Vasculitis-Prevention, Diagnosis, and Management....

 

 

  Vasculitis is an inflammation and necrosis of the blood vessels, leading to hemorrhage, ischemia, and infarction.. Treatment of the condition is entirely dependent on the extent of the disease. In many instances, cutaneous vasculitis is a self-limited condition, relieved by leg elevation, avoidance of standing, and therapy with non-steroidal anti-inflammatory drugs (NSAIDs). However, more extensive or severe disease can prove more difficult to manage.

Treatment of vasculitis should begin with a confirmatory diagnosis to eliminate conditions with a similar appearance. A tissue biopsy may confirm diagnosis of cutaneous vasculitis, and can sometimes be used to identify the type of immunoglobin involved. Once a diagnosis is confirmed histologically, other organ systems should be evaluated to identify potential causative factors.

The first and preferred treatment for cutaneous vasculitis should always be avoidance of triggers known to exacerbate the condition, such as excessive standing, infection, or drugs.  For mild recurrent or persistent disease, colchicine and dapsone are first-choice agents.

Severe cutaneous disease requires treatment with systemic corticosteroids or more potent immunosuppression (azathioprine, methotrexate, or cyclophosphamide are typical treatments). A combination of corticosteroids and cyclophosphamide is required therapy for systemic vasculitis, which is associated with a high risk of permanent organ damage or death. Intravenous immunoglobin or plasmapheresis may be useful in the treatment of severe, refractory vasculitis, or in patients who have contraindications to traditional immunosuppression.

New biologic therapies that act via cytokine blockade or lymphocyte depletion, such as the tumor necrosis factor-α inhibitor infliximab and the anti-B-cell antibody rituximab, respectively, appear to offer some benefit in certain settings, such as connective tissue disease and anti-neutrophil cytoplasmic antibody-associated vasculitis.

This is article 3 in a series of four articles pertaining to vasculitis.  To read the additional articles click title link, or  click here.

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Vasculitis is the inflammation of blood vessels. There are many types of vasculitis. Diseases in which vasculitis is a primary process are called primary systemic vasculitides. Vasculitis may also occur as a secondary feature in other rheumatic diseases and syndromes
WHAT YOU NEED TO KNOW ABOUT VASCULITIS What is vasculitis? Vasculitis is a general term that refers to the inflammation of blood vessels. When blood vessels become inflamed, they can only react in limited ways. They may become weakened, stretch and increase in size, or become narrow – even to the point of closing off entirely. What are the consequences of vasculitis? In an extreme situation, when a segment of a blood vessel becomes weakened, it may then stretch and bulge (called an “aneurysm”). The wall of the blood vessel can become so weak that it ruptures and bleeds. Fortunately, this is a very rare event. If a blood vessel becomes inflamed and narrowed, blood supply to that area may be partially or completely eliminated. If collateral blood vessels (thought of as alternate routes of blood supply) are not available in sufficient quantity to carry the blood to such sites, the tissue supplied by the affected blood vessels will die. This is called infarction. Because vasculitis can occur in any part of the body, any tissue or organ can be at risk. Who is affected by vasculitis? Vasculitis can affect people of all ages from childhood to adulthood. There are some types of vasculitis that occur in certain age groups more than others. What are the causes of vasculitis? Vasculitis may occur secondary to an identified underlying disease or trigger. Occasionally, an allergic reaction to a medicine may trigger vasculitis. Vasculitis can sometimes develop in conjunction with an infection. Usually in these cases, the infection causes an abnormal response in the person’s immune system, damaging the blood vessels. Viral hepatitis (a type of liver infection), is a specific infection that can be associated with vasculitis. Vasculitis may also be related to other diseases of the immune system that the patient had for months or years. For example, vasculitis could be a complication of rheumatoid arthritis, systemic lupus erythematosus, or Sjögren’s syndrome. In many cases though, the causes of vasculitis are not known. These diseases are collectively sometimes referred to under the broad heading of primary forms of vasculitis. In such settings, the appearance and location of the vasculitis often behaves in a distinct way allowing it to be diagnosed as a unique type of vasculitis and is given a specific name. What are the types of primary vasculitis? There are many types of primary vasculitis including disease entities such as Wegener’s granulomatosis, microscopic polyangiitis, Henoch-Schönlein purpura, polyarteritis nodosa, Kawasaki disease, giant cell arteritis, Takayasu’s arteritis, and Behçet’s disease. Some are named after doctors (Wegener, Takayasu, Kawasaki) who were among those to provide the best original descriptions of the illness or are named based on features seen on biopsies (giant cell arteritis, angiitis, arteritis nodosa) of affected tissues or blood vessels. Although most of these are systemic (or generalized) vasculitides where the vasculitis may affect many organ systems at the same time, they often differ a great deal among each other. Some of the primary systemic vasculitic diseases may be quite mild and require little or even no treatment. Other forms may be severe, affecting critical organs and, if left untreated, may lead to death within days or months. Some forms of primary vasculitis may be restricted in their location to certain organs (these are called isolated forms of vasculitis). Examples include vasculitis that only occurs either in the skin, eye, brain (isolated CNS vasculitis) or certain internal organs. What are the symptoms of vasculitis? Because any organ system may be involved, an enormous number of symptoms are possible. If the skin is involved, there may be a rash. If nerves suffer loss of blood supply, there may initially be an abnormal sensation followed by a loss of sensation. Vasculitis in the brain may cause a stroke, or in the heart may result in a heart attack. Kidney inflammation usually is not associated with symptoms and is detected by the doctor by examination of the urine. This is important to recognize as inflammation in the kidneys can lead to kidney failure unless promptly detected. Sometimes the symptoms are nonspecific. When inflammation is present in the body, we tend to respond in ways that tell us that we are not well, but those responses may not be unique to vasculitis at all. For example, along with the symptoms mentioned previously, a person with vasculitis may also have a fever or experience loss of appetite, weight loss and loss of energy. How is vasculitis treated? Treatment depends entirely upon the diagnosis, the organs that are affected, and the severity of the vasculitis. When vasculitis represents an allergic reaction, it may be “self limiting,” or will go away on its own and not require treatment. There are other instances also where minimal to no treatment is required and the person can be closely observed. In instances where critical organs such as the lungs, brain or kidneys are involved, the outlook is less positive and aggressive and timely treatment is necessary. For most forms of systemic vasculitis, treatment generally includes corticosteroid medications (prednisone is the most commonly prescribed). For some forms of vasculitis, treatment must also include another immunosuppressive medication used in combination with the prednisone. Some of these medications are chemotherapy agents like those used to treat cancer, but are given in doses considerably lower than people with cancer may receive. The goal of this type of chemotherapy is to suppress the abnormal immune response that has led to blood vessel damage. What is the outlook for people with vasculitis? The outlook for a person who has vasculitis will vary with the type of vasculitis that is present, what organs are being affected, how severe the vasculitis is, and how the person responds to treatment. Knowing the type of vasculitis allows the doctor to predict the likelihood of illness severity and outcome. Prior to the time of available treatment, people with severe vasculitis may have had anticipated survival of only weeks to months. However, today with proper treatment, normal life spans are possible. The success of therapy is related to prompt diagnosis, aggressive treatment and careful follow-up to be sure that side effects from medications do not develop. Once vasculitis is under control (often referred to as “remission”), medications may be cautiously withdrawn, with the hope that the patient will sustain a long remission, independent of treatment. Because some forms of vasculitis can recur (referred to as a “relapse”) after a period of remission, it is very important for patients with vasculitis to remain under the care of a knowledgeable physician.

HIV Update.....The changing Epidemic....

SINCE ITS EMERGENCE in the early 1980s, HIV infection in the United States has evolved from an acute debilitating condition to a chronic, treatable illness. Patients with HIV infection are at risk for various comorbidities and adverse reactions associated with long-term medication administration, as well as disorders associated with normal aging and chronic HIV infection.


Because HIV infection is seen in every age group and can cause multisystem disease, you're likely to care for patients with HIV infection across all settings. This article provides an update on HIV infection assessment and treatment, and discusses how you can help your patients manage this chronic disease.


Global problem

An estimated 33.4 million people throughout the world are living with HIV infection.1 Two-thirds of these people can be found in sub-Saharan Africa, which accounts for 22.4 million people living with HIV. In contrast, approximately 1.1 million adults and adolescents in the United States are living with HIV infection or AIDS (the most serious stage of HIV infection)


The estimated number of people with HIV infection or AIDS has increased because treatment advances have significantly prolonged the lives of people with HIV. Each year, approximately 56,000 people in the United States are newly infected with HIV. With increased public awareness of the effects of HIV infection and the simple strategy of using a latex condom to prevent HIV transmission, the infection rate should, ideally, be going down. Various social, cultural, biological, political, and even financial factors help explain why HIV transmission continues to occur at such an alarming rate.


Screening for HIV infection
Of the 1.1 million Americans with HIV infection, an estimated 21% are unaware they're infected.2,3 These people account for 54% to 70% of newly transmitted infections.4,5 Transmission risk behaviors decrease among people who are aware of their HIV status, so knowing one's status can be an important prevention strategy.



The CDC recommends that all people between ages 13 and 64 be screened for HIV infection as a routine part of healthcare, regardless of their risk.2 Annual screening is recommended for individuals who are at continued risk for HIV infections, such as those who continue to inject illicit drugs or engage in unprotected sexual intercourse.


Patients can be screened for HIV infection during a routine healthcare visit, along with screenings for dyslipidemia, hypertension, and diabetes. Because not all Americans receive routine healthcare, the CDC also recommends routine HIV infection testing in acute care hospitals and EDs. The percentage of patients who test positive for HIV infection in hospitals and EDs (2% to 7%) exceeds that seen nationally at publicly funded HIV counseling and testing sites (1.5%) and STD clinics (2%) that treat people at high risk for HIV.2 Testing for HIV infection is easily done in most any setting (see HIV testing and results in 20 minutes). Testing staff must be aware of applicable state laws that may or may not include requirements for pretest counseling, written consent, and posttest counseling.

For specific state requirements, you can find a useful guideline at http://www.nccc.ucsf.edu/docs/quickstatelawguidelines.pdf.



Refining treatment options
Since 1996, HIV infection treatment has focused on combining drugs from different HIV drug classes. A combination of drugs from at least two anti-HIV drug classes provides the best long-term clinical outcomes. Currently 6 different anti-HIV drug classes, 22 unique drugs, and 6 combination tablets are available (see Common drugs used to treat HIV).


The decision to begin anti-HIV therapy, or what's commonly called antiretroviral (ARV) therapy, in patients with HIV infection is based primarily on the patient's CD4 cell count. The CD4 cell count is a key marker of immune system health in patients with HIV infection. The lower the count, the more damage HIV has done. Anyone with a CD4 cell count less than 200 T-lymphocytes/mm3, or a CD4 T-lymphocyte percentage of total lymphocytes of less than 14, is considered to have AIDS.8 Without treatment, people with AIDS are at higher risk for AIDS-related illnesses commonly known as opportunistic diseases. Because the immune system is weakened in people with AIDS, some of these illnesses can be life-threatening.


ARV therapy is usually given to patients with a history of an AIDS-defining illness (an illness that's generally seen in patients with a weakened immune system, such as Pneumocystis jiroveci pneumonia and Kaposi sarcoma); a CD4 cell count under 350 cells/mm3; HIV-associated nephropathy (HIVAN); hepatitis B virus (HBV) coinfection; or women with HIV who are pregnant.


Current guidelines also recommend starting ARV therapy if the CD4 cell count is less than 500 cells/mm3.8 For patients with CD4 cell counts over 500 cells/mm3, starting ARV therapy is considered optional because of the lack of any conclusive clinical studies that demonstrate a clinical benefit (such as a reduction in mortality or new cancers) at this stage.8 The current recommended HIV therapy in patients who've never been on therapy (treatment-naive patients) is a regimen of tenofovir disoproxil fumarate/emtricitabine combined with one of the following: efavirenz; atazanavir with ritonavir; darunavir with ritonavir; or raltegravir with ritonavir.8 Each of these combinations has been shown, in randomized controlled trials, to fully suppress viral replication, avoid the development of HIV medication resistance, and adequately increase the patient's CD4 cell count when compared with other drug combinations. These regimens are also preferred because they're usually well tolerated with few adverse reactions, and with the exception of raltegravir, all of the regimens can be administered once a day. In addition to these benefits, the regimen of tenofovir disoproxil fumarate/emtricitabine plus efavirenz has been combined into one pill that can be taken once a day. Combining drugs into one pill decreases the patient's "pill burden," reducing the complexity of therapy, and may improve adherence to therapy.


Before patients are started on a new ARV regimen, assess their readiness (see Is your patient ready for ARV therapy?). Therapy with these medications is lifelong, and once started, generally continues without interruption. Teach patients that these medications must be taken exactly as prescribed. If they miss doses, the virus can become resistant to the medication, rendering the therapy ineffective. A virus that's resistant to one drug in a class can become resistant to other drugs in the same class, limiting the number of drugs available for treating the patient.


All ARV medications cause adverse reactions; without proper education, patients who experience unpleasant reactions may discontinue their medication. For example, most patients who take efavirenz experience vivid hallucinations during sleep or dizziness during the day for the first 2 weeks after taking the drug. To minimize these reactions, teach patients to take this medication at bedtime and advise them to alter their activities until they can work through the period of medication adjustment.


Tell patients to report any adverse reactions they experience to their healthcare provider and stress that they should never stop taking the medication on their own.


Advise patients that their healthcare provider will ask them to return within 2 weeks to evaluate their response to the new regimen. This includes monitoring the patient for such adverse reactions as blood dyscrasias and abnormal serum glucose or lipid levels that can occur with most ARV medications. After 4 to 6 weeks on therapy, the healthcare provider will also order several blood tests to evaluate patient response to therapy.



Treatment goals
The two most important biomarkers of successful response to ARV therapy are the evaluation of the viral load, by measuring serum HIV RNA levels, and the CD4 cell count. The goal of ARV therapy is to achieve a viral load below the limit of detection, which is generally less than 20 to 75 copies of HIV RNA. (The specific value depends on the commercial test that's used; check the manufacturer's instructions.)


The second treatment goal is an increase in CD4 cell count. With effective therapy, patients should have a 50- to 100-cell increase in their CD4 cell counts per year. Many patients who start therapy with CD4 cell counts over 350 and have a good response to therapy can expect to normalize their CD4 cell counts.


Assess patients who don't meet these therapeutic goals for adherence to therapy, drug-drug interactions, and drug resistance.

Long-term problems: It's complicated

0With more effective therapy for HIV infection, the incidence of once-common opportunistic diseases, such as cryptococcus, histoplasmosis, and bacillary angiomatosis, has decreased. But as patients live longer, cardiovascular disease (CVD), chronic renal disease, and cancers that usually aren't seen in patients with AIDS (such as anal and lung cancers) are increasingly common. These complications may be due to a combination of:


* chronic immune system activation triggered by HIV

* ARV medication adverse reactions (as discussed below)

* human papillomavirus (HPV) coinfection

* behavioral factors such as smoking, chronic alcohol abuse, and illicit drug use

* normal age-related changes.



HIV and CVD

HIV infection is a strong risk factor for CVD. An analysis of acute myocardial infarction (AMI) in a large healthcare system found that the rate of AMI among patients with HIV infection was nearly double that in those without HIV, even after adjusting for age, sex, race, hypertension, diabetes mellitus, and dyslipidemia.10 The Data Collection on Adverse Events of Anti-HIV Drugs Study Group demonstrated that subjects had an increased incidence of AMI that was proportionate to the cumulative duration of therapy with ARVs, particularly protease inhibitors (PIs) and the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir and didanosine. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) weren't linked to a higher incidence of AMI. Newer ARV agents weren't in use at the time of the study.


Conversely, the HIV Out-Patient Study didn't find any association of CVD with any specific ARV agents or classes, but detected a significantly increased association with traditional CVD risk factors.

Compared with people in the general population, a greater proportion of patients with HIV infection have one or more risk factors for CVD (such as smoking, hypertension, or insulin resistance/diabetes) that may cumulatively contribute to higher rates of CVD. HIV treatments may also contribute to CVD because NRTIs, NNRTIs, and PIs are associated with dyslipidemia. How these drugs cause dyslipidemia varies by drug class.


To combat the effect of lipid accumulation, a non-PI-based regimen (such as raltegravir combined with tenofovir and emtricitabine) may be prescribed. If a PI-based regimen is indicated, atazanavir without ritonavir (and combined with two NRTIs) can be used. If the PI must be combined with ritonavir, atazanavir with ritonavir produces less of an increase in low-density lipoprotein and triglycerides than other PIs.

Teach patients about CVD risk reduction strategies that include smoking cessation, diet modification, and physical activity. Monitor the patient's fasting lipid profile at baseline, at 3 to 6 months after starting a new regimen, and then annually or more frequently if indicated (in high-risk patients or in patients with abnormal baseline levels). Generally, if lifestyle or ARV regimen modifications don't achieve lipid goals, adding antidyslipidemic agents to the regimen is considered. When using antidyslipidemic agents in HIV-infected patients, it's important to consider potential drug-drug interactions with ARVs. For example, certain statins such as simvastatin and lovastatin are contraindicated with PIs due to a serious drug-drug interaction.


HIV and renal disease

HIV infection is associated with several renal syndromes, including chronic renal failure. Renal disease linked to HIV infection includes thrombotic microangiopathic renal diseases, immune-mediated glomerulonephritis, and HIVAN.




Kidney function is abnormal in up to 30% of HIV-infected patients.13 The most common complication is HIVAN, a disease characterized by massive nephrotic proteinuria (often more than 10 g/day), the absence of edema, and large echogenic kidneys seen on ultrasound. If left untreated, HIVAN can progress to renal failure in 1 to 2 years. HIVAN is almost always seen in patients with advanced immunosuppression (a CD4 cell count under 100).


HIV medications can also cause renal dysfunction. Indinavir (rarely used today) and atazanavir may cause nephrolithiasis. Tenofovir, the most widely prescribed NRTI and the preferred drug in treatment-naive patients, can cause tubular injury that leads to renal tubular dysfunction and a decrease in glomerular filtration rate (GFR).Studies have shown only minimal decreases in the GFR of patients taking tenofovir and a low incidence (0.3%) of renal failure. Because patients may have concurrent illnesses that may affect the kidneys (such as dehydration), it's hard to be certain that any one drug alone is responsible for renal disease.

Minor lab abnormalities are also associated with tenofovir. Fanconi syndrome, which causes phosphate wasting along with renal losses of potassium, bicarbonate, uric acid, amino acids, and glucose, can be reversed with discontinuation of the drug. Patients with diabetes mellitus or hypertension, a GFR less than 90 mL/minute/1.73 m2, and who receive medications excreted renally or PIs in combination with ritonavir (a "boosted" PI) should undergo biannual renal function and serum phosphorus testing and urinalysis while taking tenofovir.13 Due to the potential renal toxicity with tenofovir, use this drug with caution if your patient has baseline renal insufficiency or other risk factors for renal dysfunction (hypertension, diabetes, older age).


Monitor patients for abnormalities in glucose metabolism or hypertension, which are common risk factors for renal disease. Work with patients to help them meet treatment goals. When patients experience gastrointestinal (GI) symptoms such as diarrhea or vomiting, advise them to drink plenty of water to prevent dehydration, which may result in acute kidney injury.


Many drugs administered as part of treatment or used to prevent opportunistic infection (such as trimethroprim/sulfamethoxale for P. jiroveci prevention) are nephrotoxic. Screen for changes in renal function by calculating the patient's GFR by using either the modified Cockcroft-Gault formula or the Modification of Diet in Renal Disease equation.



HIV and cancer

The early HIV epidemic was defined by malignancies such as Kaposi sarcoma and central nervous system lymphomas. The incidence of these two AIDS-defining malignancies (ADMs) has declined dramatically. Today, non-AIDS-defining malignancies (non-ADMs) are more common than ADMs, and the risk of both types is higher for patients with lower CD4 cell counts. The four most frequently reported fatal non-ADMs are lung cancer (20%); cancer of the GI tract, such as gastric or hepatocellular carcinomas (13%) and anal cancer (7%); and cancers of the hematologic system, such as Hodgkin lymphoma (7%). The increased incidence of non-ADMs may be related to the fact that HIV-infected patients, either due to their lifestyle or other circumstances, are more subject to the traditional risk factors than non-HIV patients. For example, the rates of smoking in those with HIV infection far exceed the rates of smoking in the general population.12 The incidence of anal cancers is increased in HIV-positive men who have sex with men; there's a 60-fold increase in the relative risk increase of anal neoplasia in this population when compared with the general population.



In general, patients with HIV infection receive age-appropriate cancer screenings according to the same guidelines as noninfected patients. The greatest difference is screening for anal cancer.



Anal cancer is rare in the United States, with an incidence of 1 per 100,000 in the general population. In contrast, the risk of anal cancer for women and men of all ages with HIV infection is 6.8 per 100,000-37 times greater than that in their respective general populations.

HPV causes anal cancer. (See "HPV-Related Cancer: An Equal Opportunity Danger" in the October issue of Nursing2010.) Patients with HIV disease are at higher risk for developing anal cancer because HIV infection attenuates the host response to HPV infection. Patients with low CD4 cell counts have a higher incidence of persistent HPV infection and greater incidence of anal intraepithelial neoplasia (AIN), changes in the anal canal that are precursors to invasive anal cancer.20 AIN grades 1, 2, and 3 reflect low-, moderate-, and high-grade dysplasia. Grades 2 and 3 are often grouped together as high-grade squamous intraepithelial lesions and associated with a higher risk of invasive cancer.


Annual anal cancer screenings are recommended for HIV-infected men with a history of sex with other men, HIV-infected women with a history of cervical or vulvar dysplasia (because HPV is associated with these cancers too), and anyone with a history of anogenital condyloma. Anal cancer screening may include an anal Pap test or anoscopy. An anal Pap test is the same type of test used to screen women for cervical cancer.


Anoscopy is the endoscopic evaluation of the anus, anal canal, and lower rectum. Anyone with an abnormal anal Pap test should have a follow-up anoscopy.


Assess patients' sexual history for risk factors that put them in the high-risk category to ensure they're appropriately screened for anal cancer. Keep in mind that women with dysplasia on their cervical Pap tests are at high risk for anal dysplasia and should also be screened.


Be prepared

Thanks to the effectiveness of combination ARV therapy, people with HIV infection are living longer than ever. But complications and adverse reactions arising from treatment can affect the patient's quality of life or psychosocial functioning. Advise your patients about what to expect during therapy and carefully monitor them for complications. With your help, patients with HIV infection can live long, productive lives.



HIV TESTING AND RESULTS IN 20 MINUTES

Conventional testing for HIV infection is done via lab analysis of a blood sample, which may delay diagnosis. More rapid testing that produces results in 20 minutes is now available. It's easy to use and doesn't require lab facilities or highly trained staff.

To perform an oral test, place the pad of the device above the patient's teeth along the outer gum and swab once around both the upper and lower gums to collect oral mucosal transudate from the patient's mouth. Insert the device into a vial containing the developing solution.

In 20 minutes, the device indicates whether HIV-1 or HIV-2 antibodies are present. If one line appears on the strip, the person isn't infected with HIV (with 99.8% accuracy). If two lines appear, the patient is likely infected (99.3% accuracy).


If the result is positive, it must be confirmed with additional, more specific tests to detect HIV antibodies.



IS YOUR PATIENT READY FOR ARV THERAPY?

Before starting therapy, assess your patient's:

* basic knowledge of HIV infection, transmission, and prevention

* understanding of ARV treatment and potential adverse reactions

* ability to comprehend, cope, and adhere to the prescribed therapy

* willingness to create support systems to cope with HIV status and facilitate treatment, such as disclosing status to family, friends, and partners.



After starting therapy, assess your patient's:

* advanced knowledge and skills to cope and manage HIV status and treatment

* ability to recognize and seek care for opportunistic diseases and complications.



Evaluate your patient's:

* level of HIV knowledge, personal autonomy, skills, and confidence to manage the consequences of HIV status and treatment

* capacity to take action that encourages health and discourages the determinants of ill health, such as substance abuse and unsafe sexual practices.

Source link...Adapted from: Gebrekristos HT, Mlisana KP, Karim QA. Patients' readiness to start highly active antiretroviral treatment for HIV. BMJ. 2005;331(7519):772-775.

Immune System tips...

IMMUNITY – body’s reaction to any foreign body that might enter our tissues
2 types:
•NON SPECIFIC/ CELLULAR / Innate immunity present in our body since we were born
•SPECIFIC
Mediators (non specific)

1. MECHANICAL BARRIERS

•Skin (keratinized)
•Body secretions ( sweat, oil)
•Cilia (transports)
•Mucus (traps organism entering the Respiratory tract)
2. CHEMICAL BARRIERS

•Enzymes (lysozymes)
•Acids ( kills bacteria by denaturation)
Fatty acids – skin
Gastric acids – stomach
•Complement system – becomes activated in cascade fashion 1,2,3…..
Activated Complements System – presents antigen to the bacteria; once activated, has to be removed from the body
3. INFLAMMATORY RESPONSE

Presents the 5 Cardinal signs which is chemically mediated that can come from:


•Damaged tissues
•Inflammatory cells
•Even from the bacteria itself

5 Cardinal signs & symptoms of inflammation:
1. redness (rubor)
2. swelling (tumor)
3. pain (dolor)
4. heat (calor)
5. loss of function (functiolaesa)


FXN:


•forms a barrier to confine infection
•tries to eliminate infectious agent
•initiates repair of damaged tissues
4. CELLS – WBC’s


a) GRANULOCYTES – granulocytic leukocytes; WBC’s with granules inside the cytoplasm


1. Neutrophiles – plenty; 1st line of defense; 1st to respond during an infection
HALLMARK OF ACUTE INFECTION (10days)
Once they leave, they cannot go back (through “DIAPEDESIS”)
CBC - increased Neutrophiles = acute infection
Disease is current; can be bacterial

HOW DO NEUTROPHILES KILL BACTERIA?

•Phagocytic – active engulfing
•Degranulation – release granules in the cytoplasm which contains cytotoxins that kill the bacteria
2. Eosinophiles – mediate for Allergies; Hypersensitivity reaction; Anaphylactic reaction;

Contains vasoactive dilators:

•Serotonin
•Histamine
•Bradykinin
Limited phagocytic activities
“Picky eaters” eat only * complement system, * Ag aggregated with Ab

3. Basophiles – HEPARIN – anti coagulant; lesser blood clots

b) AGRANULOCYTES


1. Monocytes – found in the blood which rids bacteria, virus, and other debris
“scavengers” (10 days in circulation)
ACTIVE phagocytes
DIAPEDESIS – mode of escape w/o damage
MACROPHAGES – once they are out, monocytes take this form; derivative
Neutrophiles, Monocytes, Macrophages = 3 active phagocytic cells

2. Lymphocytes – non phagocytic cells
HALLMARK OF CHRONIC INFECTION


a) T –CELLS/ T-LYMPHOCYTES = (Cellular Immunity)
T- cells mature in the Thymus glands(Lymphoid organs)
Once there is an infection, they become ACTIVE EFFECTOR CELLS


•Natural killer cells – non phagocytic cells which kills by secreting LYMPHOKINES
kills ON CONTACT; has intimate contact with bacteria (sila ang Police na pumapatay sa kahit sinong magnanakaw - virus,bacteria)
•Helper cells – calls for other WBC’s which circulate around the body by secreting “OPSONINS” (chemically attract WBC). WBC aids in the attack; (nagtatawag para may katulong ang Police sa laban)
•Suppressor cells – the absence of these mediators will cause destruction of normal tissues
(taga awat kung bugbog na ang kalaban, kung walang aawat sila-sila din ang magpapatayan kahit kakampi nila- "Autoimmune disease")

b) B CELLS/ B LYMPHOCYTES - mediator of specific immunity


•must 1st recognize specific Ag (nag draw-drawing ng cartographic sketch ng magnanakaw the 1st time na pumasok sya sa bahay)
•acquires Ab’s once exposed to microorganism (ipapakita niya yung drawing niya sa police para next time na papasok ang magnanakaw kilala na ng police at bubugbugin na niya ang magnanakaw)
•improves with exposure (mas madalas niya makita at mas madalas sya manakawan, mas lalo na niya nakikilala ang magnanakaw para lalong maituro at mahuli ng police )
•Humoral immunity

ACTIVE EFFECTOR B CELLS:


•MEMORY CELLS – (Ang "WITNESS" na nag draw-drawing ng cartographic sketch ng magnanakaw the 1st time na pumasok sya sa bahay)
•PLASMA CELLS – makes Ab’s specific to description of the memory cells; (bumubuo ng "TASK FORCE POLICE" para lumaban sa muling pagbalik, dun lang sa magnanakaw na nai-drawing ng witness - "Antigen-Antibody Response")


IMMUNIZATION – is the process by which we reinforce our immune system by introducing antigens that stimulate antibody responses

•ACTIVE – our own body participates in the production of Ab’s
slow acting so it is introduced during our childhood; last longer than passive
VACCINES – made up of dead, inactivated organisms; parts of Ag’s; or attenuated (weakened virus or bacteria)

•PASSIVE – giving antibodies (Ab’s) especially during epidemic
Gives immediate protection but temporary (3-6months)
Ex. Equine vaccine from horses
A) NATURAL – from mother to baby
B) PASSIVE – Ab’s from other sources