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4. HDS Multisystem > Immunocompromised Hosts > Flashcards

Immunocompromised Hosts Flashcards

1
Q

Physical Defense Barriers

A
  • Skin and mucosa ⇒ 1° defense against endogenous and exogenous infection
  • Causes for disruption:
    • Trauma
    • Tumor invasion
    • Effects of chemo- or radiotherapy
    • Use of invasive procedures (IV catheters)
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2
Q

Neutropenia

Overview

A
  • Quantitative Phagocyte Defect
  • Absolute neutrophil count < 1,000 mm3 ⇒ ↑ risk of infection
  • Absolute neutropenia < 500 cells/mm3 ⇒ sign. neutropenia
  • Risk of infection is higher if count is falling
  • ↑ Duration of neutropenia ⇒ ↑ risk
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3
Q

Neutropenia

Etiologies

A
  • Congenital cyclic neutropenia
  • Malignancy and Rx w/ cytotoxic effect
  • Hematologic malignancies
  • Primary bone marrow failure, e.g. aplastic anemia
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4
Q

Neutropenic Fever

Etiologies

A
  • Bacterial infections
    • Gram ⊖s
      • Enterics (E.coli, Klebsiella, Enterobacter) and Pseudomonas aeruginosa
      • Presumed sources are lines, GI tract, GU tract, respiratory tract, or exogenous sites
    • Gram ⊕s
      • S. aureus, Coagulase ⊖ staph, Enterococci, Bacillus species, Corynebacterium
      • Common source is indwelling vascular catheters
  • Fungal Infections
    • Candida species
      • Usually occurs after at least 3-5 days of neutropenia
      • ↑ in pts on abx
      • Albicans is most common
      • Types of infection include candidemia, catheter infection, disseminated candidiasis often w/ hepatosplenic involvement, mucosal candidiasis (oral, esophageal, lower GI), or skin infection
    • Aspergillus
      • Primary sites upper airways (oral or nasal cavity, sinuses) or lungs
    • Other fungi
      • Mucor, Fusarium, Trichosporon beigelli
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5
Q

Phagocyte Qualitative Defects

A

Major functions of neutrophils for microbicidal activity include:

  • Chemotaxis
  • Cell activation
  • Phagocytosis
  • Intracellular and extracellular killing
  • Defects in any of these may ↑ risk for infection
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6
Q

Chronic Granulomatous Disease

A
  • PMNs do not make peroxide
  • Defective oxidative metabolism ⇒ impaired oxidative burst
  • ↑ infections occur 1° due to catalase ⊕ organisms
  • Catalase ⊖ organisms produce peroxidase which is sufficient for polys to use for killing
  • In catalase producing organisms, catalase degrades the peroxide produced by the bacteria
  • Infections usually begin in 1st year of life
  • Common pathogens: S. aureus, Enteric gram-⊖ rods, Pseudomonas, Nocardia, Aspergillus
  • Common sites of infections: lung common (pneumonia and abscesses), skin and soft tissue infections, visceral abscesses, osteomyelitis
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7
Q

Myeloperoxidase Deficiency

A
  • Most common granulocyte disorder
  • Myeloperoxidase ⇒ lysosomal enzyme that catalyzes H2O2 → hypochlorous acid
  • Despite defect, infectious complications rare; most individuals are healthy
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8
Q

Chediak Higashi

A
  • AR, rare disease
  • Characterized by impaired degranulation and defective chemotaxis of neutrophils
  • Pts may have recurrent infections, oculocutaneous albinism, central and peripheral neuropathy, and ↑ bleeding time
  • Some have neutropenia
  • Typically see infections of skin, mucous membranes, and respiratory tract
  • Common organisms: S. aureus, Gram ⊖ bacilli
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9
Q

Lazy Leukocyte Syndrome

A

Gingivitis, recurrent otitis media, stomatitis

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10
Q

Hyperimmunoglobulin E Syndrome (Job’s syndrome)

A

Multiple cutaneous abscesses due to staphylococci

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11
Q

Malignancy or Myelodysplasia

A
  • Neutrophils are functionally defective d/t impaired phagocytosis, chemotaxis, and/or bactericidal activity
  • Infectious complications ↑ but still rare
  • However, borderline ↓in neutrophil number can lead to significant infectious complications
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12
Q

Phagocyte Qualitative Defects

Non-Malignant Hematologic Disease

A
  • Aplastic anemia
    • In addition to neutropenia, neutrophils also have impaired bactericidal activity
  • Paroxysmal Nocturnal Hemoglobinuria (PNH)
    • Impaired chemotaxis
  • Sickle cell anemia
    • Impaired bactericidal activity
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13
Q

Phagocyte Qualitative Defects

Iatrogenic Causes

A
  • Pharmacologic agents
  • Glucocorticoids
  • ↑ risk of infection
  • Several effects on neutrophils:
  • impaired chemotaxis
  • impaired phagocytosis
  • impaired microbicidal activity
  • Steroids also contribute to infection by multiple other mechanisms:
  • impair wound healing
  • ↑ skin fragility
  • ↓ lymphocyte function
  • ↓ cytokine production
  • ↓ humoral immune responses
  • In addition, signs and symptoms of infection may be dangerously masked in pts on steroids
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14
Q

Disorders of Cell-mediated Immunity

Overview

A

Causes infections predominantly due to intracellular pathogens

Organisms include bacteria, fungi, viruses and protozoa Mycobacteria, Legionella, Nocardia, Salmonella, Cryptococcus, Histoplasma, Coccidiodes, VZV, HSV, CMV, EBV, Pneumocystis, Toxoplasma, Cryptosporidium, Strongyloides

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15
Q

Disorders of Cell-mediated Immunity

Etiologies

A
  • Malignancy
  • Hodgkin’s lymphoma, Leukemias
  • HIV
  • Pharmacologic agents:
  • Corticosteroids
  • Degree of immunosuppression depends on dose and duration of steroids
  • Give prophylaxis w/ INH if previously untreated ⊕ PPD pt to start steroids
  • Cytotoxic therapy ⇒ Methotrexate, Cyclophosphamide, 6-MP, Azathioprine
  • Anti-rejection drugs ⇒ Cyclosporine, antilymphocyte Ab
  • Radiotherapy, especially when combined w/ other immunosuppressive agents
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16
Q

Severe Combined Immunodeficiency Syndrome (SCID)

A
  • 1° Disorder of Cell-Mediated Immunity
  • Infants develop failure to thrive and recurrent infections in 1st few months of life
  • Infections due to S. aureus, S. pneumoniae, H. influenzae, Pneumocystis, Candida and herpes group
  • Children usually die by age 2
17
Q

Wiscott-Aldrich Syndrome

A
18
Q

Ataxia-Telangectasia

A
  • 1° Disorder of Cell-Mediated Immunity
  • Absent serum and secretory IgA
  • Pts have recurrent sinopulmonary infections w/ encapsulated bacteria
  • W/ progressive loss of T cell function they develop additional associated infections
19
Q

Digeorge Syndrome

A
  • 1° Disorder of Cell-Mediated Immunity
  • Absence of thymus and parathyroid glands
  • Susceptible to overwhelming infections w/ HSV, VZV, albicans, pneumocystis
20
Q

Disorders of Humoral Immunity

Overview

A
  • Major components:
    • Immunoglobulins
    • Complement
  • Infection risk:
    • Infection w/ encapsulated bacteria
    • Infections w/ other streptococci, S. aureus, gram ⊖ rods
    • To a lesser extent see infections w/ enteroviruses and Giardia
21
Q

Multiple Myeloma

A
  • Malignant plasma cells induce a protein that selectively suppresses B cell function
  • Recurrent infections are predominantly due to encapsulated bacteria
  • Infections due to enteric GNR and S. aureus are also seen
  • Infections usually occur in the upper respiratory tract, urinary tract or skin.
22
Q

B Cell CLL

A
  • Unbalanced immunoglobulin chain synthesis results in hypogammaglobulinemia
  • Infection risk is associated w/ duration and stage of disease and IgG levels
  • Recurrent infections are predominantly due to encapsulated bacteria
  • Infections due to enteric GNR and S. aureus are also seen
  • Infections usually occur in the upper and lower respiratory tract, urinary tract or skin
23
Q

Disorders of Humoral Immunity

Non-malignant Etiologies

A
  • Non-malignant Etiologies
  • Etiologies include ↑ immunoglobulin loss or ↑ immunoglobulin catabolism
  • Examples
  • Nephrotic syndrome, burns, protein-losing enteropathy
  • ↓ Ab levels result in ↑ infection risk
24
Q

B-Cell Immunodeficiency States

1° Disorders of Humoral Immunity

A
  • Sex-linked hypogammaglobulinemia
    • Recurrent pyogenic infections and septicemia due to S. pneumonia, H. influenzae, S. aureus, N. meningitidis, P. aeruginosa
  • Hyperimmunoglobulin M
    • Recurrent respiratory, soft tissue and GI infections
  • Selective IgM Deficiency
    • Recurrent pyogenic infections
  • Selective IgA Deficiency
    • Some pts have ↑ upper respiratory tract infections or chronic diarrhea due to Giardia
  • Common Variable Immunodeficiency
    • Respiratory infections w/ S. pneumonia, H. influenza and S. aureus, diarrhea due to Giardia lamblia
25
Q

Complement Deficiencies

1° Disorders of Humoral Immunity

A
  • Early components (C1, C2, C4) deficiencies
    • Infection is rare
  • C3 or C5 deficiencies
    • Pts develop severe infections w/ encapsulated bacteria, S. aureus and enteric GNR
  • Deficiencies of later components (C5b, C6, C7, C8, C9)
    • Pts present w/ recurrent Neisseria infections (both N. menigitidis and N. gonorrhoeae)
    • Infectious episodes typically begin in the teen years
26
Q

Splenectomy or Splenic Dysfunction

A
  • Major infectious complication can be fulminant infection due to encapsulated organisms
  • Classic organisms include S. pneumoniae, H. influenzae, Neisseria species and Capnocytophaga
  • Sickle cell asplenia ⇒ ↑ risk for Salmonella infection
27
Q

Prevention of Infection

A
  • Prevent acquisition or suppress flora
  • Hand Washing
  • Isolation
  • Prophylactic antibiotics, antivirals, antifungals, and antiparasitics as indicated
  • Useful in high risk neutropenic and transplant pts
  • Improve or Modify Host Defenses
  • Immunization
  • Active
  • Pneumococcus, VZV
  • Passive
  • VZIG
  • Accelerate granulocyte recovery
  • G-CSF, GM-CSF
  • Cell component replacement
  • Leukocyte transfusions
28
Q

Clinical Pearls

A

Time

Clinical Pearls

Neutropenia:

1st few days ⇒ bacterial

4-5 days ⇒ fungal

Transplant:

1st month ⇒ bacterial, HSV

> 1 month ⇒ HSV, VZV, CMV, Aspergillus, Nocardia, Pneumocystis pneumonia (PCP)

> 3 months ⇒ Cryptococcus

Pace

Clinical Pearls

Fast ⇒ bacterial

Indolent ⇒ Nocardia, Cryptococcus, Mycobacterial

Symptoms

Clinical Pearls

Pleuritic chest pain, think fungus, especially aspergillus

Chest XR or CT

Nodules ⇒ Aspergillus, Nocardia

Interstitial ⇒ CMV, Pneumocystis pneumonia (PCP)

Focal ⇒ bacterial, mycobacterial, fungal

Sinus involvement
Think fungus, especially Mucor or Aspergillus

29
Q

Common Management Approach

A

Fever and Neutropenia

History

P.E.

Cultures

Chest x-ray

Begin broad spectrum abx active vs gram ⊖ enteric pathogens + S. aureus (esp. if central venous catheter in place)

If fever persists for > 3 days on broad antibiotics, add antifungal Rx

G-CSF may shorten duration of neutropenia and resultant infectious complications

4. HDS Multisystem (43 decks)

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