white blood cells

Question 1

define pancytopenia

Answer 1

all lineages reduced

Question 2

define haemopoiesis

Answer 2

production of blood cells in bone marrow

Question 3

when does normal haemopoiesis occur

Answer 3

usually polyclonal healthy or reactive, in normal and reactive marrow

Question 4

when does malignant haemopoiesis occur

Answer 4

abnormal clonal cells (divided from same mother cell), includes leukaemia (lymphoid, myeloid), myelodysplasia, myeloproliferative

Question 5

6 groups of cells produced from haemopoetic stem cell in normal haemopoiesis in bone marrow, including precursors

Answer 5

T-cell (from pre T), B-cell (from pre B), red cells (from BFU-E), megakaryocytes/platelets (from meg-CFC), granulocytes and monocytes (from GM-CFC)

Question 6

neutrophil differentiation and maturation in normal haemopoiesis

Answer 6

in bone marrow: myeloblast -> promyelocyte -> myelocyte -> metamyelocyte; in peripheral blood: -> neutrophil

Question 7

what hormones or cytokines are used to influence differentiation and proliferation in erythroid, lymphoid and myeloid cells

Answer 7

erythroid: erythropoietin; lymphoid: IL2; myeloid: G-CSF, M-CSF (if excess e.g. exogenous drugs, sepsis, stress or bone marrow cancer, cause immature precursors to be released into peripheral blood; if white cells, acute lymphoblastic leukaemia)

Question 8

effect of damaged DNA directing differentiation and proliferation

Answer 8

cancer (leukaemia, lymphoma or myeloma)

Question 9

3 groups of leucocytes and location of production

Answer 9

lymphoblasts (bone marrow), immunocytes (peripheral blood), phagocytes (peripheral blood)

Question 10

4 types of lymphoblast

Answer 10

myeloblasts, promyeloblasts, myelocytes, meamyelocytes, some mature neutrophils

Question 11

3 types of immunocytes

Answer 11

T lymphocytes, B lymphocytes, natural killer cells

Question 12

2 classes of phagocytes

Answer 12

granulocytes and monocytes

Question 13

3 types of granulocytes

Answer 13

neutrophils, eosinophils, basophils

Question 14

abnormal white blood cell: reactive and malignant causes of increased cell production (leucocytosis)

Answer 14

reactive: infection, inflammation, increased cytokine production; malignant: cancers of haemopoietic cells, leukaemia, myeloproliferative

Question 15

abnormal white blood cell: causes of decreased cell production (leucopenia)

Answer 15

impaired bone marrow function, B12/folate deficiency, bone marrow failure

Question 16

abnormal white blood cell: 4 causes of bone marrow failure, causing decreased cell production (leucopenia)

Answer 16

aplastic anaemia, post chemotherapy, metastatic cancer, haematological cancer

Question 17

abnormal white blood cell: cause of increased cell survival (leucocytosis)

Answer 17

failure of apoptosis (e.g. acquired cancer causing mutations in some lymphomas)

Question 18

abnormal white blood cell: cause of decreased cell survival (leucopenia)

Answer 18

immune breakdown

Question 19

white blood cell production, proliferation and differentiation in haemopoietic cancers (leukaemia)

Answer 19

produced in bone marrow but enter peripheral blood as immature (and mature) cells

Question 20

2 causes of increased cytokine production in normal reactive haemopoiesis

Answer 20

distant tumour, haemopoietic or non-haemopoietic

Question 21

how is leukaemia characterised

Answer 21

myeloid or lymphoid, acute or chronic

Question 22

malignant haematopoiesis in chronic myeloid leukaemia: effect on differentiation

Answer 22

haemopoietic stem cell mutation favours GM-CFC, causing huge increases in megakaryocyte/platelets, granulocytes and monocytes as no apoptosis

Question 23

4 ways to investigate a raised white cell count

Answer 23

history and examination (distinguish if symptomatic, increased risk if smoker, hepatosplenomegaly), Hb and platelet count (if white cell count raised in isolation then normally reactive not malignant), automated differential (e.g. exogenous GCSF treatment), examine blood film

Question 24

3 questions to answer when investigating raised white cell count

Answer 24

abnormality white cells only, ot all 3 lineages (red, white, platelet); white cell 1 type only, or all lineages (e.g. granulocytes, monocytes, lymphocytes; if all types then reactive, except in chronic myeloid leukaemia); mature cells only or immature also

Question 25

elevated white cell count due to increased mature cells: lymphocytes

Answer 25

reactive e.g viral or primary e.g. chronic lymphocytic leukaemia

Question 26

elevated white cell count due to increased mature cells: granulocytes

Answer 26

all lineages or only one -> reactive/infection

Question 27

elevated white cell count due to increased mature and immature cells

Answer 27

neutrophils, melanocytes and basophils -> chronic myeloid leukaemia

Question 28

elevated white cell count due to increased immature cells

Answer 28

blasts, low Hb, low platelets -> acute leukaemia

Question 29

common causes of abnormal white cell counts

Answer 29

phagocytes (neutrophils, eosinophils, monocytes), immune cells (lymphocytes)

Question 30

where are neutrophils present

Answer 30

bone marrow, blood and tissues

Question 31

life span of neutrophils: blood vs tissues

Answer 31

hours in blood, 2-3 days in tissues (50% marginated so not counted in full blood count)

Question 32

what 3 time frames can neutrophilia develop in and why

Answer 32

minutes by demargination, hours by early release from bone marrow, days by increased production (e.g. x3 in infection)

Question 33

neutrophilia due to infection vs chronic myeloid leukaemia

Answer 33

infection: appear abnormal, with white spots (vacuoles) in cytoplasm, toxic granulation; leukaemia: different stages of myeloid maturation with precursor cells e.g. band cells

Question 34

4 reactive causes of neutrophilia

Answer 34

infection, tissue inflammation (e.g. colitis, pancreatitis), phsyical stress (adrenaline, corticosteroids), underyling neoplasia

Question 35

2 causes of malignant neutrophilia

Answer 35

myeloproliferative disorders, chronic myeloid leukaemia

Question 36

what infections does neutrophilia occur in

Answer 36

localised and systemic; acute bacterial, fungal and certain viral

Question 37

what infections don't produce neutrophilia

Answer 37

brucella, typhoid, many viral

Question 38

5 reactive causes of eosinophilia

Answer 38

exogenous drugs e.g. GCSF, parasitic infestation, allergic diseases (e.g. asthma, rheumatoid, polyarteritis, pulmonary eosinophilia), neoplasms (especially Hodgkin’s lymphoma, T-cell NHL), hypereosinophilic syndrome

Question 39

malignant cause of eosinophilia

Answer 39

clonal malignant chronic eosinophilic leukaemia (mutation in PDGFR fusion gene)

Question 40

what is released in Hodgkin’s and T-cell NHL to cause reactive eosinophilia

Answer 40

IL-5

Question 41

malignant chronic eosinophilic leukaemia: effect on differentiation

Answer 41

haemopoietic stem cell favours GM-CFC, causing huge increase of malignant clonal cells

Question 42

when is monocytosis seen

Answer 42

in certain chronic infections and primary (malignant) haematological disorders

Question 43

3 chronic infection types causing monocytosis

Answer 43

TB, brucella, typhoid; viral: CMV, varicella zoster; sarcoidosis

Question 44

primary (malignant) haematological disorder causing monocytosis

Answer 44

chronic myelomonocytic leukaemia (MDS)

Question 45

reactive elevated phagocyte count: infection - neutrophil, eosinophil, basophil, monocytes

Answer 45

neutrophil: bacterial; eosinophil: parasitic; basophil: pox viruses; monocytes: chronic (TB, brucella)

Question 46

reactive elevated phagocyte count: inflammation - neutrophil, eosinophil

Answer 46

neutrophil: auto-immune, tissue necrosis; eosinophil: allergic (asthma, atopy, drug reactions)

Question 47

reactive elevated phagocyte count: neoplasia (not part of malignant population) - neutrophil, eosinophil

Answer 47

neutrophil: all types; eosinophil: Hodgkin's, NHL

Question 48

2 causes of lymphocytosis if only mature cells present

Answer 48

polyclonal reactive response to infection (polymorphic), chronic inflammation or underlying malignancy; primary disorder with monoclonal lymphoid proliferation (monomorphic)

Question 49

cause of lymphocytosis if immature cells present

Answer 49

primary disorder (leukaemia/lymphoma)

Question 50

lymphocytosis: 2 primary disorders if mature cells

Answer 50

chronic lymphocytic leukaemia, autoimmune/inflammatory disease

Question 51

lymphocytosis: primary disorder if immature cells, and blood film

Answer 51

acute lymphoblastic leukaemia; very high nucleocytoplasmic ratio (blasts)

Question 52

5 causes of reactive lymphocytosis

Answer 52

smoking, infection, autoimmune disorders, neoplasia, sarcoidosis

Question 53

examples of infections causing reactive lymphocytosis

Answer 53

mainly viral; EBV, CMV, toxoplasma; infectious hepatitis, rubella, herpes

Question 54

reactive vs malignant lymphocytosis

Answer 54

reactive: all cell lineages increased; malignant: other cell lineages not usually affected, and lymphocytes look the same morphologically (monoclonal)

Question 55

glandular fever: characteristics and infection cause

Answer 55

infectious mononucleosis with atypical lymphocytes (very large); EBV infection of B lymphocytes via CD21 receptor

Question 56

glandular fever: effect of infected B-cell

Answer 56

prolferation and expression of EBV associated antigens

Question 57

glandular fever: response to EBV associated antigens

Answer 57

cytotoxic T-lymphocyte response, causing resolution and lifelong sub-clinical infection

Question 58

differentials of lymphocytosis

Answer 58

reactive to underlying autoimmune disorder or chronic lymphocytic leukaemia

Question 59

3 techniques used to distinguish differentials of lymphocytosis

Answer 59

morphology (clonal vs polyclonal; lineages affected), immunophenotype, gene re-arrangement

Question 60

evaluating lymphocytosis (B cells) using light chain restriction: polyclonal (reactive) vs monoclonal (malignant)

Answer 60

polyclonal: kappa and lambda; monoclonal: kappa only or lambda only as from same mother cell

Question 61

evaluating lymphocytosis using gene re-arrangement: identifying primary monoclonal (malignant) proliferation

Answer 61

Ig and TCR genes undergo recombination in antigen stimulated B cells or T cells; with primary monoclonal proliferation all daughter cells carry identical configuration of Ig or TCR gene, which can be detected by Southern Blot analysis