. with leukemias and other myeloid malignancies---can stimulate proliferation of these cancers

Biological Response Modifiers - BRMs (Interferon, Interleukin, etc.)

Agents that:

• Initiate, modify or restore the immune response
• Have direct antitumor activity, or
• Have other biologic effects, such as affecting differentiation of cells or ability to metastasize

May be used in the diagnosis of CA or given as treatment

Corticosteroid Hormones

• Often used to increase the effectiveness of Chemotherapy by slowing CA cell growth
• Examples: Prednisone, Dexamethasone

Most hormones are used to slow the growth of breast, prostate and endometrial cancers, which normally grow in response to hormone levels in the body

-Ex: tamoxifen (anti-estrogen) effective for estrogen receptor positive tumors, Arimodex

Uses ionizing radiation to kill cancer cells and shrink tumors

About half of all people with cancer are treated with radiation, either alone or in combination

Useful for almost every type of tumor. Can also be used for leukemia and lymphoma

Radiotherapy can be external, internal, or systemic

Most common

Generally outpatient, similar to having an Xray

Intraoperative radiation therapy (IORT) is a form of external radiation that is given during surgery after the tumor is removed. Most often used for thyroid, colorectal and gynecological cancers

Prophylactic cranial irradiation (PCI) – external radiation given to the brain when the primary site has a high risk of spreading to the brain, ie: small cell lung CA

-Sealed in the form of: wires, catheters, ribbons, capsules, seeds or a small holder (implant)

-Interstitial is implanted in the tissues at or near the site, ie: head/neck cancers

-Intracavity or intraluminal is inserted into the body with an applicator, ie: uterine

Internal radiation taken orally or injected.

Useful for non-Hodgkins and thyroid cancers

Usually out of the system within 48 hours

Sealed sources deliver their radiation mainly around the area of the implant, so the whole patient’s body is not radioactive but the general area is

Systemic radiation uses unsealed radiation that travel thru out the body. Some of this is excreted in the saliva, sweat, and urine before it decays.

Generally hospitalized for internal and systemic

Rotate nursing assignments

Private room

Restrict visitors

Radiation badges

Worry about depression - isolated

Administration of cytotoxic (carcinogenic agents) drugs to intervene and interrupt the cell cycle -- also causes some degree of injury to normal cells

Can be cell-cycle specific or non-specific

• Review figure for phases:  G0, G1, G2, S, M

• Alkylating agents & Platinum compounds
• Hormones
• Steroids
• Most antibiotic antitumor drugs
  

Tumor burden:  The sum of cancer cells present in the body

# cell mutations:  Better response when tissues have a high growth fraction, usually have more blood supply

Drug resistance:  decreased uptake of drug

Dose intensity

Pt specific factors

Toxicity to normal cells is dose limiting

Cure requires 100% cells killed- just one remaining cell can proliferate

Failure of early detection (large tumors and solid tumors have less blood supply)

To eradicate as many cancer cells as possible with as little damage to normal cells as possible

• Very hard to accomplish
• At any one time, only a portion of the total # of tumor cells will be in a cell cycle stage that is susceptible to chemotherapy. Therefore several courses of chemotherapy are generally necessary to ensure that all tumor cells have been erradicated

Intermittent dosing to allow normal cells to repopulate

Different drug deliveries:

• Intrathecal - because most do not cross blood brain barrier

Combination therapy

• Most are treated with 2 or more drugs

Alopecia: Hair follicles rapidly divide like CA cells. Chemo targets rapidly dividing cells

Nausea and Vomiting

Bone Marrow depression

Diarrhea

Stomatitis

Anorexia

Extravasation and infiltration

Cardiac:  CHF, arrhythmia's, MI, cardiomegaly

Pulmonary:  pulmonary edema, SOB, resp. alkalosis

Nephrotoxicity

Neurotoxicity:  CNS & ANS

Vesicant: any agent given IV that causes blisters, tissue sloughing, ie: necrosis

Stay with patients receiving vesicant therapy

What do you do if it extravastes?

• Stop the infusion
• Ice pack or moist Heat?
  

Extravasation Protocols

Nonvesicant:  Usually administered first, no severe tissue destruction

Irritant:  Causes cellulitis, thrombophlebitis, possible necrosis

1.  Antimetabolites

2.  Alkylating Agents & Platinum Cmpds.

3.  Mitotic Inhibitors

4.  Antineoplastic Antibiotics

5.  Nitrosureas

6.  Hormones/Hormone Antagonists

7.  Radioactive Drugs

*See Drug Chart

Intefere with DNA and RNA growth

Work during the ____________Phase

Used to treat chronic leukemias, cancers of the breast, ovary and GI tract

Examples:

• 5-fluorouracil
• Methotrexate

Can inhibit or stop mitosis, and work during the M phase of the cell cycle

Examples: Vinblastine, Vincristine, Paclitaxel

Intefere with DNA

work in all phases of the cell cycle

Widely used for a variety of cancers

Examples:

• Adriamycin: cardiotoxic, get baseline data & monitor
  
• Dactinomycin
• Mitoxantrone

Act similar to alkylating agents, not phase specific

Interfere with enzymes that help repair DNA

Useful for cancers that travel to the brain, ie: lymphomas, malignant melanoma

Examples:

• Carmustine
• Lomustine

With most anticancer drugs, onset of neutropenia is rapid and recovery develops relatively quickly. Neutropenia begins to develop a few days after dosing and generally the lowest neutrophil count, (Nadir), occurs by 10-14 days

Pts. are at high risk during Nadir for…..infection

Specific to the area of cancer or organ affected

Pain - little to none in early stages; tumors create pain b/c of invasion, compression of nerve endings, or stretching of organs

Fatigue - most common, Cachexia, anorexia, early satiety, weight loss, anemia; all contribute to wasting

Anemia - associated with malignancy

Leukopenia and thrombocytopenia

Infection

C – Changes in bowel or bladder habits

A – A sore that does not heal

U – Unusual bleeding or discharge

T – Thickening or lump in breast or elsewhere

I – Indigestion, chronic

O – Obvious change in wart or mole

N – Nagging cough or hoarseness