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MCD Haematology > Abnormal WBC count > Flashcards

Abnormal WBC count Flashcards

1
Q

what term defines the reduction of all three blood cell lineages?

A

pancytopenia

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2
Q

in which two situations that normal haemopoiesis occur?

A

normally and in reaction

to malignancy for example in leukaemia, myelodysplasia and myeloproliferative conditions

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3
Q

where should the neutrophil usually be found?

where should precursors be found?

A

in the peripheral blood

precursors should be found within the bone marrow, as maturation occurs here

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4
Q

what changes occur in the differentiation and maturation of neutrophils in pathological conditions?

A

cells become smaller
cytoplasm become clearer
multi-lobed nucleus

precursors found in the periphery

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5
Q

which cytokine controls the differentiation of RBCs?

A

EPO

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6
Q

which cytokine controls the differentiation of lymphoid cells?

A

IL-2

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7
Q

which cytokine controls the differentiation of myeloid cells?

A

Colony Stimulating Factors
G-CSF
GM-CSF

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8
Q

what affects the regulatory role of these cytokines?

what is the consequence of this?

A

DNA damage in cancer affects their regulating signals

this leads to cancer proliferation

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9
Q

where is malignant process occurring in leukaemia?

A

bone marrow

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10
Q

what is found in the blood in lymphoma/leukaemia?

A

lymphatic cell tumours

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11
Q

what is myeloma the disease of?

A

disease of the bone marrow

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12
Q

what are the two main umbrella reasons for increased WBCC?

A

1) increased cell production
- reactive e.g. infection
- malignant e..g leukaemia

2) increased cell survival
- failure of apoptosis

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13
Q

what are the two main umbrella reasons for decreased WBCC?

A

1) decreased cell production
- Bone marrow function impaired
- b12 or folate deficiency

2) decreased cell survival
- immune breakdown of cells

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14
Q

what is the difference in cell release in normal infection and heamo. cancers?

A

in normal infection: mature cells are released in reaction

in cancer: immature AND mature cells are released

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15
Q

two types of causes of eosinophilia

A

1) reactive- infection/inflammation
2) primary- malignancy

like with lymphocytosis

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16
Q

where does the mutation occur to cause CML?

A

GM-CSF

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17
Q

how would you go about investigating a raised WBCC?

A
  • history and examination
  • Hb and platelet count
  • automated differential
  • blood film
  • pancytopenia? (all cell linages)
  • one WC type or more?
  • immature or mature cells?
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18
Q

what is eosinophilia characteristic of?

A

myeloproliferative disorders
parasitic infection (metazoan)
allergy
neoplasm e.g. Hodgkins (lymphatics)

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19
Q

what is the presence of immature cells indicative of?

A

malignancy like leukaemia
if mature cells are also present–> chronic leukaemia

acute leukaemia will present with low Hb and platelets

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20
Q

what cell types are present in the chronic leukaemia?

A

neutrophils and myelocytes

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21
Q

what cells add to the abnormal WBCC?

A

phagocytes- neutrophils, eosinophils, monocytes

immune cells- lymphocytes

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22
Q

which sites are neutrophils present in?

A

Bone marrow
blood
tissues

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23
Q

life span of neutrophils in varying locations

A

tissues: 2-3 days

peripheral blood: hours

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24
Q

why is the FBC for neutrophils not strictly accurate?

A

50% of neutrophils are marginated i.e. stuck onto the wall of a damaged vessel

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25
Q

time scale of development of neutrophils

A

minutes- demargination

hours- early release from BM i.e. sepsis

days- increased production i.e. x3 in infection

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26
Q

what can be seen in infection in the peripheral blood?

A

neutrophilia
toxic granulation
vacuoles

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27
Q

what can be seen in leukaemia in the peripheral blood?

A

neutrophilia
lymphocytosis (primary)
myelocytes (precursor)
absence of granules (no toxic granulation)

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28
Q

what are the main causes of neutrophilia?

A
  • infection
  • tissue inflammation
  • physical stress
  • adrenaline
  • corticosteroid
  • neoplasia
  • malignancy e.g. CML
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29
Q

what is the normal cause for neutrophilia?

A

infection (local and systemic) : bacterial, fungal and certain viral infections

some infections do not produce neutrophilia e.g. Brucella, typhoid and many viral infections

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30
Q

what are the reactive causes of eosinophilia?

A
  • parasitic infection
  • allergic disease
  • neoplasm e.g. HL
  • hypereosinophillic syndrome
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31
Q

Hodgkins Lymphoma presentation on X ray

A

increased mediastinal mass

with increased IL-5 secretion

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32
Q

what are the causes of monocytosis (rare)?

A
  • TB, Brucella, typhoid
  • viral
  • sarcoidosis
  • CML
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33
Q

when are immature cells seen?

A

only in primary disorders (malignant)
disease of the bone marrow e.g. leukaemia

i.e. not in reaction

34
Q

when are mature cells seen?

A

reactive to infection

35
Q

what do immature lymphoblasts looks like?

A

larger than usual

nucleolus can be seen indicating immaturity

36
Q

what are the reactive (secondary) causes of lymphocytosis?

A
  • polyclonal response to infection: EBV, toxoplasma, hep, rubella, herpes
  • chronic inflammation
  • underlying malignancy, neoplasia
  • autoimmune
  • sarcoidosis
37
Q

primary cause of lymphocytosis

A

malignant cause e.g. CLL

–>MONOclonal lymphoid proliferation

38
Q

what causes mononeuclosis?

A

infection by the EBV of B lymphocytes via the CD21 receptor

common in the young

39
Q

what happens in the mononucleosis?

A

glandular fever caused

infective B cells proliferates and expressed EBV associated antigens causing cytotoxic T-cell response

40
Q

what is the most likely cause of lymphocytosis in the elderly?

A

CLL or an autoimmune disorder

41
Q

what is the difference between polyclonal and monoclonal expansion?

(light chain restriction)

A

polyclonal involves more than one mother cells so light chains express kappa and lambda

monoclonal has all antibodies come from one mother cell therefore express either kappa or lambda

42
Q

what are polyclonal and monoclonal expansion indicative of?

A

polyclonal: infection (reactive)
monoclonal: cancer (primary)

43
Q

gene recombination in lymphocytosis

A

Ig genes and TCR genes undergo recombination in antigen stimulated B or T cells.
With primary monoclonal proliferation, ALL daughter cells carry the IDENTICAL TCR gene arrangement which isn’t normal for infection – indicative of cancer.
Detected by southern blot analysis.

i.e. if recombination has taken place, it means reactive lymphocytosis

44
Q

upon investigation of raised WBCC, what is a lack of automated differential indicative of?

A

either they have had an G-CSF injection or there is an underlying malignant condition

45
Q

what is the difference in immunophenotype between between primary (immature) lymphocytosis and secondary/reactive (mature) lymphocytosis?

A

primary–> monoclonal B cell expansion therefore express kappa OR lambda

secondary/reactive –> polyclonal B cell expansion therefore express either kappa AND lambda

46
Q

what can lymphocytosis be split into?

A
  • release of mature cells (primary or reactive)

- release of immature cells (primary–> lymphoproliferative disorder (ALL)

47
Q

what are the 3 stimuli for leucocytosis (of various leucocytes)?

A
  • infection (bacterial, viral, parasitic)
  • inflammation (autoimmune, allergic)
  • neoplastic
48
Q

what are the leucocytes involved in the different types of infection?

  • bacterial
  • viral
  • parasitic
  • chronic infections
A

bacterial–> neutrophils
viral–> basophils
parasitic–> eosinophils
chronic infections–> monocytosis

49
Q

what are the leucocytes involved in the different types of inflammation?

  • autoimmune
  • allergic
A

autoimmune–> neutrophils

allergic–> eosinophils

50
Q

what is normal in terms of neutrophils behaviour during pregnancy?

A

toxic/heavy granulation

51
Q

what is left shift neutrophilia?

A

increased in non-segmented neutrophils known as band cells (immature neutrophils/neutrophils precursors)

52
Q

how many lobes do hypersegmented neutrophils have?

A

5+

53
Q

what kinds of neoplasm do eosinophils reacts to?

A

Hodgkins and Non-Hodgkins Lymphoma

54
Q

what kinds of neoplasms do neutrophils react to ?

A

most neoplasms

55
Q

what are neoplasms?

A

cells that don’t respond to normal growth mechanisms

56
Q

what are the triggers for toxic granulation?

A
  • tissue necrosis
  • pregnancy
  • infection
57
Q

what are the causes of the release of hypersegmented neutrophils?

A

low folate or B12

in megaloblastic anaemia

58
Q

what may cause atypical lymphocyte production?

A

glandular fever (EBV infection)

59
Q

how can you differentiate between primary and secondary mature lymphocytosis?

A
  • Clinical context e.g. age
  • Morphology
  • Immunophenotype (just kappa or just lambda or both)
  • Gene rearrangement (evidence of Ig gene recombination indicative of secondary/reactive)
60
Q

what infection causes glandular fever?

A

EBV (infectious mononucleosis)

61
Q

what are the features of glandular fever?

A
  • RBCS: mildy hypochromic and microcytic

- WBCs: atypical (look like monocytes)

62
Q

what are the features of acute myeloid leukaemia?

A
  • RBCs are normal
  • WBCs: lots of blast cells, may stick together, unable to differentiate between myeloid or lymphoid until granules appear
63
Q

investigating leucocytosis

A
  • is it one cell type that is elevated? or multiple cell types?
  • is it mature cell? or immature cells?
  • morphological changes? reactive changes? e.g. toxic granulation of neutrophils

this is useful for further investigations:
e.g. I see high number of eosinophils only –> underlying parasitic infection

e.g. I see high number of immature blast cells–> underlying leukaemia

64
Q

what is the significance of seeing immature white cells like myeloblasts and lymphoblasts in the peripheral blood?

A

immature cells shouldn’t be seen in the periphery, they are usually confined to the bone marrow
increase in immature cells in the periphery is seen in bone marrow disease like leukaemia

65
Q

what are the common explanations for neutrophilia in clinical practice?

A
  • bacterial infection
  • inflammation and tissue necrosis
  • underlying neoplastic disease
  • myeloproliferative disorder
  • demmargination
66
Q

bacterial infection as a cause of neutrophilia

A
  • most common of neutrophilia
  • toxic granulation
  • cytoplasmic granules and vacuoles increased
67
Q

inflammation and tissue necrosis as a cause of neutrophilia

A

appendicitis
MI
autoimmune tissue damage

68
Q

underlying neoplastic disease as a cause of neutrophilia

A

carcinoma or lymphoma may cause reactive neutrophilia due to aberrant production of stimulatory cytokines

69
Q

myeloproliferative disorders as a cause of neutrophilia

A

e.g. CML where less mature (not completely immature) cells are seen

70
Q

demargination as a cause of neutrophilia

A

physical stress increases the circulating neutrophil number by moving them from the endothelial surface of small vessels into the flowing blood

corticosteroids raise neutrophil count

71
Q

what are the common causes of eosinophilia?

A
  • parasitic infection e.g. schistosomiasis
  • atopic allergic condition e.g. eczema
  • pulmonary eosionphilia
  • Hodgkin’s disease (lymphatic system cancer causing reactive eosinophilia)
72
Q

what causes monocytosis?

A

CHRONIC BACTERIAL infections which don’t produce a neutrophil response

e.g. TB, brucellosis, typhoid, chronic myelomonocytic leukaemia

73
Q

how does pyogenic bacterial infection increase white cell count?

A
  • cause the production of G-CSF and GM-CSF (inflammatory cytokines- colony stimulating factors)
  • they lead to increased granulocytes and monocytes production by the BM
  • in acute response, there is a release of less mature cells
  • this gives a left shifted appearance in peripheral blood
74
Q

chemotaxis

A

the phagocytes will circulate in the peripheral blood, at the site of infection they will move out of the circulation and into the tissues moving to the site of inflammation in response to chemotactic factors.

75
Q

phagocytosis

A

The neutrophils and monocytes will encounter foreign material that has been opsonised by immunoglobulin or complement.
Using their Fc and C3b receptors they are able to recognise and phagocytose the foreign material.

76
Q

what are the 2 types of lymphocytosis?

A

reaction to cancer:
- primary (malignant monoclonal proliferation) e.g. lymphoma

reaction to infection:

  • secondary reactive (polyclonal reactive proliferation)
    e. g. infection and autoimmune disease
77
Q

infections that cause reactive lymphocytosis

A

Epstein-Barr virus (EBV), cytomegalovirus (CMV), toxoplasmosis, rubella, adenovirus infection, varicellazoster, infectious hepatitis, pertussis, tuberculosis, brucellosis.

78
Q

glandular fever due to atypical lymphocytes

A

infectious mononucleosis

reactive lymphocytosis

79
Q

how would you distinguish between someone with primary or secondary (reactive) lymphocytosis when both release mature cells?

NB primary lymphocytosis can release mature cells OR immature cells, Reactive releases only mature cells

A
  • age
  • clinical features
  • lab investigations (maturity)
80
Q

how would you know someone has primary lymphocytosis?

A 
immature cells (blasts) 
abnormal cells (smears)

suggests lymphoproliferative disorder like leukaemia or lymphoma

81
Q

how can the proliferation of the two types of lymphocytosis be distinguished?

A

primary–> monoclonal

secondary–> polyclonal (oh shit!)

82
Q

how can the two types of lymphocytosis be distinguished by the receptors on the B lymphocytes produced?

A

primary–> either kappa or lambda light chains (mono)

secondary–> both kappa and lambda light chains (poly) mixed population

MCD Haematology (11 decks)

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