CH6 - White Blood Cell Disorders Flashcards
What does hematopoetic CD34+ stem cells produce?
Myeloid stem cells and lymphoid stem cells
What does myeloid stem cells produce?
Erythroblast, Myeloblast, Monoblast, Megakaryoblast
What does erythroblast produce?
RBCs
What does myeloblast produce?
Neutrophils, basophils, Eosinophils
What does monoblast produce?
Monocytes
What does megakaryoblast produce?
megakaryocytes
What does lymphoid stem cells produce?
B lymphoblast and T Lymphoblast
What does B lymphoblast produce?
Naïve Bcells
What does Naïve B cells produce?
Plasma cells
What does T lymphoblast produce?
Naïve Tcells
What does Naïve T cells produce?
CD8+ and CD4+ T cells
How does hematopoiesis occur?
via a stepwise maturation of CD34+ hematopoietic stem cells
What happens to hematopoetic stem cells?
Cells mature and are released from the bone marrow into the blood.
What is the normal white blood cell (WBC) count?
it is approximately 5-10 K/pL
What is a low WBC count? What is it called?
(< 5 K) is called leukopenia.
What is a high WBC count? What is it called?
(> 10 K) is called leukocytosis.
What is a low or high WBC count usually due to?
a decrease or increase in one particular cell lineage.
What is neutropenia?
refers to a decreased number of circulating neutrophils
What are some of the causes of neutropenia?
1) Drug toxicity 2) severe infection
How can drug toxicity lead to neutropenia?
e.g., chemotherapy with alkylating agents, cause damage to stem cells resulting in decreased production of WBCs, especially neutrophils.
How does severe infection lead to neutropenia?
e.g., gram-negative sepsis leads to increased movement of neutrophils into tissues resulting in decreased circulating neutrophils.
What is GM-CSF or G-CSF?
granulocyte monocyte stimulating factor or granulocyte stimulating factor, it can be used to boost the neutrophil count decreasing the risk of infection
What is lymphopenia?
it refers to a decreased number of circulating lymphocytes
What are the some of the causes of lymphopenia?
1) immunodeficiency 2) high cortisol state 3) autoimmune destruction 4) whole body radiation
What are some examples of immunodeficiency that lead to lymphopenia?
e.g., DiGeorge syndrome or HIV
How does a High Cortisol state lead to lymphopenia?
exogenous corticosteroids or Cushing syndrome, induces apoptosis of lymphocytes
What is an example of autoimmune destruction leading to lymphopenia?
e.g., systemic lupus erythematosus
How can whole body radiation lead to lymphopenia?
Lymphocytes are highly sensitive to radiation; lymphopenia is the earliest change to emerge after whole body radiation
What are the different types of leukocytosis?
1) neutrophilic leukocytosis 2) monocytosis 3) Eosinophilia 4) Basophilia 5) Lymphocytic leukocytosis
What does neutrophilic leukocytosis refer to?
increased circulating neutrophils
What are the causes of neutrophilic leukocytosis?
1) Bacterial infection 2) tissue necrosis 3) High cortisol state
How does Bacterial infection or tissue necrosis lead to neutrophilic leukocytosis?
It induces release of marginated pool and bone marrow neutrophils, including immature forms (left shift)
When immature cells are released into the blood, how are they characterized?
by decreased Fc receptors
What is the marker for the decreased Fc receptor?
CD16
Why are Fc receptors important?
They help the neutrophil to recognize immunoglobulin which is going to act as an opsonin for phagocytosis
How does high cortisol state lead to neutrophilic leukocytosis?
impairs leukocyte adhesion, leading to release of marginated pool of neutrophils
What does monocytosis refer to?
increased circulating monocytes
What are the causes of monocytosis?
inflammatory states (e.g., autoimmune and infections) and malignancy.
What does eosinophilia refer to?
increased circulating eosinophils
What are the causes of eosinophilia?
include allergic reactions (type I hypersensitivity), parasitic infections, and Hodgkin lymphoma,
What is eosinophilia driven by?
increased eosinophil chemotactic factor
What does basophilia refer to?
increased circulating basophils
What is basophilia classically seen in?
chronic myeloid leukemia
What does lymphocytic leukocytosis refer to?
increased circulating lymphocytes
What are the causes of lymphocytic leukocytosis?
1) viral infection 2) Bordetella pertussis infection
How does viral infections lead to lymphocytic leukocytosis?
T lymphocytes undergo hyperplasia in response to virally infected cells
How does Bordetella pertussis infection lead to lymphocytic leukocytosis?
Bacteria produce lymphocytosis-promoting factor, which blocks circulating lymphocytes from leaving the blood to enter the lymph node.
What is infectious mononucleosis?
EBV infection that results in a lymphocytic leukocytosis comprised of reactive CD8+ T cells; CMV is a less common cause
How is EBV transmitted?
by saliva (kissing disease); classically affects teenagers
What does EBV primarily infect?
- Oropharynx, resulting in pharyngitis 2. Liver, resulting in hepatitis with hepatomegaly and elevated liver enzymes 3. B cells
CD8+ T-cell response leads to what?
1) LAD 2) Splenomegaly 3) High WBC count with atypical lymphocytes (reactive CD8+ T cells) in the blood
How does the CD8+ T cell response lead to generalized lymphadenopathy (LAD)?
It is due to T-cell hyperplasia in the lymph node paracortex
How does CD8+ T cell response lead to splenomegaly?
It is due to T-cell hyperplasia in the periarterial lymphatic sheath (PALS)
What is used for screening of IM?
The monospot test
What does the monospot test do?
Detects IgM antibodies that cross-react with horse sheep red blood cells (heterophile antibodies)
When would the monospot test turn positive?
Usually turns positive within 1 week after infection
What would a negative monospot test suggest?
CMV as a possible cause of IM
How is a definitive diagnosis for IM made?
by serologic testing for the EBV viral capsid antigen.
What are the complications of EBV?
1) increased risk for splenic rupture 2) Rash 3) Recurrence and B cell lymphoma
What are patients told who have an increased risk for splenic rupture?
patients are generally advised to avoid contact sports for one year.
When might a rash develop as a complication of EBV?
if exposed to ampicillin
With EBV complications, why is there a risk of recurrence and B cell lymphoma?
Dormancy of virus in B cells leads to increased risk for both recurrence and B-cell lymphoma, especially if immunodeficiency (e.g., HIV) develops.
What is acute leukemia?
Neoplastic proliferation of blasts; defined as the accumulation of >20% blasts in the bone marrow.
What is the acute presentation for acute leukemia?
Anemia (fatigue), thrombocytopenia (bleeding), or neutropenia (infection)
What is the reason for the acute presentation of acute leukemia?
Increased blasts crowd-out normal hematopoiesis,
In acute leukemia, why is there a high WBC count?
Blasts usually enter the blood stream, resulting in a high WBC count
Describe blasts.
they are large, immature cells, often with punched out nucleoli
What is acute leukemia subdivided into?
acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML)
The subdivision of acute leukemia is based on what?
the phenotype of the blasts.
What is acute lymphoblastic leukemia?
Neoplastic accumulation of lymphoblasts (> 20%) in the bone marrow
Why is TdT useful in characterizing lymphoblasts?
It is absent in myeloid blasts and mature lymphocytes.
Acute lymphoblastic leukemia most commonly arises in whom?
children
What is acute lymphoblastic leukemia associated with and when does it usually arise?
Down syndrome (usually arises after the age of 5 years)
Acute lymphoblastic leukemia is subclassified into? What is it based on?
B-ALL and T-ALL based on surface markers
What is the most common type of ALL?
B-ALL
What is B-ALL usually characterized by?
lymphoblasts (TdT+) that express CD10, CD19, and CD20.
What is the treatment for B-ALL?
Excellent response to chemotherapy; requires prophylaxis to scrotum and CSf
What is the prognosis B-ALL based on?
It is based on cytogenetic abnormalities,
Which B-ALL has a good prognosis and is more commonly seen in children?
t(12;21)
Which B-ALL has a poor prognosis and in what population is it seen?
t(9;22) has a poor prognosis; more commonly seen in adults (Philadelphia+ALL)
What is T-ALL characterized by?
lymphoblasts (TdT+) that express markers ranging from CD2 to CDH (e.g., CD3, CD4, CD7). The blasts do not express CD10.
How does T-ALL usually present?
Usually presents in teenagers as a mediastinal (thymic) mass (called acute lymphoblastic lymphoma because the malignant cells form a mass)
What is acute myeloid leukemia?
Neoplastic accumulation of myeloblasts (> 20%) in the bone marrow
How are myeloblasts usually characterized?
by positive cytoplasmic staining for myeloperoxidase (MPO)
What may be seen in the characterization of myeloblasts?
Crystal aggregates of MPO may be seen as Auer rods
In whom does acute myeloid leukemia most commonly arise?
older adults (average age is 50-60 years)
What is the subclassification of AML based on?
cytogenetic abnormalities, lineage of myeloblasts, and surface markers.
What are the high-yield subtypes?
Acute promyelocytic leukemia, Acute monocytic leukemia and acute megakaryoblastic leukemia
What is acute promyelocytic leukemia characterized by?
t(15;17), which involves translocation of the retinoic acid receptor (RAR) on chromosome 17 to chromosome 15
What is the effect of RAR disruption?
It blocks maturation and promyelocytes (blasts) accumulate
How does acute promyelocytic leukemia lead to increased risk for DIC?
Abnormal promyelocytes contain numerous primary granules that increase the risk for DIC
What is the treatment for acute promyelocytic leukemia?
with all-trans retinoic acid (ATRA, a vitamin A derivative)
How does ATRA work?
It binds the altered receptor and causes the blasts to mature (and eventually die)
What is acute monocytic leukemia?
Proliferation of monoblasts; usually lack MPO
In acute monocytic leukemia what do blasts characteristically do?
infiltrate gums
What is acute megakaryoblastic leukemia?
Proliferation of megakaryoblasts; lack MPO
What is acute monocytic leukemia associated with?
Down syndrome (usually arises before the age of 5)
What is myelodysplastic syndrome?
acute myeloid leukemia may also arise from pre-existing dysplasia = myelodysplastic syndromes, especially with prior exposure to alkylating agents or radiotherapy
What do myelodysplastic syndromes usually present with?
cytopenias, hypercellular bone marrow, abnormal maturation of cells, and increased blasts < 20%
With myelodysplastic syndromes resulting in acute myeloid dysplastic syndrome what do most patients die from?
Most patients die from infection or bleeding, though some progress to acute leukemia.
What is chronic leukemia?
Neoplastic proliferation of mature circulating lymphocytes
What is chronic leukemia characterized by?
a high WBC count
Describe the onset of chronic leukemia?
Usually insidious in onset and seen in older adults
What is chronic lymphocytic leukemia?
Neoplastic proliferation of naive B cells that co-express CD5 and CD20;
What is the most common leukemia overall?
Chronic lymphocytic leukemia (CLL)
In CLL what is seen on the blood smear?
Increased lymphocytes and smudge cells are seen on blood smear
small lymphocytic lymphoma
In CLL, with involvement of lymph nodes leads to generalized lymphadenopathy
What are the complications of CLL?
1) Hypogammaglobulinemia, 2) autoimmune hemolytic anemia, 3) Richter transformation
What is the most common of death in CLL?
infection
What is Richter transformation?
transformation to diffuse large B-cell lymphoma
What is Richter transformation marked clinically by?
an enlarging lymph node or spleen
What is Hairy cell leukemia?
Neoplastic proliferation of mature B cells
What characterizes hairy cell leukemia?
hairy cytoplasmic processes