1. While many patients with a diagnosis of asthma have relatively uneventful anesthetics, all children who carry that diagnosis should be carefully and thoroughly evaluated prior to induction and plans made to treat intraoperative bronchospasm.
2. A variety of medications are used to treat patients with juvenile idiopathic arthritis, many of which have anesthetic implications. Classes of drug used include NSAIDs, disease-modifying agents such as methotrexate or leflunomide, anti-TNF medications such as etanercept, anti-CD20 drugs such as rituximab, and others.
3. Children with HIV/AIDS may have significant myocardial dysfunction that is not clinically apparent if the illness has led to the child having less physical activity.
The immunologic system is a complex of organs, vessels, humoral and cellular elements whose function is protection of the body from infection. Dysfunction of this system leads to autoimmune disorders, allergic conditions, immunodeficiency syndromes, and malignancies. Children with disorders of the immune system undergo a variety of diagnostic and therapeutic procedures as a result of their chronic disease.
EMBRYOLOGY/ANATOMY
1. Hematopoiesis is first seen in the primitive yolk sac as early as 3 weeks of gestation. (see Fig. 28.1) The pluripotential stem cells move to the liver first, and then to their final location in the bone marrow. The pluripotential stem cells give rise to lymphoid cells, which then further differentiate into B, T, or natural killer (NK) cells. The thymus and bone marrow form in the first trimester followed by the spleen, lymph nodes, and gut-associated Peyer Patches (1).
2. B-cell development begins as early as the 7th week of gestation with antigen-independent development, the addition of various cell surface receptors. This stage is completed by the 14th week of gestation and is followed by antigen-dependent development. Antigen-dependent development occurs in response to external antigens and leads to the production of memory B-cells and plasma cells. Maternal immunoglobins, primarily IgG, cross the placental barrier from the 12th week onward suggesting the possibility that some allergic reactions seen in newborns may be due to fetal exposure to maternal-derived antigens.
3. T-cell development begins at around the 8th week of gestation. The rudimentary thymus, the site of initial T-cell development, is formed from the third branchial cleft and pouch. T-cell subtypes, based on the expression of receptor subtypes such as clusters of differentiation (CD)-4, are seen in the first trimester. Differentiation into the many receptor subtypes continues by the processes of cell multiplication and differentiation and also by significant apoptosis. More than 90% of fetal thymocytes die by this process. Final T-cell development occurs once these cells leave the thymus and migrate to the lymph nodes, spleen, and appendix.
4. NK-cell development begins in the fetal liver at approximately the 10th to 12th week of gestation. NK precursors are also found in the fetal bone marrow. These lymphocytes do not undergo any processing in the thymus, as do T-cells. NK-dells mediate cytotoxicity not mediated by the major histocompatibility complex. NK-cells do not change their surface receptors during fetal development, as do the B- and T-cell precursors. Most NK-cells migrate to the spleen. Overall, NK-cells make up a small percentage of the total lymphocyte population.
DISORDER: Immunodeficiency disorders
BACKGROUND
1. B-cell disorders: Deficiency of antibodies is the more common of the inherited immunodeficiencies with deficiency of secretory IgA being the most common. This condition occurs in up to 0.3% of the population.
a. Clinically, patients with secretory IgA deficiency can present with infection of the respiratory, gastrointestinal (GI), or genitourinary (GU) tract.
b. Many affected individuals have detectable antibodies against secretory IgA and these antibodies can be of the IgE subtype (2).
c. Administration of blood products containing IgA may lead to an anaphylactic reaction from the complex of IgA and the anti-IgA IgE.
d. Common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA) are characterized by a deficiency of antibodies.
1. These patients have infections with pyogenic organisms.
2. In CVID, normal-appearing B-cells are present (3).
3. Patients with XLA lack circulating B-cells, have few palpable lymph nodes and small or absent tonsils (4).
4. Other than XLA, which can be treated definitively with a bone marrow transplant, management of deficiencies of antibody involves the regular administration of antibodies, and careful surveillance for and treatment of infections.
2. Defects in cell-mediated immunity are more severe than defects in antibody production.
a. DiGeorge syndrome results from abnormal development of the third and fourth pharyngeal pouches.
1. When fetal development is abnormal in this way, the thymus, thyroid, and parathyroid glands are hypoplastic or completely absent.
2. Associated defects seen in these individuals include abnormalities of the great vessels, congenital heart disease, esophageal atresia, and mandibular hypoplasia.
3. Affected newborns often present with severe hypocalcemia.
4. The immunologic defect has been treated with transplantation of matched bone marrow (5).
b. Other, more rare disorders in T-cells include a defective CD3 receptor complex, and impaired activation of T-cell or cytokine production.
3. Combined deficiencies in humoral and cell-mediated immunity are often fatal in early infancy or childhood. Bone marrow transplantation is an accepted therapy for affected individuals.
a. Severe combined immunodeficiency (SCID) and combined immunodeficiency (CID) have been described.
1. Infants with SCID generally present in the first few months of life with bacterial infections of the respiratory tract and skin, and also with GI symptoms such as diarrhea. In addition to bacterial infections, these infants are also afflicted with infections by Candida species, and viruses.
2. Since these infants lack any immunologic competence, graft-versus-host (GVH) disease may occur following transfusion of nonirradiated blood products.
3. Children with CID do not completely lack T-cell function but are still afflicted with infection by opportunistic organisms and, if untreated, have a much shortened lifespan. Impaired humoral immunity and reduced numbers and activity of T-cells characterize Wiskott–Aldrich syndrome, an X-linked disorder. Clinically, these individuals also have atopic dermatitis and thrombocytopenic purpura.
b. Ataxia-telangiectasia is a complex syndrome with a variable degree of cellular and humoral immunodeficiency in addition to ataxia, skin and ocular telangiectasias, chronic respiratory infections, and cancers of the lymphoid tissues (6,7).
4. Disorders of phagocytic function are relatively uncommon. Specific diagnoses in this group include: Chediak–Higashi syndrome, a defect in degranulation, chronic granulomatous disease, the inability to kill catalase-positive organisms and the more common but not clinically significant myeloperoxidase deficiency.
5. Acquired immunodeficiency syndrome
The AIDS epidemic has primarily affected adults, but children certainly have not been spared.
a. In 1997, the World Health Organization (WHO) estimated that there were more than 1.1 million people <15 years of age afflicted with AIDS/HIV.
1. The United States CDC National HIV/AIDS surveillance system reported that the distribution of pediatric AIDS cases was: 58% African-American, 23% Hispanic, and 18% Caucasian. Most cases have been reported in the Northeast and South.
2. Most cases of AIDS in children <13 years of age are the result of perinatal transmission (8). Approximately 6,000 to 7,000 infants are born to HIV-positive mothers each year in the United States. Transmission is most likely during delivery and the chance of transmission is increased in preterm births and in cases with low maternal CD4 counts. Transmission is decreased if delivery is by C-section and, in vaginal deliveries, if zidovudine (AZT) is administered to the mother (8).
3. The number of adolescents with AIDS from direct contact is growing. Children with AIDS have progressive depletion of CD4 lymphocyte counts with the development of opportunistic infections.
b. Children with AIDS have involvement of all important organ systems.
1. Up to 80% of patients have lung damage, both from lipoid interstitial pneumonia and prior pulmonary infections.
2. Significant cardiac involvement is seen in up to 20% of children with AIDS. Tachycardia, left ventricular systolic and diastolic function, and sinus arrhythmias are seen in these children.
3. Anemia is commonly seen in these children.
4. Renal insufficiency, various skin rashes, and their poor nutritional status contribute to the overall inanition of children with AIDS.
DISORDER: Allergy; allergic conditions
BACKGROUND: Antigenic molecules (usually proteins) capable of stimulating IgE antibody production may cause IgE-mediated anaphylaxis after initial sensitization and subsequent reexposure. Once produced, IgE antibodies to these antigens become fixed to tissue mast cells and/or circulating basophils, both of which contain high-affinity IgE receptors. Reexposure to antigens or haptens, with subsequent cross-linking of cell surface IgE antibody, induces activation of membrane-associated enzymes, causing complex biochemical cascades that lead to an influx of extracellular calcium and a mobilization of intracellular calcium with subsequent release of preformed granule-associated mediators and the generation of new mediators from cell membrane phospholipids. IgE levels are elevated in atopic disorders (allergic or extrinsic asthma, hay fever, atopic dermatitis) and parasitic infections.
The complex of allergen, IgE, and high-affinity receptor for IgE on the surface of the mast cell triggers a noncytotoxic, energy-dependent release of preformed, granule-associated histamine and tryptase and the membrane-derived lipid mediator leukotrienes, prostaglandins, and platelet activating factor. Mediators released include those preformed and stored in granules and those newly generated on appropriate stimulation. Release of these mediators may cause various pathophysiologic responses that may result in acute or chronic reactions. Mast cells produce the three cysteinyl leukotrienes C4, D4, and E4 which cause the contraction of smooth muscles, vasodilatation, increased vascular permeability, and the hypersection of mucus. Collateral sources of cysteinyl leukotrienes are eosinophils, macrophages, and monocytes. Mast cell tryptase activates receptors on endothelial and epithelial cells which cause the upregulation of adhesion molecules that selectively attract eosinophils and basophils.
SPECIFIC MEDICAL CONDITIONS
CLINICAL PEARL Allergic rhinitis can be difficult to distinguish from the rhinitis associated with a viral upper respiratory infection. The anesthetic implications for children with allergic rhinitis as opposed to viral URIs are not well known.
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