Ch 6 Pathoma WBC Disorders Flashcards
Hematopoiesis occurs via a stepwise maturation of CD__ hematopoietic stem cells. From the stem cell, they can become either __ stem cells or __ stem cells.
34+; myeloid; lymphoid
____ stem cells give rise to erythroblasts, myeloblasts, monoblasts, and megakaryoblasts.
Myeloid
____ stem cells give rise to B lymphoblast and T lymphoblast
lymphoid
____ give rise to neutrophils, basophils, and eosinophils.
Myeloblast
A normal WBC count is ___ K/microL. A low WBC is less than ___ and called ___. A high WBC count is greater than ___ and called ____. A low or high WBC count is usually due to a decrease or increase in ONE particular cell lineage
5-10; 5; leukopenia; 10; leukocytosis
Name the 2 main causes of neutropenia and the 2 tx.
drug toxicity (e.g. chemo with alkylating agents - cause damage to stem cells); severe infection (e.g. gram negative sepsis - increased mvmc of neutrophils into tissues results in decreased circulating neutrophils); GM-CSF or G-CSF boost granulocyte production
Name 4 main causes of lymphopenia.
1) Immunodeficiency (eg DiGeorge’s or HIV); 2) high cortisol state (exogenous corticosteroids or Cushings - induce apoptosis of lymphocytes); 3) autoimmune destruction (e.g. SLE produces ABs against blood); 4) whole body radiation (lymphocytes are highly sensitive to radiation - its the earliest change after WBodRT)
Name the 3 major causes of neutrophilic leukocytosis.
Bacterial infection; tissue necrosis; high cortisol state (all 3 induce release of marginated pool (cortisol impairs leukocyte adhesion) (1st two also induce bone marrow neutrophils including immature forms (left shift)
Bacterial infection or tissue necrosis can both induce release of bone marrow ___, including immature forms (right/left shift). Immature cells are characterized by decreased ___ (CD__)
neutrophils; left; Fc receptors; CD16
Monocytosis is seen in ___ and ___
chronic inflammatory states (e.g. autoimmune and infectious); malignancy
Eosinophilia is caused by allergic reactions (type __ hypersensitivity), ___ infections, and this malignancy (due to increased IL-__). Eosinophilia is driven by increased ____ factor.
I; parasitic; Hodgkin lymphoma (mixed cellularity type); IL5; eosiniphil chemotactic
Basophilia is classically seen in ____.
Chronic myeloid leukemia (CML)
Name 2 causes of lymphocytic leukocytosis
Viral infections (T lymphocytes undergo hyperplasia in response to virally infected cells); bordetella pertussis (*exception since it’s a bacteria)
Bordella pertussis (bacteria) infection causes lymphocytic leukocytosis (usually bacteria cause ___ leukocytosis), because it produces ___, which blocks circulating lymphocytes from leaving the blood to enter the ___.
neutrophilic; lymphocytosis-promoting factor; LN
Infectious mononucleosis is a __ infection that results in ___ leukocytosis comprised of ____. ___ is a less common cause. It is transmitted by ___, and classically infects ___.
EBV; lymphocytic; reactive CD8+ t cells; CMV; saliva; teenagers
EBV primarily infects these 3 places
oropharynx (resulting in pharyngitis); liver (resulting in hepatitis w/hepatomegaly and elevated liver enzymes); B cells
The CD8+ T cell response in infectious mononucleosis leads to these 3 clinical/lab findings (and why)
1) Generalized lymphadenopathy (due to T cell hyperplasia in LN paracortex); 2) splenomegaly (due to T cell hyperplasia in the periarterial lymphatic sheath (PALS)); 3) high WBC count with atypical lymphocytes (reactive CD8+ t cells)
The CD8+ T cell response causes splenomegaly due to T cell hyperplasia in the ____ of the spleen, and causes generalized LAD due to t-cell hyperplasia in the lymph node ___.
periarterial lymphatic sheath; paracortex (outer layer is cortex, middle is paracortex, inner is medulla)
In infectious mononucleosis, the ___ test is used for screening. It detects ___ that cross react with horse or sheep red blood cells, and usually turns positive within 1 hour/day/week after infection. A negative test suggests __ as possible cause of IM. Definitive dx is ___.
monospot; IgM antibodies (heterophile antibodies); week; CMV; serologic testing for EBV viral capsid antigen
Name the 3 complications of infectious mononucleosis.
1) splenic rupture (advised to avoid contact sports); 2) rash if exposed to ampicillin; 3) dormancy of virus in B cell can lead to recurrence and/or B cell lymphoma (esp if pt is immunodeficient (HIV))
Acute leukemia is a neoplastic proliferation of ___, defined as the accumulation of greater than __% ___ in the bone marrow.
blasts; 20; blasts
In acute leukemia, increased blasts “crowd out” normal hematopoiesis, resulting in “acute” presentation with these 3 things (and symptoms)
anemia = fatigue; thrombocytopenia = bleeding; neutropenia = infxn
In acute leukemia, blasts usually enter the blood stream, resulting in a high ___ count. Blasts are large/small, immature/mature cells, often with ___. Acute leukemia is subdivided into ___ or ___ based on the phenotype of the blasts.
WBC; large; immature; punched out nucleoli; acute lymphoblastic leukemia (ALL); acute myelogenous leukemia (AML)
____ is a neoplastic accumulation of lymphoblasts (greater than __%) in the bone marrow. Lymphoblasts have positive nuclear staining for ___, a DNA polymerase (found in the ___). It is absent in ___ and ___.
Acute lymphoblastic leukemia; 20; TdT; nucleus; myeloid blasts; mature lymphocytes
Acute lymphoblastic leukemia most commonly arises in ___, and is associated with ____. It can be sub-classified into ___ and ___ based on ___ (which one is more common?).
children; Down syndrome (after age of 5); B-ALL; T-ALL; surface markers; B-ALL is more common
Which leukemia is seen in down syndrome before age of 5 and which one after?
Acute megakaryoblastic leukemia (under the umbrella of acute myeloid leukemia); after 5 is acute lymphoblastic leukemia
B-ALL is characterized by lymphoblasts (__+), that express these 3 markers. There is excellent/poor response to chemo, and it requires prophyalxis to __ and __.
TdT; CD10, CD19, and CD20; excellent; scrotum; CSF
There are 2 common cytogenic abnormalities in B-ALL, ___ has a good prognosis and is more commonly seen in children; __ has a poor prognosis and is more commonly seen in adults.
t(12;21); t(9;22) (Philadelphia+ ALL)
T-ALL is characterized by lymphoblasts (__+) that express markers ___. The blasts do not express ___. T-ALL usually presents in ___ as a ___ mass (and is therefore called acute lymphoblastic __, since the malignant cell form a mass)
TdT; CD2 to CD8; CD10; teenagers; mediastinal (thymic); lymphoma
Acute myeloid leukemia is a neoplastic proliferation of ___ (greater than __%) in the bone marrow. Myeloblasts are usually characterized by positive cytoplasmic staining for ___, which can form crystal aggregates called ___.
myeloid cells; 20; myeloperoxidase (MPO); Auer rods
A ___ shift, is a shift to a more immature cell in the maturation process
left
Acute myeloid leukemia most commonly arises in ___. Subclassifcation is based on ___ abnormalities, ___ of immature myeloid cells, and ___ markers.
older adults (50-60 yrs); cytogenetic; lineage; surface
Name 3 common subtypes of acute myeloid leukemia
acute promyelocytic leukemia (APL); acute monocytic leukemia; acute megakaryoblastic leukemia
Acute promyelocytic leukemia (APL) is characterized by a ___ translocation, which involves disruption of the ___ (move it from chromosome __ to __). This disruption blocks ___ and ___ accumulate.
t(15;17); retinoic acid receptor (RAR); 17; 15; maturation; promyelocytes (blasts)
In acute promyelocytic leukemia, abnormal promyelocytes contain numerous ___ that increase the risk for ___. Treatment is with ___ (a vitamin A derivative), which binds the altered retinoid acid receptor and causes the blasts to ___.
primary granules (Auer rods); DIC; all-trans-retinoic acid (ATRA); mature/differentiate (and eventually die)
____ is a proliferation of mono blasts (usually lack ___). The blasts classically infiltrate ___.
Acute monocytic leukemia; MPO; gums
___ is a proliferation of megakaryoblasts (lack ___); it is associated with ____.
acute megakaryoblastic leukemia; MPO (since plts don’t need to do oxygen dependent killing); Down syndrome (before age 5)
Acute myeloid leukemia may arise from pre-existing ___ (___ syndromes), especially with prior exposure to ___ or ___.
dysplasia; myelodysplastic; alkylating agents; radiotherapy
Myelodysplastic syndromes usually present with ___, ___ bone marrow, abnormal ___ of cells, and increased ___ (less than __%). Most patients die from __ or __, though some progress to ___.
cytopenias, hypercellular (though its hyper cellular, its being formed poorly so cells don’t get out into blood); maturation; blasts; 20% (greater than would be leukemia); infection or bleeding; acute leukemia
Chronic leukemia is a neoplastic proliferation of ___. It is characterized by a high/low WBC count. Usually insidious (slow) in onset and seen in ___.
mature circulating lymphocytes; high; older adults
What is the most common leukemia overall?
Chronic lymphocytic leukemia (naive B cells)
___ is a neoplastic proliferation of naive B cells that co-express CD__ and CD__.
Chronic lymphocytic leukemia; CD5 and CD20
Chronic lymphocytic leukemia (CLL), increased ___ and ___ are seen on blood smear. Involvement of lymph nodes leads to generalized ___, and is called ___.
lymphocytes; smudge cells; lymphadenopathy; small lymphocytic lymphoma
(naive B cell proliferation)
Name 3 complications of chronic lymphocytic leukemia, and what is the most common cause of death in CLL?
1) hypogammaglobulinemia (B cells are not turning in to plasma cells to make Ig; infxn is the most common cause of death); 2) autoimmune hemolytic anemia (if cell manages to make Ig, it attacks RBCs); 3) transformation to diffuse large B cell lymphoma (Richter transformation - marked by enlarging LN or spleen)
