Benign WBC Abnormalities-Usera Flashcards
What are 4 ways to take lab measurements of WBCs?
- automated hematology analyzers-gives CBC
- bone marrow aspirate & biopsy
- flow cytometry
- peripheral blood smears
What are 3 factors affecting neutrophil conc’n in blood?
- bone marrow production & release
- rate of egress to tissue or survival time in blood
- ratio of marginated to circulating neutrophils in peripheral blood (MGP/CGP)
What is the definition of neutrophilia?
lots of neutrophils!
absolute neutrophil count>7X10^9
could be b/c of physiologic or pathologic process
What are the 3 types of neutrophilia kinetics? What is the timeframe for each?
Immediate: 20-30 min
Acute: 4-5 hrs
Chronic: days after
What happens in the immediate stage of neutrophilia kinetics?
20-30 min
redistribution from marginated to circulating pool
**can be stimulated by stress, steroids, epinephrine, IL-6
What happens during the acute stage of neutrophilia kinetics?
release of neutrophils from marrow storage pool to blood
**prompted by IL-6
What happens during the chronic stage of neutrophilia kinetics?
increase in marrow mitotic pool
Give 6 causes of neutrophilia.
- Acute inflammation
- Acute Infection
- Tissue Necrosis
- Drugs, Toxins, Metabolites
- Physiologic Cause
- Neoplastic Process
What are some possible causes of tissue necrosis–leading to neutrophilia?
burns
ischemic necrosis
tissue damage
What are some possible causes of neutrophilia via drugs, toxins, metabolites?
corticosteroids smoking growth factors uremia ketoacidosis lithium
What are some possible physiologic causes of neutrophilia?
stress
exercise
pregnancy
From a myeloblast to a mature neutrophil…what are the in between steps?
- Myeloblast
- Promyelocyte
- Myelocyte
- Metamyelocyte
- Band
- Mature Neutrophil
What is a myeloblast like?
a ton of nucleus
not much cytoplasm
high N/C ratio
only seen in the bone marrow
What is the promyelocyte like?
condensed chromatin in the nucleus
granules in the cytoplasm
still high N/C ratio
What is the myelocyte like?
smaller granules
chromatin super condensed in nucleus
there is a paranuclear glob that is the golgi
it is committed cell
What is the metamyelocyte like?
nucleus is kidney-bean shaped
What is a band like?
C shaped nucleus
still some granules
What is a mature neutrophil like?
polymorphonuclear
nuclear segmentation
still some granules
What does it mean when a doc says that a patient has left shifted & has more bands?
this is an acute response to infection
the bone marrow is just trying to spit out neutrophils to fight…get immature bands.
What is the lifespan of a mature neutrophil?
4-5 hours
What is an example of ischemic necrosis that could cause neutrophilia?
MI
What level of neutrophils qualifies as reactive neutrophilia? What does this form of neutrophilia do to myeloid maturation?
neutrophils<30X10^9
shift left in myeloid maturation
Give some morphologic alterations in neutrophils & precursors that are frequently seen in reactive neutrophilia.
toxic granulation
dohle bodies
vacuolization
What is the leukemoid reaction?
looks like leukemia, but isn’t.
A benign leukocyte proliferation with WBC usually >50 x 109/L with many circulating immature leukocyte precursors
Blasts are occasionally present; exclude chronic myelogenous leukemia with cytogenetics and LAP score
Give some examples of cases with the leukemoid reaction.
perforated appendicitis
whooping cough (lots of lymphocytes)
cutaneous larva migrans (lots of eosinophils)
What is the leukoerythroblastic 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
white nucleated RBCs, left shift
**bone marrow responding to a deficit in the body
What neutrophil count qualifies as neutropenia? In Caucasian? In African Americans?
Caucasians: ANC<1.3X10^9
What qualifies as agranulocytosis?
ANC<0.5X10^9
WHat are 3 mechanisms for neutropenia?
- decreased marrow production
- increased cell loss or tissue egress
- pseudoneutropenia (endotoxin)
What are some drug causes of neutropenia?
EtOH benzene chloramphenicol chemotherapy antibiotics benzodiazepines clozapine
What are some intrinsic defects (rare) that could possibly cause neutropenia?
Fanconi’s
Kostmann’s
Cyclic Neutropenia
Chediak-Higashi
What are some overwhelming infectious causes of neutropenia?
TB
sepsis
brucellosis
What are some hematologic disorder causes of neutropenia?
megaloblastic anemia
myelodysplasia
marrow failure
hypersplenism
What are some autoimmune causes of neutropenia?
lupus
rheumatoid arthritis
T/F Cachexia & debilitated states can cause neutropenia.
True.
What’s the deal with clozapine?
the FDA no longer approves it in the US
it is a good anti-psychotic med
it rarely causes agranulocytosis, neutropenia
What’s the fun pneumonic to remember the deal with brucellosis?
brucella is a gram neg coccus
infects bone marrow
comes from livestock
Betsy the Bovine had Brucellosis in the Bone Marrow
Give some viral infections associated with neutropenia.
Influenza, Measles, Chicken pox, Colorado tick fever, Dengue, Infectious mononucleosis, Poliomyelitis, Psittacosis, Sand-fly fever, Smallpox, Rubella, Infectious hepatitis
Give some bacterial infections associated with neutropenia.
Typhoid, Bacillary dysentery, Paratyphoid, Brucellosis, Ehrlichiosis
Give some rickettsial causes of neutropenia.
Rickettsial pox, Typhus, Rocky Mountain Spotted Fever
Give some protozoal causes of neutropenia.
Malaria, Kala-azar (visceral leishmoniasis), Relapsing fever
Give some causes of myeloid hypoplasia.
fanconi’s anemia
kostmann’s syndrome
cyclic neutropenia
Give a condition of maturation defects that can cause neutrophil disorders.
chediak higashi
What’s the deal with fanconi’s anemia?
PANMYELOID HYPOPLASIA-affects everything in the bone marrow.
HETEROGENOUS DISEASE CAUSED BY CHROMOSOMAL INSTABILITY, DNA breakagex
PRESENTS IN CHILDHOOD WITH APLASTIC ANEMIA AND CONGENITAL PHYSICAL MALFORMATIONS-no thumbs, radius problems.
SUSCEPTIBLE TO HEMATOPOIETIC AND SOLID ORGAN MALIGNANCIES
What’s the deal with Kostmann’s syndrome?
SYNDROME (INFANTILE GENETIC CONGENITAL AGRANULOCYTOSIS)
ANC <200/UL
VARIABLE MODES OF INHERITANCE
EARLY MYELOID PRECURSORS IN MARROW, BUT DO NOT MATURE
ELA2 AND HAX-1 IMPLICATED
What’s the deal with cyclic neutropenia?
Presents in infancy or childhood
Rare autosomal dominant trait with variable expression
21-30 day periodicity
ANC < 0.2 x 109/L for several days
Infection, fever, malaise during neutropenic period
Associated with transient marrow hypoplasia
Associated with ELA2 gene mutation (neutrophil elastase
How would you go about diagnosing cyclic neutropenia? What would you order?
CBC
peripheral smear
bone marrow aspirate & biopsy
flow cytometry
What are the 2 most common causes of congenital neutropenias?
pregnancy induced HTN
infection
What are some things that are found in lab error neutropenia–spurious neutropenia?
EDTA-dependent agglutinin, affects calcium, platelets, neutrophil counts
Old specimen
WBC fragility
Paraprotein-found in patients with multiple myelomas
How can you clinically differentiate b/w a folate & a Vit B12 deficiency?
folate has no neurological symptoms.
B12 does have neurological symptoms
put a tuning fork on the foot…if can’t feel it–TVP compromised. B12 problem.
What’s the deal with chronic granulomatous disease?
- *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
- *Defects in membrane-associated cytochrome b (subunits gp91 and p22), and cytosol-associated p47 and p67.
How do you go about diagnosing chronic granulomatous disease? how do you treat it?
Nitroblue Tetrazolium Test (NBT): normal neutrophils produce H2O2 and O2- which reduce yellow NBT to blue formazan; CGD neutrophils cannot reduce NBT.
**treat with prophylactic antibiotics
