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Year 2 - MCD Haem > Abnormal White Blood Cell Count > Flashcards

Abnormal White Blood Cell Count Flashcards

1
Q

How to describe raised/reduced cell counts?

A

Reduced - cytopenia/penia

Raised - cytosis/philia

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2
Q

What is it called when ALL cell lineages are reduced?

A

Pancytopenia

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3
Q

What is haemopoiesis and how can it occur?

A

Production of blood cells in the bone marrow

o Normal haemopoiesis (polyclonal healthy/reactive)

  • normal marrow
  • reactive marrow

o Malignant haemopoiesis (abnormal/cloncal)

  • leukaemia (lymphoid, myeloid)
  • myelodysplasia
  • myeloproliferative
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4
Q

What cell starts haematopoiesis?

A

HSC - haemopoeitic stem cells

Can differentiate into many cell lines

BFU-E (blast forming unit erythrocyte) goes on to form RBCs

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5
Q

Explain differentiation and maturation in haematopoiesis in the myeloid lineage

ONENOTE!!

A

Myeloid lineage go on to form granulocytes!!

Normally the FIRST 4 STEPS occur within the bone marrow
AND
The neutrophil is formed in the peripheral blood

BUT in pathology this can change

e. g. after chemotherapy see myeoblasts iin blood
e. g. in sepsis see meyoblasts in the blood and nucleated RBCs

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6
Q

How do you control cell numbers? What are the specifics for each type?

A

Regulation is via. CYTOKINES
o RBCs = EPO
o Lymphoid cells = IL-2
o Myeloid cells = G-CSF, M-CSF

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7
Q

What can affect the regulating signals in controlling cell number?

A

DNA damage in cancer can affect the regulating signals leading to cancer proliferation

o Leukaemia - malignant process in 1o lymphoid process
o Lymphoma/leukaemia - lymphatic cell tumours in blood/tissues
o Myeloma - disease of bone marrow

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8
Q

What can increase WBC count?

A

Leukocytosis

o Increased cell production

  • REACTIVE e.g. infection/inflammation
  • MALIGNANT e.g. leukaemia/myeloproliferative

o Increased cell survival
- failure of apoptosis (e.g. acquired cancer causing mutations in some lymphomas)

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9
Q

What can decrease WBC count?

A

Leukopaenia

o Decreased cell production

  • Impaired BM function
  • B12 or folate deficiency
  • BM failure (aplastic anaemia, post chemotherapy, metastatic ca, haematological ca)

o Decreased cell survival
- Immune breakdown

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10
Q

Difference between normal infections and haematopoietic cancers

A

In normal infections

  • increased WBC is reactive
  • mature cells are released

In haematopoietic cancers
- immature AND mature cells are released

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11
Q

Example of an increase in cell number?

A

Eosinophilia - 2 causes!

  1. Reactive (infection/inflammation)

i.e. Normal haemopoiesis - stimulated by
o inflammation/infection/increased cytokine production

  1. Primary (malignant)
i.e. Abnormal haemopoiesis
 o autonomous cell growth
 o cancers of haemopoietic cells
 o Leukaemia (myeloid OR lymphoid/ chronic OR acute)
 o myeloproliferative disorders
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12
Q

Exampel of malignant haematopoiesis?

A

Chronic myeloid leukaemia

o Mutation occurs at GM-CFC (onenote!)
o Instead of cellular death, have an overun proliferation

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13
Q

How would you investigate a raised WBCC?

A

History, examination, Hb & platelet count, automated differential, examine blood film

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14
Q

What indications should make you think further when investigating a rasied WBCC?

A

If see IMMATURE cells in blood film

  • think about LEUKAEMIA
  • in a normal reactive response you would not see this in peripheral blood

If see IMMATURE & MATURE cells
- think about CHRONIC LEUKAEMIA if in the presence on neutrophils & myelocytes

o Acute leukaemia will present w. LOW Hb & LOW platelets

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15
Q

Normal FBC NR?

A

Hb = 120-160g/L

Platelet = 150-400 x 10^9/l

WCC = 4-11 x 10^9/l

Neutrophils = 2.5-7.5 x 10^9/l

Lymphocytes = 1.5-3.5 x 10^9/l

Monocytes = 0.2-0.8 x 10^9/l

Eosinophils = 0.04-0.44 x 10^9/l

Basophils = 0.01-0.1 x 10^9/l

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16
Q

Common causes of abnormal WCC in terms of the FBC?

A
  1. Phagocytes
    - neutrophils
    - eosinophils
    - monocytes
  2. Immune cells
    - lymphocytes
17
Q

Neutrophils properties?

A

Present in BM, blood and tissues

Life span 2-3days in tissues (hours in PB)

50% circulating neutrophils are marginated (NOT counted in FBC)

PB = peripheral blood

18
Q

Neutrophilia?

A

INCREASE

Can develop in:
o minutes - demargination
o hours - early release from BM
o days - increased production (x3 in infection)

19
Q

Blood film of PB in infection?

A

o Neutrophilia
o Toxic granulation
o Vacuoles

20
Q

Blood film of PB in leukaemia?

A

Shows neutrophilia & myelocytes

NOTE - the absence of granules in leukaemia (NO toxic granulation)

21
Q

When does neutrophilia normally present?

A

Causes include:
o INFECTION
o Tissue inflammation
o physical stress, adrenaline, corticosteroids
o underlying neoplasia
o malignant neutrophilia (myeloproliferative disorders, CML)

22
Q

Main cause of neutrophilia?

A

INFECTION

o localised and systemic infections
e.g. acute bacterial, fungal, certain viral infections

SOME infections do NOT produce a neutrophilia e.g. tyhpoid, many viral infections, Brucella

23
Q

Causes of REACTIVE Eosinophilia?

A

o Parastitic infection
o Allergic disease

o Neoplasms e.g. Hodgkin’s, T-cell NHL

  • Hodgkins will show on x-ray with increased mediastinal mass and an increase in IL-5 secretion
  • can also get a mutation in GM-CFC

o Hypereosinophilic syndrome

24
Q

Causes of MALIGNANT Eosinophilia?

A

Malignant Chronic Eosinohpilic Leukaemia (PDGFR fusion gene)

RARE!

25
Q

Monocytosis?

A

INCREASE!

Rare BUT seen in certain
o chronic infections
AND
o primary haematological disorders

26
Q

Causes of monocytosis?

A

o TB, brucella, typhoid
o Viral - CMV, VZV
o Sarcoidosis
o CML (M=muelomonocytic)

27
Q

Summary of reactive elevated phagocyte count?

A

ONENOTE!!

28
Q

Lymphocytosis?

A

INCREASE

Is it:
o Mature cells?
- either reactive to infection OR 1o disorder

o Immature cells?
- 1o disorder ONLY (not reactive)

29
Q

Mature vs. Immature cells in Lymphocytosis?

A

o Mature lymphocytes

  • cells are LIKE each other i.e. oligoclonal expansion
  • could be CLL OR autoimmune/inflammatory disease

o Immature lymphoblasts

  • Much larger
  • Can see a nuclelous = shows immaturity
  • due to ACUTE LYMPHOBLASTIC LEUKAEMIA
30
Q

Causes of primary vs. secondary (reactive) lymphocytosis?

A

Is it 1o or reactive (2o)?

Secondary/Reactive

  • POLYCLONAL response to infection
  • chronic inflammation OR underlying malignancy

Primary

  • MONOCLONAL lymhpoid proliferation
  • e.g. CLL - all cells look the same as mutated cell making clones of itself
31
Q

Causes of reactive lymphocytosis?

A

o Infection e.g. EBV, CMV, toxoplasma, infectious hepatitis, rubella, herpes

o Smoking
o Autoimmune
o Neoplasia
o Sarcoidosis

32
Q

Explain Mononucleosis Syndrome on a blood film

A

Shows a reactive-looking lymphocyte
- looks like an immature lymphocyte seen in ALL

BUT

These lymphocytes tend to have RBCs clump them

  • they are jagged
  • and are NOT self-clumped
33
Q

Glandular Fever?

A

High WCC with reactive-looking lymphocytes

Causes by an EBV infection

  • of B-lymphocytes via. CD21 receptor
  • infected B-cell proliferated and expresses EBV-associated antigens
  • causes a CYTOTOXIC T-CELL response

Common in the young!

34
Q

Lymphocytosis in the elderly and how to identify?

A

Most often going to be caused by
o CLL
OR
o an autoimmune disorder

Will see MATURE lymphocytes (& smear cells)

35
Q

How can you distinguish between the different causes of lymphocytosis in the elderly?

A

o Morphology

o Immunophenotype (what antigens are expressed on the surface)

o Gene rearrangement

36
Q

How can you evaluate lymphocytosis?

A

Light chain restriction

OR

Gene rearrangement

37
Q

Evaluating lymphocytosis with light chain restriction?

A

POLYCLONCAL expansion

o invovles MORE than one mother cell
o SO the light chain expresses BOTH 
  - kappa
  - lambda
o this is indicative of a response to INFECTION

MONOCLONAL expansion

o ALL Abs from ONE mother cell
o SO light chain EITHER
  - kappa
OR
  - lambda
o indicative of a cancer
38
Q

Evaluating lymphocytosis with gene rearrangement?

A

Ig genes and T-cell R genes undero recombination in antigen stimulated B or T-cells

With 1o monoclonal proliferation
o ALL daughter cells carry IDENTICAL TCR gene arrangement
o this is NOT normal for infection
o SO idicative of cancer

Detect via. Southern Blot Analysis

39
Q

Cases?

A

4 CASES in ONENOTE!!

DO THEM!!

Year 2 - MCD Haem (11 decks)

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