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Y2 MCD Haematology > white blood cells > Flashcards

white blood cells Flashcards

leucocytosis: explain how to analyse the cause of a leucocytosis (differential count / blood film), list the common causes of a neutrophilia, eosinophilia and lymphocytosis, explain how a reactive polyclonal response may be differentiated from a lymphoproliferative disorder

1
Q

define pancytopenia

A

all lineages reduced

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2
Q

define haemopoiesis

A

production of blood cells in bone marrow

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3
Q

when does normal haemopoiesis occur

A

usually polyclonal healthy or reactive, in normal and reactive marrow

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4
Q

when does malignant haemopoiesis occur

A

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

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5
Q

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

A

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)

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6
Q

neutrophil differentiation and maturation in normal haemopoiesis

A

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

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7
Q

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

A

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)

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8
Q

effect of damaged DNA directing differentiation and proliferation

A

cancer (leukaemia, lymphoma or myeloma)

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9
Q

3 groups of leucocytes and location of production

A

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

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10
Q

4 types of lymphoblast

A

myeloblasts, promyeloblasts, myelocytes, meamyelocytes, some mature neutrophils

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11
Q

3 types of immunocytes

A

T lymphocytes, B lymphocytes, natural killer cells

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12
Q

2 classes of phagocytes

A

granulocytes and monocytes

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13
Q

3 types of granulocytes

A

neutrophils, eosinophils, basophils

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14
Q

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

A

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

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15
Q

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

A

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

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16
Q

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

A

aplastic anaemia, post chemotherapy, metastatic cancer, haematological cancer

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17
Q

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

A

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

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18
Q

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

A

immune breakdown

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19
Q

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

A

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

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20
Q

2 causes of increased cytokine production in normal reactive haemopoiesis

A

distant tumour, haemopoietic or non-haemopoietic

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21
Q

how is leukaemia characterised

A

myeloid or lymphoid, acute or chronic

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22
Q

malignant haematopoiesis in chronic myeloid leukaemia: effect on differentiation

A

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

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23
Q

4 ways to investigate a raised white cell count

A

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

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24
Q

3 questions to answer when investigating raised white cell count

A

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

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25
Q

elevated white cell count due to increased mature cells: lymphocytes

A

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

26
Q

elevated white cell count due to increased mature cells: granulocytes

A

all lineages or only one -> reactive/infection

27
Q

elevated white cell count due to increased mature and immature cells

A

neutrophils, melanocytes and basophils -> chronic myeloid leukaemia

28
Q

elevated white cell count due to increased immature cells

A

blasts, low Hb, low platelets -> acute leukaemia

29
Q

common causes of abnormal white cell counts

A

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

30
Q

where are neutrophils present

A

bone marrow, blood and tissues

31
Q

life span of neutrophils: blood vs tissues

A

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

32
Q

what 3 time frames can neutrophilia develop in and why

A

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

33
Q

neutrophilia due to infection vs chronic myeloid leukaemia

A

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

34
Q

4 reactive causes of neutrophilia

A

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

35
Q

2 causes of malignant neutrophilia

A

myeloproliferative disorders, chronic myeloid leukaemia

36
Q

what infections does neutrophilia occur in

A

localised and systemic; acute bacterial, fungal and certain viral

37
Q

what infections don’t produce neutrophilia

A

brucella, typhoid, many viral

38
Q

5 reactive causes of eosinophilia

A

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

39
Q

malignant cause of eosinophilia

A

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

40
Q

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

A

IL-5

41
Q

malignant chronic eosinophilic leukaemia: effect on differentiation

A

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

42
Q

when is monocytosis seen

A

in certain chronic infections and primary (malignant) haematological disorders

43
Q

3 chronic infection types causing monocytosis

A

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

44
Q

primary (malignant) haematological disorder causing monocytosis

A

chronic myelomonocytic leukaemia (MDS)

45
Q

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

A

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

46
Q

reactive elevated phagocyte count: inflammation - neutrophil, eosinophil

A

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

47
Q

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

A

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

48
Q

2 causes of lymphocytosis if only mature cells present

A

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

49
Q

cause of lymphocytosis if immature cells present

A

primary disorder (leukaemia/lymphoma)

50
Q

lymphocytosis: 2 primary disorders if mature cells

A

chronic lymphocytic leukaemia, autoimmune/inflammatory disease

51
Q

lymphocytosis: primary disorder if immature cells, and blood film

A

acute lymphoblastic leukaemia; very high nucleocytoplasmic ratio (blasts)

52
Q

5 causes of reactive lymphocytosis

A

smoking, infection, autoimmune disorders, neoplasia, sarcoidosis

53
Q

examples of infections causing reactive lymphocytosis

A

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

54
Q

reactive vs malignant lymphocytosis

A

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

55
Q

glandular fever: characteristics and infection cause

A

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

56
Q

glandular fever: effect of infected B-cell

A

prolferation and expression of EBV associated antigens

57
Q

glandular fever: response to EBV associated antigens

A

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

58
Q

differentials of lymphocytosis

A

reactive to underlying autoimmune disorder or chronic lymphocytic leukaemia

59
Q

3 techniques used to distinguish differentials of lymphocytosis

A

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

60
Q

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

A

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

61
Q

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

A

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

Y2 MCD Haematology (20 decks)

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