Usera: Benign WBC Abnormalities Flashcards
What are 3 factors that affect the neutrophil concentration in the blood?
- bone marrow production and release
- survival time in the blood or rate of transport to tissue
- ratio of marginated to circulating neutrophils
What constitutes neutrophilia in adults?
neutrophils > 7 (E^9)/L in adults
What is the difference b/w immediate, acute, and chronic neutrophilia?
immediate: 20-30 minutes; redistribution from marginated to circulating pool
acute: 4-5 hours; release from marrow storage pool to blood
chronic: days; increase in marrow mitotic pool
Causes of neutrophilia?
acute inflammation acute infection tissue necrosis drugs, toxins, metabolic physiologic neoplastic
What are two features associated with REACTIVE neutrophilia?
shift to the left in myeloid maturation (Bands - not fully mature)
morphological alterations in neutrophils and precursors
A benign leukocyte proliferation with WBC usually >50 x 109/L with many circulating immature leukocyte precursors; Blasts are occasionally present
leukemoid reaction
Characterized by presence of nucleated RBC and a shift to the left in granulocyte maturation; Often associated with myelophthisic processes, severe hemorrhage, hemolytic anemia, or myelodysplastic syndromes
leukoerythroblastic reaction
What cell count constitutes neutropenia?
less than 2/L in whites
absolute neutrophils <1.3 in blacks
What cell count constitutes agranulocytosis?
<0.5/L
3 mechanisms for neutropenia?
decreased or ineffective marrow production
increased cell loss or neutrophils moving into tissues
pseudoneutropenia
Causes of neutropenia?
drugs *like clozapine intrinstic defects overwhelming infection hematologic disorders autoimmune debilitated states
T/F: Infections associated w neutropenia can be viral, bacterial, rickettsial, or protozoal
True
This is a heterogenous childhood disease caused by chromosomal instability; presents with aplastic anemia and congenital physical malformations
Fanconi’s anemia
What kind of hypoplasia occurs in Fanconi’s anemia?
panmyeloid –> all cells in the bone marrow are underproduced
Infantile genetic congenital agranulocytosis in which ANC <200/uL; variable modes of inheritance; early myeloid precursors in marrow, but they do not mature; associated with ELA2
Kostmann’s syndrome
Rare autosomal dominant trait that presents in infancy or childhood and causes period fluctuation in neutrophil count; it is associated with infection, fever and malaise during the neutropenic period; also associated with ELA2 gene mutation
cyclic neutropenia
What are the two most common “congenital” neutropenias?
pregnancy induced hypertension
infection
What are some reasons for false, or “spurious” neutropenia?
old specimen
WBC fragility
paraprotein
What does a neutrophil look like with toxic granulation?
large, blue-black granules; primary granules retain basophilia; Dohle bodies and vacuolization
Remnants of free ribosomes and rough endoplasmic reticulum; Seen in severe bacterial infections, pregnancy, burns, cancer, aplastic anemia, and toxic states; Often occur with toxic granulation and vacuolization
Dohle bodies
End stage of phagocytosed material, or fat or other substance; Often associated with Döhle bodies and toxic granulation; Often a predictor of sepsis; May be artifactual in stored blood
vacuolization
Autosomal dominant trait occurring in 1:5,000 people; Clinically ASYMPTOMATIC with normal neutrophil function; Heterozygous form
Homozygous form; Distinguish from reactive left-shift
Pelger-Huet Anomaly
Definition: >5% neutrophils with five lobes or any with six
hypersegmentation
What is hypersegmentation of neutrophils associated with?
megaloblastic anemia (B12 deficiency)
chronic infection
myelodysplastic syndromes
Autosomal recessive trait; Large, purplish GRANULES in cytoplasm; Granules stain metachromatically with Toluidine blue; Associated with mucopolysaccharidoses (Hunter’s syndrome, Hurler’s syndrome)
Alder-Reilly anomaly
Autosomal recessive trait; Giant gray-green peroxidase- positive bodies in cytoplasm of leukocytes and other cells; Defects in fusion of cytoplasmic membranes, locomotion, and chemotaxis; Abnormal melanosomes (skin hypopigmentation, photophobia); Lymphadenopathy and hepatosplenomegaly
Chediak-Higashi
Autosomal dominant trait; Large Döhle body-like inclusions in granulocytes; Involves myosin heavy chain 9; Associated with thrombocytopenia and GIANT OVAL PLATELETS with few granules; Typically present with BLEEDING disorder due to platelet defect
May-Hegglin anomaly
Sex-linked and autosomal recessive inheritance patterns
Defect in RESPIRATORY BURST oxidase system
Presents in childhood with recurrent infections with low-grade pathogens
Formation of granulomas when neutrophils phagocytose, but do not kill, organisms
chronic granulomatous disease
Patients with chronic granulomatous disease are more prone to infection by what organisms? Why?
catalase + bactertia, because catalase + bugs can break down H202 from the respiratory burst and can survive its toxic effects
What test is used to check for chronic granulomatous disease?
Nitroblue Tetrazolium Test
**normal neutrophils produce H202 and )2- which will turn yellow NBT to BLUE; CDG neutrophils cannot reduce NBT
Autosomal recessive inheritance
Absence of myeloperoxidase in neutrophils and monocytes (takes H202 –> HOCl)
Infections not a usual complication
myeloperoxidase deficiency
Leukocyte adhesion deficiency involved low levels of what coreceptor? How does type 1 differ from type 2 and type 3?
CD18;
type 1: deficiency in CD18
type 2: deficiency in selectins on endothelial cells
type 3: failure to ACTIVATE CD11a/CD18
Popular finding in leukocyte adhesion deficiency?
delayed separation of the umbilical cord
What constitutes eosinophilia in a patient?
absolute eosinophils > 0.45/L
Causes of eosinophilia? Most common cause?
most commonly idiopathic INVASIVE parasites allergic disorders (asthma) infections addison's disease malignancies collagen disease leukemia
Persistent absolute eosinophil count >1.5 x 109/L in adults with tissue infiltration and no apparent cause
eosinophilic leukemia
Pulmonary infiltrate with eosinophilia syndrome
Tropical eosinophilia
Löffler’s syndrome
What do corticosteroids do to eosinophil level?
DECREASE them bc they sequester in lymph nodes
What cell count constitutes basophilia?
> 0.2/L
Causes of basophilia?
immediate hypersensitivity reactions chronic myeloproliferative disorders CML basophilic leukemia irradiation
What is the normal range for monocytes? Monocytosis vs monocytopenia?
- 2 - 0.8
0. 8 is monocytosis
Causes of monocytosis? (too many monocytes)
chronic inflammation hematologic disease ** monocyte disorders infectious recovery state post-splenectomy
Causes of monocytopenia? (low monocytes)
stem cell disorders (aplastic anemia)
hairy cell leukemia
glucocorticoid therapy
This in an inherited functional abnormality of monocytes, particularly macrophages; glucocerebrosidase deficiency leads to big sea foam blue macrophages in bone marrow, lymph nodes, liver, and spleen; serum acid phosphatase increased
Gaucher disease
At what level are lymphocytes too high? In which cells do most changes in lymphocyte count occur?
> 4/L or >9/L in kids;
most changes in lymphocyte count are in T cells (T cells account for 60-80% of peripheral blood lymphocytes - mostly CD4 T cells)
CONTAGIOUS, MAINLY OCCURRING IN CHILDREN PERSISTENT HIGH WBC COUNT VARIABLE SYSTEMIC MANIFESTATIONS COXSACKIE VIRUSES A, B6, ECHOVIRUS, ADENOVIRUS 12-21 DAY INCUBATION LYMPHOCYTOSIS LASTS 3-5 WEEKS
acute infectious lymphocytosis
uncommon event; should raise suspicion for a chronic leukemia; persistent high levels of B cells; diagnose with flow cytometry
persistent polyclonal B cell lymphocytosis
SELF-LIMITED, USUALLY UNNOTICED (3-5 WK INCUBATION)
VIRUS GAINS ENTRY VIA CD21 (RECEPTOR), INFECTS OROPHARYNGEAL MUCOSA AND LYMPHOID TISSUE
SORE THROAT, MALAISE, LYMPHADENOPATHY, SPLENOMEGALY
WBC 12-25 X 109/L
ATYPICAL LYMPHOCYTOSIS
POSITIVE HETEROPHIL ANTIBODY
infectious mononucleosis (Mono)
Absolute lymphocyte count <2.0 x 109/L in children
lymphocytopenia
Causes of lymphocytopenia? (low lymphocytes)
destructive - radiation, chemo debilitative - starving, cancer, anemia infectious AIDS congenital immunodeficiency- wiskott aldrich abnormal lymph circulation
Who most commonly gets SCID? What are the symptoms of SCID?
males (75%); recurrent infections, failure to thrive, deficient T and B cells
X-linked recessive inheritance (Xp11.3-Xp11.22)
Eczema, thrombocytopenia, and immunodeficiency
Increased risk of secondary neoplasm
Progressive decrease in thymus-dependent immunity
Absent antibodies to blood group antigens
Abnormal antibody production by B cells
No mitogenic response to CD43
May present with abnormal bleeding in neonatal period
Wiskott Aldrich Syndrome
Absence or hypoplasia of thymus Hypoparathyroidism Congenital heart defects Dysmorphic facies Hypocalcemia Normal B cell function Pathogenesis: del(22)(q11.2)
DiGeorge Syndrome
Frequent respiratory and skin infections
Xq21.3-22
Block in B cell maturation at pre-B cell stage due to failure of variable and constant regions of IgM to connect
Decreased B lymphocytes and absent plasma cells
Marked decrease in serum immunoglobulins
X-linked agammaglobulinemia
Autosomal recessive inheritance
Progressive ataxia, immune dysfunction, increased risk of malignancy
Defect in cell-mediated immunity with thymic hypoplasia or dysplasia
Diagnosis: increased chromosome breakage, t(14;14)
Gene product functions in DNA repair
Hereditary Ataxia-Telangiectasia
