CH6 - 1) Leukopenia and Leukocytosis

Question 1

What does hematopoetic CD34+ stem cells produce?

Answer 1

Myeloid stem cells and lymphoid stem cells

Question 2

What does myeloid stem cells produce?

Answer 2

Erythroblast, Myeloblast, Monoblast, Megakaryoblast

Question 3

What does erythroblast produce?

Answer 3

RBCs

Question 4

What does myeloblast produce?

Answer 4

Neutrophils, basophils, Eosinophils

Question 5

What does monoblast produce?

Answer 5

Monocytes

Question 6

What does megakaryoblast produce?

Answer 6

megakaryocytes

Question 7

What does lymphoid stem cells produce?

Answer 7

B lymphoblast and T Lymphoblast

Question 8

What does B lymphoblast produce?

Answer 8

Naïve Bcells

Question 9

What does Naïve B cells produce?

Answer 9

Plasma cells

Question 10

What does T lymphoblast produce?

Answer 10

Naïve Tcells

Question 11

What does Naïve T cells produce?

Answer 11

CD8+ and CD4+ T cells

Question 12

How does hematopoiesis occur?

Answer 12

via a stepwise maturation of CD34+ hematopoietic stem cells

Question 13

What happens to hematopoetic stem cells?

Answer 13

Cells mature and are released from the bone marrow into the blood.

Question 14

What is the normal white blood cell (WBC) count?

Answer 14

it is approximately 5-10 K/pL

Question 15

What is a low WBC count? What is it called?

Answer 15

(< 5 K) is called leukopenia.

Question 16

What is a high WBC count? What is it called?

Answer 16

(> 10 K) is called leukocytosis.

Question 17

What is a low or high WBC count usually due to?

Answer 17

a decrease or increase in one particular cell lineage.

Question 18

What is neutropenia?

Answer 18

refers to a decreased number of circulating neutrophils

Question 19

What are some of the causes of neutropenia?

Answer 19

1) Drug toxicity 2) severe infection

Question 20

How can drug toxicity lead to neutropenia?

Answer 20

e.g., chemotherapy with alkylating agents, cause damage to stem cells resulting in decreased production of WBCs, especially neutrophils.

Question 21

How does severe infection lead to neutropenia?

Answer 21

e.g., gram-negative sepsis leads to increased movement of neutrophils into tissues resulting in decreased circulating neutrophils.

Question 22

What is GM-CSF or G-CSF?

Answer 22

granulocyte monocyte stimulating factor or granulocyte stimulating factor, it can be used to boost the neutrophil count decreasing the risk of infection

Question 23

What is lymphopenia?

Answer 23

it refers to a decreased number of circulating lymphocytes

Question 24

What are the some of the causes of lymphopenia?

Answer 24

1) immunodeficiency 2) high cortisol state 3) autoimmune destruction 4) whole body radiation

Question 25

What are some examples of immunodeficiency that lead to lymphopenia?

Answer 25

e.g., DiGeorge syndrome or HIV

Question 26

How does a High Cortisol state lead to lymphopenia?

Answer 26

exogenous corticosteroids or Cushing syndrome, induces apoptosis of lymphocytes

Question 27

What is an example of autoimmune destruction leading to lymphopenia?

Answer 27

e.g., systemic lupus erythematosus

Question 28

How can whole body radiation lead to lymphopenia?

Answer 28

Lymphocytes are highly sensitive to radiation; lymphopenia is the earliest change to emerge after whole body radiation

Question 29

What are the different types of leukocytosis?

Answer 29

1) neutrophilic leukocytosis 2) monocytosis 3) Eosinophilia 4) Basophilia 5) Lymphocytic leukocytosis

Question 30

What does neutrophilic leukocytosis refer to?

Answer 30

increased circulating neutrophils

Question 31

What are the causes of neutrophilic leukocytosis?

Answer 31

1) Bacterial infection 2) tissue necrosis 3) High cortisol state

Question 32

How does Bacterial infection or tissue necrosis lead to neutrophilic leukocytosis?

Answer 32

It induces release of marginated pool and bone marrow neutrophils, including immature forms (left shift)

Question 33

When immature cells are released into the blood, how are they characterized?

Answer 33

by decreased Fc receptors

Question 34

What is the marker for the decreased Fc receptor?

Answer 34

CD16

Question 35

Why are Fc receptors important?

Answer 35

They help the neutrophil to recognize immunoglobulin which is going to act as an opsonin for phagocytosis

Question 36

How does high cortisol state lead to neutrophilic leukocytosis?

Answer 36

impairs leukocyte adhesion, leading to release of marginated pool of neutrophils

Question 37

What does monocytosis refer to?

Answer 37

increased circulating monocytes

Question 38

What are the causes of monocytosis?

Answer 38

inflammatory states (e.g., autoimmune and infections) and malignancy.

Question 39

What does eosinophilia refer to?

Answer 39

increased circulating eosinophils

Question 40

What are the causes of eosinophilia?

Answer 40

include allergic reactions (type I hypersensitivity), parasitic infections, and Hodgkin lymphoma,

Question 41

What is eosinophilia driven by?

Answer 41

increased eosinophil chemotactic factor

Question 42

What does basophilia refer to?

Answer 42

increased circulating basophils

Question 43

What is basophilia classically seen in?

Answer 43

chronic myeloid leukemia

Question 44

What does lymphocytic leukocytosis refer to?

Answer 44

increased circulating lymphocytes

Question 45

What are the causes of lymphocytic leukocytosis?

Answer 45

1) viral infection 2) Bordetella pertussis infection

Question 46

How does viral infections lead to lymphocytic leukocytosis?

Answer 46

T lymphocytes undergo hyperplasia in response to virally infected cells

Question 47

How does Bordetella pertussis infection lead to lymphocytic leukocytosis?

Answer 47

Bacteria produce lymphocytosis-promoting factor, which blocks circulating lymphocytes from leaving the blood to enter the lymph node.

Question 48

What is infectious mononucleosis?

Answer 48

EBV infection that results in a lymphocytic leukocytosis comprised of reactive CD8+ T cells; CMV is a less common cause

Question 49

How is EBV transmitted?

Answer 49

by saliva (kissing disease); classically affects teenagers

Question 50

What does EBV primarily infect?

Answer 50

1. Oropharynx, resulting in pharyngitis 2. Liver, resulting in hepatitis with hepatomegaly and elevated liver enzymes 3. B cells

Question 51

CD8+ T-cell response leads to what?

Answer 51

1) LAD 2) Splenomegaly 3) High WBC count with atypical lymphocytes (reactive CD8+ T cells) in the blood

Question 52

How does the CD8+ T cell response lead to generalized lymphadenopathy (LAD)?

Answer 52

It is due to T-cell hyperplasia in the lymph node paracortex

Question 53

How does CD8+ T cell response lead to splenomegaly?

Answer 53

It is due to T-cell hyperplasia in the periarterial lymphatic sheath (PALS)

Question 54

What is used for screening of IM?

Answer 54

The monospot test

Question 55

What does the monospot test do?

Answer 55

Detects IgM antibodies that cross-react with horse sheep red blood cells (heterophile antibodies)

Question 56

When would the monospot test turn positive?

Answer 56

Usually turns positive within 1 week after infection

Question 57

What would a negative monospot test suggest?

Answer 57

CMV as a possible cause of IM

Question 58

How is a definitive diagnosis for IM made?

Answer 58

by serologic testing for the EBV viral capsid antigen.

Question 59

What are the complications of EBV?

Answer 59

1) increased risk for splenic rupture 2) Rash 3) Recurrence and B cell lymphoma

Question 60

What are patients told who have an increased risk for splenic rupture?

Answer 60

patients are generally advised to avoid contact sports for one year.

Question 61

When might a rash develop as a complication of EBV?

Answer 61

if exposed to ampicillin

Question 62

With EBV complications, why is there a risk of recurrence and B cell lymphoma?

Answer 62

Dormancy of virus in B cells leads to increased risk for both recurrence and B-cell lymphoma, especially if immunodeficiency (e.g., HIV) develops.