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IMMUNOLOGIC FUNCTION The immune system functions as the bodys defense mechanism againts invasion and allows a rapid

response to foreign substances ina specific manner. Tolerance is the mechanism by which the immune system is programmed to eliminate foreign substances such as microbes, toxins, and cellular mutations but maintains the ability to accept self-antigens. IMMUNE SYSTEM (ANATOMY AND PHYSIOLOGY ) The immune system is composed of an integrated collection of various cell types, each with a designated function in defending againts infection and invasion by other organisms. BONE MARROW. The white blood cells (WBCs) involved in immunity are produced in the bone marrow. Like other blood cells, lymphocytes are generated from stem cells, which are undifferentiated cells. There are two types of lymphocytes: B lymphocytes (B cells)- mature in the bone marrow and then enter the circulation. T lymphocytes (T cells)- move from the bone marrow to the thymus, where they mature into several kinds of cells with different functions.

LYMPHOID TISSUES The spleen, composed of red and white pulp, acts somewhat like a filter. The red pulp is the site where old and injured cell proliferation.

FUNCTION OF THE IMMUNE SYSTEM The basic function of the immune system is to remove foreign antigens as viruses and bacteria to maintain homeostasis. There are two general types of immunity: Natural (innate) and, Acquired (adaptive).

NATURAL IMMUNITY Present at birth. Nonspecific. Provides a broad spectrum of defense againts and resistance to infection. It is considered the first line of host defense following antigen exposure. Co-ordinates the initial response to pathogens through the production of cytokines and and other effector molecules, which either activate cells for control of the pathogen or promote the development of the acquired immune response. Monocytes, macrophages, dendritic cells, natural killer (NK) cells, basophils, eosinophils, and granulocytes ( cells that involved in this response).

Natural immune mechanism can be divided into two stages: Immediate (generally occurring within 4 hours) Delayed (occurring between 4 and 96 hours after exposure)

ACQUIRED IMMUNITY Develops after birth. Develops as a result of prior to an antigen through immunization (vaccination) or by contracting a disease, both of which generate a protective immune response. The acquired immune response is broadly divided onto two mechanisms: The cell-mediated response, involving T-cell activation, and Effectors mechanisms, involving B-cell maturation and production of antibodies. Acquired immunity has two types: Active acquired immunity-immunologic defenses developed by the persons own body. This immunity typically lasts many years or even a lifetime. Passive acquired immunity- temporary immunity transmitted from a source outside the body that has developed immunity through previous disease or immunization.

RESPONSE TO INVASION When the body is invaded or attacked by bacteria, viruses, or other pathogens, it has three means of defense: The phagocytic immune response Primarily involves the WBCs (granulocytes and macrophages), which have ability to ingest foreign particles and destroy the invading agen; eosinophils are only weakly phagocytic. The humoral or antibody immune response (antibody response) Begins with the B- lymphocytes,which can transform themeselves into plasma cells that manufacture antibodies. The cellular immune response Involves the T-lymphocytes, which can turn into special cytotoxic (killer) T cells that can attack the pathogens.

The structural part of the invading or attacking organism that is responsible for stimulating antibody production is called antigen (immunogen). Once produced, an tibody is released into the bloodstream and carried to the attacking organism. There are four well-defined stages in an immune response: Recognition Proliferation Response and Effector

RECOGNITION STAGE Recognition involves the use of lymph nodes and lymphocytes for surveillance. Lymph nodes are widely distributes internally throughout the body and in the circulating blood, as well as externally near the bodys surfaces. The exact way in which they recognize antigens on foreign surfaces is not known; however, recognition is thought to depend on specific receptor sites on the surface of the lymphocytes. Macrophages play an important role in helping the circulating lymphocytes process the antigens.

PROLIFERATION STAGE The circulating lymphocytes containing the antigenic message return to the nearest lymph node. Once in the node, these sensitized lymphocytes stimulate some of the resident T and B lymphocytes to enlarge, divide, and proliferate. T lymphocytes differentiate into cytotoxic T cells, whereas B lymphocytes produce and release antibodies.

RESPONSE STAGE In the response stage, the differentiated lymphocytes function in rither a humoral or a cellular capacity. This stage begins with the production of antibodies by B lymphocytes in response to a specific antigen. The cellular response stimulates the resident lymphocytes to become cells that attack microbes directly rather than through the action of antibodies. Viral rather than bacterial antigens induce a cellular response. Most immune response to antigen involve both humoral and cellular response, although one usually predominates.

EFFECTOR STAGES In the effector stage, either theantibody of the humoral response or the cytotoxic T cell of the cellular response reaches and connects with the antigen on the surface of the foreign invader.

HUMORAL IMMUNE RESPONSE Characterized by the production of antibodies by B lymphocytes in response to specific antigen. B lymphocytes is responsible for the production of antibodies , both the macrophages of natural immunity and the special T lymphocytes of cellular immunity are involved in recognition.

ANTIGEN RECORNITION B lymphocytes recognize and respond to invading antigens in more than one way. B lymphocytes respond to some antigens by directly triggering antibody formation. In response to other antigens,B lymphocytes need the assistance of T cells to trigger antibody formation.

ROLE OF ANTIBODIES Antibodies are large proteins, called immunoglobulins, that consist of two subunits. Each subunit has one portion that serves as a binding site for a specific anigen and another portion that allows the antibody molecule totake part in the complement system. Antibodies defend againts foreign invaders in several ways, and the type of defense used depends on the structure and composition of both antigen and the immunoglobulin. Antibodies also promote the release of vasoactive substances, such as histamine and slowreacting substances, two of the chemical mediators of the inflammatory response. Antibodies do not function in isolation; rather, they mobilize other components of the immune system to defend againts the invader.

CELLULAR IMMUNE RESPONSE T lymphocytes are primarily responsible for cellular immunity. Stem cells continously migrate from the bone marrow to the thymus gland, where they develop into T cells. T cells attack foreign invaders directly rather than by producing antiboodies.

TYPES OF T LYMPHOCYTES Effector T cells Helper T cells- activated on recognition of antigens and stimulate the rest of the immune system. When activated, helper T cells secrete cytokines, which attract and activate B cells, cytotoxic T cells, NK cells, macrophages, and other cells of the immune system. Helper T cells also produce lymphokines, one category of cytokines. Cytotoxic T cells (killer T cells)- attack the antigen directly by altering the cell membrane and causing cell lysis (disintegration) and by releasing cytolytic enzymes and cytokines. Suppressor T cells- have the ability to decrease B-cell production, thereby keeping the immune response at a level that is compatible with health. Memory T cells- responsible for recognizing antigens from previous exposure and mounting an immune response.

NULL LYMPHOCYTES AND NATURAL KILLER CELLS Null lymphocytes Subpopulation of lymphocytes, destroy antigens already coated with antibody. These vcells have special receptor sites on their surface that allow them to connect with the end of antibodies; this is known as antibody-dependent, cell mediated cytotoxicity.

Natural killer cells Class of lymphocytes that recognize infected and stressed cells and respond by killing these cells and by secreting macrophage-activating cytokine.

COMPLEMENT SYSTEM Circulating plasma protein, made in the liver and activated when an antibody connects with its antigen. Plays an important role in the defense against microbes. It has three physiologic functions: Defending the body against bacterial infection Bridging natural and acquired immunity, and Disposing of immune complexes and the byproducts associated with inflammation. The proteins that comprise complement interact sequentially with one another in a cascading effect. The complement cascade is important to modifying the effector arm of the immune system. Activation of complement allows important events, such as removal of infectious agents and initiation of the inflammatory response, to take place. The complement cascade may be activated by any of three pathways: Classic- triggered after antibodies bind to microbes or other antigens and is part of the humoral type of adaptive immunity. Lectin- activated when a plasma protein binds to terminal mannose residue on the surface glycoproteins of microbes. Alternative- triggered when complement proteins are activated on microbial surfaces.

IMMUNOMODULATORS Immunomodulator (biologic response modifier) affects the host via direct or indirect effects on one or more components of the immunoregulatory network. Interferons and colony-stimulating factors are two of the more commonly used immunomodulators.

Interferons one type of biologic response modifier,is a nonspecific viricidal protein that is naturally produced by the body and is capable of activating other components of the immune system. Interferons have antiviaral and antitumor properties. Interferons are produced by T lymphocytes, B lymphocytes, and macrophages in response to antigens. They are thought to modify the immune response by suppressing antibody production and cellular immunity. They also facilitate the cytolytic role of macrophages and NK cells. Interferons are used to treat immune-related disorders (multiple sclerosis) and chronic inflammatory conditions (chronic hepatitis).

Colony-stimulating factors Group of naturally occurring glycoproteun cytokines that regulate production, differentiation, survival, and activation of hematopoietic cells.

ADVANCES IN IMMUNOLOGY Genetic engineering One of the more remarkable evolving technologies. It uses recombinant deoxyribonucleic acid (DNA) technology. Two facets of this technology exist: The first permits scientists to combine genes of a second organism. This type of technology allows cells and microorganisms to manufacture proteins, monokines, and lymphokines, which can alter and enhance immune system function. The second facet of recombitant DNA technology involves gene therapy.

Stem cells Capable of self-renewal and differentiation; they continually replenish the bodys entire supply of both RBCs and WBCs. Some stem cells, described as totipotent cells, have tremendous capacity to self-renew and differentiate. Embryonic stem cells, described as pluripotent, give rise to numerous cell types that are able to form tissues.

ASSESSMENT OF THE IMMUNE SYSTEM Assessment of immune function begins during the health history and physical examination. Areas to be assessed include nutritional status; infections and immunizations; allergies; disorders and disease states, such as autoimmune disorders, cancer, and chronic illnesses; surgeries; medications; and blood transfusions.

HEALTH HISTORY Gender There are differences in the immune system functions of men and women.

Example: many autoimmune diseases have a higher incidence in females than in males, a phenomenon believed to be correlated with sex hormones.

Gerontologic considerations Immunosenecence is a complex route in which the aging process stimulates changes in the immune system. The immune system undergoes age-associated alterations that lead to a progressive deterioration in the ability to respond to infections. There is a notable decline in the total number of phagocytes, coupled with an intrinsic reduction in their activity. The cytotoxicity of NK cells decreases, contributing to a decline in humoral immunity may be negatively affected; the efficacy of vaccines is frequently decreased in older adults. The incidence of autoimmune diseases also increases with age, possibly from a decrease ability of antibodies to differentiate between delf and non-self. The effects of the aging process and psychological stress interact, with the potential to negatively influence immune integrity. Nutrition The relationship of infection to nutritional status is a key determinant of human health. Traditionally this relationship focused on the effect of nutrients on host defenses and the effect of infection on nutritional needs. The list of nutrients affecting infection, immunity, inflammation, and cell injury has expanded from traditional proteins to several vitamins, mulyiple minerals, and more recently specific lipid components of the diet. Infection and immunization The patient is asked about childhood and adult immunizations, including vaccinations, to provide protection againts influenza, pneumococcal disease, pertussis, herpes simplex, and the usual childhood diseases. Teaching about the importance of adhering to the recommended schedule for these vaccines should be initiated. Recent exposure to any infections and the exposure dates are elicited. A history of STDs such as gonorrhea syphilis, human papillomavirus (HPV) infection, and chlamydia can alert the nurse that the patient may have been exposed to HIV or hepatitis. A history of past and present infections ao any multiple persistent infections, fevers of unknown origin, lesions or sores, or any type of drainage, as well as the response to the treatment are obtain.

Allergy The patient is asked about any allergies, including types of allergens(eg, pollens, dust, plants, cosmetics, food, medication, vaccines, latex), the symptoms experienced, and seasonal variations in occurrence or severity in the symptoms. All medication and food allergies are listed on an allergy alert sticker and placed on the front of the p*atients health record or chart to alert others.

DISORDERS AND DISEASES Autoimmune disorders Autoimmune disorders affect people of both genders of all ages, ethnicities, and social classes. The patient is asked about any autoimmune diksorders, such as lupus erythematosus, rheumatoid arthritis, multiple sclerosis, or psoriais. The onset, severity, remissions, and exacerbations, functional limitations, treatments that the patient has received or is currently receiving, and is effectiveness of the treatments are described.

Neoplastic disease If there is a history of cancer in the family, the type of cancer, age at onset, and relationship (maternal or paternal) of the patient to the affected family members is noted. A history of cancer in the patient is also obtained, along with the type of cancer, date od diagnosis, and treatment modalities used. Immunosuppression contributes to the development of cancers; however , cancer itself is immunosuppressive, as is the treatment for cancer. All treatments that the patient has received or is currently receiving, such as radiation or chemotherapy, are recorded in the health history.

Chronic illness and surgery The health assessment oncludes a history of chronic illness, such as diabetes mellitus, renal disease, chronic obstructive pulmonary disease(COPD), or fibromyalgia. The onset and severity of the illness, are obtained. Additionally, a history of organ transplantaion or surgical removal of the spleen, lymph nodes, or thymus is noted, because these conditions may place the patient at risk for impaired immune function.

Special problems Conditions such as burns and other forms of injury and infection may contribute to altered immune system function. Major burns causeimpaired skin integrity and compromise the bodys first line of defense. Medications and blood transfusions

A list of past and present medications is obatined. In large doses, antibiotics, corticosteroids, cytotoxic agents, salicylates, non-steroidal anti-inflammatory drugs (NSAIDs), and anesthetic agents can cause immune suppression. A history of blood transfusions is obtained, because previous exposure to foreign antigens through transfusions may be associated with abnormal immune function. The patient is also asked about used of herbal agents nad over-the-counter medications. Because many of these products have not been subjected to rigorous testing, their effects have not been fully identified. It is important, therefore, to ask patients about their use of these substaces, to document their use, and to educate patients about untoward effects that may alter immune responsiveness.

Lifestyle factors Like any other body system, the functions of the immune system depend on other body system. Poor nutritional status, smoking, excessive consumption of alcohol, illicit drug use, STDs, and occupational or residential exposure to environmental radiation and pollutants have been associated with impaire dimmune function and are assessed in a detailed patient history. Psychoneuroimmunologic factors Patient assessment must also address psychoneuroimmunologic factors. The bidirectional pathway between tha brain and immune system is reffered to as psychoneuroimmunology, afield that has been the focus of research and discussion overvthe last several decades. It is thought that the immune response is regulated in part by neuroendocrine influences.

Management of patients with immunodeficiency Immunodefiiency disorder may be caused by defect in or a deficiency of phagocytic cells, B lymphocytes, T lymphocytes, or the complement system. The specific symptoms and their severity, age at onset, and prognosis depend on the immune system components affected and their degree of functional impairment.

Immunodeficiencies may be acquired spontaneouslyor as aconsequence of medical treatment. These disorder can be classified as either primary or secondary and by the affected components of the immune system. Primary immunodeficiencydiseases are genitic origin and result from intrinsic defects in the cell of immune system. Secondary immunodeficiencies result from external factorsuchs as infection.

Primary immunodeficiencies

Represent inborn errors of immune function that predispose people to frequent, severe infections; autoimmunity; and cancer.

The type of malignancy depends on the immunodeficiency, the age of the patient, and possible viral infection, which suggest that different pathogenic mechanism are implicated in each case. Non-hodgkin lymphomas account for the majority of cancers. This primary immunodeficiencies known to be associated with increased incidence of malignancy are common variable immunodeficiency, immunoglobulin A (IgA) deficiency, and deoxyribonucleic acid (DNA) repair disorders. The majority of primary immunodeficiencies are diagnosed in infancy, with a male-to-female ratio of 5 to 1. Diagnosis at this stage frequenty is confounded by frequent use of antibiotics that mask symptoms. Common primary immunodeficiencies include disorders of humoral immunity (affecting B-cell differentiation or antibody production), T-cell defects, combined B- and T-cell defects, phagocytic disorders, and complement deficiencies. Symptoms of immune deficiency disorders are related to the deficient component.

Phagocytic dysfunction Pathophysiology A variety of primary defects of phagocytes may occur; almost all of them are genetic in origin and affect the natural (innate) immune system. In some types of phagocytic disorders, the neutrophils are impaired so that they cannot exit the circulation and travel to sites of infection.

Clinical manifestations In phgocytic cell disorders there is an increased incodence of bacterial and fungal infection. People with these disorders amy also develop fungal infections from candida organisms and viral infections from herpes simplex or herpes zoster. Thses patients experience recurrent cutaneous anscesses, chronic eczema, bronchitis pneumonia, chronic otitis media, and sinusitis. In one rare type of phagocytic disorder, hyperimmunoglobunemia E syndrome (job syndrome), white blood cells cannot initiate an inflammatory responce to infectious organisms. Although patients with phagocytic cell disorders may be asymptomatic, severe neutopenia may present and may be accompanied by deep and painful mouth ulcres, gingivitis, stomatitis, and cellulitis.

Assessment and diagnostic findings Diagnosis is based on the history, signs and symptoms, and laboratory analysis by the nitrobluetetrazolium reductase test, which indicates the cytocidal activity of the phagocytic cells.

Medical management. Patients with neutropeniaa continue to be at increased risk for development of severe indections despite substantial advances in supportive care. Although it is effective in preventing some bacterial and some fungal infections, prophylactic drug treatment must be used with caution, because it has been implicated in the emergence of resistant organisms. While granulocyte transfusions are used as a medical treatment, they are seldom successful because of the short half-life of these cells. Treatment with granulocyte-macrocolonystimulating factor (GM-CSF) may prove successful, because these proteins draw nonlymphoid stem cells from the bone marrow and hasten their maturatuion. o Hematopoietic stem cell transplantation (HSCT), another form of cell therapy, has proven to be a successfull curative modality. The stem cells may be form embryos or adults.

B-cell deficiencies Pathophysiology Two types ofinherited B. cells deficiencies exist . The first type result from lack of diffenrentiation of B. cells precursors into mature B cells. This syndrome is called X- linked agammaglobulinemia (Brutons disease), patients plasma. B cells in the peripheral blood and IgG,IgM, IgD, and IgE are low absent infant born This disorder suffer from severe infection starting soon birth.

Males are at a high risk for having X-linked aggamaglobulinemia if they have an affected male relative. Atosomal agammaglobulinemia refers to a rare instance in which normal hypogommaglobulinemia of infancy is prolonged. It can result from mutative on in a variety gene whose product are require for differentiation of B cells. The second type of B cells deficiency results from a lack of differentiation into plasma cells. This syndrome, called hypogammaglobulinemia, is a frequently occurring immunodeficiency. It is also called CVID; this disorder encompasses a variety of defects ranging from IgA deficiency, in which only the plasma cells that produce IgA are absent, to the other extreme , in which there is severe panhypoglobulinemia (general lack of immunoglobulins in the blood) CVID is the most common primary immunodeficiency seen in adults; it can occur in people of either gender.

Clinical Manifestations Infants with X-linked agammaglobulinemia usually become symptomatic after the natural loss of maternally transmitted immunoglobulins, which occurs at about 5 to 6 months. Patients with CVID are at increasedrisk for autoimmune disease, granulomatous disease, and malignancy, indicating CVID is a disease of abnormal immune regulation as well as of immunodeficiency. Other autoimmune diseases, such as arthritis and hypothyroidism, frequently occur. More than 50% of patients with CVID develop perniciousanemia. Lymphoid hyperplasia of the small intestine and spleen as well as gastric atrophy,which is detected by biopsy of the stomach, are common finding,Gastrointestinal malabsorption may occurs. Patients with CVID are susceptible to infection with encapsulated bacteria, such as Haemophilus influenzae, streptococcus pneumoniae.

Assessment and Diagnostics Finding X-linked agammaglobulinemia may be diagnosed by the marked deficiency or complete absent of all serum immunoglobulins, The diagnosis of CVID is based on the history of repeated bacterial infections, quantification of B- cell activity, and reported signs and symptoms.

Medical management Patients with primary phagocytic disorders may be treated with intravenous immunoglobulin (IVIG) Other interventions aimed at overcoming the immunologic defects in CVID, such as interleukin-2 therapy, are being studied.

T-cell deficiencies Pathophysiology Defects in T-cells lead to opportunistic infections. Most primary T-cell immunodeficiencies are genetic in origin. Partial T-cell immunodeficiencies constitute a heterogeneous cluster of disorders characterized by an incomplete reduction in T-cell number or activity. Digeorge syndrome or thymic hypoplasia is an example of primary T-cell immunodeficiency. The symptom variation is a result of differences in the amount of genetic material affected The syndrome often manifests in the neonatal period as a cardiac anomaly, although hypocalcemic tetany and facial abnormalities may also occur. Chronic mucocutaneous candidiasis is a rare T-cell disorder, which is thought to be autosomal recessive disorder that affects both males and females.

Clinical manifestation Infants born with DiGeorge syndrome have hypoparathyroidism with resultant hypocalcemia resistant to standard therapy, congenital heart disease, cleft palate and lip, dysmorphic facial features, and passively renal abnormalities. These infants are susceptible to yeast, fungal, protozoan, and viral infections and are particularly susceptible to childhood diseases, which are usually severe and may be fatal. Many affected infants are also born with congenital heart defects, which can result in heart failure. The most frequent presenting sign in patients with DiGeorge syndrome is hypocalcemia that is resistant to standard therapy.

Assessment and diagnostic findings Prompt diagnosis is necessary for appropriate management. A comprehensive immunologic therapy analysis isnecessary. Findings in children with DiGeorge syndrome include cardiac, nutritional, and developmental abnormalities.

Medical management Patients with T-cell deficiency should receive prophylaxis for PCP. General care includes management of hypocalcemia and correction of cardiac abnormalities. In children with DiGeorge syndrome, attention must be given to cardiac, nutritional, and developmental needs. IVIG may be used if an antibody deficiency exists. T-cell function improves with age and often is normal by 5 years of age.

Combine B-cell and T-cell deficiencies Pathophysiology T-cell and B-cell immune deficiencies comprise a heterogeneous group of disorders, all characterized by profound impairment in the development of function of cellular, the humoral, or both parts of the immune system. Ataxia-telagiectasia is an autosomal recessive neurodegenerative disorder characterized by cerebellar ataxia, telangiectasia, and immune deficiency. The disorder is characterized by some degree of T-cell deficiency, which becomes more severe with advancing age. Severe combined immunodeficiency is a disorder in which both B-cells and T-cells are missing. SCID is marked by susceptibility to serious fungal, bacterial, and viral infections. It refers to a wide variety of congenital and hereditary immunologic defects characterized by early onset of infections, defects in both B-cell and T-cell systems, lymphoid aplasia, and thymic dysplasia. It is one of the most common causes of primary immunodeficiencies. Wiskott-Aldrich syndrome (WAS), a variation of SCID, is an inherited immunodeficiency caused by a variety of mutations in the gene encoding the WAS protein. It is characterized by frequent infection, thrombocytopenia with small platelets, eczema, ad risk of autoimmune disorders and malignancies.

Clinical manifestations The onset of ataxia and telangiectasia occurs in the first 4 years of life. Many patients, however, remain symptom free for 10 years or longer. The onset of symptoms occurs within the first 3 months of life in most patients with SCID. Symptoms include respiratory infections and pneumonia, thrush, diarrhea, and failure to thrive.

Medical management Treatment of ataxia-telangiectasia includes early management of infections with antimicrobial therapy, management of chronic lung disease with postural drainage and physical therapy, and management of other presenting symptoms. Treatment options for SCID include stem cell and bone marrow transplantation. HSCT in the definitive therapy for SCID; the best outcome is achieved if the disease is recognized and treated early in life. Genetic therapy has been used, but the results have been disappointing.

Nursing management Many patients require immunosuppression to ensure engraftment of depleted bone marrow during transplantation. Continual monitoring of the patients condition is critical, so early signs of impending infection may be detected and treated before they seriously compromise the patients status.

Deficiencies of the complement system The complement system is an integral part of the immune system, and deficiencies in normal levels of C2 and C3 complement result in increased susceptibility to infectious diseases and immune-mediated disorders. Hereditary angioneurotic edema results from the deficiency of C1-esterase inhibitor, which opposes the release of inflammatory mediators. Paroxysmal nocturnal hemoglobinuria is an acquired clonal stem cell disorder resulting from a somatic mutation in the hematopoietic stem cell.

Secondary immunodeficiencies Secondary immunodeficiencies are more common than primary immunodeficiencies and frequently occur as a result of underlying disease processes or the treatment of these disorders. In secondary immunodificiencies, abnormalities of the immune system affect both naural and acquired immunity, may be subtle, and are usually heterogeneous in their clinical manifestations. Patients with secondary immunodeficiencies are known as immunocompromised hosts.

Medical management Medical management of secondary immunodeficeincies includes: Diagnosis Treatment of the underlying disease process. Treatment of the primary condition often results in the improvement of the affected immune components.

Nursing management for patients with immunodeficiencies. Nursing management includes assessment, patient teaching, selected interventions, and supportive care. Nursing care of patients with primary and secondary immunodeficiencies depends on the underlying cause of the immunodeficiency, the type of immunodeficiency, and its severity. The assessment focuses on the: history of past infections, particularly the type and frequency of infection methods of and response to past treatment signs and symptoms of any current skin, respiratory, oral, gastrointestinal, or genitourinary infection and, measures taken by the patient to prevent infection. Because of the inflammatory response may be blunted, the patient is observed for subtle and unusual signs and changes in physical status.

Vital signs and the development of pain,neurologic signs, cough, and skin and oral lesions are monitored and reported immediately. Pulse rate and respiratory rate should be counted for a full minute, because subtle changes can signal deterioration in the patient clinical status. Auscultation of the breath sounds is important to detect changes in respiratory status that signal an existing or impending infection If the patient is a candidate for any of the newer or experimention therapies ( gene therapy , bone marrow transplantation, immunomodulators such as interferon-y), the patient and family must be informed about the potential risk and benefits of the treatment regimen.

Promoting home and community based care The patient and caregivers require instruction about the signs and symptoms that indicate infection and about the potential for occurrence of atypical symptoms secondary to underlying immunosuppression. Patients should be advised that they know themselves best; therefore, whenever they experience a symptom that is not typically for them, they should contact their health care provider, who will determine and initiate appropriate therapy. Patients and their families are also instructed about the importance of continuing treatment regimens without interruption and incorporating this routines into their daily living patterns. The patients is instructed about the importance of avoiding others with infections and avoiding crowds, and about other ways to prevent infection.

Continuingcare. Encouraging the patient and family to be active in partners in the management of the immunodifieciency is the key to successful and outcomes and a favorable prognosis. If the patients treatment includes IVIG and the patient or family cannot administer treatment, a peripheral for home care or an infusion service is warranted.

MANAGEMENT OF PATIENTS WITH HIV INFECTION AND AIDS HIV INFECTION AND AIDS AIDS was first identified almost 30 years ago,remarkable progress has been made in improving the quality and duration of life for people living with HIV disease. During the first decade , this progress was associated with the recognition and treatment of opportunistic diseases and introduction of prophylaxis againts common opportunistic infections. The second decade witnessed progress in the development of highly active antiretroviral therapies (HAARTs) as well as continuing progress in the treatment of oppoetunistic infections. The third decade has focused on issues on adherence to antretroviral therapy, development of second-generation medications that affect different stages of viral life cycle, and continued need for an effective vaccine.

Epidemiology In the fall of 1982, after the first 100 cases were reported, the centers for disease control and prevention (CDC) issued case definition of AIDS. The CDC now uses a new and precise method to identify cases of HIV. Almost 7000 people around the world still contact HIV infection every day. Estimated 33 million people are living with HIV/AIDS;however, the number of new infections declined from 3 million in 2001 to 2.7 million in 2007. Sub-saharan africa continues to be most heavily affected by HIV/AIDS, with 67% of all people living with the disease.

Hiv transmission HIV-1 is transmitted in body fluids that contain free virions and infected CD4+ T cells. These fluids include blood, seminal fluid, vaginal secretions, amniotic fluid, and breast milk. Blood and blood products can transmit HIV to recipients can transmit HIV to recipients.

Gerontologic considreations The number of ppeople between the ages of 55 and 64 years living with AIDS more than doubled between the years 1998 and 2003. Several factors put older adults at risk for HIV infection: Many older adukts are sexually active but do not use condoms, viewing them only as a means of unneeded birth control. Many older adults do not consider themselves at risk for HIV infection. Older gay men, who grew up and lived in an era when disclosure of their sexual orientation was not acceptable and who have lost long-time partners, may begin new relationship with younger men. Older adults may be intravenous (IV)/injection drug users. Older adults may have received HIV-infected blood through transfusions before 1985. Mormal age-related changes include a reduction in immune system function, which puts the older adult at greater risk for infections, cancers, and autoimmune disorders.

Prevention of HIV infection Combination of evidence-based prevention strategies that include behavioral, structural, and biochemical approaches tempered by the wisdom and ownership of communities offers the best hope for prevention.

Preventive education Evidence-based programs have been used to educate the public regarding sexual practices to decrease the isk of transmitting HIV infection to sexual partners. Other than abstinence, consistent and correct use of condoms is the only effective method to decrease the risk of sexual transmission of HIV infection. Microbicides are chemical products such as gels, creams, films, or suppositories that are inserted into the vagina or rectum before sexual intercourse to prevent HIV transmission. Microbicide research is moving in three directions: New microbicides that contain antireroviral agents suvh as tenofovir gel or dapivirine gel and ring. Long acting dispersal methods suc as vaginal rings that remain in place or do not require frequent applications, and Combinations products with different mechanisms of action. The harm reduction model recognizes that toatl abstinence from from addictive drugs might not be a realistic short term goal. Extensive research has demonstrated that needle exchange programs do not promote increased drug use;on the contrary , they have been found to decrease the incidence of bloodborne infections in people who use IV/injection drugs.

Related reproductive education. Because HIV infection in women often occurs during the childbearing years, family planning issues need to be addressed. Efforts at artificial insemination using processed semen from an HIV-infected partner continue.\ Women who are HIV positive should be instructed not breast-feed their infants, because HIV is transmitted through breastmilk. Estrogen in oral contraceptives may increase a womans risk of HIV infection. The intrauterine contraceptive device (IUD) may also increase the risk of HIV transmission because the string of the IUD may serve as a means to transmit the virus.

Transmission to health care providers. Standard precaution To reduce the risk of exposure of health care workers to HIV, the CDc developed standard precautions . Standard precautions are used when working with all pateints in all health care settings, regardless of their diagnosis or presumed infectious status.

Postexposure prophylaxis for health care providers. Postexposure prophylaxis in rreponse to the exposuer of health care personnel to blood or other body fluids reduces the risk of HIV infection. The CDC recommends that all health care providerss who have sustained a significant exposure to Hiv be counseled and offered anti-HIV postexposure prophylaxis, if appropriate. Those who choose postexposure prophylaxis must be prepared for the side effects of the medications, as well as the unknown long-term risks, because HIV often becomes resistant to the mediactions used to trest it.

Vaccination Hopes were dahed when a vaccine efficacy trial was halted in september 2007, after interium results showed taht the vaccine being tested did not protect againts HIV and did not reduce viral load after infection. Cooperation among all nations continues to grow, and resources are being allocated to develop a vaccine and to create and support the infrastructure needed to facilitate vaccine testing.

Pathophysiology Viruses are intracellular parasites. HIV belongs to a group of viruses known as retroviruses, which carry their genetic material in the form of ribonuvleic acid (RNA) rather than deoxyrebonucleic acid (DNA). HIV targets cells with CD4 receptors, which are expressed on thesurface of T lymphocytes, monocytes, dendritic cells, and brain microglia. Mature T cells (T lymphocytes) are composed of two major subpopulations that are defined by cell surface receptors of CD4 or CD8. Most people have about 700 to 1000 CD4+ cells/mm3, but a level as low as 500 cells/mm3 can be considered within normal lilmits. Once HIV has attached to the host cell, the virus can replicate. The HIV cycle is complex and consist of the following steps: Attachment. In this first step, the GP120 and GP41 glycoproteins of HIV bind with The hosts uninfected CD4+ receptor and chemokine coreceptors, usually CCR5, which results in fusion of HIV with the CD4+ T cell. Uncoating. The contents of HIVs viral core (two single strands of viral RNA and three viral enzymes: reverse transcriptase, integrase, and protease) are emptied into the CD4+ T cell. DNA synthesis. HIV changes its genetic material from RNA to DNA through action of reverse transcriptase, resulting in double-stranded DNA that carries instruction for viral replication.

Integration. New viral DNA enters the nucleus of the CD4+ T cell and through action of integrase is blended with the DNA of the CD4+ T cell, resulting in permanent, lifelong infection. Prior to this step, the uninfected person has been only exposed to, not infected with, Hiv. With this step, HIV infection is permanent. Transcription. When the CD4+ T cell is activated, the double-stranded Dna forms singlestranded messenger RNA (mRNA), which builds new viruses. Translation. The mRNA creates chain of new proteins and enzymes (polyproteins) that contain the components needed in the construction of new viruses. Cleavage The HIV enzyme protease cuts the poluprotein chain into the individual proteins that make up the new virus. Budding. New proteins and viral Rna migrate to the membrane of the infected CD4+ T cell, exit from the cell, and start the process all over. In resting (nondividing) CD4+ T cells, HIV can survive in a talent state as an integrated provirus that produces few or no viral particles. HIV -1 mutates quickly, at a relatively constant rate, with about 1% of the virus genetic material changing anually. HIV-1 exhibits substantial genetic diversity and several different genotypes of HIV-1 exist.

Stages of HIV disease The stage of HIV disease is based on clinical history, phusical examination, laboratory evidence of immune dysfunction, signs and symptoms, and infections and malignancies. The CDC standard case definition of of AIDS categorizes HIV infection and AIDS in adults and adolescents on the bsis of clinical conditions associated with HIV infection and CD4+ T cell counts. The classification system groups clinical conditions into one of three categories, denoted A, B, and C.

Primary infection (acute/recent HIV infection, acute HIV syndrome. The period from infection with HIV to the development of HIV-specific antibodies is known as primary infection. Initially, there is a window period during which an HIV-positive person tests negative on the HIV antibody blood test, although he or she infected and highly infectious because his or her viral load is very high. Primary infection is characterized by high levels of viral replication, widespread dissemination of HIV throughout the body, and destruction of CD4+ T cells.

The primary infection stage is part of CDC category A and includes the acute symptomatic and aerly infection phases. During this stage, the virus is widely disseminated in lymphoid tissue, and a latent reservoir within resting memory CD4+ T cells is created.

Hiv asymptomatic (CDC category A: more than 500 CD4+ T lymphocytes/mm3) After the viral set point reached, HIV-positive people enter into chronic stage in which the immune system cannot eliminate the virus despite its best efforts. This set of point varies greatly from patient to a patient and dictates the subsequent rate of disease progression; on average, 8 to 10 years pass before a major HIV-related complication develops. In this prolonged, chronic stag, patients feel well and have few, if any, symptoms.

HIV symptomatic (CDC category B: 200 to 499 CD$+ T lymphocytes/mm3) Category B consist of symptomatic conditions in HIV-infected patients that are not included in thw conditions listed in catgory C. These conditionsmust also meet one of the following criteria: The condition is caused by Hiv infection or a detect in cellular immunity, or The conditionis considered to ahve a clinical course or to require management that is complicated by HIV infection. If a person was once treated for category B condition and has not developed a category C disease but is now symptom-free, that persons stage of HIV disease is considered category B.

AIDS (CDC category C: fewer than 200 CD4+ T lymphocytes/mm3) Once a patient has had a category C condition, he or she remains in category C even if CD4+ T cells rebond with treatment. This classification has implications for entitlements (ie, disability benefits, housing, and food stamps), because these programs are often linked to an AIDS diagnosis.

Assessment and diagnostic findings in HIV infection During the first stage of HIV infection, the patient may be asymptomatic or may exhibit various signs and symptoms. Patients who are in later stages of HIV infection may ahve a variety of symptoms related to their immunosuppressed state. Several screening tests are used to diagnose HIV infection.

HIV antibody tests. In 2006, the CDC issued recommendations for HIV testing in public and private health care settings, including hospital emergency departments, impatient facilities, urgent care clinics, primary care settings, public health clinics, community clinics, substance abuse treatment clinics, and correctional health acre facilities. The objectives of those recommendations were: To increase HIV screening of patients, including pregnant women, in health care setting. Foster earlier detection of HIV infection. Identify and counsel people with unrecognized HIV infection and refer them to clinical nd preventive services And further reduce perinatal transmission of HIV. The major changes from previously published guidelines are: HIV screening is recommended for patients (18 to 64 years of age) in all health care settings after the patient is notified taht testing will be performed unless he or she declines (opt-out screening). People at high risk for HIV infection should be screened for atleast anually. Separate written consent for HIV testing should not be required; general consent for medical care should be considered sufficient to encompass consent for HIV testing. Prevention counseling should not be required with HIV diagnostic testing or as part of HIV screening programs in health care settings. Before HIV antibody test is performed, the meaning of the test and possible test results are explained, and informed consent for the test is obtained from the patient. When a person is infected with HIV, the immune system responds by producing antibodies againts the virus, usually within 3 to 12 weeks after infection. The EIA (enzyme immunoassay) test, formerly referred to as the ELISA (enymed-linked immunosorbent assay) test, identifies antibodies directed specifically againts HIV. The western blot assay is used to confirm seropositivity when EIA result is positive.

Viral load tests Target amplification methods include reverse transciprtase-polymerase chain reaction ( RT-PCR) and nucleic acid sequence-based amplification. Widely used viral load test measures plasma HIV RNA levels. Currently these tests are used to tract viral load and response to treatment of HIV infection. RT-PCR is also used to detect HIV in high risk seronegative people before antibodies are measurable, to confirm a positive EIA result, and to screen neonates.

Treatment of HIV infection The CD4+ T-cell count is usually the most important consideration in deciding whether antiretroviral medications should be offered to people with a T-cell count of less than 350 cells/mm3 or plasma HIV RNA levels exceeding 100,000 copies/ml.

Clinicians, in partnership with patients, make treatment decisions based on a number of factors, including CD4+ T-cell count, viral load, severity of HIV/AIDS-related symptoms, and willingness of the patient to adhere tothe lifelong treatment regimen. To achieve sustained viral suppression, patients must take more than one antiretroviral medication. Some pharmaceutical companies have combined two to three agents into one tablet or capsule, such as Kaletra (Lopinavir and Ritonavir) and Atripla (efavirenz, emtricitabine, and tenofovir) ina single tablet for once-a-day use. The goals of treatment include maximal and sustained suppression of viral load to a nondetectable level, restoration or preservation of immunologic function, improved quality of life, and reduction of HIV-related morbidity and mortality. Results of therapy are evaluated with viral load tests. Viral load levels should be measured immediately before initiation of antiretroviral therapy and again after 2 to 8 weeks. Adverse effects associated with all HIV treatment regimens include hepatoxicity, nephrotoxicity, and osteopernia, along with increased risk of cardiovascular disease and myocardial infarction.

Drug resistance It can be broadly defined as the ability of pathogens to withstand the effects of medications that are intended to be toxic to them. There are two major components of antiretroviral drug resistance: Transmission of dug-resistant HIV at the time of initial infection, and Selective drug resistance in patients who are receiving nonsuppressive regimens. Genotypic testing determines the sequence of viral RNA encoding relevant genes, which allows detection of amino acid mutations that are either proven or suspected be associated with phenotypic resistance. Phenotypic testing determines the drug concentration needed to inhibit replication of a recombinant virus bu 50% of a patients isolate, whwn compared with a susceptible reference.

Treatment interruption Unplanned interruption of antiretroviral therapy may become necessary because of severe drug toxicity, intervening illness, surgery that precludes oral therapy, pregnancy, or unavailability of antiretroviral medications. Planned treatment interruption, outside of clinical research trials, is not recommended.

Immune reconstitution inflammatory syndrome Results from rapid restoration of pathogen-specific immune responses to opportunistic infections that cause either the deterioration of a treated infection or new presentation of a subclinical infection.

This syndrome typically occurs during the initial months after beginning antiretroviral treatment and is associated with a wide spectrum of pathogens, most commonly mycobacteria, herpes viruses, and deep fungal infections. It is characterized by fever, respiratory and/or abdominal symptoms, and worsening of the clinical manifestations of an opportunistic infection or the appearance of new manifestations.

Clinical manifestations The clinical manifestations of HIV/AIDS are widespread and may involve virtually any organ system. Diseases associated with HIV infection and AIDS result from infections, malignancies, or the direct effect of HIV on body tissues. Fatigue is frequently cited by people living with HIV/AIDS as one of the most bothersome symptoms.

Respiratory manifestations Shortness of breath Dyspnea Cough Chest pain Fever

Pneumocystis pneumonia The most common infection in people with AIDS. It is caused by P. Jiroveci. It is the most common opportunistic infection associated with AIDS. The clinical presentation of PCP in HIV infection is generally less acute than in people who are immunosuppressed as a result of other conditions. PCP may be present despite the absence of crackles. If left untreated, PCP eventually progresses and causes significant pulomonary impairment and, ultimately, respiratory failure. PCP can be diagnosed definitively by identifying the organism in the lung or bronchial secretions.

Mycobacterium avium complex Common opportunistic infection in people with AIDS. It comprises a group of acid-fast bacilli (mycobacteria) that includes M. Avium, M. Intracellulare, and M. Scrofulaceum. MAC usually causes respiratory infection but is also commonly found in the gastrointestinal tract, lymph nodes, and bone marrow.

Tuberculosis TB can develop in the lungs as well as in extrapulmonary sites such as te central nervous system (CNS), bone, pericardium, stomach, peritoneum, and scrotum. Important issues in the use of antiretroviral therapy in patients with active TB disease are: The sequencing of treatments The value of directly observed therapy Risk of significant drug interactions with rifamycins The addictive risk of hepatotoxicity and neuropathy associated with agents used to treat HIV and TB Developments of IRIS with TB after initiation of antiretroviral therapy The effect of an antiretroviral therapy on results of tuberculin skin testing, and The need for integration of therapy for HIV and TB.

Gastrointestinal manifestations Gastointestinal manifestations of AIDS include: Loss of appetite Nausea Vomiting Oral and oesophageal candidiasis,and Chronic diarrhea Diarrhea is a problem in 50% to 90% of all AIDS patients. Gastrointestinal synptoms may be related to the direct effect of HIV on the cells lining the intestines. In patients with AIDS, the effects of diarrhea can be devastating in terms of profound weight loss, fluid and electrolyte imbalances, perianal skin excoriation, weakness, and inability to perform the usual activities of daily living.

Oral candidiasis Candidiasis Fungal infection Occurs in almost all patients with AIDS and AIDS related conditions. It is characterized by creamy-white patches in the oral cavity. If left untreated, oral candidiasis progress to involve the esophagus and stomach. Associated signs and symptoms include difficult and painful swallowing and retrosternal pain.

Wasting syndrome Part of the category C case definition for AIDS. Diagnostic criteria include profound involuntary weight loss exceeding 10% of baseline body weight and either chronic diarrhea for more than 30 days or chronic weakness and documented intermittent or constant fever in the absence of any concurrent illness that could could explain these findings. This protein-energy malnutrition is multifactorial. Anorexia, diarrhea, gastrointestinal malabsorption, and lack of nutrition in chronic disease all contribute to wasting syndrome.

Oncologic manifestations Certain types of cancer occur when in people with AIDS. HIV is a clear sign that AIDS has developed. These AIDS related cancers include Kaposis sarcoma. Lymphoma, (especially non-hodgin lymphoma and primary central nervous system lymphoma), and invasive cervical cancer

Kaposis sarcoma The most common HIV related malignancy. A disease that involves the endothelial layer of blood and lymphatic vessels. AIDS related KS exhibits a variable and aggressive course, ranging from localized cuyaneous lesions to disseminated disease involving multiple organ systems. Cutaneous signs may be the first manifestation of HIV, appearing in more than 90% of HIVinfected patients as immune functions deteriorate. Thsese skin signs correlate to low CD4+ counts. They may be flat or raised and sorrounded by ecchymoses (hemorrhagic patches) and edema. the most common sites of visceral involvement are the lymph nodes, gastrointestinal tract, and lungs. Diagnosis of KS is confirmed by biopsy of suspected lesions. Death may result from tumor progression.

B cell lymphomas Second most common malignancy occurring in people with AIDS. Lymphomas associated with AIDS usually differ from those occurring in the general population. AIDS related lymphomas tend to develop outside the lymph nodes, most commonly in the brain, bone marrow, and gastrointestinal tract. The course of AIDS-related lymphomas includes multiple sites of organ involvement and complications related to opportunistic infections.

Neurologic manifestation Neurologic dysfunction results from direct effects of HIV in nervous system tissue, opportunistic infections, primary or matastatic neoplasms, cerebrovscular changes, metabolic encephalopathies, or complications secondary to therapy. Immune responseincludes inflammation, atrophy, demyelination, degeneration, and necrosis.

Peripheral neuropathy HIV associated peripferal neuropathy is common across the trajectory of HIV disease May occur in a variety of patterns, with distal sensory polyneuropathy (DSON) or distal symmetric polyneuropathy the most frequently occurring type. DSPN occurs in advanced HIV disease as a result of immunosuppression, antiretroviral drug toxicity, and/or mitochodrial toxicity. It can lead to significant pain and decrease function.

HIV encephalopathy Formerly referred to as AIDS dementia complex. It is clinical syndrome that is characterized by a progressive decline in cognitive, behavioral, and motor functions. Signs and symptoms may be subtle and difficult to distuish from fatigue, depression, or the adverse effects of treatment for infections and malignancies. Early manifestations include memory deficits, headache, difficulty concentrating, progressive confusion, psychomotor slowing, apathy, and ataxia. Later stages include global cognitive impairments, delay in verbal responses, a vacant state, spastic paraparesis, hyperreflexia, psychosis, hallucinations, tremor, incontinence, seizures, mutism, and death. Extensive neurologic evaluation includes a computed tomography scan, which may indicate diffuse cerebral atrophy and ventricular enlargement.

Cryptococcus neoformans Fungal infection. C. Neoformans is another common oppeortunistic infection among patients with AIDS, and it causes neologic disease. Cyptococcal meningitis is characterized by symptoms susch as fever, headache, malaise, stiff neck, nausea, vomiting, mental statuschanges, and seizures. Diagnosis idcomfirmed by CSF analysis.

Progressive multifocal leukoencephalopathy It is demyelinating CNS disorder that affects the ologodendroglia. Clinical manifestations often begin with mental confusion and rapidly progress to include blindness, aphasia, muscle weakness, paresis (partial or complete paralysis), and death.

Other neulogic disorders Other coomon infections involving the nercous system include toxoplasma gondii, CMV, and myobacterium tuberculosis infections. Vascular myelopathy is a degenarative disorder that affects the lateral and posterior columns of the spinal cord, resulting in progressive spastic paraparesis, ataxia, and inconntinence.

Depressive manifestations The causes of depression are multifactorial and may include a history of preexisting mental illness, neuropsychiatric disturbances, and psychosocial factors. Depression also occurs in people with HIV infection in response to the physical symptoms, including pain and weight loss, and the lack of someone to talk with about their concerns. People with HIV/AIDS who oare depressed may experience irritational guilt and shame, loss of self-esteem, feelings of helplessness and worthlessness, and suicidal ideation.

Integumentary manifestations KS (decribed earlier) and opportunistic infections such as herpes zoster and herpes simplex are associated with painful vesicles that disrupt skin integrity. Malluscum contagiosum is a viral infection characterized by deforming plaque formatiob. Seborrheic dermatitis is assciated with an indurated, diffuse, scaly rash involving the scalp and face. Patients with AIDS may also exhibit a generalized folliculitis associated with dry, flacking skin or atopic dermatitis, such as eczema or psoriasis.

Endocrine manifestation The endocrine manifestations of HIV infection are not completely understood. At autopsy, endocrine glands show infiltration and destruction from oppoetunistic infections or neoplasms.

Gynecologic manifestations Persistent, recurrent vaginal candidiasis may be the first sign of HIV infection in women. Women with HIV infection are more susceptible to genetal ulcers and venereal warts and have increased rates of incidence and recurrence of thsese conditions. Ulcerative sexually transmitted diseases (STDs) such as chancroid, syphilis, and herpes are more severe in women with HIV infection. Human papilloma virus (HPV) causes venereal warts and is a risk factor for cervical intraepithelial neoplasia, a cellular change that is frequently a precursor to cervical cancer.

Medical management Treatment of opportunitic infections Despite the availability of antiretroviral medications, oppoetunistic infections (OIs) continue to cause considerable morbidity and mortality for three main reasons: Many patients are unaware for their HIV infection and present with OI as the initial indicator of their disease Some patients are aware of their HIV infection but do not take antiretroviral agents because of psychosocial or economic factors, and Others receive prescriptions for antiretroviral medications but fail to attain adequte virologic and immunologic response as a result of issues relate dto adherene , pharmacokinetics, or unexplained biologic factors.

Pneumocystis pneumonia TMP-SMZ is the treatment of choice for PCP It is effective as aprenteralpentamidine and more effective than other regimens. Oral outpatient therapy using TMP-SMZ is highly effective among patients with mild t-moderate PCPO. Alternative therapeutic regimens for patients with mild to moderate disease include: Dapsone and TMP Primaquine plus clindamycin, and Atovaqoune suspension. alternatives for patients with moderate to severe disease include: primaquine plus clydamycin, or IV pentamidine (generally drug of second choice for severe disease; it can cause severe hypotension if it is administered too rapidly).

The recommended duration of therapy for PCP is 21 days.

Mycobacterium avium complex HIV-infected adults and adolescents should receive chemprophylaxis againts disseminated MAC diesease if they have CD4+ count less than 50 cells/L. Azithromycin (zithromax) or clarithromycin (biaxin) are the preferred prophylactic agents.

Cryptococcal meningitis Current primary therapy for cryptococcal meningitis is IV amphotericin B with or without oral flucytosine (5-FC, ancobon) or fluconazole (diflucan.

Cytomegalovirus retinitis Oral valganciclovir, IV gangiclovir, IV ganciclovir fillowed by oral valganciclovir, IV foscarnet, IV cidofovir, and the ganciclovir intraocular implant coupled with valganciclovir are all effective treatments for CMV retinitis.

Oral infections Oral acyclovir, famciclovir, or valacyclovir may be used to treat infections caused by herpes simplex or herpes zoster. Esophageal or oral candidiasis is treated topically with clotrimazole (mycelex) oral troches or nystatin suspennsion.

Prevention of oppertunistic infections TMP-SMZ is an antivbacterial agent used to treat various organism causing infection. People with HIV infection who have a T-cell count of less than 200 cells/mm3 should receive chemoprophylaxis with TMP-SMZ to prevent PCP.

Antidiarrheal therapy Therapy with octreotide acetate (sandostatin), a synthetic analogue of somatostatin, hsa been shown to be eefctive in managing chronic severe diarrhea. Soamtostatin inhibits many phisiologic functions, including gastrointestinal moyility and intestinal secretion of water and electrolytes.

Chemotherapy Kaposis sarcoma Management of KS is usually difficult because of the varaibility of symptoms and the organ sysytem involved. The treatment goals are to reduce discomfort associated with edema and ulcerations, and to control symptoms associated with mucosal or visceral involvement. Radiation therapy is effective as a palliative measureto relieve localized pain due to tumor mass and for KS lesions taht are in sites such as the oral mucosa, conjunctiva, face, and soles of the feet. Patients with cutaneous KS treated with alpha-interferon have experienced tumor regression and improved immune system function.

Lymphoma Combination chemotherapy and radiation therapy regimens may produce an initial response, but it is usually short-lived.

Antidepressant therapy Treatment for depression in people wuth HIV infection involves psychotherapy integrated with pharmacotherapy. Antidepressants such as imipramine (tofrantil), desipramine (norpramine), and fluoxetine (prozac) may be used, because these medications also alleviate the fatigue and lethargy that are associated with depression. A psychostimulant such as methylphenidate (ritalin) may be used in low doses in patients with neuropsychiatric impairment.

Nutrition therapy Malnutrition increases the risk infection and the incidence of opportunistic infections. For all patients with AIDS who experience unexplained weight loss, calorie counts should be obatined to evaluate nutritional status and initiate appropriate therapy. Appetite stimulants have been successfully used in patients with AIDS related anorexia. Megastrol acetate (megace), a synthetic oral progesterone preparation, promotes significant weight gain and inhibits cytokine IL-1 synthesis. In patients with HIV infection, it increases body weight primarily by increasing body fat stores. Oral supplements may be used to supplement diets that are deficient in calories and protein. Parenteral nutritionis the final option because of its prohibitive cost and associated risks, including risk of infections.

Complement and alternative modalities Complementary and alternative medicine (CAM ) is often viewed as consisting of unconventional and unorthodox treatments or interventions that are not traditionally taught in medical schools. The use of CAM oin HIV infection and AIDS often results because disillusionment with standard medical treatment, which to date has provided no cure. CAM can be divided into four categories: Spiritual or psycholigical therapies may include humor, hypnosis, faith healing, guided imagery, and positive affirmations. Nutritiona ltherapies may include vegetarian or macrobiotic diets, vitamin C or betacarotene supplements, and turmeric, which contains curcumin, food spice supplement. Chinese herbs, such as traditional herbal mixtures, are also used, in addition to compound Q (a chinese cucumber extract) and mormodica charantia( bitter melon), which is given as an enema. Drug nad biologic therapies include medications and other substances not approved by the FDA. Treatment with physical forces and devices may include acupuncture, acupressure, message therapy, relexology, therapeutic touch, yoga, and crystals.

Supportive care Nutritional support may be as simple as providing assisstance in obtainingor prepairing meals. Management skin breakdown associated with KS, perineal skin excoriation, or immobility entails thorough and meticulous skin care that involves regular turning, cleansing , and applications of medicated ointments, and dressings. Pulmonary symptoms, such as dyspnea and shortness of breath, may be related to infection, KS, or fatigue. For patients with these symptoms, oxygen therapy, relaxation training, and energy conservation techniques may be effective.

Nursing process Assessment Nursing assessment inclufesidentification of potential riskk factors, including a history oof risky sexual practices or IV/injection drug use. The patient physical status and psychological status are assessed.

Nutritional status It is assessed by obtaining a dietary history and identifying factors that may interfere with oral intake, such as annorexia, nausea, vomiting, oral pain, or difficulty of swallowing The patients ability to puurchase and prepare food is assessed. Weight history (ie,changes over time; anthroprometric measurements; and bloo urea nitrogen (BUN), serum protein, albumin, and transferrin levels provide objective measurements of nutritional status.

Skin integrity The skin and mucus membranes are inspected dialy for evidence of breakdown, ulceration, or infection. The oral cavity is monitored forredness, ulcerations, and the ppresence of creamy-white patches indicative of candidiasis. Assessmet of perianal area for excoriation and infection in patients with profuse diarrhea is important.

Respiratory status It is assessed by monitoring the patient for cough, sputum production (ie, amount and color), shortness of breath, orthopnea, tachypnea, and chest pain. The presence and quality of breath sounds are investigated.

Neurologic status It is determine by assessing level of consciousness; orietation to person, place, and time; and memory lapses. Mental status is asessed as early as possible to provide baseline The patient is also assessed for sensory deficits (visual changes, headache, or numbness and tingling in the extremities), motor involvement (altered gait, paresis, or paralysis), and seizure activity.

Fluid and electrolyte imbalance It is a assessed by examining the skin and mucous membranes for turgor and dryness. Electrolyte imbalances, such as decreased serum sodium, potassium, calcium, magnesium, and chloride, typically result from profuse diarrhea.

Knowledge level The patients level of knowledge about the disease and the modes of disease transmission is evaluated. The level of of knowledge of family and friends are also assessed. The patients resources for support are also identified.

Diagnosis Nursing diagnosis Impaired skin integrity r/t cutaneous manifeatations of HIV infection, excoriation, and diarrhea. Diarrhea r/t enteric pathogens or HIV infection Risk for infection r/t immunodeficiency Activity intolerance r/t weakness, fatigue, malnutrition, impaired fluid and electrolyte balance, abd hypoxia associated with pulmonary infections. Disturbed thought proess r/t shortened attention span, impaired memory, confusion, and disorientation associated with HIV enecphalopathy Ineffective airway clearance r/t PCP, increased bronchial secretions, and decreased bronchial secretions, and decreased ability to cough related to weakness and fatigue. Pain r/t impaired perianal skin integrity secondary to diarrhea, KS, and peripheral neuropathy Imbalanced nutrition, less than body requirements, r/t decreased oral intake. Social isolation r/t stigma of the disease, withdrawal of support systems, isolation procedures, and fear of infecting others. Anticipatory grieving r/t changes in lifestyle and roles and unfavorable prognosis Deficient knowledge r/t HIV infection, means of preventing HIV transmission, and self care.

Collaborative problems/ potential complication Based on the assessment data, possible complications may include the following: Opportunistic infections Impaired breathing Wasting syndrome and fluid and electrolyte imbalance Adverse reaction to medications.

Planning and goals Goals for patient may include: Achievement and maintenance of skin integrity. Resumption of usual bowel patterns Absence of infection Improved activity tolerance Improved thought process Improved nutritional status Increased socialization Expression of grief Increased knowledge regarding disease prevention and self-care and, absence of complication.

Nursing interventions Promoting skin integrity The patient is encouraged to maintain balance between rest and mobility whenever possible. Patients whon are immobile are assisted to change position every 2 hours. Patients are encouraged to avoid scratching; to use nonabrasive, nondrying soaps,and To apply nonperfumed skin moisturizers to dry skin. Regular oral care is also encouraged. Medicated lotions, ointments, and dressings are prescribed. Patients with foot lesions are advised to wear cotton socks and shoes that do not cause feet to perspire. The perianal region is assessed frequently for impairment of skin integrity and infection.

Promoting usual bowel patterns Bowel patterns are assessed for diarrhea. The patient is counseled about ways to decrease diarrhea. Small frequent meals help to prevent abdominal distention. Administering antidiarrheal agents on regular schedule may be more beneficial than administering them on as-needed basis. Antibiotics and antifungal agents may also be prescribed to combat pathogens identified by stool cultures.

Preventing infection The patient caregivers are instructed to monitor for signs and symptoms of infection: Fever Chiils Night sweats Cough with or without sputum production Shortness of breath Difficulty of breathing Oral pain ordifficulty of swallowing Creamy-white patches in the oral cavity Unexplained weght loss Swollen lymph nodes Nausea vomiting Persistent diarrhea Frequency Urgency, or pain on urination Headache Visual changes or memory lapses

Redness Swelling, or drainage from skin wounds And vesicular lesions on the face, lips, or perianal area. The patient is instructed to avoid others with active infections such as upper respiratory infections.

Improving activity tolerance It is assessed by monitoring the patients ability to ambulate and perform activities of daily living. Measures such as relaxation and guided imagery may be beneficial because they decrease anxiety, which contributes to weakness and fatigue.

Maintaining thought processes The patient is assessed for alterations in mental status that may be related to neurologic involvement, metabolic abnormalities, infection, side effects of treatment, and coping mechanisms. Activities that the patient previously enjoyed are encouraged. The nurse encourages the social support network to remain calm and not to argue with the patient while protecting the patient from injury. Around-the-clock supervision may be necessary, and strategies can be implented to prevent the patient from engaging in potentially dangerous activities, such as driving, using the stove, or mowing the lawn.

Improving airway clearance Respiratory status, including rate, rythm, use of accessory muscles, and breath sounds; mental status; skin color must be assessed at least daily. Pulmonary therapy is provided as often as every 2 hours to prevent stasis of secretions and to promote airway clearance. Adequate rest is essential to minimize energy expenditure and prevent excessive fatigue. The fluid volume status is evaluated so that adequate hydration can be maintained.

Relieving pain and discomfort The patient is assessed for the quality and severity of pain associated with impaired perianal skin integrity, the lesions of KS, and peripheral neuropathy. Topical anesthetic medications or ointments may be prescribed. The patient is instructed to avoid foods that act as bowel irritants. Antipasmodic and antidiarrheal medications may be precribed to reduce discomfort and frequency of bowel movements. Pain from KS is frequently described as a sharp, throbbing pressure, and heaviness, if lymphedema is present

Pain management may include use of NSAIDs and opiods plus non pharmacologic approaches such as relaxation techniques. Tricyclic antidepressants hve been found to be helpful in controlling the symptoms of neuropathic pain.

Improving nutritional status It is assessed by monitoring weight, dietary intake, and serum albumin, BUN, protein, and transferrin levels. The patient is also assessed for factors that interfere with oral intake such: Anorexia Oral and esophageal candidal infection Nausea Pain Weakness Fatigue Lactose intolerance Control nusea and vomiting with antiemetic medications administered on a regular basis may increase the patients dietary intake. The patient is also encouraged to eat foods that are easy to swallow and to avoid rough, spicy or sticky food items and foods that are extensively hot or cold. Oral hygiene before and after meals are encouraged. If fatigue and weakness interfere with intake, the nurse encourages the patient to rest before meals. The patient with diarrhea and abdominal cramping is encouraged to avoid foods that stimulate intestinal motility and abdominal distention. The patient is instructed about ways to enhance nutritional value meals.

Decreasing the sense of isolation People with AIDS are at risk for double stigmatization. They have what society refers to as a dreaded disease, and they may have a lifestyle that differs from what is considered acceptable by many people. Nurses are the key position to provide an atmosphere of acceptance and understanding for people with AIDS and their families and partners. Providing information about how to protect themselves and others may help patients to avoid social isolation. Education of ancillary personnel, nurses, and physicians helps redufce factors that might contribute to patients feelings of isolation.

Coping with grief The nurse can help the patient verbalize feelings and identify resources for support and mechanisms for coping, especially ehen the patient is grieving anticipated losses. The patient is encouraged to maintain contact with family, friends, and coworkers and to use local or national AIDS support groups and hotlines. The patient is encouraged to continue usual activities whenever possible.

Monitoring and managing potential complications Opportunistic infections Patients who are immunosuppressed are at risk for opportunistic infections Signs and symptoms of oppoetunistic infections including: Fever Malaise Difficulty of breathing Nausea or vomiting Diarrhea Difficulty of swallowing And any occurrences of swelling or discharge

Respiratory failure The patient is instructed to to report shortness of breath and increasing difficulty in carrying out usual activities. Pulse rate and rhythm, blood pressure, and oxygen saturation is monitored. Suctioning and oxygen therapy may be prescribed to ensure an adequate airway and to prevent hypoxia. Mechanical ventilation may be necessary for the patient who cannot maintain adequate ventilation as a result of pulmonary infection, fluid and electrolyte imbalance, or respiratory muscle weakness.

Cachexia and wasting Fluid and electrolyte status is monitored on an ongoing basis; fluid intake and output and urine specific garvity may be monitored daily if the patient is hospitalized with complications. VS are monitored for decreased systolic blood pressure or increase pulse rate on sitting or standing. The nurse helps the patient select foods that will replenish electrolytes, such as oranges and bananas, and cheese and soups.

If fluid and electrolyte imbalance persist, the nurse administers IV fluids and electrolytes as prescribed.

Promoting home and community-based care Patients, families, and friends are instructed about the routes of transmission of HIV. Clear guideline about avoiding and controlling infection, regular health care appointments, symptom management, nutrition, rest, and exercise are necessary. The importance of personal and environmental hygiene is emphasized. Patients with pets are encouraged to have another person clean areas soiled by animals. Patients are advised to avoid exposure to others who are sick or who have been recently vaccinated. The importance of avoiding smoking, excessive alcohol, and over-the-counter and street drugs is emphasized.

Evaluation Expected patient outcomes Expected patient outcomes may include: Maintain skin integrity Resumes usual bowel habits Experiences no infections Maintains adequate level of activity tolerance Maintains usual level of thought processes Maintains effective airway clearance Experiences increased sense of comfort and less pain Maintains adequate nutritional status Experiences decreased sense of social isolation Progress through grieving process Reports increased understanding of AIDS and participates in self-care activities as possible Remains free of complications.

Emotional and ethical concerns Nurses in all setting are called on to provide care for patients with HIV infection. The concerns raised by health care professionals involve issues such as fear of infection, responsibility for giving care, values clarification, confidentiality, developmental stages of patients and caregivers, and poor prognostic outcomes. Nurses are responsible for protecting the patients right to privacy by safeguarding confidential information.

HIV/ AIDS infected

Pulmonary tuberculosis