HAEM; Lecture 11 and Tutorial 12, 13 - Abnormal White Cell count Flashcards

1
Q

What is haemopoiesis?

A

Production of blood cells in Marrow

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2
Q

What is normal haemopoiesis?

A

Polyclonal healthy/reactive -> normal/reactive marrow

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3
Q

What is malignant haemopoiesis?

A

Abnormal/clonal -> leukaemia (lymphoid, myeloid), myelodysplasia, myeloproliferative

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4
Q

How does normal haematopoiesis work?

A

Self-renewing cells (haemopoietic cells)

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5
Q

How does a myeloblast differentiate into a neutrophil?

A

NB: In peripheral blood the precursors are not seen in normal conditions -> BUT in CML you will see all precursors in peripheral blood or in chemotherapy with GCSF; in septic blood you can also find some myeloid precursors

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6
Q

What factors control differentiation and proliferation?

A

Cytokines -> Erythroid part = erythropoietin, lymphoid = IL2, myeloid = G-CSF and M-CSF

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7
Q

What happens if DNA is damaged during differentiation and proliferation of white cells?

A

Cancer -> leukaemia, lymphoma, myeloma

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8
Q

What are the different lymphoblasts in the bone marrow?

A

Myeloblasts, promyelocytes, myelocytes, metamyelocytes

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9
Q

What are the immunocytes and phagocytes present in peripheral blood?

A

Immunocytes: T/B and NK cells. Phagocytes: Granulocytes - neutrophils, eosinophils, basophils; monocytes

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10
Q

What are the different reasons why abnormal WBC occur?

A

Increased or decreased number of WBC -> either increase/decrease cell production, decreased/increase cell survival

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11
Q

When do WBC pass from the bone marrow to the peripheral blood and how does that differ in Haemopoietic cancers?

A
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12
Q

What are the 2 types of eosinophilia infections causing increased cell numbers?

A

Reactive and Primary (malignant)

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13
Q

How does reactive eosinophilia affect haemopoiesis and what are the causes?

A

Keeps it normal, stimulating by inflammation, infection, increased cytokine production (distant tumour, haemopoietic or non haemopoietic)

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14
Q

How does primary eosinophilia affect haemopoiesis and what are the causes?

A

Causes abnormal haemopoiesis (autonomous cell growth) -> cancers of haemopoietic cells, leukaemia (myeloid/lymphoid, chronic/acute), myeloproliferative disorders

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15
Q

How does malignant haematopoiesis affect differentiation?

A

Haemopoietic stem cells have had DNA damage which means that when it differentiates can lead to an increased number of megakaryocytes, granulocytes and monocytes

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16
Q

How do you investigate a raised WCC?

A

History and examination (if recent infection, enlarged spleen), Hb and platelet count, Automated differential (machine can’t recognise immature cells), examine blood film (most important to make a diagnosis), abnormality in white cells only or all 3 (red/platelets/white), 1 white cell type only or all (common in reactive conditions to see more than one), mature cells only or mature and immature?

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17
Q

If mature white cells ONLY are elevated, what could the diagnosis be?

A

No underlying leukaemia as no immature cells

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18
Q

If immature white cells ONLY are elevated, what could the diagnosis be?

A

Blasts +, low Hb, low platelets = acute leukaemia(?) (leukocytosis or pancytopoeina associated)

19
Q

If mature and immature white cells are elevated, what could the diagnosis be?

A

Neutrophils+ (not a good sign as = neoplastic process), myelocytes+, basophils, = Chronic myeloid leukaemia (?)

20
Q

What is a normal range of a FBC?

A
21
Q

What are the common causes of abnormal neutrophil counts?

A

If develops in: minutes = demargination (move from tissues into PB), hours = early release from BM, days = increased production (3* in infection)

22
Q

What are neutrophils?

A

Present in BM, blood and tissues; life span of 2-3d in tissues, 50% circulating neutrophils are marginated (not counted in FBC)

23
Q

What occurs to peripheral blood in infection?

A

Neutrophilia and toxic granulation vacuoles in the neutrophils (abnormal distribution of vacuoles), cytoplasmic granulation

24
Q

What occurs to peripheral blood in leukaemia?

A

Chronic (myeloid) leukaemia, neutrophilia and precursor cells (myelocytes)

25
Q

What are the causes of neutrophilia?

A

Infection (most common), Tissue inflammation (colitis/pancreatitis), physical stress, adrenaline, corticosteroids, underlying neoplasia (could be a tumour/malignancy), malignant neutrophilia causes: myeloproliferative, disorders, CML

26
Q

Which infections cause neutrophilia?

A

Localised and systemic infections - acute bacterial, fungal, certain viral infections

27
Q

Which infections characteristically don’t produce neutrophilia?

A

Brucella, typhoid, many viral infections

28
Q

What are the causes of eosinophilia?

A

Reactive: Parasitic infection, allergic diseases (asthma, rheumatoid, polyarteritis, pulmonary eosinophilia), neoplasms (Hodgkin’s or T-cell NHL), hypereosinophilic syndrome. Malignant Chronic Eosinophilic Leukaemia (PDGFR fusion gene)

29
Q

What is monocytosis?

A

Rare but seen in certain chronic infections and primary haematological disorders -> TB, brucella, typhoid, Viral, CMv, varicella zoster, sarcoidosis, chronic myelomonocytic leukaemia

30
Q

What causes reactive elevated phagocyte count?

A
31
Q

How do you differentiate between mature or immature lymphocytosis?

A

Mature if reactive to infection or primary disorder; immature if primary disorder (leukaemia/lymphoma)

32
Q

What are the types of mature lymphocytosis?

A

CLL, autoimmune/inflammatory disease

33
Q

What are the types of immature lymphocytosis?

A

Acute lymphoblastic leukaemia

34
Q

How do you know if mature lymphocytosis is primary or reactive?

A

Secondary: polyclonal response to infection, chronic inflammation or underlying malignancy; Primary: monoclonal lymphoid proliferation

35
Q

What causes reactive lymphocytosis?

A

Infection: EBV, CMV, Toxoplasma, infectious hepatitis, rubella, herpes infections; AI disorders, neoplasia, sarcoidosis

36
Q

What is glandular fever?

A

EBV infection of B-cells via CD21 receptor; infected B-cell proliferates and expresses EBV associated antigens, cytotoxic T-cell response, acute infection resolved resulting in lifelong sub-clinical infection

37
Q

How do you differentiate lymphocytosis?

A

Mature lyphocytes (with smear cells), reactive to underlying AI disorder or chronic lymphocytic leukaemia -> morphology (blood film = if pliomorphic lymphocytes is reactive, if all the same then malignant), immunophenotype, gene re-arrangement

38
Q

How do you evaluate lymphocytosis?

A

Light chain restriction -> polyclonal (kappa and lambda); monoclonal (kappa only or lambda only); Ig genes and TCR genes undergo recombination in antigen stimulated B/T cells -> primary monoclonal proliferation = all daughter cells carry identical config of Ig/TCR gene which is detected with Southern Blot

39
Q

What is eosinophilia?

A

Increase numbers of eosinophils

40
Q
A

Parasitic infestation (schistosomiasis), underlying lymphoma (HL or T NHL), allergic AI disorder (asthma/urticaria)

41
Q
A

Mature lymphocytes -> yes it could be leukaemia (CLL); next investigation - immunophenotype test which indicates all cells are monoclonal and all antigens are B-cell markers with one T cell marker. Reactive (viral infection, TB), primary monoclonal (CLL)

42
Q
A

Acute leukaemia

43
Q
A

Secondary to Chronic myeloid leukaemia