White blood cells

Question 1

What is pancytopenia?

Answer 1

When all blood cell lineages are reduced.

Question 2

What is leucocytosis?

Answer 2

Too many white cells.

Question 3

What is leucopoenia?

Answer 3

Too few white cells.

Question 4

What is neutrophilia?

Answer 4

Too many neutrophils.

Question 5

What is neutropenia?

Answer 5

Too few neutrophils.

Question 6

What is lymphocytosis?

Answer 6

Too many lymphocytes.

Question 7

What is eosinophilia?

Answer 7

Too many eosinophils.

Question 8

What is thrombocytosis?

Answer 8

Too many platelets.

Question 9

What is thrombocytopenia?

Answer 9

Not enough platelets.

Question 10

What is lymphopenia?

Answer 10

Not enough lymphocytes.

Question 11

What is anaemia?

Answer 11

Reduced Hb/RBCs.

Question 12

What is polycythaemia?

Answer 12

Another term or erythrocytosis – meaning having a high concentration of RBCs in the blood.

Question 13

Summary of blood cell level suffixes?

Answer 13

-penia means reduced; -cytosis and -philia mean increased.

Question 14

What is hemopoiesis?

Answer 14

Production of blood cells in the bone marrow.

Question 15

What is the difference between normal (x2 cases) and malignant hemopoiesis?

Answer 15

• NORMAL: polyclonal production in a normal or a REACTIVE bone marrow. Reactive bone marrow describes a change in hemopoiesis when the bone marrow is inflamed/infected. Hemopoiesis is still normal because the cells produced are normal, but levels of production may change. Peripheral blood contains only mature cells. • MALIGNANT: abnormal production of cells that is clonal (not polyclonal) – so you will see certain types of cells being produced in abnormally HIGH QUANTITIES (usually quite DIFFERENTIATED too), indicating there is a cancer in that cell lineage that also SUPPRESSES OTHER BLOOD CELLS from being produced e.g. leukaemia, myelodysplasia and myeloproliferative. In addition, peripheral blood will contain a mixture of mature and immature blood cells.

Question 16

What are all blood cells derived from in the bone marrow?

Answer 16

In the bone marrow, there is a small population of multipotent stem cells which self-renew called HAEMOPOIETIC STEM CELLS. These differentiate into blood cell precursors, then mature cells.

Question 17

What is the process of differentiation of granulocytes?

Answer 17

These are neutrophils, basophils and eosinophils. Haemopoietic stem cell > myeloblast > promyelocyte > myelocyte > metamyelocyte > neutrophil.

Question 18

What is the process of differentiation of lymphocytes?

Answer 18

Lymphoblasts > prolymphocytes > lymphocytes.

Question 19

How is haematopoiesis affected hormonally? Three examples.

Answer 19

Cytokines influence differentiation and development of blood cells. For example, Erythropoietin is a cytokine produced in the kidneys which promotes development of RBCs. IL2 stimulates production of lymphoid cells. G-CSF and M-CSF stimulates production of myeloid cells.

Question 20

What are myeloid cells?

Answer 20

Include basophils, neutrophils, eosinophils, monocytes, macrophages, mast cells, erythrocytes and megakaryocytes.

Question 21

What’s the difference between myelocyte and myeloid? !!!

Answer 21

Myeloid describes cells which arise from myeloid progenitor cells (granulocytes, monocytes, erythrocytes). Myelocytes are precursors of granulocytes and a type of myeloid cell.

Question 22

What should the blood cell precursor and mature blood cell levels be like in peripheral blood vs. lymphoid tissue?

Answer 22

PERIPHERAL BLOOD: only mature cells; LYMPHOID TISSUE (bone marrow, thymus, spleen and lymph nodes): mix of immature and mature cells. Confused about lymph nodes? Remember, lymph nodes are key to produce lymphocytes. NB: lymphoid tissue produce LYMPHOCYTES.

Question 23

What are causes of increased white cell count? (x2 (x2 and x1))

Answer 23

• INCREASED PRODUCTION: can be normal e.g. reactive bone marrow during inflammation or infection; OR can be from malignancy e.g. leukaemia or myeloproliferative. • INCREASED SURVIVAL: failure of apoptosis.

Question 24

What are the causes of decreased white cell count? (x2 (x5 and x1))

Answer 24

• DECREASED PRODUCTION: impaired bone marrow function as a result of (i) B12/folate deficiency, (ii) aplastic anaemia – from bone marrow failure, (iii) chemotherapy leading to bone marrow failure, (iv) metastatic cancer leading to bone marrow failure, (v) haematological cancer leading to bone marrow failure. • DECREASED SURVIVAL: immune breakdown.

Question 25

What are the three cancerous types that characterise abnormal differentiation of blood cells? Basic mechanism of each.

Answer 25

• LEUKAEMIA: malignant progressive disease in which bone marrow and blood forming organs produce increased number of immature or abnormal leukocytes (suppresses other blood cells such as erythrocytes). Leukocytes are any white blood cell. • LYMPHOMA: blood cell tumours developing from lymphatic cells – closely linked to leukaemia. • MYELOMA: malignant disease of the plasma cells (produce antibodies) in the bone marrow characterised by 2+ of: (i) excess abnormal malignant PLASMA CELLS in bone marrow, (ii) lytic deposits in bone on X-ray (appears as holes), (iii) abnormal gamma-globulin.

Question 26

What are the four types of leukaemia?

Answer 26

The leukaemia can be LYMPHOID (lymphocytes) or MYELOID (granulocytes, erythrocytes, monocytes, megakaryocytes), and ACUTE (rapid increase in number of immature blood cells) or CHRONIC (excessive build-up of relatively mature but still abnormal white blood cells).

Question 27

What is a myeloproliferative disorder?

Answer 27

A group of diseases of the bone marrow in which excess cells are produced. They arise from precursors of the myeloid lineages in the bone marrow. The lymphoid lineage may produce similar diseases, the lymphoproliferative disorders. Examples include CML (chronic myeloid leukaemia) and chronic eosinophilic leukaemia.

Question 28

What is a myelodysplasia disorder?

Answer 28

Immature blood cells in the bone marrow do not mature. Example includes acute myeloid leukaemia.

Question 29

How is raised white blood cell count investigated? (x4)

Answer 29

• History and examination. • Haemoglobin and platelet count. • Automated differential blood count (measures blood cell parameters, compares to normal ranges to reveal abnormal white blood cell populations). • Examine blood film.

Question 30

What are the two causes of eosinophilia?

Answer 30

Reactive or malignant.

Question 31

What differentiates reactive and malignant eosinophilia – causes?

Answer 31

• REACTIVE: NORMAL HEMOPOIESIS which is stimulated by inflammation, infection (particularly parasitic), allergic diseases, neoplasms or increased cytokine production (from a distant tumour, haemopoietic cancer or non-haemopoietic cancer). • MALIGNANT: ABNORMAL HEMOPOIESIS from cancers hematopoietic cells, leukaemia (myeloid or lymphoid, chronic or acute), and myeloproliferative disorders.

Question 32

Where are neutrophils normally found? Levels marginated and effect on FBC?

Answer 32

Present in bone marrow, blood and tissues (marginated – adhere and migrate to tissues). 50% of circulated neutrophils are marginated so will not be counted in FBC.

Question 33

What is the life span of neutrophils?

Answer 33

2-3 days in tissues.

Question 34

What are the causes of neutrophilia? (x2 (x5 and x2))

Answer 34

• REACTIVE CAUSES: from infection/tissue inflammation (e.g. colitis, pancreatitis), physical stress, adrenaline, corticosteroids and underlying neoplasia (abnormal growth tissue – benign or malignant). • MALIGNANT CAUSES: myeloproliferative disorders, CML (chronic myeloid leukaemia).

Question 35

What infections do not cause neutrophilia? (x3)

Answer 35

Viral infections, typhoid and brucella cause lymphocytosis instead.

Question 36

What is the mechanism of CML (chronic myeloid leukaemia)?

Answer 36

There is a malignant mutation causing unregulated proliferation of myeloid cells in the bone marrow. Proliferation is seen mostly in the granulocytic cells, as well as increases in monocytes and megakaryocytes. No increase in red cells, B cells or T cells.

Question 37

What can be seen in blood film in neutrophilia from infection/inflammation?

Answer 37

Cells tend to have cytoplasmic vacuoles and toxic granulation (dark coarse granules).

Question 38

What can be seen in blood film in neutrophilia from chronic myeloid leukaemia?

Answer 38

Very high numbers of granulocytes, monocytes and megakaryocytes. No increase in erythrocytes, B cells or T cells. Presence of immature band cells (lack of segmentation).

Question 39

What does time-scale that neutrophilia present show about mechanism? (x3)

Answer 39

• Minutes: demargination • Hours: early BM release • Days: increased production

Question 40

What are the causes of monocytosis? (x6)

Answer 40

Monocytosis – increase in number of monocytes. Causes: TB, brucella, typhoid, CMV (virus), sarcoidosis, chronic myelomonocytic leukaemia (not CML).

Question 41

What are the causes of lymphocytosis? (x2 (x2 and x1))

Answer 41

• Lymphocytosis where cells are MATURE: means that the cause is REACTIVE (or SECONDARY!!!) to INFECTION i.e. polyclonal response to infection, chronic inflammation or underlying malignancy; or there is a PRIMARY DISORDER i.e. monoclonal lymphoid proliferation e.g. CLL (chronic lymphocytic leukaemia). • Lymphocytosis where cells are IMMATURE: means that the cause is a PRIMARY DISORDER such as leukaemia or lymphoma e.g. acute lymphoblastic leukaemia (ALL).

Question 42

How do the blood films of reactive and malignant lymphocytosis differ?

Answer 42

* REACTIVE: Lymphocytes differ in size – some small, some large – remember, marrow is polyclonal, so this is NORMAL. All cells are mature. * MALIGNANT: marrow is monoclonal, so all cells look the same and immature cells are present. Larger cytoplasm (so, larger than mature cells) and presence of nucleoli still – shows immature.

Question 43

How do you distinguish between a reactive polyclonal response and lymphoproliferative disorder (lymphocytosis)?

Answer 43

• ASSESS MATURITY IN BLOOD FILM: if there are immature lymphocytes, then the cause is a PRIMARY, lymphoproliferative disorder (cancer such as ALL). If cells are mature, then the cause can be secondary (i.e. reactive polyclonal), or primary (i.e. CLL). • SUMMARY: if mature, then we can’t differentiate between reactive polyclonal and lymphoproliferative. If immature, cause if lymphoproliferative. • Next stage: DISTINGUISH PRIMARY AND SECONDARY REACTIVE: study clinical context, morphology, immunophenotype or gene rearrangement.

Question 44

How does immunophenotype differentiate between primary and secondary reactive lymphocytosis?

Answer 44

Polyclonal cells, in response to infection, show BOTH kappa and lambda short chains on immunoglobulins, while monoclonal shows kappa OR lambda, but not both – because the cause is cancer which causes monoclonal production in the bone marrow (production of lymphocytes from the tumour).

Question 45

How does immunophenotype differentiate between primary and secondary reactive lymphocytosis?

Answer 45

Immunoglobulin genes and T cell receptor genes undergo recombination in antigen stimulate B cells or T cells. Therefore, recombination is suggestive of an infection, and the cause is therefore secondary reactive. No recombination occurs in cancer; cells are just dividing without activation – all daughter cells carry identical configuration of immunoglobulin or T-cell receptor gene.