Non-neoplastic WBC abnormalities-Usera Flashcards
What are the four major lab measurements of WBCs?
Automated hematology analyzers
Bone marrow aspirate and biopsy
Flow cytometry
Peripheral blood smears
What does automated hematology do?
gives cell count
Are aspirate and biopsy the same thing?
no biopsy is taken from the core of bone marrow and aspirate is the jelly fluid stuff but you take both and look at both separetly
What does flow cytometry do?
helps to identify lineage by looking at cell markers
When do you do peripheral blood smears?
ONLY WHEN THERE IS NOT OTHER EXPLAINABLE CAUSE
What are the three factors that affect neutrophil concentration in blood?
Bone marrow production and release
Rate of egress to tissue or survival time in blood
Ratio of marginated to circulating neutrophils in peripheral blood (MGP/CGP)
Where do you find neutrophils when you have an infection? What do you call this and why is this significant?
line up around the periphery (next to endothelium)-> called margination, When you take needle aspirate you will get low number of neutrophils cuz none of them will be in the middle
Absolute neutrophil count greater than (blank) X 10^9/L in adults is considered neutrophilia
7
What is neutrophilia a response to?
physiologic or pathologic processes
why can you get immediate neutrophilia and how long does it take?
redistribution from marginated to circulating pool-> 20-30 minutes
What are some things that can cause immediate neutrophilia?
stress, steroids, epinephrine, IL-6
Why can you get an acute neutrophilia and how long does it take?
release from maroow storage pool to blood (IL-6) 4-5 hours
Why can you get a chronic neutrophilia and how long does it take?
increase in marrow mitotic poo
days
(blank) will immediately increase your neutrophil count
epinephrine
If you have a cell population with more bands than mature neutrophils, what do you call this? WHat does this mean?
a left shift
means you have an acute inflammatory response
Explain the matureation of neutrophil
Myoblast-> promylocyte-> myelocyte-> metamylocyte-> band-> mature neutrophil
What phase of maturation of a neutrophil is this:
have a giant N to C ratio (i.e the nucleus is huge compared to the cytoplasm) should only be found in bone marrow.
Myoblast cells
What phase of maturation of a neutrophil is this:
A cell you with a slightly smaller N but still high N to C ratio than myoblast cells and then there are some granules present.
Promyelocyte
What phase of maturation of a neutrophil is this is this:
semicircle nucleus and lots of condensed granules
myelocyte
What phase of maturation of a neutrophil is this:
looks like a pacman
metamyelocyte
What phase of maturation of a neutrophil is this:
looks like a C shaped nucleus
Band cell
What phase of maturation of a neutrophil is this:
multi lobed nucleus
neutrophils
Lifespan of neutrophils is only a couple of (blank) so they are just for acute responses
hours
What are these causes of: Acute inflammation Acute infection Tissue necrosis Drugs, toxins, metabolic Physiologic Neoplastic
Causes of neutrophilia
What do these cause:
collagen vascular, vaculitis
Acute inflammation -> which causes neutrophilia
What do these cause:
Corticosteroids, smoking, growth factors, uremia, ketoacidosis, lithium
Neutrophilia
Can carcinomas, sarcomas and MPDs cause neutrophilia?
yes!
What physiological things can cause neutrophlia?
pregnancy, exercise, stress
What can cause acute infections and thus neutrophilia?
bacteria, fungi, parasites, viruses, spirochetes
What are features associated with REACTIVE neutrophilia?
Usually <30 x 109/L
Shift to the left in myeloid maturation
Frequently associated with morphologic alterations in neutrophils and precursors
Toxic granulation
Döhle bodies
Vacuolization
Is there a heritable cause for neutrophilia?
no
WHo has higher amounts of neutrophils, adults or children?
Children
What morphologic alterations in neutrophils and precursors are seen in reactive neutrophilia?
toxic granulation, Dohle bodies, vacuolization
What is a leukemoid raction?
a reaction that resembles leukemia but isnt
What is this: a benign leukocyte proiferation with WBC usually greater than 50 X 10^9/L with many circulating immature leukocyte precursors.
Leukemoid reaction
Since blasts are occasionally present in leukemoid reactions, how can you exclude CML?
with cytogenetics and LAP score
What is this:
characterized by presence of nucleated RBC and a shift to the left in granulocyte maturation
Leukoerythroblastic reaction
What are leukoerythroblastic reactions aften associated with?
myelopthisic processes, severe hemorrhage, hemolytic anemia, or myelodysplastic syndromes
Why will you get a leukemoid reaction?
perforated appendicitis (neutrophils), whooping cough (lymphs), cutaneous larva migrans (eos).
Why can you get a leukoerythroblastic reaction?
marrow infiltration (fibrosis, mets)
What drug can make it look like a leukemoid or leukoerythroblastic reaction? WHy?
neupogen
it is used after bone marrow transplants to increase hemmopoietic activity
What is the definition of neutropenia?
less than 2.0 X 10^9 /L in whites and less than 1.3 X 10 ^ 9/L in blacks
What is the definition of agranulocytosis?
less than 0.5 X 10 ^9 /L
What are mechanisms for neutropenia?
decreased or ineffective marrow production
increased cell loss or tissue egress
pseudoneutropenia (endotoxin)
What are the 6 major causes of neutropenia?
Drugs Intrinsic Defects Overwhelming Infection Hematologic disorders Autoimmune Cachexia and Debiiatate States
WHat are the drugs that can cause neutropenia?
EtOH, benzene, chloramphenicol, chemotherapy, antibiotics, benzodiazepines
AND
CLOZAPINE!!!!!!!! (Anitpsychotic)
What hematologic disorders can cause neutropenia?
megaloblastic anemia
myelodysplasia
marrow failure
hyperslepnism (splenomegaly)
What autoimmune diseases cause neutropenia?
Lupus, Rh Arthritis
What intrinisic defects (rare) cause neutropenia?
Fanconi’s, Kostmann’s, Cyclic neutropenia, chediak-higashi
What overwhelming infections can cause neutropenia?
miliary TB, sepsis, brucellosis
Many conditions causing agranulocytosis affect both (blank) and (blank) lines
erythroid and myeloid lines
How do you remember what Brucella does?
Besty the Bovine had Brucella in her Bone marrow-> brucella causes bone marrow problems and you get it from cattle
What infections are associated with neutropenia?
Viral, Bacterial, Rickettsial, Protozoal
What do these cause:
Influenza, Measles, Chicken pox, Colorado tick fever, Dengue, Infectious mononucleosis, Poliomyelitis, Psittacosis, Sand-fly fever, Smallpox, Rubella, Infectious hepatitis
neutropenia via infection
What do these cause:
Typhoid, Bacillary dysentery, Paratyphoid, Brucellosis, Ehrlichiosis
Neutropenia via infection
What are these:
Rickettsial pox, Typhus, Rocky Mountain Spotted Fever
What do they cause?
Rickettsial infections
infections that cause neutropenia
What are these:
Malaria, Kala-azar, Relapsing fever
What do they cause?
protozoal infections
Infections associated with neutropenia
What causes quantitative neutrophil disorders?
Myeloid hypoplasia and maturation defects
What are the three major disorders that cause myeloid hypoplasia?
Fanconi’s anemia
Kostmann’s syndrome
Cyclic neutropenia
What are the maturation defects that cause quantitative neutrophil disorders?
chediak-higashi
What is this:
Panmyeloid hypoplasia
Heterogenous disease caused by chromosomal instability
Presents in childhood with aplastic anemia and congenital physical malformations
Susceptible to hematopoietic and solid organ malignancies
Fanconi’s anemia
What is a tell tale sign of fanconi’s anemia?
no thumbs, hand deformity
What is this: ANC <200/ul Variable modes of inheritance Early myeloid precursors in marrow, but do not mature Ela2 and hax-1 implicated
Kostmann’ syndrome
What exactly is Kostmann’s syndrome?
an infantile genetic congenital agranulocytosis
What are the 2 genes super implicated in Kostmann’s syndrome?
ELA2 and HAX-1
What is this: Presents in infancy or childhood Rare autosomal dominant trait with variable expression 21-30 day periodicity ANC
Cyclic neutropenia
What is the periodicity of cyclic neutropenia?
21-30 days
What gene is associated with cyclic neutropenia?
ELA2 gene mutation (neutrophil elastase)
How do you diagnose cyclic neutropenia?
routine CBC
then Bone marrow aspirate and biopsy
If you have an infection what will the neutrophil count be like?
low because they are making love to the endothelium
What are the most common ways to get congenital neutropenia?
Pregnancy induced hypertension (i.e eclampsia)
Babies born to pregnant moms who have overwhelming infections (babies get chorionamniotitis)
What are the five ways to get spurious neutropenia?
EDTA-dependent agglutinin
Old specimen
WBC fragility
Paraprotein
How can paraproteins cause spurious neutropenia?
a lot of antibodies circulating can effect N counts
What is spurious neutropenia?
fake/false neutropenia
What do toxic granullations look like?
large, blue-black granules
Primary (azurophilic) granules retain basophilia (easily stain with basic dye), perhaps due to lack of maturation.
What are toxic granulations associated with?
Dohle bodies and vacuolization
When do you see toxic granulations?
septicemia, sepsis
Toxic granulations found in neutrphils make (blank) activity decreased compared to normal granulocytes
peroxidase activity
What are Dohle bodies?
remnants of free ribosomes and RER
When do you see Dohle bodies?
in severe bacterial infections, pregnancy, burns, cancer, aplastic anemia, toxic states
What do you often see associated with Dohle bodies?
occur with toxic granulation and vacuolization
What is this:
end stage of phagocytosed material, or fat or other substance
Vacuolization
What is vacuolization often associated with?
Dohle bodies and toxic granules
What is vacuolization a predictor for?
sepsis
What is a shistocyte?
a fragmented RBC
(blank) is an autosomal dominant disorder characterized by abnormal nuclear shape and chromatin organization in blood granulocytes. Heterozygotes show hypolobulated neutrophil nuclei with coarse chromatin
Pelger-Huet anomaly
Is pelger huet anomaly detrimental?
no, it is clinically asymptomatic with normal neutrophil function
Why is it important to know what pelger huet is?
so that you dont confuse it with leukemia.
What is the definition of hypersegmentation?
greater than 5% neutrophils with five lobes or any with six
What is hypersegmentation associated with?
Megaloblastic anemia (B12 deficiency), chronic infection, myelodysplastic syndromes
What is the characteristics of hereditary hypersegmentation?
autosomal dominant, rare, not associated with disease
Which deficiency will you have neurological symptoms; folate deficiency or B12 deficiency?
B12 deficiency
What is this:
autosomal recessive trait,
large purplish granules in cytoplasm
granules stain toluidine blue
Alder-Reilly anomaly
What is Alder-Reilly anomaly associated with?
mucopolysaccharidoses (hunters syndrome, hurler’s syndrome)
So when you see dark granules what diseases should you be thinking?
hunters or hurlers syndrome
What is this:
- autosomal recessive trait
- Giant gray-green peroxidase positive bodies in cytoplasm of leukocytes and other cells.
- defects in fusion of cytoplasm membranes, locomotion and chemotaxis
Chediak-Higashi
What are some notable systems of Chediak-Higashi?
abnormal melanosomes (skin hypopigmentation , photophobia, lymphadenopathy, hepatosplenomegaly
If you see inclusions in neutrophils what does this narrow your differential to?
Chediak higashi or Ehrlichia
What is this
partial albinism, photophobia, immunodeficiency, frequent pyogenic infections
Chediak-higashi
What is this: autosomal dominant trait Large Dohle body-like inclusions in granulocytes Involves myosin heavy chain 9 inclusions contain RNA
May-Hegglin Anomaly
What is may-hegglin anomaly associated with?
thrombocytopenia, giant oval platelets with few granules
What does may hegglin anomaly typically present with?
bleeding disorder due to platelet defect
If you are looking at a histo slide and you see May Hegglin anomaly, what will you see in the slide?
giant platelets and inclusions in granulocytes
Does may hegglin anomaly have normal granulocyte function?
yes!
What is this:
- 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
- MESSED UP NADPH OXIDASE SYSTEM
Chronic granulomatous disease
How is chronic granulomatous disease passed on
sex linked and autosomal recessive inheritance patterns
Chronic granulomatous disease is caused by defects in membrane associated (blank) and cytosol associated (blank)
cytochrome b
p47 and p67
If you have a messed up NADPH oxidase system what cant you make?
hydrogen peroxide (means you have a defect in respiratory burst)
How do you diagnose chronic granulomatous disease?
Nitroblue tetrazollum test (NBT)
Normal neutrophils reduce H202 and 02 to a blue product, CGD neutrophils cannot reduce NBT so you dont have blue
What is the treatment for CGD?
prophylactic antibiotics
To diagnose CGD, Incubate with NBT and if your NADPH peroxidase (NADPH) is working then you will have (blank) cells cuz the catalase bugs wll break it down, if you don’t have it it will be (blank) becase the catalase bugs will have nothing to break down.
purple
pink
What are the characteristics of MPO (myeloperoxidase deficiency)?
autosomal recessive inheritance (can be acquired)
absence of MPO in neutrophils and monocytes
Infections not a usual complication
How do you diagnose MPO?
histochemistry: myeloperoxidase stain
NB: may be recognized on WBC histogram using technicon instruments
How do you get acquired myeloperoxidase deficiency (MPO)?
myeloid neoplasms, drugs, severe infections, DM, pregnancy
WHy dont you have a lot of recurrent infections with myeloperoxidase deficiency (MPO)?
because you still got your other lethal oxygen radicals
In leukocyte adhesion deficiency type I, what is missing?
integrins; CD11a and CD18
In leukocyte adhesion type II, what is missing?
you have integrin but you dont have your selectins (i.e. nothing to bind to)
In leukocyte adhesion type III, what is missing?
you dont have activation of your integrins (super rare) so you get margination but no diapedesis
What are these symptoms of:
delayed separation of umbilical cord
recurrent pyoderma gangrenosum
Leukocyte Adhesion deficiencies
What is the summary of LAD?
cant fight cells and get things where they need to go
If you have a neonate with delayed separation of the umbilical cord, what type of LAD do they have?
1
What is the definition of eosinophilia?
greater than 0.45 X 10^9 /L adults
What is eosinophilia associated with?
cellular immune response
What are the causes of reactive eosinophilia?
parasitic infection allergic disorders infections addisons disease malignancies collagen disease idiopathic leukemias GI disorders
What infections cause a reactive eosinophilia?
leprosy, brucellosis, TB, fungal infections, scarlet fever
What interleukins produce IgE?
IL-4
What are 2 hypereosinophilic syndromes?
Eosinophilic leukemia
Loffler’s syndrome
What is eosinophilic leukemia?
persistent absolute eosinophil count greater than 1.5 X 10^9 /L in adults with tissue infiltration and no apparent cause
What is lofflers syndrome?
pulmonary infiltrate with eosinophilia syndrome
-tropical eosinophilia
Hypereosinophilic syndromes may cause extensive tissue damage, especially (blank) due to release of granule contents.
heart
Where do you find Charcot-leyden crystals in exudates and what are they?
Hypereosinophilic syndromes-> condensation of granule proteins
If you see a lot of crystals, what does this tell you and why is it worrisome?
a lot of eosinophils were there and it is worrisome because this is very damaging to heart valves.
What are the clinical features of hypereosinophilic syndromes?
Fever Fatigue Cough Angioedema Pruritis Diarrhea
What causes eosinopenia?
hypercortilism
What do corticosteroids due to eosinophils?
it sequesters eosinophils in lymph nodes
What can cause hypercortisolism?
Cushing’s syndrome ACTH Acute Stress/Epinephrine Inflammation Prostaglandins Bacterial infection
What is the definition of basophilia?
absolute basophil count greater than 0.2 X 10^9 /L in adults
What are causes of basophilia?
Immediate hypersensitivity reactions Chronic myeloproliferative disorders (PV) CML Basophilic Leukemia Irradiation
If you have degranulation of basophils you will be super itchy because of the (blank) degranulation
histamine
Basophils are sensitive to (blank) so they will often itch after taking a shower
temperature
What is the definition of monocytosis?
absolute monocyte count greater than 0.8 X 10^9 /L in adults
**monocyte count varies with age*
Unexplained (blank) is a frequent finging in malignancies
monocytosis
What is the definition of monocytopenia?
Absolute monocyte count ess than 0.2 X 10^9/L in adults
What are the causes of monocytosis (6)?
Inflammatory monocyte disorders infections hematologic malignancy recovery states post-splenectomy
What can cause inflammation that leads to monocytosis?
collagen vascular,
UC/Chrons, PAN, TA
What are monocyte disorders that cause monocytosis?
langerhand cell
histoiocytosis
letterer siwe disease
What are infectious disorders that cause monocytosis?
TB, SBE, Syphillis, protozoa/ricketssiae
What hematologic malignancies cause monocytosis?
AML, MDS, MPD, HD, NHL, MM
(blank) is a marker of chronic disease.
monocytosis
What are causes of monocytopenia?
stem cell dsorders (aplastic anemia)
Hairy cell leukemia
Glucocorticoid therapy
(blank) appear within th emonocyte gate on flow cytometry, which often masks the cytopenia.
Hairy cells
What are the lipid storage disorders (abnormalities of monocytes)?
Gaucher Disease Neimann-Pick Disease Tay-Sachs Disease Fabry Disease Wolman's Disease Tangier Disease
What is this:
AR, glucocerebrosidase def.
Gaucher Disease
What is this:
AR, sphingomyelinase def.
Neimann-Pick Disease
What is this:
AR, hexamindise A def.
Tay-Sachs Disease
What is this:
XLR, alpha-galactosidase def.
Fabry disease
What is this:
AR, lysosomal acid lipase def.
Wolman’s Disease
What is this:
AR, alpha-lipoprotein def.
Tangier Disease
What is this: Autosomal recessive trait Glucocerebrosidase deficiency Macrophages in bone marrow, lymph node, liver, spleen Serum acid phosphatase increased Types I, II, and III
Gaucher Disease
What are the three types of Gauchers disease?
Disease manifested in macrophages.
Type 1 non neurological
Type 2 neurologic and fatal
Type 3 neurologic but can live
What is lymphocytosis?
absolute lymphocyte count greater than 4.0 x 10^9/L in adults and greater 9.0 X 10 ^9/L children
Most changes in lymphocyte count are due to changes in numbers of (blank), which normally acounts fo 60-80% of peripheral blood lymphocytes.
T lymphocytes
What cells are the majority of the circulating cells in the lymph?
CD4+ T helper cells
What are these: Acute infectious lymphocytosis Persistent polyclonal B cell lymphocytosis Infectious mononucleosis (EBV) Bordatella pertussis infection Cytomegalovirus infection (CMV) Toxoplasmosis Retrovirus infection (HTLV-1) lymphocytic leukemias
absolute lymphocytosis with leukocytosis
What is this:
- contagious, mainly occuring in children
- caused by coxsackie virus A, B6, ehovirus, adenovirus
- 12-21 day incubation
Acute infectious lymphocytosis
How long does acute infectious lymphocytosis last?
3-5 weeks
What is this: happens in a lot of female smokers postsplenectomy uncommon event should raise suspicious for a chronic leukemia diagnosis-> use flow cytometry
Persistent polyclonal B cell lymphocytosis
What is this:
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 (NOT unique to this disease)
Positive heterophil antibody
INFECTS B CELLS NOT MONOCYTES
Infectious mononuleosis (monomer)
How does infectious mononucleosis infect B cells?
virus gains entry via CD21 (receptor),
What kind of antibody will you find in infectious mononuleosis?
Positive heterophil antibody
What is the definition of lymphocytopenia?
absolute lymphocyte count less than 1.0 X 10^9/L in adults and less than 2.0 X 10^9/L in children
What are the causes of lymphocytopenia?
Destructive Debilitative Infectious AIDS Congenital Immunodeficiency Abnormal Lymph Circ
What are some destructive causes of lymphocytopenia?
radiation, chemo, steroids
What are some debilitative causes of lymphocytopenia?
starvation, aplastic anemia, cancer, renal failure CV
What are some infectious causes of lymphocytopenia?
viral hep, influenza, TB
What are the congenital causes for lymphocytopenia?
wiskott-aldrich syndrome
What abnormalities in lymph circulation can cause lymphocytopenia?
Intestinal lypmhangiectasia, thoracic duct drainage/rupture, CHF
What is the most severe immunodeficiency?
severe combined immunodeficiency syndrome
What is severe combined immunodeficiency syndrome?
75% of males affected
Both T and B lymphoid systems deficient
recurrent infections, failure to thrive
What are the characteristics of the X-linked (Xq13) form of SCIS?
absent to severely reduced T cells, thymic hypoplasia
What are the characteristics of the autosomal form of SCIS?
severe deficiency of T and B cells (ADA deficiency)
How do you treat SCIS?
bone marrow transplant
What is this:
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
In Wiskott-Aldrich syndrome, there is not mitogenic response to (blank)
cd43
In wiskott-aldrich syndrome, there is abnormal (blanK) production by B cells
antibody
What can wiskott aldrich present as in the neonatal period?
abnormal bleeding
What is this: absence or hypoplasia of thymus hypoparathyroidism congenital heart defects dysmorphic facies hypocalcemia NORMAL B CELL function
DiGeorge Syndrome
WHat is the pathogenesis of DiGeorge syndrome?
del(22)(q11.2)
How can you tell someone has DiGeorge syndrome by looking at them?
dysmorphic faces
What is this:
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-link agammaglobulinemia
How do you treat x-linked agammaglobulinemia?
gammaglobulin
What is this:
autosomal recessive inheritance
Progressive ataxia, immune dysfunction, increased risk of malignancy
Defects in cell-mediated immunity with thymic hypoplasia or dysplasia
Hereditary ataxia-telangiectasia
How do you diagnose hereditary ataxia-telengiectasia?
increased chromosome breakage, t(14;14)
(this gene is what helps repair DNA :(
