e161CHAPTER 136 Board Review Questions Rationale B cells mature into antibody producing plasma cells Rituximab is a monoclonal antibody that binds to CD20 on the B cell sur face and leads to B cell ly[.]
CHAPTER 136 Board Review Questions Rationale B cells mature into antibody-producing plasma cells Rituximab is a monoclonal antibody that binds to CD20 on the B cell surface and leads to B cell lysis Cyclosporine and tacrolimus are examples of calcineurin inhibitors Mycophenolate mofetil inhibits lymphocyte proliferation by inhibiting purine synthesis Basiliximab and daclizumab are examples of monoclonal antibodies that prevent T-cell activation by blocking the IL-2 receptor You are caring for a 14-year-old girl who presents with fever, fluid-refractory hypotension, and erythroderma You suspect toxic shock syndrome and consider adding intravenous immunoglobulin (IVIG) in addition to empiric antibiotic therapy A medical student asks you why IVIG may be efficacious for toxic shock syndrome What you tell him? A The Fc portion of the delivered antibodies binds to inhibitory Fc receptors on B cells and innate immune cells, thus decreasing native antibody production and inflammation B The delivered antibodies bind to and neutralize bacterial toxins, thus decreasing nonspecific T-cell/MHC molecule cross-linking C The delivered antibodies provide long-lasting protective immunity against Streptococcus and Staphylococcus species, the primary causes of toxic shock syndrome D The delivered antibodies bind to Fc receptors on phagocytes that have ingested bacteria, augmenting microbial killing Preferred response: B Rationale Certain staphylococcal and streptococcal bacterial species are capable of producing toxins that function as superantigens Super antigens crosslink T-cell receptors and major histocompatibility complex (MHC) molecules in a much less specific manner than is typically required for T-cell activation In this way, larger numbers of T cells are activated at once, causing a systemic inflammatory response that manifests as the signs and symptoms of toxic shock syndrome The major theoretic benefit of IVIG in this setting is to deliver toxin neutralizing antibodies to block microbial-derived superantigens Response A describes the proposed mechanism for empiric IVIG treatment of autoimmune diseases, particularly those associated with autoantibodies Response C is incorrect because intravenously administered immunoglobulins not persist in the circulation long enough to provide lasting immunity For response D, although antibody-mediated opsonization and augmentation of microbial killing may help control causative infection, this is not likely the most important mechanism of IVIG treatment for toxic shock syndrome Of the following, which does not describe a mechanism of peripheral T-cell tolerance? A Antigen/MHC molecule recognition in the absence of costimulatory receptor binding B Binding of the inhibitory T-cell costimulatory receptor, CTLA-4, to B7 molecules on antigen presenting cells C Ingestion and destruction of self-reacting T cells by phagocytes D Maintenance of a pool of CD41 immunosuppressive regulatory T cells (Treg) Preferred response: C e161 Rationale Responses A, B, and D describe mechanisms of peripheral T-cell tolerance Peripheral T-cell tolerance provides vital protection against autoimmune disease Particularly, because CD41 helper T cells play integral roles in the activation and modulation of both cell-mediated and humoral immunity, peripheral tolerance of helper T cells may be especially relevant to autoimmune disease pathophysiology Chapter 102: Critical Illness and the Microbiome Critical illness is associated with which of the following changes in the host microbiome? A Increased bacterial diversity B Increase in obligate anaerobes C Presence of pathogens at high levels of abundance D Preservation of site specificity Preferred response: C Rationale Prospective studies of the gut, skin, and oral microbiome of critically ill adults and children have demonstrated a high incidence of “ICU dysbiosis” characterized by a loss of microbial diversity, loss of site specificity, and presence of pathogens at high levels of abundance Commensal bacteria in the human intestine are primarily composed of: A Aerobic bacteria B Facultative anaerobic bacteria C Microaerophilic bacteria D Obligate anaerobic bacteria Preferred response: D Rationale Outside of the early neonatal period when children are first colonized by microbiota, commensal bacteria in the gut are characteristically obligate anaerobes which require the low oxygen environment present in the gut lumen and maintained by oxygen consumption of gut epithelium If the gut epithelium is compromised (e.g., colitis), the oxygen content of the gut lumen may rise and allow for growth of facultative anaerobic bacteria such as pathogens from the Enterobacteriaceae family Which ICU factor has NOT been associated with changes in the microbiome of patients? A Antibiotics B Endotracheal intubation C Enteral feeds D Pharmacologic DVT prophylaxis E Proton pump inhibitors Preferred response: D Rationale The therapies listed have all been associated with changes to the host microbiome Endotracheal intubation is associated with changes to the oral and tracheal microbiome Enteral feeds and proton pump inhibitors are associated with changes to the gut microbiome Antibiotics, depending on class and method of administration, have markedly disruptive effects on the host microbiome e162 S E C T I O N XV Pediatric Critical Care: Board Review Questions Chapter 103: Congenital Immunodeficiencies What is the most morbid feature of patients with primary immune deficiency diseases? A Atopy B Autoimmunity C Cancers D Infections Preferred response: B Rationale Patients with primary immune deficiency disease have a dysfunctional immune system in addition to their specific immune system defects, resulting in complex disimmunity/autoimmunity and numerous comorbidities A 13-year-old boy is admitted with uncontrolled hemolysis due to autoimmune hemolytic anemia (AIHA) He was diagnosed months before this admission and initially responded to oral corticosteroids and intravenous immunoglobulin (IVIg), but has worsened since His complete blood cell count revealed extremely low hemoglobin and lymphocyte count and normal platelets and neutrophils Which of the following is the next best step in the investigation of this patient? A Autoantibody screen to rule out SLE B EBV serology C Enumeration of lymphocyte subsets D Hepatitis B serology E Serum immunoglobulin levels Preferred response: C Rationale Although AIHA can occur in association with autoimmune disease such as systemic lupus erythematosus (SLE), there are no other indications in this case supporting this diagnosis Serologies will not be helpful in making the diagnosis and serum immunoglobulins may be normal or even high when a patient has dysregulation of the immune system Given the lymphopenia, it is important to determine which subsets are decreased A 12-year-old boy with sickle-cell disease presents to the emergency department with new-onset seizures His vaccinations are up-to-date The initial work up revealed a Neisseria meningitis brain abscess Which of the following primary immunodeficiency is most likely to occur in this child? A Alternative complement defect B Asplenia C Phagocytic defect D Terminal complement defect Preferred response: B Rationale Sickle-cell disease causes functional asplenia and places those patients at an increased risk for invasive encapsulated bacteria such as Neisseria Complement defect is also possible and should not be excluded but is less likely in this child 4 A toddler is being evaluated for recurrent Neisseria infections Which of the following tests would most likely reveal an associated immunodeficiency? A Absolute CD41 count B CH50 C Erythrocyte adenosine deaminase activity D IgG serum concentration Preferred response: B Rationale CH50 provides an assessment of overall complement activity Recurrent Neisseria infections are known to be associated with defects in the terminal complement pathway Which of the following immune cells are characterized by the production of reactive oxygen species as a host defense mechanism for foreign antigens and microbes? A B lymphocytes B Natural killer cells C Neutrophils D T lymphocytes Preferred response: C Rationale Following activation, neutrophils and other phagocytes generate superoxide anion and several other reactive oxygen species as an aspect of the respiratory burst via NADPH oxidoreductase Congenital absence of components of this enzyme complex results in chronic granulomatous disease A 6-year-old boy demonstrates anaphylaxis with a blood transfusion administered during surgery to resect a newly diagnosed brain tumor Past medical history reveals involvement in a motor vehicle collision as a toddler resulting in multiple traumas and requiring a unit of transfused erythrocytes Aside from his brain tumor the child has generally been healthy Which of the following should be strongly considered as an underlying mechanism for the anaphylaxis? A Ataxia-telangiectasia syndrome B C1 esterase inhibitor deficiency C Combined variable immune deficiency D IgA deficiency Preferred response: D Rationale This child with IgA deficiency was likely sensitized with his first blood transfusion as a toddler He subsequently developed anaphylaxis to IgA with his subsequent transfusion Other potential diagnoses would all likely include some chronic comorbidity The only child of healthy parents is admitted at months of age to the ICU with a 1-week history of loose, watery stools Upon arrival he is dehydrated and in shock On the fifth day of hospitalization, tachypnea and hypoxemia develop The child was delivered at full-term after a normal pregnancy, labor, and delivery and had not been breast-fed Previously he had been healthy and growing and thriving well He received his 2-month immunizations without complications Two weeks prior to admission, he received his immunizations, including rotavirus vaccine Examination reveals that he is pale and tachypneic, with 55 breaths per minute His heart rate is 150 beats per minute Pulses are easily accessible Chest CHAPTER 136 Board Review Questions radiography shows diffuse perihilar reticular (interstitial) infiltrates and absent thymic shadow A nasopharyngeal swab is positive for respiratory syncytial virus, and a complete blood cell count (CBC) on admission demonstrated a white blood cell count of 7.3 103 cells/µL (82% polymorphonuclear leukocytes, 5% bands, 8% lymphocytes, and 5% monocytes) A review of other studies demonstrates a low total protein level What is the best course of action? A Continue supportive care; bronchoalveolar lavage (BAL) is not indicated because the viral etiology has been identified B Determine quantitative immunoglobulins (IgG, IgA, IgM) and lymphocyte subpopulations; BAL may be indicated because of a concern for Pneumocystis jirovecii pneumonia C Determine quantitative immunoglobulins (IgG, IgA, and IgM) and total hemolytic complement; BAL may be indicated because of a concern for bacterial superinfection D Perform BAL only Preferred response: B Rationale The clinical scenario should suggest severe combined immunodeficiency syndrome (SCID) in the differential diagnosis Male sex, age at presentation, live rotavirus vaccine given within a week of presentation, and subsequent severe diarrheal illness, lymphopenia, and absent thymic shadow on a chest x-ray are features of the clinical presentation of a child with SCID The low total protein level is a clue for hypogammaglobulinemia, and thus quantitative immunoglobulins should be assessed The diffuse interstitial pattern on a chest x-ray in a child with the indicated clinical and laboratory findings may suggest P jirovecii Determining lymphocyte subpopulations is essential to establishing the diagnosis of SCID BAL may be indicated because P jirovecii is a common presentation of children with SCID, and its diagnosis changes management procedures In addition, coinfections with different organisms are seen commonly in children with SCID This child does not display a classic presentation for a complement defect, because children with a complement defect have normal lymphocyte counts A 9-month-old girl is transferred to the intensive care unit from a community hospital She has had a daily fever as high as 40°C for days, progressive respiratory insufficiency, and persistent confluent right middle lobe and right lower lobe infiltrates She has been treated for days with azithromycin and for the past days with ceftriaxone at the community hospital Her medical history is significant for previous pneumonias and cervical adenitis On examination, prominent cervical, axillary, and inguinal adenitis is found A review of chest x-rays demonstrates no changes in confluent right middle lobe and right lower lobe infiltrates A complete blood cell count reveals the following: hemoglobin, 10.5 g/dL, and white blood cells, 26,000/µL (60% polymorphonuclear cells, 15% bands, 5% monocytes, and 20% lymphocytes) IgG is 1800 mg/dL, IgA is 250 mg/dL, and IgM is 200 mg/dL Her erythrocyte sedimentation rate is 85 Inspection of bronchoalveolar lavage fluid reveals gramnegative bacilli, probably a Serratia species, and blood cultures on admission also have identified gram-negative bacilli Which of the following is the most likely diagnosis? A Chronic granulomatous disease B Common variable immunodeficiency C Hyper IgM D Leukocyte adhesion deficiency Preferred response: A e163 Rationale Nosocomial pneumonia due to Serratia species occurs less frequently in children than in adults Infections with catalasepositive organisms are commonly seen in patients with chronic granulomatous disease (CGD) Both X-linked and autosomal recessive forms of the disease have been described Serratia species were a common cause of suppurative adenitis in an extensive report of 368 patients of CGD Hypergammaglobulinemia is commonly seen in patients with CGD IgG and IgA are low in persons with hyper IgM The diagnosis of common variable immunodeficiency cannot be made in children who are younger than years of age Any child with community-acquired infection that is shown to be due to Serratia species should be evaluated for CGD A 6-month-old infant with failure to thrive is involved in a motor vehicle collision resulting in a grade III splenic laceration, but no other injury In the setting of a declining hematocrit and progressive metabolic acidosis, the child receives a transfusion of packed erythrocytes (20 mL/kg) Results of admission laboratory studies include the following: hematocrit, 24%; hemoglobin, g/dL; platelet count, 150,000/µL; white blood cell count, 9500/µL with a differential including 70% polymorphonuclear cells, 10% bands, 10% monocytes, and 10% lymphocytes; Na, 140 mEq/L; K, 3.5 mEq/L; Cl, 116 mEq/L; bicarbonate, 15 mEq/L; aspartate aminotransferase, 150 IU/L; alanine aminotransferase, 130 IU/L; and amylase, 75 units/L Subsequently the child’s hemodynamic status normalizes, and he is discharged from the hospital days following the initial injury Two weeks following discharge from the hospital, the child experiences a diffuse erythema with multiple bullous lesions, diarrhea, abdominal cramping, and scleral icterus What is the most likely diagnosis? A Cytomegalovirus infection B Graft-versus-host disease C Non-A, non-B hepatitis D Peritoneal sepsis Preferred response: B Rationale This child initially presents with failure to thrive and absolute lymphopenia in addition to traumatic splenic laceration Overwhelming and life-threatening graft-versus-host disease (GVHD) due to clonal expansion of donor-derived leukocytes present in the nonirradiated blood product can occur in children with severe combined immunodeficiency, which is the underlying diagnosis in this patient Close evaluation of this patient might also reveal oral thrush in addition to classical manifestations of GVHD 10 Which of the following is inconsistent with a diagnosis of DiGeorge syndrome (DGS)? A Aortic arch anomaly B Chromosomal 22q11 deletion C Hypercalcemia D Lymphopenia Preferred response: C Rationale DiGeorge syndrome (DGS) is recognized as a heterogeneous disorder characterized by a triad of clinical features: congenital heart disease, immunodeficiency, and hypocalcemia secondary to parathyroid dysplasia Cytogenetic and molecular studies have e164 S E C T I O N XV Pediatric Critical Care: Board Review Questions demonstrated that in more than 90% of patients with DGS, a deletion of chromosomal region 22q11 occurs Other genetic disorders such as velocardial facial syndrome and the conotruncal anomaly facial syndrome represent genetic syndromes with overlapping characteristics with DGS Common features of children with the 22q11 syndrome are facial characteristics (small dysmorphic ears, narrow up-slanted palpebral fissures, prominent nose with large tip and hypoplastic nares, periorbital fullness); midline defects including palatal abnormalities, cleft lip, and palate; swallowing difficulties; umbilical hernia; skeletal, renal, and urogenital anomalies; learning disabilities; and neuropsychiatric disorders Chapter 104: Acquired Immune Dysfunction Lipopolysaccharide (LPS) is a gram-negative bacterial pathogen associated molecular pattern (PAMP) recognized by the pattern recognition receptor (PRR) toll-like receptor (TLR-4) Which immune cell recognizes LPS first? A B lymphocytes B Basophils C Mast cells D Neutrophils E T lymphocytes Preferred response: D Rationale Toll-like receptors are PRRs that sense pathogen associated molecular patterns (PAMPS) or damage associated molecular patterns (DAMPS) and initiate an immune response LPS is recognized by TLR-4, which is highly expressed on neutrophils and macrophages Basophils and mast cells don’t express TLR-4 T and B lymphocytes express TLR-4, but at a significantly lower level than neutrophils and macrophages As infection with the human immunodeficiency virus (HIV) progresses to acquired immunodeficiency syndrome (AIDS) because of a declining CD4 T-lymphocyte count, which cytokine is responsible for the loss of phagocytosis and bactericidal activity? A Granulocyte-macrophage colony-stimulating factor (GM-CSF) B Interferon gamma (INF-g) C Interleukin (IL-6) D Interleukin 10 (IL-10) E Interleukin 12 (IL-12) Preferred response: B Rationale INF-g is a cytokine produced by T lymphocytes supporting the function of neutrophils and macrophages As the CD4 T-lymphocyte count declines, the support of innate immune cells, specifically macrophages becomes impaired leading to opportunistic infections IL-10 is associated with immunosuppression IL-12 is produced by macrophages to support T-lymphocyte maturation and proliferation IL-6 is a cytokine with pro- and antiinflammatory effects, notable as an acute phase reactant activating complement release, coagulation activation, and T/B-lymphocyte activation GM-CSF is a growth factor for phagocytic immune cells and is associated with restoring antigen presentation function 3 A 7-year-old boy presents to a rural South African clinic with a 2-day history of loose stools and a 2-day history of profuse diarrhea He appears thin and severely dehydrated His mother notes that there has been no blood in the stool and that he was without fever until yesterday During further questions, she also notes that his vision has been poor for the past year Which micronutrient is most likely to improve his clinical condition? A Iron B Vitamin A C Vitamin D D Vitamin C E Zinc Preferred response: B Rationale Micronutrients are important cofactors for cellular processes that promote normal growth and development This boy presents with gastrointestinal symptoms likely consistent with bacterial overgrowth related to a nutritional deficiency He likely has limited access to foods rich in vitamin A, which is necessary for eye development and enterocyte integrity This ties together his symptoms of diarrhea, which progressed from mild and subacute to severe, and his poor vision Vitamin A deficiency is the number one cause of blindness worldwide Studies have shown that supplementation of vitamin A to deficient patients hastens the recovery from diarrheal illness Vitamin C, zinc, and iron are associated with other immune processes, such as skin integrity (vitamin C), innate and adaptive immune cell function (zinc), and anemia (iron) Vitamin D is necessary for bone and calcium growth and development, and deficiencies are not associated with enterocyte integrity An 8-month-old boy presents to the emergency department with severe hypoxia, tachypnea, and retractions He is on a nonrebreather mask with a peripheral oxygen saturation measurement (Spo2) of 92% Chest auscultation demonstrates good air movement with scattered wheezing and rales; no murmurs, clicks, or rubs noted A chest radiograph (CXR) reveals mild bilateral diffuse interstitial infiltrates and a normal cardiac silhouette His laboratory values are as follows: white blood cell count, 4,500/uL; hemoglobin, 13 g/dL; hematocrit, 34%; platelet count, 186,000/µL Leukocyte differential reveals neutrophils, 88%; lymphocytes, 5%; monocytes, 6%; eosinophils 1% He was born full term via spontaneous vaginal delivery to a mother who did not receive prenatal care Child protective services have been involved with the family because of a history of maternal substance abuse What additional test should be ordered? A Acid-fast bacilli (AFB) culture B Echocardiogram C Enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) D Polymerase chain reaction (PCR) for HIV E Pro–brain natriuretic peptide (Pro-BNP) Preferred response: D Rationale This infant boy is presenting with hypoxemic respiratory failure and CXR findings suggestive of Pneumocystis jirovecii pneumonia CHAPTER 136 Board Review Questions (PJP) This is an acquired immunodeficiency syndrome (AIDS)defining illness and can be confirmed with an HIV PCR Maternal antibodies may still be present in the infant’s serum and an HIV ELISA may be falsely positive Clinical data suggestive of pneumocystis pneumonia is the cough, fever, tachypnea, profound hypoxemia on significant supplemental oxygen therapy, and a CXR with mild pulmonary involvement Clinical data suggestive of HIV/AIDS is an absolute lymphocyte count below 200 Associated risk factors indicating increased likelihood of HIV are maternal history of substance abuse and no prenatal care during the pregnancy Vertical transmission of HIV presenting as an AIDS-defining illness often presents later during infancy PJP is the most common pathogen causing respiratory insufficiency in untreated HIV patients The infant in this vignette has a normal cardiac silhouette on the CXR, so the utility of an echo or proBNP is questionable and will not explain his significant hypoxemia An AFB culture may be of help, especially if pulmonary nodules had been seen on the CXR Atypical mycobacterial infections can occur in pediatric HIV/AIDS patients, often as an AIDS-defining illness, but the typical presentation involves gastrointestinal signs and symptoms A 9-year-old boy who had a liver transplant at year of age for biliary atresia presents to the emergency department with a 2-day history of fever His vital signs at presentation are temperature, 38.8°C; heart rate, 168 beats per minute; blood pressure, 86/40 mm Hg; respiratory rate, 33 per minute; and pulse oximetry, 94% in room air His current medication regimen is tacrolimus twice a day, trimethoprim and sulfamethoxazole three times per week, esomeprazole twice a day, and a tapering dose of prednisolone for a recent history of acute rejection status posttreatment He received intravenous broad-spectrum antimicrobials in the emergency department, and his mental status deteriorated; he required aggressive fluid support to manage worsening hypotension He was admitted to the PICU after intubation for acute respiratory failure and norepinephrine infusion for septic distributive shock What laboratory finding is the most likely indicator of increased mortality? A Decreased free T4 level B Elevated C-reactive protein C Elevated TNF-a serum levels D Persistent lymphopenia Preferred response: D Rationale Sepsis is a devastating illness with mortality in pediatrics estimated to be 10% Sepsis is a process of proinflammatory and antiinflammatory activation and can lead to prolonged immunosuppression, increasing a patient’s risk of secondary infections and mortality If prolonged immunosuppression occurs, a patient’s ability to clear subsequent infectious processes remains impaired Persistent lymphopenia is a strongly associated predictor of mortality after the diagnosis of septic shock Drewry and colleagues demonstrated increased mortality rates if the patient has persistent lymphopenia days after the diagnosis of septic shock Serum cytokine levels in septic patients have been extensively studied and TNF-a serum levels may indeed be elevated, but TNF-a serum levels have not been conclusively associated with increased mortality Sick euthyroid does occur in critically ill patients but is not a laboratory finding associated with increased mortality in septic shock e165 A 10-month-old child with cerebral palsy experiences respiratory failure as a result of respiratory syncytial virus After showing initial improvement, the patient requires increased respiratory support for hypoxemia Secretions from the patient’s endotracheal tube are clear, and the Gram stain of the secretions shows few white blood cells (WBCs) and no bacteria The total WBC count is normal, but the absolute lymphocyte count is 200 cells/µL Which of the following statements is true? A If the child had normal lymphocyte counts in the past, it is likely that the lymphopenia is a result of the respiratory syncytial virus infection B A secondary bacterial infection is likely, and the child should be treated with broad-spectrum antibiotics C If cytomegalovirus is recovered from the endotracheal tube, treatment with ganciclovir should be initiated D The child should be evaluated for chronic granulomatous disease as an etiology for this immunodeficiency Preferred response: A Rationale A change in sputum color, quantity, or bacteria on the Gram stain would be seen in a bacterial infection The diagnosis of cytomegalovirus pneumonia requires the visualization of intracellular viral inclusion bodies in alveolar macrophages It would be appropriate to evaluate the child for HIV infection but not granulomatous disease Chapter 105: Immune Balance in Critical Illness Which of the following has been shown to reverse immunoparalysis in vivo in critically ill patients? A Dexmedetomidine B GCSF C GM-CSF D Interferon-a E Methylprednisolone Preferred response: C Rationale Immunoparalysis appears to be reversible through the use of immunostimulatory therapy The drug granulocyte macrophagecolony stimulating factor (GM-CSF) stimulates the production of both monocytes and neutrophils by the bone marrow as well the restoration of function in both cell types GM-CSF has been shown to reverse immunoparalysis in vivo in critically ill adults and children GCSF does not promote recovery of function of the monocyte/macrophage lineage While interferon-g has been shown to reverse immunoparalysis in septic adults, interferon-a has not been used for this purpose Dexmedetomidine is a sedative which may be less likely to exacerbate immunoparalysis compared to opiates or benzodiazepines, but it does not reverse immunoparalysis Methylprednisolone is a glucocorticoid which may promote immunoparalysis ... disease such as systemic lupus erythematosus (SLE), there are no other indications in this case supporting this diagnosis Serologies will not be helpful in making the diagnosis and serum immunoglobulins... children with severe combined immunodeficiency, which is the underlying diagnosis in this patient Close evaluation of this patient might also reveal oral thrush in addition to classical manifestations... Rationale This infant boy is presenting with hypoxemic respiratory failure and CXR findings suggestive of Pneumocystis jirovecii pneumonia CHAPTER 136 Board Review Questions (PJP) This is an