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Study Guide for Exam 31. Make sure you know study guide 1 and 2!!!! Including the drugs. This will be

crucial for the final and the HESI.2. There are 100 questions total on the final. 80 multiple choice and 10(with two

boxes per drug) drugs to fill out on the chart. ¾ of the multiple choice questions are new content and ¼ is old content. 6 of the 10 drugs is from the new content and 4 of the drugs are from the old content.

Pressure Ulcers : result from any unrelieved pressure on the skin, causing underlying tissue damage

CAUSES:-Pressure-Immobility- they are not able to move and are laying on a hard surface, which is causing DECREASED CIRCULATION to that area cell tissue starts to die-Shearing forces- We do this to every pt: we lay the head of the bed down- they either scoot themselves up, or we scoot them up. Then we put the head of bed back up, & BUTT SLIDES DOWN/ if the person has good mobility, they can wiggle themselves around and get good blood flow back there. If that person is IMMOBILE, the skin that has been moved against a bone will stay that way -look under immobile pt. for bunched up skin if u lifted the head of the bed up/make sure no skin bunched up -especially older pts. that lost a lot of weight- they have a lot of skin -Friction-Moisture

STAGES:

Stage 1: NONBLANCHABLE (when you put your finger on it, it does not blanch) erythema of intact skin, usually over bony prominenceStage 2: Partial thickness skin loss (erosion or blister)/ involves epidermis or dermis/ skin not intact -when we cover burns, we talk about burns the same way as pressure ulcers- as being partial thickness or full thicknessStage 3: Full-thickness skin loss (erosion or blister)/ involving epidermis &/or dermisStage 4: Full-thickness loss w/ exposure of muscle, bone, or supporting structures (tendons or joint capsules); can include undermining and tunneling.

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-Pressure ulcers are PAINFUL -they cause an inflammatory response w/ hypereremia, FEVER, and ELEVATED WBC count -this is what causes the SWELLING around a pressure ulcer

-can pressure ulcers get INFECTED? YES. -If it was all the way to a stage 4, what would be the risk of infection? OSTEOMYELITIS (on final! ) -osteomyelitis is from exam 2, pressure ulcers is from exam 3- comprehensive3. What is a keloid? Why do they develop?

Keloids: Elevated, rounded, FIRM/ basically scar tissue that would normally forms under the skin, forms ON TOP of the skin

-CLAWLIKE MARGINS that extend beyond the original site of injury-Common in darkly pigmented skin types & BURN scars

Who is at risk for getting keloids? DARK SKINNED people -The darker the skin, the worse you are for getting keloids/ it has to do with the melanin

WHY DO THEY DEVELOP:-Excessive collagen formation during dermal connective tissue repair (that’s why it happens w/ burn scars)-Type III collagen is increased that’s why it feels spongy, & there’s a greater LOSS OF ELASTICITY

What is the risk of keloids if a person has a lot of keloids? Is there a lot of ELASTICITY in that tissue? NOIs there DEPTH to that tissue? NOT REALLY. So it’s kind of SPONGY -if that keloid ruptures open, or if you get a wound on top of that keloid the risk for deeper injury is greater

4. What is pruritus-why does it occur?

Pruritus : ITCHING/ fancy word for “I itch!”-the most common symptom of a primary skin disorder -Do your hands itch after clinical? You’ve washed your hands so many times. If they don’t itch- you aren’t washing your hands enough-Itch is carried by specific UNMYELINATED C-nerve fibers (travels SLOW)/ its triggered by a number of ITCH MEDIATORS-The CNS can modulate the itch response-pain stimuli at a lower intensity can cause itching-CHRONIC itching: can result in INFECTION and scarring due to persistent scratching

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-there’s a lot of pruritis assoc. w/ dermatitis, so that’s why we talked about this

INFLAMMATORY DISORDERS: Allergic contact dermatitis, irritant contact dermatitis, seborrheic dermatitis

2 most common inflammatory disorders of the skin: dermatitis & eczema There are various types of dermatitis The disorders are generally characterized by: pruritus(itching), lesions w/ INDISTINCT BORDERS, & epidermal changes (meaning redness & inflammation around that)

5. What is allergic contact dermatitis? Clinical manifestations, treatment (Betamethasone & Hydrocortisone)

Allergic contact dermatitis Caused by : a hypersensitivity type IV reaction

-As the allergen contacts the skin, it binds to a carrier protein forming a sensitizing antigen

-the Langerhans cells process the antigen & carry it to the T cells -T cells become sensitized to the antigen, inducing the release of inflammatory

cytokines & the symptoms of dermatitis.

A common form of cell-mediated or delayed hypersensitivity. The response is an interaction of skin barrier functions, reaction to irritants, & neuronal responses, such as pruritus. Various allergens can form the sensitizing antigen. Contact with poison ivy is a common example.

MANIFESTATIONS : Erythema(it’s red), swelling(you have vasodilation & release of histamine at the site), pruritus (UNMYELINATED C FIBERS), vesicular lesions(little WELTS that come up)

TREATMENT : you want whatever is causing this hypersensitivity reaction off the skin -The antigen must be removed for the inflammatory response to resolve & tissue repair to begin -Treatment may require topical or systemic steroids. Topical Corticosteriods

-If you’re using a steroid cream, it will suppress the inflammation at that spot & take the redness away. You have to look for systemic signs of infection: TEMPERATURE-Betamethasone (Diprolene): anti-inflammatory steroid/ topical -KNOW: *a lot of times patient go home and think they can put it on whenever it

itches. that’s not true because they can get too much of it and it wont work -Skin needs to be clean before they put it on -wash the other hand after they put it on

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-they need to make sure to put the cap up when they have the cap off of a topical solution

Side effects: they can have a reaction to the cortisone cream on that will look just like dermatitis if they

are allergic to it

-Hydrocortisone (Hycort): anti-inflammatory corticosteroid

6. What is irritant contact dermatitis- clinical manifestations and treatment

Irritant contact dermatitis :-would get this when the gloves had powder in them. Don’t have powder in gloves anymore. Would wash hands a lot b/c hands itched after you took gloves off/ wash hands a lot, scratch all these nurses would have open wounds on their hands-NONIMMUNOLOGIC inflammation of the skin-Cause: Chemical irritation from acids or prolonged exposure to irritating substances-Symptoms similar to allergic contact dermatitis- BUT this type DOES NOT have vesicular lesions (bubble blisters) -the reason you get them w/ this type of dermatitis b/c u scratch too much, you irritated the skin-Treatment—remove stimulus -we don’t use any types of ointment for this

7. What is seborrheic dermatitis-clinical manifestations, treatment

Seborrheic dermatitis : Inflammation of the skin involving scalp, eyebrows, eyelids, nasolabial folds, & ear canals-Have you taken care of a baby w/ cradle cap? An old pt. w/ white flakies around their nose or ears?

-Common CHRONIC inflammation of the skin -Infants: get cradle cap. -Elderly: get in their old age/ on their scalp or eybrows or eyelids

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Should you completely scrape it all off? NO. It’s stuck, and if you scrape it all off you will have an open wound

-it’s Scaly, white, or yellowish color plaquesCause: is unknown but an inflammatory reaction to yeasts has been proposed.

TREATMENT: -shampoos: containing sulfur, salicylic acid or tar. (Neutrogena T gels shampoo, Selcin Blue shampoo) -have to be careful w/ babies, b/c they can have an allergic reaction to it Just wash hair more frequently w/ a baby brush and wash it off-Topical therapy: antifungal & low dose steriods

8. What is psoriasis—different types. Clinical manifestations, treatment (Protopic and Dovonex)

Psoriasis : Chronic, relapsing, proliferative skin disorder Caused by T cell immune-mediated skin disease Scaly, thick, silvery, elevated lesions, usually on the scalp, elbows, or knees -caused by: a high rate of mitosis in the basal skin layer Shows evidence of dermal and epidermal thickening of the skin over a period of time Epidermal turnover goes from 26 to 30 days to 3 to 4 days/ high turnover rate Cells do not have time to mature or adequately keratinize -that’s why they stay really red can’t get the keratin in the skin

DIFFERENT TYPES:Plaque-most common and affects 80 to 90% of individuals with psoriasis. -Typical plaque psoriatic lesion is a well-demarcated (you can see the beginning & end piece of it), thick, silvery, scaly erythematous plaque surrounded by normal skin. -On the face, scalp, elbows and knees

Inverse-involves lesions that develop in skin folds/ ex: in obese peopleGuttate: small papules appear suddenly on the trunk and extremities after STREP INFECTIONPustular: appears as blisters of NONINFECTIOUS pusErythrodermic is often accompanied by pruritus or pain w/ widespread red, scaling lesions that cover a large area of the body.

TREATMENT:

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Tacrolimus (Protopic) Immunosuppressant- give b/c it is a T-cell immune complex that happens

Calcipotriene (Dovonex)9. What is Acne Rosacea, clinical manifestations and treatment (MetroGel and Finacea)

Acne rosacea : Inflammation of the skin that develops in adulthood (basically adult acne) Lesions

4 subtypes: Erythematotelangiectatic, papulopustular, phymatous, and ocular Cause : Assoc. w/ chronic, inappropriate vasodilation results in flushing &

sensitivity to the sun- The exact cause is unknown but an altered innate immune response is involved.

Manifestations: red, erythematous, can be pustules on the cheeks/ in the middle 1/3 of the face- forehead, nose, cheeks, chin The most common lesions are erythema, papules, pustules, and talangiesctasis. They

occur in the middle third of the face, including the forehead, nose, cheeks, and chin. They are associated with chronic, inappropriate vasodilation resulting in flushing and

sensitivity to the sun

Treatment: -b/c pustules can get infected you want to kill any BACTERIA that can be in those pustules on the face

-all the same stuff for topicals wash hands, put on a clean dry space Topical metronidazole (MetroGel) Azelaic acid (Finacea)

10. Know the difference between the bacterial infections of the skin and treatment

Bacterial infections: all of these are caused by STAPH INFECTION-treatment: up until cellulitis- use warm compresses, keep the area dry and clean, soap and water Folliculitis : bacterial infection of the hair follicle-Staph aureus causes the infections.

Clean with soap and water -folliculitis is just one little hair follicle that’s inflamed. Are you going to put someone on antibiotics just for that? No. Warm compresses & Soap & water

Furuncles : it’s a boil- inflammation of the hair follicles. Cause is Staph aureus. -warm compresses until it pops on it’s own/ you don’t want to pop someone else’s! It can get on you!

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Carbuncles : a collection of infected hair follicles & usually occur on the back of the neck, the upper back-Abscesses may develop. Chills, fever—treat with warm compresses may need systemic antibiotics

*All of these could turn into cellulitis!

Cellulitis : infection of the dermis and SQ tissue usually caused by Staph Aureus. Usually in treated with systemic antibiotics

-treatment: NOW we give an IV or PO SYSTEMIC ANTIBIOTIC PO Keflex or if they think it is a high risk for infection- IV vancomycin-it’s a bacterial infection, so how do we treat it? Antibiotics.

11. What is herpes zoster and varicella, clinical manifestations and treatment (acyclovir)

Viral infections Herpes zoster and varicella

- Herpes zoster (shingles) and varicella (chickenpox) are caused by the SAME herpes virus

- Varicella: occurs as a primary infection usually as a child/ followed years later by activation of the virus to cause shingles. During this time, the virus remains latent in trigeminal & dorsal root ganglia -usually STRESS response brings it on- Herpes zoster: has initial symptoms of PAIN & PARESTHESIA localized to the affected dermatome -followed by VESICULAR ERUPTIONS that follow a facial, cervical or thoracic lumbar dermatome.

-follows a DERMATOME so it will be in a straight patterns -a person can have shingles more than once -they have developed a shingles vaccine that helps the elderly patients

Treatment : -Local symptoms are alleviated by: alternating warm & cold COMPRESSES & CALAMINE LOTION to reduce inflamm -Antiviral drugs, tricyclic antidepressants and analgesics are helpful.

Acyclovir (Zovirax)*MUST BE STARTED 24 hrs from the BREAKOUT to be effective. If you’re 4 days from breakout it wont work! -it is renal toxic monitor BUN & creatinine

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12. Difference btwn. the different fungal infections, manifestations, treatment (monistat and lotrimin)

Fungal Infections : (Table 39-4, p. 1055) Fungi causing superficial skin lesions are called dermatophytes Fungal disorders are called mycoses; mycoses caused by dermatophytes are termed

tinea-the big thing: we don’t ever see people in the hospital for a fungal infection. We see people that come in, that we then have a fungal infection we have to treat. The biggest one isn’t on here: yeast infection of females!-usually they bring their own Lotrimin w/ them Tinea capitis (scalp) Tinea pedis (athlete’s foot) Tinea corporis (ringworm) Tinea cruris (groin, jock itch) Tinea unguium (nails) or onychomycosis

Treatment: Lotrimin: it’s OTC Monistat- know this b/c we do swish and swallow too for oral candidiasis

Candidiasis : Caused by the yeastlike fungus Candida albicans/ Table: 39-5, page 1056 Normally found on the skin, in the GI tract, and in the vagina it’s normally

always there C. albicans can change from a commensal organism to a pathogen

Causes : Local environment of MOISTURE & WARMTH, pregnancy, diabetes mellitus, Cushing’s disease(they have high blood sugar), debilitated states(immobile- can’t get up & can’t clean themselves), age <6 months, immunosuppression, & neoplastic diseases- systemic administration of antibiotics >3 days kills off normal flora

-frequently a problem for DIABETICS/ both males(jock itch) & females(vaginal yeast infections) -for antibiotics moist, warm AND sweet!

Treatment : you want to get the moisture out, you need to clean up the moisture

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-topical or systemic antifungal agents-typically Monistat: can be in a swoosh & swallow, ointment, creams, spray powder -if you overuse it- you can get a reverse effect. What’s length of time for using it? 7-14 days -longer than 14 days, you run the risk of overgrowth of candidiasis

13. Diff. btwn. the different types of benign skin tumors & cancerous skin lesions, & general treatment.

BENIGN Tumors : Most benign tumors of the skin are associated with aging-If it’s a mole & it’s not in an area we want it, or if it’s in an area that gets irritated- what do we do with it? They remove it. If the lesion is too big, they will excise it & cut it off. These are benign skin lesions. -the reason we remove them- usually for cosmetic purposes except for moles(nevi). The reason moles are removed, is if they are in an area of manipulation (like if a guy shaves and he always nicks it) the skin around that mole tissue can change in cell structure and become MALIGNANT-usually they are removed 100% b/c of cosmetic reason

Seborrheic keratosis : (age spot)/ is a benign proliferation of cutaneous basal cells that produce flat or slightly elevated lesions that may be SMOOTH OR WARTY in appearance. Causes is unknown. Size varies. Treatment: cryotherapy with liquid nitrogen and laser tx

Keratoacanthoma : is a benign, self-limiting tumor of squamous cell differentiation arising from hair follicles. -It usually occurs on sun damaged skin and smokers. –can be removed with excision

Nevi (moles)

CANCER : (last 13 mins of 11/6 lecture + cancer lecture)-skin cancers are the most prevalent form of cancer- The most common types are basal cell carcinoma & squamous cell carcinoma-Box 39-1 pg. 1058- Important trends for skin cancer (peach box) KNOW risk factors, warning signs, early detection, treatment, survival!

Basal cell carcinoma : most common skin cancer in individuals w/ light colored skin. -Lesions are seen most often on the FACE & NECK b/c of sun

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-The lesion starts as a nodule that is pearly or ivory and slightly elevated above the skin surface w/ small blood vessels on the surface. As the tumor grows it usually has a DEPRESSED CENTER & ROLLED BORDER (raw looking)-The lesion grows slowly, often ulcerates, develop crusts & is firm to the touch. (over time this will heal and it will become crusty on top)-Metastasis is RARE because these tumors do not invade blood or lymph vessels. Treatment: Go in, cut it out, & cut the tissue around it.

Squamous cell carcinoma : of the skin is a tumor of the EPIDERMIS-2 types: in situ and invasive -In situ: is usually confined to the EPIDERMIS but may extend into the dermis. -usually does not metastasize -Invasive: arise from premalignant lesions of the skin/ grow RAPIDLY/ CAN SPREAD to regional lymph nodes-Treatment: In situ: surgical EXCISIONInvasive: has metastasized to lymph tissues- surgical excision & RADIATION treatment

Malignant melanoma: originates from MELANOCYTES- cells that synthesize the pigment melanin-Most SERIOUS skin cancer- poor outcome if it has metastasized/ 95% don’t make it-arise as a result of malignant degeneration of melanocytes that are located either along the basal layer of the epidermis or in a benign mole. -Most moles become suspicious: follow the ABCDE rule: Asymmetry, Border irregularity, Color variation, Diameter larger than >6 mm, elevation. -look at moles on a YEARLY BASIS

Treatment:-if there’s NO evidence of metastasis: do surgical EXCISION & LOCAL RADIATION

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-if there IS metastasis: LOCAL RADIATION, follow w/ chemotherapy, & biologic response modifiers (heavy dose chemotherapy drug).

Malignant melanoma: Kaposi sarcoma:

Kaposi sarcoma : a vascular malignancy associated w/ IMMUNODEFICIENCY (such as: AIDS)-(you can have HIV all day long & will never have this. The day you have Kaposi sarcoma- that’s when u have AIDS)-lesions emerge as PURPLISH BROWN MACULES develop into plaques and nodules with ANGIOPROLIFERATION -They tend to be MULTIFOCAL rather than spreading by metastasis. -The lesions initally appear over the lower extremities/ tends to spread symmetrically over the upper body

Dx: is with SKIN BIOPSYTreated: with ALPHA INTERFERON/& radiation, cytotoxic drugs

Immune Deficiencies1. What is an immune deficiency? An Immune deficiency is the failure of the immune or inflammatory response to function normally, resulting in increased susceptibility to infections.

2. What is breakdown of tolerance?

What does immune tolerant mean? What does it mean to be tolerant? You can handle it. So you have an immune system that can handle external or environmental stimuli that trigger your immune system, and the immune system doesn’t go crazy.-Tolerance is a state of immunologic control so that the individual does not make a detrimental immune response against his or her own cells and tissues. Autoimmune disease results from a breakdown of this tolerance. What we have in people w/ autoimmunity problems, is they have breakdown of tolerance. They are unable to tolerate environmental stimuli. They lose the ability to tolerate it -Breakdown of tolerance: an individual is usually tolerant to his or her own antigens BUT NOW- the immune system REACTS AGAINST SELF-ANTIGENS

3. What is autoimmunity?

Breakdown of tolerance: Body recognizes self-antigens as foreign Autoimmunity occurs when the immune system reacts against self-antigens

-autoimmune disease: the body attacks itself & starts producing antibodies

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-if you have an autoimmune disease: you will test HIGH for ANTIBODES in your systemAutoimmune diseases originate from a genetic predisposition to mount a hypersensitivity reaction to an environmental stimulus. -Some autoimmune diseases can be familial and attributed to the presence of a very small number of susceptibility genes; -affected family members may not all develop the same disease, but several members may have different disorders characterized by a variety of hypersensitivity reactions, including autoimmune and allergic. -there is a genetic predisposition, but it doesn’t mean that if you have it everyone else is going to have it/ but they can have some other type of autoimmune disease-Although most autoimmune diseases appear as isolated events without a positive family history, susceptibility for developing such diseases appears to be linked to a combination of multiple genes.

4. What is Systemic Lupus Erythematosus, what are the clinical manifestations, the 11 common findings, and treatment (Methotrexate, Plaquenil, Prednisone, Sandimmune, Cytoxan, Imuran)

SLE: the most common, complex & serious of the autoimmune disorders. -characterized by: the production of a large variety of antibodies (autoantibodies) against (the self) self-antigens -When it’s attacking the antigens of the body it attacks: Nucleic acids, erythrocytes (RBCs), coagulation proteins, phospholipids, lymphocytes(WBCs), platelets.

It is a MULTISYSTEM PROBLEM!

-you get deposits of circulating immune complexes that contain autoantibodies against the DNA -The most characteristic autoantibodies are against nucleic acids of the DNA (e.g. single stranded DNA, double stranded DNA), histones, ribonucleoproteins, and other nuclear materials. -so throughout the body, cells will start attacking themselves like in liver, kidneys, heart, skin, eyes -you end up having MULTISYSTEM FAILURE problems

Common in:-FEMALES btwn. 20-40 yrs-African Americans

Systemic lupus erythematosus (SLE) Chronic multisystem inflammatory disease Autoantibodies against:

• Nucleic acids, erythrocytes, coagulation proteins, phospholipids, lymphocytes, platelets, etc.

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Deposition of circulating immune complexes containing antibody against host DNA

More common in females

CLINICAL MANIFESTATIONS:-Arthralgias(joint pain) & Arthritis(inflammation of the joint) happens in about 90% people that have lupus type 2 hypersensitivity/ 90% of individuals

-Vasculitis (inflammation of the vascular system) MIX btwn. Type 3 & Type 2/ 70-80% -will see this throughout the body

-Renal disease Type 3/ 40-50% -happens b/c of DNA & anti-DNA complexes causes kidney INFLAMMATION they get acute glomerulonephritis, nephrotic syndrome can lead to RENAL FAILURE

-Hematological changes Type 2/ 50% -anemia, decrease in lymphocytes (lymphopenia) -when you have a decrease in lymphocytes, can you mount an immune response? NO!-Cardiovascular disease Type 3 hypersensitivity/ 30-50% -b/c of the DNA & anti-DNA complexes that lay down in the vascular system11 COMMON FINDINGS:Test: Antibody-against Nuclear Antigen (ANA) -A person w/ lupus will have very HIGH LEVELS on the ANA

-lupus is hard to diagnose it has periods of remission and periods of exacerbation -however, just like w/ any other chronic disease, the more exacerbations you have- the lower your returning to baseline becomes you get worse over time

-11 common findings in a person w/ lupus to be diagnosed- Need AT LEAST 4 present at 1 time1. Facial rash: (butterfly rash, malar rash)/ across the nose and across the cheek2. discoid rash3. Photosensitivity: Sensitive to light4. Oral or nasopharyngeal ulcers: in the mouth or nose5. Non-erosive arthritis: the cartilage joint is not eroding, it’s not a degenerative joint disease or rheumatoid arthritis but there IS inflammation & swelling in that joint. But the joint is NOT eroding6. serositis: Inflammation of the pleural membranes of the lung7. Renal disorder: Proteinuria 0.5 g/ day of protein in urine8. Neuro disorders: Seizures & psychoses

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9. Hematological disorders: ANEMIA, decreased platelets (thrombocytopenia), decreased WBCs (leukopenia), decreased lymphocytes10. Immunologic disorders: they TEST POSITIVE (+) on the ANA -as well as they have a positive (+) lupus erythematosis11. the presence of antinuclear antibodies (ANA)

TREATMENT: (Methotrexate, Plaquenil, Prednisone, Sandimmune, Cytoxan, Imuran)

There is NO CURE since it’s an autoimmune diseaseTreatment: just control the symptoms b/c there is no cure

Some drugs we give:NSAIDS: ibuprofenHow does it work: Inhibits prostaglandin synthesis anti-inflammatory-if I have problems mounting an immune response, & inflammation will ensue b/c I have vascularitis, arthritis- Would I want to use an NSAID on this patient? YES. It’s the first line drug we are going to use.-why would you use Tylenol over ibuprofen in a person w/ lupus? Tylenol is an NSAID as well ibuprofen causes KIDNEY DAMAGE, & you have more of a problem w/ kidney damage in a person w/ lupus than w/ their liver. -so if you’re giving something, you don’t want to give something that can be NEPHROTOXIC. ibuprofen is nephrotoxic.-we’re going to give ibuprofen BUT you want to give it in a LOW DOSE-we’re also going to give tylenol

ibuprofen- nephrotoxic (kidneys)Tylenol- hepatotoxic (liver)/ TylenoL (“Liver”) affects the liver.

What’s the NET AMOUNT of TYLENOL a person can take per day? Don’t exceed thatTylenol net amount: *2 g/ dayIbuprofen net max dose: 2 g/ dayIf you have a person w/ lupus, if they have any RENAL PROBLEMS do NOT GIVE IBUPROFEN b/c it directly affects the kidneys.*Check their RENAL FUNCTION before you give them ibuprofen

Can you give them aspirin? It’s another NSAID DON’T GIVE ASPIRIN b/c they have LOW PLATELETS. At risk for thrombocytopenia.

Q: A patient comes in to you, and they have been managing themselves on either Ibuprofen, Tylenol, or Aspirin. (one of the 3). You look at their platelets and they are

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LOW. Do you want to give them aspirin? No. They have been managing on ibuprofen. You look at their creatinine clearance, and it’s <12. Do you want to give them ibuprofen anymore? No. They’ve been managing w/ tylenol & all of a sudden their liver enzymes are elevated- do you want to give them tylenol? No. -All 3 of them are NSAIDS, and all 3 of them can be used, but you have to pick the best one for that patient. you need to figure out what is best for the person -what they have been using might not work for them anymore b/c of the systemic problems from lupus

Low platelets don’t give aspirinCreatinine clearance <12 don’t give ibuprofenElevated liver enzymes don’t give Tylenol

Methotrexate: Class: immunosuppressantHow it works: interferes w/ folic acid metabolism Inhibits DNA synthesisAdverse effects: aplastic anemia (the transcription for making red blood cells goes awry b/c interferes w/ DNA synthesis), hepatic toxicity, ALOPECIA b/c it interferes w/ DNA synthesis. It happens so quickly that you lose your hair, b/c skin & hair are the quickest turning over cells in the bodyNursing Actions: -use caution in renal impairment b/c its excreted by the kidneyPlaquenil:Class: anti-rheumatic/ anti-malarialHow it works: inhibits protein synthesis by inhibiting DNA synthesis you are preventing them from making autoantibodiesSide effects: Confusion, renal, fatigue, diarrhea, cramps, N/V, ototoxicity, N/V, alopeciaNursing actions: Use cautious in pts w/ liver or renal corticosteroids: used for exacerbation & severe diseaseSupresses inflammation & the normal immune response. HOW?-BLOCKS YOUR INFLAMMATORY MEDIATORS!

Methylprednisone: anti-inflammatory steroidWhat do your T cells do in the immune system? It helps with the whole cell-mediated immunity. If you’re giving an immunosuppressant, you’re blocking T cells so they don’t react.Am I going to be at HIGH RISK FOR INFECTIONS since it blocks the T cells? YES!

What is the cause of death for lupus? INFECTION. They get an opportunistic infection that kills them

Treatment: NSAIDS for mild disease Steroid-sparing drugs (Methotrexate) Antimalarials (Plaquenil) Corticosteriods for exacerbations and severe disease

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• Prednisone, methlprednisolone Immunosuppressive drugs

• Calcineurin Inhibitors-Cyclosporine (Sandimmune)• Cytotoxic Drugs- cyclophosphamide (Cytoxan), azathioprine

(Imuran)

5. What is Graft vs. Host Disease? What are clinical manifestations and treatments?

-Individuals w/ immune deficiencies are at HIGH risk for GVHD. -This occurs if the T cells in a transplanted graft (blood transfusion, bone marrow transplant) are mature & therefore capable of cell-mediated immunity destruction against the recipient’s human leukocyte antigen (HLA). -not problem if the person is immunocompetent: the ability of the body to produce a normal immune response following exposure to an antigen

Immunocompromised individuals are at risk for GVHD T cells in the graft are mature and capable of cell-mediated destruction tissues

within the recipient Not a problem if patient is immunocompetent

CLINICAL MANIFESTATIONS:

-The primary targets for GVHD are the skin, liver, mouth, eyes, & GI tract---GVHD may lead to death due to INFECTION. -their skin blisters from head to toe, and it sloughs off. It HURTS! -Skin is first barrier against infection. You are immunocompromised already, and now you are a big raw sore. Get a STAPH infection go septic die -mouth (mucosal lining- is the same lining that goes through the whole digestive tract (GI tract) to the anus) -eyes- they can get scleredema/ “scler”- hard, “edema”- swelling -your GI system sloughs off just like your skin sloughs off Swallowing is a huge problem. What can they eat? Their mouth is one huge, raw sore. -What can you give them to make their sore mouth feel better? MIRACLE MOUTHWASH it has Lidocaine, maylox(the coating) & benedril(antihistamine that reduces the swelling) -swoosh & spit, CAN’T SWALLOW it. It will NUMB THE HEART not the gut. Be careful how much lidocaine they take b/c it affects their heart. -make them spit it out, or put it on a toothpick and wipe it around their mouth

TREATMENTS:

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Treatment is with Steroids (Corticosteriods) OR immunosuppressive agents such as Methotrexate or cyclosporine-to supress GVHD

corticosteroids PREDNISONE. Taper it off, don’t stop quickly. It SPIKES BLOOD SUGAR. High doses linked to SUICIDAL ideation

Methotrexate: it’s steroid sparing, inhibits DNA synthesis so it causes problems w/ alopecia -huge IMMUNOSUPPRESSANT increased risk of infection throughout the body

6. What is the difference between hyperacute, acute, and chronic graft rejection—treatment for each.

GRAFT REJECTION: High risk for rejection w/ solid organ transplant

types of rejection:Hyperacute: happens IMMEDIATELY/ rare b/c the cause is we messed up matching. Not Rh compatible or not enough histocompatibility markers Treatment: take the organ out/ they go back on the transplant list -Can you give the organ you take out to somebody else? No. It’s Red bagged trash. -or the recipient had some kind of pre-existing antibody that rejected it -they will always be ABO & Rh matched. It’s usually the HLA that’s the problemAcute: happens DAYS to MONTHS after the transplant -cell-mediated immune response against UNMATCHED HLA antigens -#1 reason this happens: they are NOT TAKING their MEDS/ or we don’t have them on the right immunosuppressant regime -This is the only way they will mount that response- not on the right meds, or not taking them -treatment: -INCREASE THEIR MEDS -play around w/ the immunosuppressants to find out the best ones for them

Chronic: MONTHS to YEARS/ IRREVERSIBLE -cause: -inflammatory damage to the endothelial cells of the vessels of that organ/ as a result of weak cell- mediated reaction against minor HLA antigens or : -whatever caused the organ to fail in the first place is causing it again -people w/ lupus are NEVER transplant candidates b/c they have an autoimmune disease that affects vital organs -treatment: increase their drugs & it becomes SUPPORTIVE CARE -let’s say if it was the kidney- if they go back into end-stage renal disease they would go back

into dialysis & back on the transplant list

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7. What is AIDS—difference between HIV and AIDS- What is the patho of AIDS, clinical manifestations. Treatment: Slide 13-of the powerpoint—know the drugs listed there (Sustiva, Retrovir, Kaletra, Fuzeon)

AIDS: a secondary immune deficiency that develops in response to a viral infection. Viral infection is HIV. -HIV virus infects & destroys Th cells: Both Th (helper) cells & Tc (cytotoxic) cells rendering you immunosuppressant -are necessary for the development of both PLASMA cells & CYTOTOXIC T cells -the lower the T cell count more at risk for OPPORTUNISTIC INFECTIONS -suppresses the immune response against itself -AND secondarily: creates a generalized immune deficiency by suppressing the development of immune responses against other pathogens & opportunistic microorganisms, leading to AIDS.-people do not die of AIDS. They die of complications- opportunistic infections.-HIV virus lies dormant for a long time. When it become active, start seeing problems -first problem: *DROP in T helper cells -reduce the viral load w/ meds/ there is NO CURE

HIV is a blood borne pathogen-routes of transmission: -blood or blood products -IV drug abusers that share needles (needle exchange programs prevent this, but Nevada doesn’t have one) -heterosexual & homosexual activity -men are the higher risk carriers for HIV so WOMEN are the rising # of population to get the virus -(secretions- lives in semen/ vaginal vault is a reservoir when the HIV positive male ejaculates) -AFRICAN AMERICAN women are the highest -maternal-child transmission before or during birth (b/c of the close proximity of blood)Can you get it from kissing? Oral sex WITHOUT a condom can get HIV(any time there is blood or semen to open skin there is RISK for transmission).

Syndrome caused by a viral disease Human immunodeficiency virus (HIV) Depletes the body’s Th cells Incidence

• Worldwide: 5 million per year• United States: About 31,000 cases per year

Effective antiviral therapies have made AIDS a CHRONIC DISEASE

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Epidemiology Blood-borne pathogen Increasing faster in women than men

PATHO OF AIDS:

Pathogenesis Retrovirus

• Genetic information is in the form of RNA• Contains reverse transcriptase to convert RNA into double-stranded

DNA• Integrase

HIV is a retrovirus: have RNA instead of DNA. -retrovirus: uses a viral enzyme called reverse transcriptase to convert RNA into double stranded DNA -Using a 2nd viral enzyme, integrase: the new DNA is inserted into the infected cell’s genetic material, where it may remain dormant.

If the cell is activated, translation of the viral information may be initiated, resulting in the formation of new virions, lysis and death of the infected cells, and shedding of infectious HIV particles. During the process the viral protease is essential in processing proteins needed from the viral internal structure. If the cell remains relatively dormant, the viral genetic material may remain latent for years and is probably present for the life of the individual.

The primary surface receptor on HIV is the envelope protein gp120, which binds to the molecule CD4 on the surface of the Th cells. -Several other necessary co-receptors, particularly the chemokine receptors CCR, have been identified on target cells. -The major immunologic findings in AIDS is: striking decrease in the number of CD4-positive cells & Th Cells.

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CLINICAL MANIFESTATIONS:Numbers of T helper cells & cytotoxic T cells will drop. The CD4 count will also drop. Why? Those are your Helper T cells.

HIV is enveloped in the glycoprotein GP120- binds to the molecule of the CD4 cell. -As the HIV viral load goes higher, it causes the CD4 cell count to go lower.

What is the normal CD4 count? 400-1800When do we consider a person to go from HIV to AIDS positive? <200 -typically they will have an OPPORTUNISTIC INFECTION

Depletion of CD4+ cells has a profound effect on the immune system, causing a severely diminished response to a wide array of infectious pathogens & malignant tumors -look at box 7-3, page 185. talks about the diff. opportunistic infections that you can see.

Opportunistic Infections:Kaposi sarcoma- malignant skin tumor -Why does it happen? immune system is so weak that: you have alteration in the replication of your skin cells -severely immune compromised people can get this, they don’t have to be HIV positivePneumocystitis Pneumonia (PCP)- causes the most FATAL respiratory distress

The presence of circulating antibody against HIV protein p24 followed by ore complex tests for antibodies against additional HIV proteins (Western blot analysis) or for HIV

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DNA (e.g. polymerase chain reaction) indicates INFECTION by the virus, although many of these individuals are asymptomatic. Antibody appears rather rapidly after infection through blood products, usually within 4 to 7 weeks. After sexual transmission the individual can be infected yet seronegative for 6 to 14 months or longer. The period between infection and appearance of antibody is referred to as the window period. Although a person does not have antibody against HIV, he or she may the virus growing, have virus in the blood and body fluids, and may be infectious to others. Box 7-3 page 185

SYMPTOMS:Early stage disease usually present with relatively mild and nonspecific symptoms resembling INFLUENZA, such as headaches, fever or fatigue. These symptoms disappear after 1 to 6 weeks and the virus is actively proliferating in the lymph nodes.

At the time of diagnosis, the individual may present w/ 1 or several different conditions: serologically negative (no detectable antibody), serologically positive (positive for antibody against the HIV protein) but asymptomatic, early stages of HIV disease or AIDS.

Flu like symptoms: Fever, loss of appetite, fatigue (these symptoms can go away- but the person is still a “carrier”)Window period: the period btwn. the infection & the appearance of antibodies

The currently accepted definition of AIDS relies on both lab tests and clinical symptoms. If the individual is + for antibodies against HIV, the diagnosis of AIDS is made in association with various clinical symptoms. The symptoms include atypical or opportunistic infections and cancers as well as indications of debilitating chronic diseases such as wasting syndrome, recurrent fevers. Most commonly, new cases of AIDS are diagnosed by decreased CD4+T cell numbers— <200.

Clinical manifestations Serologically negative, serologically positive but asymptomatic, early stages

of HIV, or AIDS Window period Th cells <200 cells/mm3

Diagnosis of AIDS is made in association with various clinical conditions• Atypical or opportunistic infections, and cancer

TREATMENT:

Treatment and prevention Highly active antiretroviral therapy (HAART)

• Reverse transcriptase inhibitors ( Sustiva, & Retrovir)• Protease inhibitors (Kaletra)

New drugs

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• Entrance inhibitors• Integrase inhibitors (Fuzeon)• Vaccine development

Integrase: inserts the viral DNA (from the replicated RNA) into the infected cell’s genetic material -dormant viral DNA can remain dormant for 7-10 yrs. before it becomes activated

-when it’s activated: the translocation of the viral DNA can be initiated resulting in the formation of new virions, lysis & death of infected T cells -this is when the T cells decrease -during this process, the viral protease is essential

HAART: “cocktail” combination of 3 drugs-mix reverse transcriptase inhibitors & protease inhibitors PO given on an empty stomachAdverse: N/V, anorexia, hepatotoxic-Assess for rash-Administer at BEDTIME-test for pregnancy b/c it can cause harm to the fetus-can cause gallstones bc of the high cholesterol, can have pancreatitis problems, don’t give if they have elevated liver enzymes

Retrovir, Sustiva: reverse transcriptase inhibitor: prevents DNA synthesis from viral RNAAdminister PO around the clockRedistribution of fat (Buffalo hump), seizures, acute pancreatitis

Kaletra: protease inhibitor (for HIV)Prevents cleavage of viral proteins (prevents replication)Increases the CD4 count, and decreases the viral load to slow progression of HIVContains alcohol– don’t give to people who are allergicMonitor the liver function, pancreas enzymes (amylase, lipase)

Entrance inhbitors: anti-retroviral drug (for HIV)Interfers w/ binding fusion of entry of HIV virion to the human cell. Blocks it from getting into the cellJust know how this drug works. I don’t have a drug for this.

Fuzeon: Integrase inhibitorsPrevents the entry of HIV into cells by interfering w/fusion of the virus to cell membraneFatigue, pancreatitis, weight lossHow do we test for HIV? Do a liza? It is freq. false positive. Will say its + when it is really (-). Don’t say they have HIV take another blood test Western Blot. If this comes back +, say they are +.

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Who should be tested when and how? Anyone who has been exposed to the risk factorsHow often? If you were exposed to the risk factor. Know what the risk factors are.

Cancer:1. What is the difference between Benign and Malignant tumors?Benign tumors- They grow slowly, have a well-defined capsule, not invasive, well differentiated, low mitotic index, and they do not metastasize.Malignant tumors – grow rapidly, not encapsulated, invasive, are poorly differentiated, have a high mitotic index, and can spread distantly (metastasis)

2. Understand the classification of cancer-slide 5 & 6.Benign – Named according to the tissues from which they arise and include the suffix -omaMalignant tumors are named according to the tissues from which they arise. Malignant epithelial tumors are referred to as carcinomas. Malignant connective tissue tumors are referred to as sarcomas

• Cancers of lymphatic tissue are lymphomas• Cancers of blood-forming cells are leukemias• Carcinoma in situ (CIS)

• Preinvasive epithelial malignant tumors of glandular or epithelial origin that have not broken through the basement membrane or invaded the surrounding stroma

3. Know the tumor markers—table 9-2, pg 227

4. how does cancer develop• Cancer is predominantly a disease of aging• Clonal proliferation or expansion

• As a result of a mutation, a cell acquires characteristics that allow it to have selective advantage over its neighbors

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• Increased growth rate or decreased apoptosis• Multiple mutations are required before cancer can develop

5. What are Oncogenes and Tumor-suppressor genes,• Oncogenes

• Mutant genes that in their nonmutant state direct protein synthesis and cellular growth

• Tumor-suppressor genes• Encode proteins that in their normal state negatively regulate proliferation

(prevents mutations and repairs them)• Also referred to as anti-oncogenes

• Oncogenes and Tumor-Suppressor Genes: Accelerators and Brakes!• To understand how genetic mutations cause cancer, first it is important to

distinguish between oncogenes and tumor-suppressor genes. Look at table 9-3

page 229.

• Oncogenes are mutant genes that in their normal nonmutant state direct synthesis of proteins that positively regulate proliferations.

• Tumor-suppressor genes encode proteins that in their normal sate negatively regulate (halt or “put the brakes on”) proliferation. Hence, they also have been referred to as anti-oncogenes.

• In its normal, nonmutant state, an oncogene is referred to as a proto-oncogene. An example of a proto-oncogene would be a growth factor (e.g. epidermal growth factor) or a growth factor receptor (e.g epidermal growth factor receptor).

6. What is a point mutation, chromosome translocation, and chromosome amplification and their role in cancer.

• Point mutations• Changes in one or a few nucleotide base pairs

• Chromosome translocation• A piece on one chromosome is transferred to another

• Chromosome amplification• Duplication of a small piece of chromosome over and over• Results in an increased expression of an oncogene

• The activation and inactivation of various genes is key in the development of cancer.

• Mutation of normal genes into oncogenes can occur with Point mutations, Chromosome translocation and chromosome amplification.

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• Point mutations: small scale changes in DNA is called point mutations-which is the alteration of one or a few nucleotide base pairs. This type of mutation can have profound effects on the activity of proteins. A point mutation in the RAS gene converts it from a regulated proto-oncogene to an unregulated oncogene, an accelerator of cellular proliferations. Activating point mutation in RAS are found in many cancers, especially pancreatic and colorectal cancer.

• Chromosome translocation are large changes in chromosome structure in which a piece of one chromosome is translocated to another chromosome. Translocation can activate oncogenes in one of two mechanisms: First, translocation can cause excess and inappropriate production of a proliferation factor and 2nd it can lead to production of novel proteins with growth-promoting properties.

• Gene amplification can activate oncogenes. Amplifications are the result of duplication of a region of a chromosome over and over again so that instead of a normal two copies of a gene, ten or even hundreds of copies are preents.

7. What is loss of heterozygoisty and caretaker genes• Mutation of tumor-suppressor genes

• Allows unregulated cellular growth• Loss of heterozygosity

• Both chromosome copies of a gene are inactivated• Gene silencing

• Whole regions of chromosomes are shut off while the same regions in other cells remain active

• Tumor suppressor genes are genes whose major function is to negatively regulate cell growth and prevent mutations. Tumor suppressors may normally slow the cell cycle, inhibit proliferation resulting from growth signals or stop cell division when cells are damaged.

• Oncogenes are activated in cancers and tumor suppressors must be inactivated to allow cancer to occur.

• For the function of a tumor suppressor to be lost, both chromosomal copies (alleles) of the gene must be inactivated. This is because they act in a recessive manner at the level of a cell.

• Abnormal gene silencing is emerging as a major factor in cancer progression. Gene expression can be regulated in a heritable manner. Inheritance of silencing occurs during cell division and does not require mutations or changes in DNA sequence.

• Epigenetic silencing is caused by reversible chemical modification of histones and related chromatin components.

• Caretaker genes• Encode for proteins that are involved in repairing damaged DNA

• Chromosome instability• Increased in malignant cells• Results in chromosome loss, loss of heterozygosity, and chromosome

amplification

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• Inherited mutations can disrupt the caretaker genes that protect the integrity of the genome

8. What is autocrine stimulation, apoptosis, angiogenesis and telomeres in regard to misregulation of genes in cancer

• Progrowth and Antigrowth Signals• Autocrine Stimulation• Apoptosis

• Cancer cells must have mutations that enable them to attain self-sufficiency and proliferate in the absence of external growth signals-

• Some cancers acquire the ability to secrete their own growth factors (i.g. platelet-derived growth factor) to stimulate their own growth –called autocrine stimulation

• Other cancers have an increase in growth factors receptors which are often receptor tyrosine kinases.

• Cells also usually receive diverse “antigrowth” signals from their normal milieu. Contact with other cells, with basement membranes, and with soluble factors all normally signal cells to stop proliferating. These mechanisms can halt unregulated cell growth.

• Cells normally have a mechanism that causes self-destruction when growth is excessive and cell cycle check points have been igonored—this is called apoptosis and is trigged by diverse stimuli, including normal development and excessive growth.

• Angiogenesis: if cancers are to grow larger than a millimeter in diameter, they need their own blood supply. Advanced cancers secrete vascular endothelial growth factor, platelet-derived growth factor and basic fibroblast growth factor and develop their own blood supply.

• A hallmark of cancer cells is their immortality. Can cells and replicate telomeres cap on the end of the chromosome

9. How do viruses, bacteria, and inflammation cause cancer- Viruses alter DNA which puts people at a risk for cancer. Inflammation – risk for mutation: hyper immune due to increased glucocorticoid which suppresses immune and puts at high risk for error in replication. Suppressed – when you are replicating you are at a high risk for error in replication- Bacteria – H.Pylori – GERD – Barret’s esophagus/esophageal errosion10. What does it mean if the tumor metastases?

• Direct invasion of contiguous organs• Known as local spread

• Metastases to distant organs• Lymphatics and blood

• Metastases by way of implantation• Metastasis is the spread of cancer cells from the site of the original tumor to

distant tissues and organs through the body. Metastasis is a defining characteristic of cancer, contributes significantly to the pain and suffering from cancer and is the major cause of death from cancer.

• Metastasis is a highly inefficient process and requires many steps:

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• Direct or continuous extension • Penetration into lymphatics, blood vessels, or body cavities• Transport into lymph or blood• Transport to secondary sites• Entry and growth in secondary sites

11. Know the different types of biopsies

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12. know how to stage a tumor ABOVE13. know the clinical manifestations of cancer and why they occurParaneoplastic syndromes

• Symptom complexes that cannot be explained by the local or distant spread of the tumor or by the effects of hormones released by the tissue from which the tumor arose

• Pain• Little or no pain is associated with early stages of malignancy• Influenced by fear, anxiety, sleep loss, fatigue, and overall physical

deterioration• Mechanisms

• Pressure, obstruction, invasion of sensitive structures, stretching of visceral surfaces, tissue destruction, and inflammation

• Fatigue• Subjective clinical manifestation• Tiredness, weakness, lack of energy, exhaustion, lethargy, inability to

concentrate, depression, sleepiness, boredom, and lack of motivation• Fatigue

• Suggested causes

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• Sleep disturbance, biochemical changes from circulating cytokines, secondary to disease and treatment, psychosocial factors, level of activity, nutritional status, and environmental factors

• Syndrome of cachexia• Most severe form of malnutrition• Present in 80% of cancer patients at death• Includes:

• Anorexia, early satiety, weight loss, anemia, asthenia, taste alterations, and altered protein, lipid, and carbohydrate metabolism

• Marinol/adavan/megase/zofran drug combo for cancer patient.

• Anemia• A decrease of hemoglobin in the blood• Mechanisms

• Chronic bleeding resulting in iron deficiency, severe malnutrition, medical therapies, or malignancy in blood-forming organs

• Can be caused by drugs, and malignancies in blood forming organs• Leukopenia and thrombocytopenia

• Direct tumor invasion to the bone marrow causes leukopenia and thrombocytopenia

• Chemotherapy drugs are toxic to the bone marrow• Infection

• Risk increases when the absolute neutrophil and lymphocyte counts fall

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14. Know the following cancer treatments on slide 31: Cytoxan, Methotrexate, Doxorubicin, Vincristine, and Taxol

• Alkylating Agents• Cytoxan• Table 37.4, pg. 555

• Antimetabolites• Methotrexate• Table 37.5, pg. 555

• Antitumor Antibiotics• Doxorubicin• Table 37.6, pg. 557

• Plant Extracts and Alkaloids• Vincristine• Taxol

Table 37.7, pg 559

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14. why do we use more than one chemo drug to treat cancerCombination – cell cycle specific and cell cycle non specific so the cancer cells are definitely eradicated.

15. know the following hormones and hormone antagonisits and their role in cancer treatment: Dexamethasone, Prednisone, Lupron, Tomifen, Eulexin

16. know the following Bilogic Response Modifiers and their role in cancer treatment: Pegasys, Proleukin, Avastin, HerceptinThey target down to the exact cell…. Like throwing a dart at a bullseye. Side effects are gnarly. The person will think they are dying. Worst case flu you can think of.

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17. Know the side effects of cancer treatment: Lewis Book table that I referred you guys

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to is the best!