White Blood Cell Disorders Flashcards Preview

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Flashcards in White Blood Cell Disorders Deck (64):
1

Normal, Low, High WBC count

Normal = 5-10k
low < 5k = leuopenia
high > 10k = leukocytosis

2

Neutropenia

Decreased circulating neutrophils. Caused by
1)Drug toxicity = chemo damages stem cells and especially neutrophils. Give GM-CSF or G-CSF to boost granulocyte/neutrophils and prevent infection
2) Sever infection (gram negative sepsis) = neutrophils exit circulation and go into tissues to fight infection

3

Lymphopenia

Decreased circulating lyphocytes Causes:
1) Immunodeficiency = HIV or DiGeorge Syndrome = no thymus to make lymphocytes
2) High Cortisol state = exogenous corticosteroids or cushing syndrome. They causes apoptosis of lymphocytes
3) Autoimmune destruction = SLE
4) Whole body irradiation = lymphocytes are especially sensitive to radiation

4

Neutrophilic Leukocytosis

Increased circulating Neutrophils. Causes:
1) Bacterial infection or tissue necrosis = release of marginated pool (hanging out in tissues or latched on vessels) and bone marrow. Get immature forms (left shift). These immature cells lack Fc receptors so less likely to recognize Ig which acts as opsonin for phagocytosis , These immature neutrophils are often called "CD 16 nuetrophils"
2) High cortisol state = impairs leukocyte adhesion, so marginated pools enter circulation

5

Monocytosis

Increased circulating monocytes. Seen in chornic inflammatory states (autimmune or infections) and malignancy

6

Eosinophilia

Increased circulating eosinophils. Seen allergic reactions (Type I hypersensitivity), parasitic infections, and HODGKINS LYMPHOMA (release IL5 which is a eosinophil chemotaxic factor)

7

Basophilia

Increased basophils in circulation. Seen in CML

8

Lympocytic Leukocytosis

Increased circulating lymphocytes. Caused by
1) viral infections = t lymphocytes undergo hyperplasia in response to virally infected cells
2) Bordella pertussis = bacteria is strange in that it produces lymphocytosis-promoting factor, which blocks circulating lymphocytes from leaving the blood to enter the lymph node

9

Infectious Mononucleosis

EBV infection that results in lymphocytic leukocytosis comprised of CD8+ T cells.
Transmitted by saliva
Infects 1)oropharynx = pharyngitis 2) liver = hepatitis with hepatomegally and elevated liver enzymes 3)B cells
CD8+ T cell response leads to 1)generalized lymphadenopathy due to T cell hyperplasia in lymph node PARACORTEX 2) splenomegaly due to T cell hyperplasia in periarterial lymphatic sheath (PALS) 3)HIGH WBC with atypical lymphocytes (reactive CD8+ T cells)

10

Monospot Test

Detects IgM antibodies that cross react with horse or sheep RBCs. Positive after 1 week of infection. Definitive diagnosis is serologic testing for EBV viral capsid antigen. Negative monospot test indicates test done too early or CMV

11

Complciations of Infectious Mononucleosis

Increased risk for splenic rupture (avoid sports for 1 year)
Rash if exposed to ampicilin
Dormnacy of virus in B Cells leads to icnreased risk for recurrence and B Cell Lymphoma especially in immunodeficiency (HIV)

12

Acute Leukemia

Neoplastic proliferation of blasts (>20% blasts in bone marrow). Blasts "crowd out" normal hematopoiesis resulting in "acute" anemia (fatigue), thrombocytopenia (bleeding), and neutropenia (infection). Subdivided into ALL (TdT+) or AML (MPO+/auer rods)

13

Acute Lymphoblastic Leukemia (ALL)

Neoplastic accumulation of lymphoblasts in the bone marrow.
TdT+ (a DNA polymerase). Is absent in Mature lymphoblasts and myeloid blasts
Most commonly seen in children, see in Down Syndrome patients AFTER age of 5

14

B-ALL

Most common type of ALL
TdT+, and express CD10,19,and 20
Excellent response to to chemo but need to prophylactically treat scrotum and CNS since drugs cant cross their barriers
t(12;21) = children. great prognosis
t(9;22) = philadephia + ALL (remember philadelphia is normally seen in CML) and occurs in adults and carries poor prognosis

15

T-ALL

TdT+, express CD2-8. NOT CD10.
presents in Teenagers as Thymic mass (mediastinal mass)
Called acute lymphoblastic lymphOMA since malignant cells form a mass and do not go through blood like leukemia)

16

Acute Myeloid Leukemia

Neoplastic proliferation of immature myeloid cells (>20%) in bone marrow. Myeloperoixidase (MPO)+ (can form crystal aggreagates seen in blood smear as Auer Rods.
Usually see in older afults

17

Acute Promyelocytic Leukemia (APL)

characterized by t(15;17) that involves translocation of retinoic acid receptor (RAR) on Cr 17 to 15, RAR disruption blocks matureation and promyelocytes (blasts) accumulate)
These abnormal promyelocytes contain primary granules (auer rods) that increase risk for DIC
Treat with All-Trans Retinoic Acis (ATRA_ that binds altered ARA receptor and force blastst to mature (and therefore eventually die)

18

Acute Monocytic Leukemia

Proliferation of monoblasts (usually lack MPO).
INFILTRATES GUMS

19

Acute Megakaryoblastic Leukemia

Proliferation of megakaryoblasts (lack MPO)
Associated with Down Syndrome BEFORE age of 5

20

Risk factors for AML

Pre-existing dysplasias/myelodysplastic syndromes
Exposure to alkylating agents or radiotherapy
Down syndrome ( Acute Megakaryoblastic Leukemia)

21

Myelodysplastic Syndromes

Usually present with cytopenias, hypercellular bone marrow, and abnormal maturation cells but blasts are less than 20%.
Die from bleeding or infection but can progress to Acute leukemia

22

Leukemias in Down Syndrome

AML (especially acute megakaryoblasts) BEFORE age 5.
ALL AFTER age of 5.

23

CD10,19,20
CD2-8

B-ALL
T-ALL

24

Chronic Leukemia

Neoplastic proliferation of meture cicurlating lymphocytes.
High WBC count
insidious onset seen in older adults

25

Chronic Lymphocytic Leukemia (CLL)

Neoplastic proliferation of naive B cells that coexpress CD5 and CD 20.
Increased lymphocytes and smudge cells are seen on blood smear.
Involvement of lymph nodes leads to generalized lymphadenopathy and is called small lyphocytic lymphoma
Complications include
1) hypogammaglobulinemia - infection is most common cause of death
2) Autoimmune hemolytic anemia
3) Transformation to diffuse B cell lymphoma (Richter transfomration) marked by enlarging lymph node or spleen.

26

small lyphocytic lymphoma

CLL that involves lymph nodes and leads to generalized lymphadenopathy

27

Richter transfomration

When CLL's naive B cells transforms to diffuse B cell lymphoma marked by nlarging lymph node or spleen.

28

Hairy Cell Leukemia

Neoplastic proliferation of mature B cells characterized by hairy processes.
Cells are + for tartrate-resistant acid phosphatase (TRAP)
Clinically see splenomegaly (accumulation of hairy cells in red pulp) and "dry tap" on bone marrow aspiration (due to marrow fibrosis). LYMPHADENOPATHY USUALLY ABSENT
Excellent response to 2-CDA (cladribine) = adenosine deaminise inhibitor so adensoine accumulates to toxic levels in the B cells

29

Adult T cell Leukemia/Lymphoma (ATLL)

Neoplastic proliferation of CD4+ T cells. Associated with HTLV-1 seen in Japan and Carribean
Rash, generalized lymphadenopathy with hepatosplenomegaly, a lytic bone lesions with hypercalcemia.

30

Mycosis Fungoides

Neoplastic proliferation of CD4+ T cells that infiltrate the skin and produce a localized skin rash, plaques, and nodules. Aggregates of neoplastic cells in epidermis are called Pautrier Microabscesses.
Can spread to involve the blood, producing Sezary syndrome (see lymphocytes with cerebriform nuclei - sezary cells)

31

Pautrier Microabscesses

Aggregates of neoplastic CD4+ T cells in epidermis

32

Sezary syndrome

When mycosis fungoides spreads to involve the blood.

33

Myeloproliferative Disroder

Neoplastic proliferation of mature cells or myeloid lineage
Affects older adults
High WBC count and hypercellular bone marrow
Classify based on DOMINANT cell type
Complications include hyperuricemia and gout due to high turnover (degrading all them damn nuclei yo)
progression to bone marrow fibrosis or transformation to acute leukemia

34

Chronic Myeloid Leukemia (CML)

Neoplastic proliferation of mature myeloid Cells especially granulocytes and their precursors BASOPHILS.
t(9:22) Philadelphia chromosome - BCR-ABL fusion protein with increased tyrosine kinase activity. (treat with imatinib that blocks tyrosine kinase)
Splenomegally is common but enlarging spleen suggests progression to accelerated phase of disease or transforming into acute leukemia (2/3s become AML and 1/3 become ALL)
Negative for leukocyte alkaline phosphatase, increased BASOPHILS, t(9;22)

35

Difference between CML and Leukomoid rxn

CML =(-)leukocyte alkaline phosphatase, increased BASOPHILS, t(9;22)
Leukomoid rxn = (+)leukocyte alkaline phosphatase, no notable increase in basophils, NO t(9;22)

36

Polycythemia Vera

Neoplastic proliferation of mature myeloid cells, especially RBCs (granulocytes and platelets are also increased)
JAK2 kinase mutation
Hyperviscosity of blood causes; blurry vision and headache, increased risk for venous thrombosis (of hepativ vein = budd-chiari syndrome), flushed face due to congestion, and ITCHY AFTER TAKING SHOWER
Treat with phlebotomy or hydroxyurea or die in a year

37

Polycythemia Vera vs Reactive Polycythemia

in PV = EPO levels are decreased and Sao2 is normal
Reactive due to high altitude or diseased lung = Sao2 is low and EPO is increased
Reactive due to ectopic EPO production from renal cell carcinoma EPO is high and Sao2 in normal

38

Essential Thrombocythemia

Neoplastic proliferation of mature myeloid cells, especially platelets (RBCs and granulocytes are also increased)
JAK2 kinase mutation
Increased risk for bleeding or thrombus as platelets are either over or under functioning
Rarely progresses to marrow fibrosis or acute leukemia and no increase risk for hyperuricemia or gout (platelets never had nucleus)

39

Myelofibrosis

Neoplastic proliferation of mature myeloid cells, especially megakaryocytes.
JAK2 kinase mutation in %50 of cases
Megakaryocytes produce excess PDGF causing marrow fibrosis
Get splenomegally due to extramedullary hematopoiesis, leukoerythroblastic smear (tear drop RBCs, nucleated RBCs, and immature granulocytes)
Increased risk for infection, thrombosis, and bleeding

40

Lymphadenopathy

LAD refers to enlarged lymph nodes
Painful LAD = draining a region of acute infection
Painless LAD = chronic inflammation, metastatic carcinoma, and lymphoma
Get hyperplasia of particular regions of lymph node
(1) follicular = B-cell region. Seen wtih Rheum Arthritis and HIV infection
(2) Paracortex = T-Cell region = viral infection (mono)
(3) Sinus Histiocytes = lymph nodes draining a tissue with cancer

41

Lymphoma

Neoplastic proliferation of lymphoid cells that forms a mass
Hodgkins and Non Hodgkins.
NHL further classified based on cell type, cell size, pattern of growth, expression of surface markers, cytogenic translocations

42

Small B- Cell Lymphomas

NHL subtypes.
Follicular, mantle cell, marginal zone, small lymphocytic

43

Intermediate sized B-Cell lymphomas

NHL subtype Burkitt Lymphoma

44

Large B-Cell Lymphomas

NHL subtype diffuse large B cell lymphomas

45

Follicular Lymphoma

Neoplastic proliferation of B cells (CD20+) that orm follicle like nodules
Late adulthood and painless LAD
t(14;18) = BCL2 on 18 moves to Ig on 18 and overexpressed so inhibits apoptosis (in follicular region cells are usually going hypersomatic mutation and most fail this process and die but in this disease these cells all live)
Treat with rituximab or low dose chemo
Disrupts normal architecture, lacks tingle bodies (cells dont die so no need for macrophages), BCL2 expression, MONOCLONALITY

46

Mantle Cell Lymphoma

Neoplastic proliferation of small B Cells (CD20+) that expands the mantle zone.
Adults and painless LAD
t(11;14) Cyclin D1 on 11 moves to Ig on 14 and overexpressed promoting G1/S transition in cell cycle facilitating neoplastic proliferation

47

Marginal Zone Lymphoma

Neoplastic proliferation of intermediate B Cells (CD20+) that expands the marginal zone.
Associated with chronic inflammatory states (hashimoto thyroiditis, sjorgen syndrome, and H pylori gastritis)

48

MALToma

Special marginal zone lymphoma in mucosal sites usually caused by H pylori

49

Burkitt Lymphoma

intermediate sized B-Cells (CD20+) associated with EBV.
Presents as extranodal mass in child or young adult.
Translocation of c-myc (Cr8) which promotes cell growth.
get "starry sky" appearance
Africa = Jaw vs Sporadic = abdomen

50

African vs Sporadic Burkitt Lymphoma

Both overexpression c-myc but African = jaw and sporadic = abdomen

51

Diffuse Large B-cell Lymphoma

Neoplastic proliferation of B-Cells (CD20+) that grows diffusely in sheets.
MOST COMMON form of NHL
clinically aggressive.
Arises sporadically or from transformation of a low-grade lymphoma.
Presents in late adulthood as an enlarging lymoh node or an extranodal mass

52

Hodgkins Lymphoma

Neoplastic proliferation of Reed-Sternberg (RS) cells, which are large B Cells with multilobed nuclei and prominent nucleoli "owl eyed nuclei"
RS cells secrete cytokines results in "B" symptoms (fever, chills, weight loss, and night sweats), attracts reactive lymphocytes, plasma cells, macrophages, and eosinophils, may lead to fibrosis
Reactive inflammatory cells make up BULK OF TUMOR. and form basis of classification of HL
Subtypes include nodular necrosis, lyphocyte rich, mixed cellularity, and lymphocyte depleted.

53

Reed Sternberg Cells

arge B Cells with multilobed nuclei and prominent nucleoli "owl eyed nuclei" seen in Hodgkins Lymphoma
secrete cytokines results in "B" symptoms (fever, chills, weight loss, and night sweats), attracts reactive lymphocytes, plasma cells, macrophages, and eosinophils, may lead to fibrosis

54

Nodular Sclerosis HL

MOST COMMON HL. Classically presents as enlarging cervical or mediastinal lymph node in a young adult, female.
Lymph node is divided bands of sclerosis; RS cells are present in lake-like spaces "lacuna cells"

55

Lymphocyte Rich HL

Best prognosis of all HL

56

Mixed Cellularity HL

Often associated with abundant eosinophils (RS cells produce IL-5)

57

Lymphocyte Depleted HL

Most aggressive of all HL. Usually see in elderly or HIV

58

Plasma Cell Disroder/Dyscrasias

Malignant priliferation of plasma cells in the bone marrow
most common PRIMARY bone cancer
High serum IL-6, stimulates plasma cell growth and Ig production
Clinical features:
(1) neoplastic plasma cells activate RANK of osteoclasts leading to bone destruction. Get lytic "punched out" skeletal lesions, hypercalcemia, and increased risk for fractures
(2) Elevated serum protein - neoplastic plasma cells produce Ig, see M spike on SPEP. (usually IgA or IgG)
(2a) Increased risk of infection = monocolonal antibody lacks antigenic diversity
(2b) rouleaux formation - serum proteins decrease chagre between RBCs
(2c) Primary AL Amyloidosis = free light chains circulate in serum and deposit in tissues
(2d) Proteinuria - excess free light chain is exrected in urine as "Bence Jones protein". Can also deposit in kindey and lead to risk of renal failure = myeloma kidney

59

Monoclonal Hammopathy of Undetermined Significance

Increased serum protein with M spike on SPEP but other features of multiple myeloma are absent
Common in elderly (5% of 70 and aboce) and 1% prgoress to multiple myeloma

60

Waldenstrom Macroglobulinemia

B-Cell Lymphoma with monoclonal IgM production.
IgM is a big pentamer and makes the blood more viscous (get visual and neurological deficits = retinal hemorrage or stroke) and bleeding due to dfective platelet aggregation.
Gernalized lymphadneopathy but no lytic bone lesions
M spike is due to IgM

61

Langerhans Cell Hystiocytosis

Specialized dendritic cells found predominantly in the skin. Dervied from bone marrow monocytes and normally present antigen to naive T cells
Neoplastic proliferation of langerhans cells...see characterisitc Birbeck (tennis racket) granules.
Cells are CD1a+ and S100+

62

Letterer-Siwe Disease

Malignant proliferation of langerhan cells.
Classic presentation is skin rash, cystic skeletal defects in infant <2.
multiple organs involved = rapidly fatal

63

Eosinophilic Granuloma

Benign Proliferation of Langerhan's Cells in bone
Classic presentation is pathologic fracture in an adolescent NO SKIN INVOLVEMENT
Biopsy shows Langerhan cells with mixed inflammatory cells, esepcailly Eosinophils

64

Hand-Shuller-Christan Disease

Malignant proliferation of Langerhans cells
Classic presentation is scalp rash, lytic skull defects, diabetes insipidus, and exopthalmus in child