10. OVERVIEW OF WHITE BLOOD CELLS.scsppt

Overview of white blood cells

1. OVERVIEW OF WHITE
BLOOD CELLS
Dr Brima m sesay

2. Course Objectives
Out line different groups of white blood cells
Define the role and the morphology of each group of white
blood cells
List conditions that result in an increase or reduction of
white blood cells
Define common pathological disorders that result from
white blood cells

3. White Blood Cells
Granulocytes
Neutrophil - Cytoplasm clear, -
Basophil - Basic stained cytoplasm -blue,
Eosinophils- Acid stained cytoplasm -red
A granulocytes
Lymphocytes-Nuclear cytoplasm ration low –30 -35%
Monocytes -Nuclear indentation 3-7%

4. Neutrophils
Protect against microbial infection by phagocytosis and killing –
Mature in bone marrow -12days -12 hrs circulation-12hrs
function
Disorders that lead to increased susceptibility to infection
Absence - Agranulocytosis
Diminished Numbers
Causes of decrease in Neutrophil numbers
a.Production failure in Marrow
-Drugs
-Severe Infection
-Marrow infiltration (malignant tumours, fibrosis)
-Vitamin B12 and folate deficiency
-Idiopathic

5. b)Decrease in Neutrophil numbers contd
b.Peripheral Sequestration in Spleen and Capillaries
Hypersplenism
Shock and severe infection
Disorders of Neutrophil Function
a.Chemotaxis
Intrinsic defect of Neutrophils e.g Leucocyte
adhension deficiency -in reduction β
2integrin
expression
Plasma deficiency of chemotactic factors and
opsonins & deficiencies in the complement cascade

6. Disorders of Neutrophil function contd
b.Microbial Phagocytosis and kill
Intracellular Enzyme defect
e.g. Chronic granulomatous disease (CGD)
Chediak –Higashi syndrome
Abnormal giant granules

7. 2.Basophils
7 days in circulation -Granules contain:
Hydrolytic enzymes
Hepalan sulphate
Histamine
Slow reacting substance (SRS) of Anaphylaxis
IgE -Hypersensitivity

8. Basophil disorders
Low count is associated with
Glucorticoid treatment
Hypersensitivity reactions
High Count is associated with
-Allergic conditions
-Infections
-Endocrinopathies
-Myeloproliferative disorders(chronic myelogenous,
Leukaemia, Polycythemia vera, Myeloid Metaplasia,
Essential Thrombocytosis)
Mast cell infiltration also occurs –Excessive Histamine

9. 3.Eosinophils
Have Crystalloid body that contain major basic proteins –9 days in
Bone marrow, 3-8days in circulation
Contain: - Peroxidase
- Histaminase
•These are released at sites of inflammation
-Engage in phagocytosis of Antigen –Antibody complexes
-Found in Lamina propria of intestinal tract

10. Eosinophil Disorders
Reduced numbers (Eosinopenia)
Less well characterised
Normal range 200 cells/µl but can range from 0 -400 cells/µl
Caused By:
-Infection
-Administration of Steroids
-Prostaglandins
-Adrenaline
NB Transient not associated with significant risk of
infection

11. Increased In Number (Eosinophilia)
Characterised by Eosinophil count greater than 400/µl
Caused by:
Allergic reaction to certain drugs –(Aspirin, Sulfonamides,
Penicillins, Nitrofurantoin)
Reaction to Iodine –containing substances (Most Common
causes)
Allergy to environmental agents (e.g grass, trees, dust)

12. Eosinophilia Cont’
Asthma,
Vasculitis,
ulcerative colitis,
Dermatitis -E.G Eczema,
Malignances (e.g Hodgkin disease, Lymphoma, brain and skin,
Tumours, acute Leukaemia)
Serum Sickness
Infection with parasites both Protozoan (e.g Ascaris,
Trichinosis, Schistosomiasias)

13. Idiopathic Hypereosinophilia
Elevation of circulating Eosinophil count
May result in dysfunction of
Heart
CNS
Kidneys
Lungs
GIT
Skin

14. Agranulocytes
Lymphocytes
Lymphocyte differentiation involves Bone Marrow, Thymus,
and secondary lymphoid organs.
B –Lymphocyte
Produce қor ג
IGM –Naïve B-cells
Circulate in to organs to encounter appropriate Antigen.

15. T-Lymphocytes
Thymus where they require T-cell AG-Receptors
Develop into α/βand γ
For Recognition of MHC Peptides (i.e. CD4 or CD8)
-Acquisition of receptors required for signal
transduction through Ag. Receptor (i.e CD3)
B –Cells -Germinal Centres
T-Cells -Proliferation occurs between or deep to B –
Cells

16. Disorders of Lymphocytes
Reduction - Immunosuppresion (HIV)
- Infections
Increase - Lymphomas
- Leukaemia

17. Monocytes
Circulate to become: Macrophages
Osteoclasts
Kupfer Cells
Microglia
Disorders -Parallel those seen with Neutrophil
Monocyte counts is 300/µl can range from 0-800 cells/µl
Reduction-(Monocytopenia)
Occurs in response to stress and after Glucocorticoid
administration

18. Monocytes contd
Monocytosis-Occurs when Absolute Monocyte count
Exceeds 800/µl
Occurs in:
a.Myelodysplastic Syndrome
b.Neutropenic states (E.G. Cylic Neutropenia)
c.The recovery phase of Agranulocytosis
d.Exacerbations of Lymphoma
e.Patients who have undergone Splenectomy
f.Subtypes of Leukaemia
g.Response to infections (e.g Cytomegalovirus, T.B Subacute
Bacterial endocarditis, Syphilis)
h.Patient with Underlying inflammatory Disease

19. Neoplastic Transformation of White
Blood Cells
Diseases of Bone Marrow can be organised into 3 broad classes
a. Systemic Diseases that secondarily affect bone marrow.
-Infections
-Autoimmune Disorders
-Endocrine and Metabolic disfunction
b. Haematopoietic Production or Function from causes other than
Transformation
c. Clonal Haematopoietic Disorders –Haematopoietic Neoplasm's
i. Chronic Myeloproliferative Disorders
ii. Myelodysplastic Syndromes
iii. Acute Leukaemias

20. A.Chronic Myeloproliferative
Disorders
Arise when Acquired Genetic Alteration at stem cell
level leads to over production of 1 or more of
lymphoid elements in bone marrow
Defect does not prevent maturation
The clonal stem cells seed the spleen, resulting in splenomegaly
All can progress to acute Leukaemia(100% in CML)
Can progress to spent phase - Marrow Fibrosis
-Extensive extramedullary
Haematopoiesis

21. Examples of Myeloproliferative
Disorders
1.Chronic Myelogenous Leukaemia (CML) (Granulocytes
and Monocytes)
2.Polycythemia Vera (Erythrocytes)
3.Essential Thrombosis (Megakaryocytes and Plateletes)
4.Myelofibrosis with Myeloid Metaplasia (MMM)
Megakaryocytes and marrow fibrosis

22. Genetic Basis for CML
Develop when a reciprocal t(9,22) creates truncated
chromosome 22 carrying a functional bcr-alb
90% of cases have this Philadelphia chromosome
bcr-abl fusion gene encodes functional tyrosine kinase
Trysine kinase inhibitor can be used for treatment

23. B.Myelodysplastic Syndromes
Arise when Acquired defect at stem level produces structural
abnormalities during maturation with premature cell destruction
Patients have:
Peripheral Cytopenias, Hypercellular bone marrow
Cytologically abnormal cells at all stages of differentiation
(BM + PB) eg Abnormal granulocytes with 2 lobes(Pseudo –
Pelger –Hueet Cells)
Giant Plateletes, Avariety of Dysmorphic RBCs

24. Myelodysplastic Syndromes (Cont’)
Clonal Cytogenetic abnormalities are associated with
Myelodysplastic syndromes
Patients die of complications resulting from
Thrombocytopenia (bleeding) or Neutropenia
(infections)
Progression to Acute Leukaemia occurs in a substantial
number of patients those with treatment related
syndromes.

25. Acute Leukaemias
Acquired defects result in clonal expansion without significant
maturation beyond the earliest stages of precursor
development.
Blasts rapidly accumulate in the bone marrow-frequently enter
blood steam in large numbers
Clonal expansion compromises normal bone marrows
producing
Bruising
Fatique
Infection from cytopenias

26. Acute Leukaemias, Cont’
Presents with:
Peripheral Cytopenias
Variable (sometimes) massive numbers of blasts forms in
blood stream
Hypercellular marrow infiltrated with malignant blast forms
>20%
Divided Into:
a.Acute Lymphoblastic Laekaemia(All)
Blasts forms -Antigenic characteristics of
Pre –B. Cells
Pre –T Cells
And rarely naive B-cells.

27. Acute Leukaemias, Cont’
b. Acute Myelogenous Leukaemias
Blasts forms with Antigenic
and / or Enzymic characteristics of 1or more non Lymphoid
Precursor
Most often Granulocytic or Monocytic Precursors

28. LYMPHOMAS
A variety of Lymphoid malignancies arising outside of bone
marrow and present with tissue infiltrates
Neoplasm of Lymphoid cells may be present in
-Bone Marrow
-Peripheral Lymphoid
-Non Lymphoid Organs
Functional Attributes of the parent cell are frequently retained
after neoplastic Transformation
eg Plasma cell disorders
-Multiple Myeloma
-Waldenstrom Macroglulimia -Produce
-Monoclonal –immunoglobulins (Monoclonal
Gammopathies)

29. Lymphomas Cont’
Lymphocytes Disorders
-Non-Hodgkins Lymphomas
may retain the adhesion and chemokine receptors for
recirculation through lymph nodes
Present a mass in :
-Lymph nodes –Lymphadenopathies
Spleen –Splenomegacy
Skin, GALT, BM, Thymus
And Many non-Lymphoid organs

30. Diagnosis and classification
Obtain a biopsy
Cytologic Characteristics of malignant cells
Histopathology of tissue infiltrated
Antigenic or genetic profiles of the neoplastic cells
Classification:
Non Hodgkins Lymphomas
Hodgkins Lymphoma
Lymphomas are biologically and clinically related to
Lymphoid Leukaemias
e.g Acute Lymphoblastic Leukaemia(Pre T-Cell) and
Lymphoblastic Lymphoma (Pre T Cells)

31. Leukaemia & Lymphoma
Acute Lymphoblastic Leukaemia -BM and peripheral blood
involvement
Lymphoblastic Lymphoma –Thymic engagement is a Principal
feature.
Chronic Lymphocytic Leukaemia and small Lymphocytic
Lymphoma
-Arise from small, inactive appearing Lymphocytes that circulate
through - BM
- Spleen
- Lymph Nodes
-All three or
-Only Lymphadenopathy within minimal BM or Peripheral Blood
Involvement

32. Non-Hodgkins Lymphoma
Retain Trafficking Behaviour of normal Lymphocytes
Spread through Blood Stream and Lymphatic system
May develop Leukaemia Phase (wide stream
Haematogenous spread)

33. Lymphoid Neoplasms are divided into
4 categories (REAL)
Precursor B-Cell
Precursor T-Cell
Peripheral B-Cell
Peripheral T-Cell
Further Subdivided into:
Clinical
Morphologic
Immunophenotypic
Genotypic difference

34. Lymphoid Neoplasms Cont’
Diseases Names in Common
-Follicular
-Diffuse
-Mantle Cell
Those that present with other Leukamia or Lymphoma
e.g Precursor T Lymphoblastic Leukaemia/Lymphoma
Chronic Lymphocytic Leukaemia/small Lymphocytic
Lymphoma