CH6 - 1) Leukopenia and Leukocytosis 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.
