Chapter 13 Robbins

Question 1

What can stimulate HSCs in marrow to move from stem cell niches?

Answer 1

G-CSF

Response to stress

Question 2

Marrow response to short term needs

Answer 2

Controlled by growth factors that act on committed progenitors

Question 3

Growth factors acting on EARLY committed progenitors

Answer 3

KIT ligand and FLT3-ligand

Question 4

Growth factors acting on restricted progenitors

Answer 4

Erythropoietin, GM-CSF, G-CSF, and thrombopoietin

Question 5

Distortion of marrow architecture can lead to

Answer 5

Abnormal release of immature precursors (leukoerythroblastosis)

Question 6

Fat cells increase in bone marrow in

Answer 6

Hypoplastic states

And decrease in neoplastic or hyperplastic states

Question 7

Leukopenia usually results from

Answer 7

Decreased number of neutrophils

Usually associated with decreased function of granulocytes

Question 8

Lymphopenia most commonly from

Answer 8

HIV, glucocorticoid therapy, autoimmune disorders, malnutrition and viral infections

Usually a redistribution (to LN and tissue) rather than a decrease in number

Question 9

Cause of neutropenia

Answer 9

Inadequate/ineffective granulopoiesis

Increased destruction/sequestions

Question 10

Suppression of HSCs causing neutropenia

Answer 10

Aplastic anemia, tumors, granulomatous disease

Accompanied by anemia and thrombocytopenia

Question 11

Suppression of granulocyte committed precursors causing neutropenia

Answer 11

Drug toxicity

Question 12

Ineffective hematopoiesis causing neutropenia

Answer 12

Megaloblastic anemias, myelodysplastic syndromes (precursors die in the marrow)

Question 13

Congenital syndromes causing neutropenia

Answer 13

Kostmann syndrome

Impairs differentiation of granulocytes

Question 14

Immune mediated destruction of neutrophils

Answer 14

Can be idiopathic, associated with a disease like SLE, or drug toxicity related

Question 15

Effect of splenomegaly on neutrophils

Answer 15

Increased sequestration

Sometimes associated with anemia and thrombocytopenia

Question 16

Increased peripheral utilization of neutrophils occurs with

Answer 16

Bacterial, fungal and rickettsial infections

Question 17

Most common cause of agranulocytosis

Answer 17

Drug toxicity
Red cells and platelets also effected

Aminopyrine, chloramphenicol, sulfonamides, chlorpromazine, thiouracil, and phenylbutazone

Question 18

Chlorpromazine effect on neutrophils

Answer 18

Direct toxicity

Question 19

Sulfonamide effect on neutrophils

Answer 19

Antibody mediated destruction

Question 20

LGL leukemia effect on neutrophils

Answer 20

Monoclonal proliferation of lymphocytes suppresses production of neutrophils

Question 21

Morphological consequences of neutropenia

Answer 21

Compensatory marrow hyperplasia
Increased infections (candida and aspergillus)

Question 22

Clinical features of neutropenia

Answer 22

Related to infection - serious infections when under count of 500
Fever, malaise, and chills

Question 23

Peripheral leukocyte count

Answer 23

Size of precursor and storage pools
Rate of release into circulation
Size of marginal pool (adhering to BV)
Rate moving into tissues

Question 24

Most important cause of neutrophilic leukocytosis

Answer 24

Infection

Mediated by IL-1 and TNF

Question 25

Increased production of neutrophils in marrow

Answer 25

Chronic infection or inflammation Paraneoplastic Myeloproliferative

Question 26

Increased release of neutrophils

Answer 26

Infection Endotoxemia Hypoxia

Question 27

Decreased margination of neutrophils

Answer 27

Exercise | Catecholamines

Question 28

Decreased extravasation

Answer 28

Glucocorticoids

Question 29

IL-5 specifically stimulates

Answer 29

Eosinophils

Question 30

G-CSF specifically stimulates

Answer 30

Neutrophils

Question 31

In sepsis or severe inflammation leukocytosis in accompanied by

Answer 31

Morphological changes in neutrophils Toxic granulations Dohle bodies Cytoplasmic vacuoles

Question 32

Toxic granules

Answer 32

Appear coarser and darker | Abnormal primary granules

Question 33

Dohle bodies

Answer 33

Patches of dilated endoplasmic reticulum that appear as sky-blue cytoplas- mic “puddles"

Question 34

Reactive vs Neoplastic leukocytosis

Answer 34

Usually able to distinguish except in cases of acute viral infection in kids or severe infections leading to immature cells in the blood like in a myeloid leukemia (leukemoid reaction)

Question 35

Neutrophilic leukocytosis caused by

Answer 35

Acute bacterial | Sterile inflammation

Question 36

Eosinophilic leukocytosis caused by

Answer 36

Allergic disorders Malignancy AI disorders

Question 37

Basophilic leukocytosis is

Answer 37

Very RARE | Myeloproliferative disease

Question 38

Monocytosis caused by

Answer 38

Chronic infections AI disorders Inflammatory bowel disease

Question 39

Lymphocytosis associated with

Answer 39

Monocytosis | Viral infections

Question 40

Germinal centers

Answer 40

Pale staining, seen when primary follicles enlarge | B cells acquire capacity to make high affinity antibodies

Question 41

T cells in LN

Answer 41

Reside in paracortical zones | Undergo hyperplasia during immune response

Question 42

Acute nonspecific lymphadenitis

Answer 42

LN are swollen with large, reactive germinal centers Pyogenic organisms -> neutrophils -> necrosis/pus Seen more in cervical and mesentary

Question 43

Follicular hyperplasia

Answer 43

Chronic nonspecific lymphadenitis - Result of humoral response **Tingible body macrophages RA, toxo, HIV (looks similar to follicular lymphoma but architecture is intact and everything more organized)

Question 44

Paracortical hyperplasia

Answer 44

Chronic - T cell response (viral infection) | T cell zones are bigger and contain immunoblasts (larger)

Question 45

Sinus histiocytosis

Answer 45

Seen in LN draining cancer (breast cancer)

Question 46

Chronic LN inflammation

Answer 46

Common in axillary and inguinal | LN are nontender and large/hard

Question 47

Tertiary lymphoid organs

Answer 47

Seen with chronic immune reactions Immune cell collections in non-lymphoid tissue Classic ex. include RA (B cells in joints) and chronic gastritis from helicobacter pylori

Question 48

Hemophagocytic lymphohistiocytosis (HLH)

Answer 48

Systemic activation of macrophages and CD8+ cytotoxic T cells -> cytopenia and shock (mediators initiate systemic inflammation) Something to do with toxic granules of NK and cytotoxic T cells

Question 49

Most common trigger of HLH

Answer 49

EBV (infection)

Question 50

Clinical features of HLH

Answer 50

Acute febrile illness, hepatosplenomegaly Anemia, thrombocytopenia, high levels of plasma ferritin and soluble IL-2 receptor Treat with immunosuppressive therapy -> poor prognosis especially if not treated

Question 51

When are proto-oncogenes often activated in lymphoid cells?

Answer 51

Antigen receptor gene rearrangement and diversification - Increased AID expression -> induce MYC/Ig translocations - Increased expression of BCL6 - Precursor B and T cells express VDJ recombinase -> cuts DNA

Question 52

Pro growth mutations

Answer 52

Tyrosine kinase | MYC

Question 53

Self renewal mutations

Answer 53

MLL translocation, PML-RARA fusion gene

Question 54

Pro survival mutations

Answer 54

BCL2 translocation

Question 55

Diseases that cause genetic instability

Answer 55

Bloom syndrome, Fanconi anemia, and ataxia telangiectasia (acute leukemia) Downs and Type I NF (childhood leukemia)

Question 56

Lymphotrophic viruses

Answer 56

Human T-cell leukemia virus-1 (HTLV-1), EBV, and Kaposi sarcoma herpesvirus/human herpesvirus-8

Question 57

Chronic inflammation and lymphoid neoplasia

Answer 57

H. pylori -> gastic B cell lymphoma Celiac and breast implants -> T cell lymphomas (local) HIV -> germinal center B cell lymphomas (systemic)

Question 58

Radiation therapy and cancer

Answer 58

Increased risk of myeloid and lymphoid neoplasms

Question 59

Smoking and white cell cancer

Answer 59

Increased risk of acute myeloid leukemia