Haematology - White Blood Cells

Question 1

Granulocytes and monocytes - general

Answer 1

Granulocyte = granules in cytoplasm that contain agents essential for microbicida function, neutrophils, basophils, eosinophils; monocytes circulate in blood and are precursors of macrophages in tissues; origin of leukocytes = multi potent haemopoietic stem cell -> myeloblast -> granulocytes and monocytes

Question 2

Granulocytes and monocytes - signalling

Answer 2

Through myeloid growth factors (G-CSF and M-CSF (G=granulocyte, M=monocytes, CSF=colony stimulating factor) essential for proliferation and survival of myeloid cells

Question 3

Granulocytes and monocytes - granulocyte maturation

Answer 3

Cell division occurs in myeloblasts, promyelocytes and myeloblasts, promyelocytes and myelocytes, not in metamyelocytes or band forms, reduction in cell size and development of granules, myeloblasts -> large size+open chromatin pattern of nucleus + prominent nucleolus, precursors up to neutrophil should only be in bone marrow

Question 4

Granulocytes and monocytes - neutrophil

Answer 4

Survives 7-10 hours in circulation before migrating to tissues, nucleus of mature one=segmented (lobulated), defence against infection (phagocytoses and kills microorganisms), first step in migration to tissues = chemotaxis (become invaginated in vessel lumen, adhere to endothelium and migrate into tissues), phagocytosis following cytokines priming, release of toxic intracellular contents -> superoxide dependent mechanism -> release of O2 reactive species (respiratory burst) and provides enzyme substrate for myeloperoxidase -> O2 independent reactions -> anti microbial agents released

Question 5

Granulocytes and monocytes - eosinophils

Answer 5

Bright pink granules on standard stain (heamtoxylinn and eosin), phagocytes (usually deal with parasitic infestations), spend less time in circulation than neutrophil

Question 6

Granulocytes and monocytes - basophils

Answer 6

Granules with histamine +heparin+proteolytic enzymes, immune and inflammatory responses (mediation of immediate-type hypersensitivity reaction (IgE-coated basophils release histamine and leukotrienes, modulation of inflammatory responses by releasing heparin and proteases)

Question 7

Granulocytes and monocytes - monocytes

Answer 7

Several days in circulation, phagocytosis and presentation of antigens to lymphoid cells, migrate to tissues where they develop into macrophages (histocytes) and other specialised cells with phagocytic and scavenging function, macrophages also store and release Fe

Question 8

Lymphocytes - general

Answer 8

• Multi potent haemopoietic stem cell -> lymphoid stem cell -> T cells, B cells, natural killer (NK) cells
• Recirculate to lymph nodes, other tissues and back to blood stream, variable intravascular lifespan
• T&B lymphocytes hard to distinguish based on appearance on blood film (same for cytotoxic T cells and NK cells)

Question 9

Lymphocytes - B lymphocytes

Answer 9

Plasma cells (produce antibodies), originate in liver and foetus bone marrow, progenitor B cells develop into pre-B cells & mature B cells (gene rearrangement of immunoglobulin heavy and light chains leading to production of surface immunoglobulin against many different antigens (humoral immunity), further maturation requires exposure to antigen)

Question 10

Lymphocytes - T lymphocytes

Answer 10

Migration of lymphocyte progenitors from liver to thymus, cell-mediated immunity, gene rearrangement = many antigen receptors during maturation (also CD4 and CD8 surface markers, CD4+ = T-helper cells (majority of T-cell population in peripheral blood, produce cytokines (ie interferons) which activates monocyte macrophage system and promote antibody synthesis by B cells)), CD8+ = cytotoxic T-cells (25% circulating T-cells, destroy virus infected cells through T-cell receptor binding (cell-mediated immunity))

Question 11

Abnormalities - general

Answer 11

Leukocytosis (too many) and leukopenia (too few), transient leukocytosis associated with infection (bacterial: monocytosis/neutrophilia, viral: lymphocytosis, parasitic: eosinophilia), persistent leukocytosis may be caused by leukaemia (chronic myeloid (CML, neutrophilia, basophilia, eosinophilia), acute lymphoblastic (ALL, blast cells (lymphoblasts) in blood), chronic lymphocytic (CLL, lymphocytosis)), can be numerical/morphological/both, leukocytosis = neutro-/eosino-/basophilia/lympho-/monocytosis, leukopenia -> neutro-/lymphopenia (usually both result from changes in neutrophil count since those usually most abundant leukocytes in circulation)

Question 12

Abnormalities - neutrophilia

Answer 12

Causes = infection (particularly bacterial)+inflammation+infarction/tissue damage+myeloproliferative disorders (CML), normal feature in pregnancy and may be seen following exercise (rapid shift of neutrophils from marginated to circulating pool) and after corticosteroid administration, may be accompanied by toxic changes and left shift (ie pressure of early myeloid cells ie metamyelocytes), toxic granulation = heavy+coarse neutrophil granulation (can be pregnancy feature), in single haemopoietic stem cell

Question 13

Abnormalities - chronic myeloid leukaemia (CML)

Answer 13

• Increase in all granulocyte and precursors in both blood and bone marrow
• results from translocation between chromosomes 9 and 22 in single haemopoietic stem cell, Philadelphia (Ph) chromosome (1960, abnormally short chromosome 22 first consistent chromosome abnormality (ABL 1 gene (chr 9) and BCR gene (chr 22), ABL 1 usually encodes tyrosine kinase enzyme (tightly regulated activity, unregulated=leukaemic clone)), gene product gives cell growth and survival advantage + gives rise to leukaemic clone
• splenomegaly (can’t normally palpate spleen below left costal margin), growth factor binds to receptor for cell division, tyrosine kinase starts signal for cell division, BCR-ABL1 protein signals between cell surface and nucleus, uncontrolled cell division can be inhibited by specific tyrosine kinase inhibitors

Question 14

Abnormalities - neutropenia

Answer 14

Following chemotherapy and radiotherapy (suppress bone marrow activity), autoimmune disorders, severe bacterial infections, certain viral infections and drugs (some anticonvulsants, antipsychotics and antimalarials), physiological basis (ie benign ethnic neutropenia in people of African/Afro-Caribbean ancestry), very low neutrophil counts (<0.5 x10^-9/l)are at high serious infection risk and need urgent treatment with intravenous antibiotics

Question 15

Abnormalities - segmented neutrophil

Answer 15

Normal =3-5 lobes, increase in average number of lobes/segments (“right shift”), usually results from lack of B12/folic acid (megaloblastic anemia)

Question 16

Abnormalities - eosinophilia

Answer 16

Usually due to allergy/parasitic infection, can occur in leukaemia; eosinophils=hypersensitivity reactions, activate histamine and leukotrienes (basophils and mast cells)

Question 17

Abnormalities - monocytosis

Answer 17

Infection (particularly chronic bacterial), some types of leukaemia

Question 18

Abnormalities - leukaemia

Answer 18

• Cancer originating in haemopoietic/lymphoid cells
• ALL->increase in lymphoblasts with failure to develop into mature lymphocytes, severe and sudden onset, high nucleocytoplasmic ratio and prominent nucleolus, bone marrow infiltrated by immature lymphocytes = impaired hematopoiesis, lymphoblasts overspill into peripheral blood
• CLL -> leukaemic cells are mature (though abnormal) T/B/NK cells, chronic = disease and deterioration for long period of time

Question 19

Abnormalities - lymphocytosis

Answer 19

Often response to viral infection (transient, atypical lymphocytes), can result from lymphoproliferative disorder (persistent, lymphomas and chronic lymphocytic leukaemia (most common cause of persistent lymphocytosis in elderly)), whooping cough (Bordatella pertussis, children), characterising profile of cell surface markers expressed by lymphocytes help determine cause

Question 20

Abnormalities - ALL

Answer 20

• Haematology: leukocytosis with lymphoblasts in blood, anemia (normo -cytic and -chromic), neutropenia, thrombocytopenia, replacement of normal bone marrow cells by lymphoblasts
• Cytogenic and molecular genetic analysis: prognosis information, permitted discovery of leukaemogenjc mechanisms and development of targeted treatment
• Clinical features: bruising due to thrombocytopenia, pallor because anemia (both because of replacement of normal bone marrow cells by lymphoblasts)
• Treatment: supportive (red cells, platelets, antibiotics), systemic+intrathecal (spinal cord) chemotherapy, targeted based on translocations

Question 21

Abnormalities - lymphopenia

Answer 21

Decrease in number of circulating lymphocytes, total lymphocyte count <1x10^9/L, most lymphocytes =CD4+ T-cells, causes = HIV infection+chemotherapy+radiotherapy+corticosteroids+transient low lymphocyte count sometimes in patients with severe infection