White blood cells Flashcards
what is a left shift
> 5% increase in percent of immature precursors (usually bands)
what is a leukemoid reaction
release of immature granulocytes into circulation, often associated with bacterial infections WBC can be very high > 50 associated with increased leukocyte alkaline phosphatase (absent in leukemia)
cause of x-linked agammaglobulinemia
mutation in bruton’s tyrosine kinase (BTK) gene (expressed in all stages of B cell development) - also important for myeloid maturation (assoc with neutropenia)
defect in hyper IgM syndrome?
defective class switching - increased serum IgM with deficiency of IgG, IgA, IgE - most commonly due to mutations in CD40 ligand
what infections do neutropenic patients get?
infections with enteric / endogenous bacteria (staph from skin, gram negatives from gut and urinary tract), fungal infections (candida)
genetics of kostmann syndrome
HAX1 mutation, autosomal recessive
most common mutation causing SCN
ELANE (AD)
x-linked cause of severe neutropenia
wiskott-aldrich
triad of shwachman-diamond syndrome
neutropenia metaphyseal dysplasia pancreatic insufficiency
what is WHIM syndrome
warts hypogammaglobulinemia infections myelokathexis
what causes WHIM syndrome
mutation in CXCR4 chemokine receptor - abnormal apoptosis / migration, retention of neutrophils in bone marrow
genetics of cartilage - hair - hypoplasia?
RMRP gene mutation AR inheritance
what is the risk in patients with cartilage-hair-hypoplasia
immunodeficiency (severe combined), heme malignancy (NHL most common)
what is barth syndrome
x-linked disorder associated with dilated cardiomyopathy, short stature, neutropenia
most common translocation seen in hypereosinophilia syndrome?
Fip1-like1 (FIP1L1) and platelet derived growth factor receptor alpha (PDGFRA) - results in constitutive TK activity
end organs affected by hypereosinophilia
skin lungs liver cardiac brain
treatment of hypereosinophilia syndrome with FIP1L1-PDGFRA mutation?
imatinib
treatment of unwell patient with hypereosinophilia?
high dose steroids must rule out strongyloides infection first
what types of infections do patients with CGD get?
catalase-positive (bacterial, fungal) frequently: pneumonia, abscesses, suppurative adenitis, osteo, bacteremia/fungemia
pathogenesis of CGD?
mutation in a subunit of NADPH oxidase resulting in defective oxidative burst and phagocytosis
five most common organisms that infect patients with CGD
aspergillus staph aureus burkholderia serratia nocardia
management of CGD?
antibiotic (Septra) and antifungal (itraconazole) prophylaxis interferon-gamma 3x/week as prophy if hx of severe, recurrent infections
gene in cyclic neutropenia
ELANE (ELA2), AD
gene in SDS
SBDS (AR inheritance)
gene in reticular dysgenesis
AK2
gene in cartilage hair hypoplasia
RMRP (AR)
gene in WHIM syndrome
CXCR4
what is barth syndrome
x-linked disorder - dilated cardiomyopathy, neutropenia, short stature
what is the gene affected in agammaglobulinemia
bruton’s tyrosine kinase (failure of b-cell development, also neutropenia)
gene in hyper IgM
CD40L defective class switching sinopulmonary infections, PJP (40%)
gene in kostmann’s
HAX1
gene in SCN
ELANE
Gene in chediak-higashi
CHS1/LYST failure of lysosomal transport
Gene in emberger / monomac
GATA2
gene in hyper IgE
STAT3, AD
what is a heterophile antibody
reacts to antigen from an unrelated species ie. the antibodies produced during an EBV infection react with horse RBCs (cause agglutination)
What is the EBNA?
EBV nuclear antigen - only expressed from latent virus - appears at 6-12 weeks after infection
which antibody could be present early in an EBV infection
early antigen (EA) IgG
What antibodies persist for life after an EBV infection?
IgG to the viral capsid antigen
Describe neutrophil production
myeloblast promyelocyte myelocyte metamyelocyte band PMNs (segmented neutrophil) - myeloblast to PMN progression takes 8 days
what is this cell
Peripheral blood smear showing a normal human promyelocyte. Promyelocytes are larger than myeloblasts and myelocytes (>20 micron). The nucleus and nuclear chromatin and nucleoli resemble myeloblasts but the cardinal feature is the presence of many violet granules in the cytoplasm with either a dense or coarse pattern often obscuring other cell landmarks.
name the cell
Peripheral blood smear shows a normal human myelocyte. As the myelocyte divides and matures, the nucleus becomes smaller and irregularly round, nuclear chromatin becomes coarse and clumped, and nucleoli are sparse to absent. The nuclear to cytoplasmic ratio is reduced compared to promyelocytes. Specific granules are difficult to see on light microscopy.
name the cell
Peripheral blood smear shows a normal human metamyelocyte. The cytoplasm resembles the mature neutrophil and band forms; granules are small, fine blue-black or grey, and dispersed homogeneously throughout the cytoplasm. The nucleus is indented like a bean and the nuclear chromatin is coarse, clumped, and condensed peripherally.
name the cell
Peripheral blood smear shows a normal human band form. The nucleus is nonsegmented and elongated resembling a horseshoe shape; there are no nuclear lobulations but a constriction is visible. The nuclear chromatin is aggregated into evenly arranged clumps. The cytoplasm is like the mature neutrophil with pink staining and fine azure bluish granules.
fully functional phagocytic cell
name the cell
Peripheral blood smear shows a normal polymorphonuclear neutrophil (PMN). The nucleus is segmented into four lobes connected by thin chromatin strands. The cytoplasm is pink with fine, azure bluish granules. The predominant specific secondary granules are finely dispersed and stains the cytoplasm faintly pink.
which common beta-2 subunit is often found in integrin receptors, and important for neutrophil margination / migration?
CD18
auto-antibodies to GM-CSF results in what?
pulmonary alveolar proteinosis (progressive accumulation of surfactant lipids and proteins in alveolar space - type II pneumocytes are unable to clear this in the absence of GM-CSF)
important parts of a physical exam in a patient with neutropenia
- Growth parameters
- Inspect for dysmorphic features (associated with immune deficiency syndromes, bone marrow failure syndromes), hair, nails
- Oral mucosa (inspect for ulcerations, gingivitis, abscess)
- Respiratory exam for opportunistic infections (PCP)
- Lymphadenopathy, hepatosplenomegaly
mechanism of G-CSF action
G-CSF administration leads to a reduction in SDF-1 expression as well as CXCR4 cleavage, resulting in egress of neutrophils from bone marrow
starting G-CSF dose
5 mcg/kg/day
what medications are associated with neutropenia? what is the mechanism?
immune: penicillins, cephalosporins
toxic to cells: phenothiazine (anti-psychotic)
hypersensitivity: dilantin, phenobarbitol
infections associated with causing neutropenia
RSV, varicella, influenza A/B, measles, rubella
due to increased expression of adhesion molecules (ICAM1/2) and increased margination, migration of neutrophils to site of infection (decreased production may contribute slightly)
indications for G-CSF
severe, recurrent infections in patient with autoimmune neutropenia
in patient with promyelocyte arrest (limited bone marrow neutrophil pool to mobilize) - ie) cyclic neutropenia, SCN
long term side effects of G-CSF?
osteoporosis
splenomegaly
possible increased risk of malignancy
gene in leukocyte adhesion defect?
LAD 1 (CD18)
blood tests that are often abnormal / elevated in the presence of a FIP1L1-PDGFRa translocation causing HES?
vit b 12
tryptase
