White blood cells

Question 1

What are granulocytes?

Answer 1

Neutrophils, basophils, eosinophils - have granules and agents for phagocytic function

Question 2

What are monocytes?

Answer 2

Circulate in blood and are precursors of macrophages
Can play roles in phagocytosis and antigen presentation to lymphoid cells

Kidney / horse shoe shaped nucleus (histology)

spend several days in circulation

Question 3

Where are granulocyte precursors found?

Answer 3

In bone marrow from multipotent haemopoietic stem cell giving rise to myeloblast to band form (which undergo no cell division). Leaves as a granulocyte.

Question 4

What are the characteristics of Basophils?

Answer 4

Contain prominent cytoplasmic granules when stained

Inflammatory responses (heparin and protease release)

Immediate type hypersensitivity, IgE coated basophils release substances ( histamine and leukotrienes.

Question 5

What are the characteristics of Neutrophils?

Answer 5

Segmented nucleus

Phagocytosis occurs following cytokine priming

Migrate from blood to tissues after 7-10 hours of circulation

maturation : cell division occurs in myeloblasts, promyelocytes, myelocytes. Not band forms

Question 6

How do neutrophils migrate into tissues from capillaries?

Answer 6

Chemotaxis

Neutrophils become marginated in lumen, adhere to the endothelium and migrate to tissues.

Question 7

What are the characteristics of Eosinophils?

Answer 7

Main defence against parasitic infection although it can also phagocyte.

stained pink with eosin. Bi-lobed

spends less time in circulation than neutrophil

Question 8

What cell is Leukocytosis and leukopenia usually attributed to?

Answer 8

Changes in neutrophil count as these are most abundant leukocyte.

Question 9

What are the unnatural causes of Neutrophilia?

Answer 9

Bacterial infections
Inflammation
Infarction/tissue damage
Myeloproliferative disorders ( CML )

Question 10

When may Neutrophilia be considered normal?

Answer 10

In pregnancy (toxic granulation can be seen) and may be seen after exercise ( caused by rapid shift of neutrophils into circulation after corticosteroids )

Question 11

What toxic changes can be associated with Neutrophilia?

Answer 11

left shift : presence of early myeloid cells such as metamyelocytes. Increase in non-segmented neutrophils (band forms)

Toxic granulation - heavy course granulation in neutrophils

Question 12

What causes Chronic Myeloid Leukaemia?

Answer 12

All granulocytes increase along with their precursors in blood

Due to translocation between chromosome 9 and 22 in a single haemopoietic stem cell

Mutation gives growth advantage and clonal expansion over mutated stem cell

clonal expansion = myeloid leukaemia

Question 13

What is chromosome 22 known as (linked to CML)?

Answer 13

(Ph) Philadelphia chromosome, abnormally short

Question 14

How do genes give rise to a Leukaemic clone for CML?

Answer 14

BCR-ABL1 gene encodes protein with uncontrolled tyrosine kinase activity

A potential cure is tyrosine kinase inhibitors

chimeric gene / dual colour / dual fusion

Question 15

What are the symptoms of Chronic Myeloid Leukaemia?

Answer 15

Enlarged spleen

Question 16

How can Chemo/Radiotherapy lead to Neutropenia?

Answer 16

Surpreses bone marrow activity leading to few neutrophils being made

Question 17

What causes Neutropenia, abnormal and normal causes?

Answer 17

Low neutrophil count: < 0.5 * 10^9 / L

Autoimmune disorders
Severe bacterial, viral infections
some Anti-convulsants, antipsychotic drugs, antimalarials

Physiological basis e.g. benign neutropenia in African/Afro-Caribbean

Question 18

What is Neutrophil hypersegmentation and what is it caused by?

Answer 18

Increase in average number of lobes or segments (should be 3-5) known as right shift

Lack of V B12 (able to grow but not divide) or folic acid ( megaloblastic anaemia )

Question 19

What can Eosinophilia be attributed to?

Answer 19

Allergy to parasitic infection ( asthma, eczema, drugs)

Can occur in CML

blood film example - px with strongyloidiasis

Question 20

What can Basophilia be attributed to?

Answer 20

Uncommon finding

Leukaemia .e.g CML

Question 21

What can Monocytosis be attributed to?

Answer 21

Infection - Chronic bacterial infection and chronic inflammation

Some types of leukaemia

Question 22

What can Lymphocytosis be attributed to

Answer 22

Transient Viral infection
(Whooping cough in children)by bordatella pertussis

Persistent Lymphoproliferative disorder

Question 23

What is infectious mononucleosis?

Answer 23

Glandular fever, due to epstein-barr virus infection

Leads to lymphocytosis with atypical lymphocytes ( larger cytoplasm and nuceli, membrane squashed by r.b.cs )

common to see scalloped margins of basophilia, hugging of surrounding red blood cells

Question 24

What is Chronic lymphocytic Leukaemia (CLL)?

Answer 24

Lymphoproliferative disorder
Common cause of persistent lymphocytosis in elderly

Can see smear cells

Leukaemic cells are mature although abnormal T,B,NK cells

Question 25

What is Acute Lymphocytic Leukaemia? (ALL)

Answer 25

Increase in immature cells specifically lymphoblasts with developmental failure which can be found in peripheral blood Severe and sudden onset of symptoms. Can see Lymphoblasts, Normocytic normochromic anaemia, Neutropenia, Thrombocytopenia, Replacement of bone marrow cells by lymphoblasts

Question 26

What are some clinic features attributed to ALL? Which transfusions and therapies are available respectively?

Answer 26

Prominent bruising due to thrombocytopenia Pale as a result of Low Hb ( Anaemia ) these symptoms are a result of normal bone marrow replacement by lymphoblasts Red cells, Platelets, Antibiotics Systemic chemotherapy, Intrathecal chemotherapy

Question 27

What may cause a < 1 * 10^9 / L total lymphocyte count?

Answer 27

Lymphopenia in normal blood Most are CD4+ T cells Can be caused by HIV infection, Chemotherapy Radiotherapy Corticosteroids Px may develop a transient low lymphocyte count due to severe infection

Question 28

Extra info?

Answer 28

Common myeloid progenitor --> granulocytes and monocytes For proliferation and survival of myeloid cells need signalling through myeloid growth factors such as G-CSF, M-CSF, GM-CSF -ALL, cytogenic and molecular genetic analysis Information about prognosis, development of targeted treatment. - transcient leukocytosis is frequently seen with infection - neutrophilia and monocytosis due to bacteria Lymphocytosis due to virus eosinophilia due to parasitic - Persistent leukocytosis caused by leukaemia e.g. CLL ( lymphocytosis ) CML ( basophilia, neutrophilia, eosinophilia ) - leukopenia usually due to low neutrophil count