abnormal white cell count

Question 1

what is haemopoeisis *

Answer 1

production of mature blood cells in marrow

Question 2

what are the different types of haemopoeisis *

Answer 2

normal (polyclonal) - can be reactive or healthy

malignant (abnormal/clonal) - leaukaemia (lymphoid/myeloid), myelodysplasia, myeloproliferative

Question 3

why does malignant haemopoesis cause clonal cells *

Answer 3

cancer cells are derived from 1 mother cell

Question 4

what are the precursers for white cells

Answer 4

pre t = t cell

pre B = b cell

BFU-E = RBCs

MEG-CFC = mgakaryocytes/platelets

GM-CFC = monocytes and granulocytes

Question 5

why would earlier stages of neutrophils be found in the peripheral blood *

Answer 5

in sepsis- marrow compensate because of the stress = myeloid precurser and nucleated red cells present in peripheral blood - this is a leukerythroblastic picture

when pt recieves G-CSF to recover neutrophils after cancer - see myeloid precursers in blood film - this is an expected reaction

Question 6

what controls the production of red cells

Answer 6

erythropoeitin

Question 7

what controls the production of lymphoid cells

Answer 7

IL2

Question 8

what controls the production of myeloid cells

Answer 8

G-CSF

M-CSF - make monocytes

Question 9

how does cancer affect white cells *

Answer 9

DNA damage to the DNA controlling proliferation and differentiation

this is likely to lead to cancer - leukaemia, lymphoma, myeloma

Question 10

what cells are found in the marrow

Answer 10

matuyre lymphocytes and neutrophils

myeloblasts

promyeloblasts

myelocytes

metamyelocytes

Question 11

what cells are found in the peripheral blood

Answer 11

T and B lymphocytes

natural killer cells

granulocytes

monocytes

Question 12

why would you have an increased WBC

Answer 12

increased cell production: reactive to infection/inflammation (physiological), or malignant eg leukaemia, myeloproliferative (proliferate without control)

cell survival: failure of apoptosis eg acquireed cancer causing mutations in some lymphomas - mutation of onchosuppressive genes `

Question 13

how can you have a low wite cell count *

Answer 13

cell production reduced - imbared marrow function, folate or B12 deficiency (vegan), marrow failure - apoplastic anaemia, post chemo, met cancer or haem cancer

cell survival - immune break down by autoAb - connective tissue disorder - autoimmune

Question 14

describe 2 causes of eosinophilia *

Answer 14

normal haemopoesis (morphology normal) - stimulated by infection, inflammation (have increase in monocytes and neutrophils), increased cytokine production - distant tumour, haematopoetic or not

abnormal haemopoeisis - cancers of haemopoetic cells eg hodgekin’s lymphoma, leukaemia (myeloid or lympoid, chronic or acute), myeloproliferative disorders

Question 15

describe what is seen in chronic myeloid leukaemia *

Answer 15

mutation early in haematopoesis = increased proliferation of megakaryoytes/platelets, granulocytes, monocytes = high WBC count

see every stage of white cell on film

Question 16

how do you investigate a raised white cell count *

Answer 16

history and examination - symptomatic or not, might be a coincidence finding, travel history, look for lymphadenopathy and hepatosplenomegaly - suggest underlying lymphomyeloproliferative disorder

Hg and platelet count - isolated neutrophilia = reactive, but high neutrophil, anaemia and low platelets is a sign of leukaemia

look at automated differential - if machine cant recognise cells might be a precurser because of G-CSF injection or malignant cells

examine blood film

is abnormality in white cell only or in all lineages - red/platelets/white - raised all = myeloproliferative disorder

is it 1 type of WBC or all - cancer is clonal so abnormality will be of 1 type of cell, if raised all it would be reactive

mature cells only/mature and immature - chronic lymphocytic anaemian - is mature, CML - mature and immature, AML - immature

Question 17

what is seen in chronic lymphocytic leukaemia *

Answer 17

raised lymphocytes but otehr things rarely raised

Question 18

what is seen in chronic myeloid leukaemia *

Answer 18

increased all white cell types

eosinophils, basophils

increased number of myeloid precursers

Question 19

causes of neutrophilia *

Answer 19

normally 50% neutrophils are margniated - ie adhere to endothelial cell then migrate to tissue - balance of marginateed and circulating neutrophil changes in minutes when stressed - the pool of marginated switches to circulating

early release from marrow increases neutrophils - hours

increased production (eg from infection) - days

tissue inflammation - colitis, pancreatitis, autoimmune tissue necrosis, appendicitis, myocardial infarct

underlying neoplasia - isolated neoplasm eg carcinoma/lymphoma may produce reactive neutrophilia due to aberrent production of stimulatory cytokines

malignant neutropilia - myeloproliferative disorders and CML (myelocytes and rarely myeloblasts, usually basophilia)

corticosteroids

infection - systemic and localised - acute bacterial, fungal, certain viral, but brucella, typhoid and many virals dont produce neutrophilia

acute bacterial - chest/urinary tract, toxic granulation, increased numbers of cytoplasmic granules and vacuoles

Question 20

describe film in infection *

Answer 20

neutrophilia >7.5x10(power 9)/L

toxic granulation - distribution of granules is abnormal

vacuoles - white spots in cytoplasm

Question 21

describe film in leukaemia *

Answer 21

basophils

band cells - no segmentation of nucleus

myelocytes

Question 22

causes of eosinophilia *

Answer 22

reactive - drugs, parasitic (schistosomiasis, filariasis), allergic diseases (asthma, reumatoid arthritis, polyarthritis, pul eosinophilia, eczema), neoplasms (Hodgkin’s, T cell NHL), hypereosinophilic syndrome if >1.5 count = organ damage

malignant chronic eosinophilic leukaemia - mutation in a or B gene of PDGFR fusion gene

Question 23

describe hodgkin’s

Answer 23

eosinophilia because of production of IL 5

Question 24

describe the difference in the blood film for eosinophila - reactive and malignant *

Answer 24

reactive - no change in shape - they look normal

malignant clonal - look abnormal - toxic agranulation`

Question 25

describe monocytosis \*

Answer 25

in chronic infections and primary haematological disorders as part of inflammatory process TB, brucella, typhoid viral, CMV, varicella zoster sarcoidosis chronic myelomonocytic leukaemia

Question 26

cause of basophilia \*

Answer 26

POX virus

Question 27

describe lymphocytosis \*

Answer 27

if mature - reactive to infection (polyclonal) or primary disorder (chronic lymphocytic leukaemia - have monomorphic population of cells) , autoimmune or inflammatory disease. if immature - priamry disorder (leukaemia/lymphoma, eg acute lympoblastic leukaemia)

Question 28

describe blood film for immature or mature lymphocytosis \*

Answer 28

mature - they are small, increased nuleocytoplasmic ratio, no nucleolus, hard to see cytoplasm, chromatin dense immature - large, nucleolus

Question 29

hwo can you tell if mature lymphocytosis is primary or reactive \*

Answer 29

reactive - polyclonal response to infection/chronic inflammation/underlying malignancy primary - monoclonal lympoid prolif

Question 30

describe causes of reactive lymphocytosis \*

Answer 30

smoking infection - EBV, CMV, toxoplasma, infectious hep, rubella, herpes, adenovirus, varicellazoster, infectious hepatitis, pertussis, Tb, brucellosis autoimmune disorders neoplasma, sarcoidosis - reactive to thee underlying cancer

Question 31

describe mononucleosis syndrome \*

Answer 31

because of infection - sweat and fatigue large lymphocytes, plastic appearance RBC and platelets have no sig change

Question 32

describe glandular fever \*

Answer 32

EBV infection of B lymphocytes via CD21 receptor infected B cell proliferates and expresses EDV associated antigens lead to cytotoxic T cell response - prodduce cytokines responsible for symptoms acute infection resolved resulting in lifelong sub-clinical glandular fever for wks/months

Question 33

how can you distinguish between reactive or malignant lymphocytosis \*

Answer 33

consider age, clinical features and labatory investigation abnormal forms eg smear cells (lymphocytes damaged by film preparation) or blast cells - suggestive of lymphproliferative disorder eg leukaemia/lymphoma look at blood film - polyclonal in normal or monoclonal if malignant look at light chain restriction - expect similar amounts of kappa and lambda in polyclonal, in monoclonal there will be K/L only - meaning not equal proportion in entire blood smaple gene rearrangement - Ig and TCR genes undergo recombination in antigen stimulated B or T cells - in monoclonal prolif all daughter cells have identical Ig or TCR - detected by southern blot analysis

Question 34

what is suggested by an elevated total white cell count due to blasts \*

Answer 34

underlying leukaemia

Question 35

define neutrophilia \*

Answer 35

an absolute neutrophil count of \>7.5x10(power 9)/L

Question 36

describe the response to pyogenic bacterial infection \*

Answer 36

tissue damage = release of inflamm cytokines eg G-CSF and GM-CSF = stimulated granulocyte and monocyte production in the bone marrow and early release of immature cells = increase in circ granulocyte count and a L shifted appearance in the blood chemotaxis - phagocytes circ in periphery - at site of infection they will move out of circulation and into tissues (response to chemotactic factors) phag - phagocytes use Fc and C3b receptors to recognise and phagocytose opsinated material killing and digestion - ingested material killed in phagocytic vacuoles by oxidative and non-oxidative mechanisms

Question 37

what is lymphocytosis \*

Answer 37

lymphocyte count \>4x10(power 9)/l

Question 38

what do you check a blood film for after observing lymphocytosis \*

Answer 38

typical/reactive lymphocytesseenin mononucleosis syndromes immediate response to acute stress - heart attack/other severe pain small lymphocytes and smudge cells seen in chronic lymphocytic leukaemia primitive blasts seen in acute lymphoblastic leukaemia