2. Benign disorders of WBCs
By/
Mr. Waqqas Elaas;
M.Sc; MLT

3. References
For theory : Essential Haematology, John Wiley & Sons Ltd ,6th Edition,Victor Hoffbrand.
For practical : Practical Haematology, Churchill Livingstone, Eighth edition, John V. Dacie, S. M. Lewis,
Internet site(s):
= MCQs
Final Theoretical exam : 40
Final Practical exam : 20 (including written questions)
1st Periodic exam : 10 theory, 5 Practical
2nd Periodic exam : 10 theory, 5 Practical
Homework and class activities : 5 Theory, 5 Practical
Total : 100
Marks

4. Objectives
To differentiate between the qualitative & quantitative WBCs benign disorders.
To understand the etiology and pathology of reactive changes in the number and morphology of granulocytes.
To understand the etiology and pathology of reactive changes in the number and morphology of lymphocytes and monocytes.
To know the definition & causes of Infectious Mononucleosis.
To know the definition & causes of Leukemoid reactions.
To be able to differentiate between Eosinophilia & Hypereosinophilic syndromes.

5. Phagocytes Immunocytes (Granulocytes) (A granulocytes)
Leucocytes (WBCs)
Phagocytes Immunocytes
(Granulocytes) (A granulocytes)
Neutrophils Lymphocytes
Eosinophils small & Large
Basophils B & T Lymphocytes
Monocytes*
*sometimes Monocytes are considered as A granulocytes

6. Normal leucocytes morphology

7. LEUCOCYTES BENIGN DISORDERS
Quantitative
Change in number
Terminology
Cytosis / philia
Increase in number
Cytopenia/penia
Decrease in number
Qualitative
Morphologic changes
Functional changes

8. LEUCOCYTES BENIGN DISORDERS Quantitative changes
Relative & Absolute values
To make an accurate assessment, consider both relative and absolute values. For example a relative value of 70% neutrophils may seem within normal limits; however, if the total WBC is 20,000, the absolute value (70% of 20,000) would be an abnormally high count of 14,000.

9. Normal reference range (adults)
LEUCOCYTOSIS
Definition
Raised TWBC above 11.0 x 109/L in adults, due to elevation of any of a single lineage.
Note: elevation of the minor cell populations can occur without a rise in the total white cell count.
Normal reference range (adults)
x 109/L

10. LEUCOPENIA Definition TWBC lower than 4.5 x 109/L in adults
Leucopenia may affect one or more lineages and it is possible to be severely neutropenic or lymphopenic without a reduction in total white cell count.

11. Increase in the count of all or one of the granulocytic component:
(contd.)
Granulocytosis
Increase in the count of all or one of the granulocytic component:
Neutrophils
Basophils
Eosinophils

12. NEUTROPHILIA Definition
Increase in the number of neutrophils and / or its precursors
In adults count >7.5 x 109/L but the counts are age dependent
Increase may results from alteration in the normal steady state of
Production
Transit
Migration
Destruction

13. Causes of Neutrophilia
NEUTROPHILIA (contd.)
Causes of Neutrophilia
Infection
Bacterial
Inflammatory conditions
Autoimmune disorders
Gout
Neoplasia
Metabolic conditions
Uraemia
Acidosis
Haemorhage
Corticosteroids
Marrow infiltration/fibrosis
Myeloproliferative disorders

14. Leukemoid reactions
Excessive reactive leucocytosis.
Applied to chronic Neutrophilia with marked leucocytosis (>20 x 109/L)
The usual feature is the shift to the left of myeloid cells
Causes include
Infections
Marrow infiltration
Systemic disease (e.g.: Acute liver failure)
(Left shift : indicates that the neutrophils present in the blood are at a slightly earlier stage of maturation than usual. The Band and the stages before. This is often seen in acute infections).
(Right shift : an increase in the percentage of multilobed neutrophils).

15. NEUTROPENIA
Neutropenia is an absolute reduction in the number of circulating neutrophils
Mild ( x 109/L)
Moderate (0.5 – 1 x 109/L)
Severe (<0.5 x 109/L)
Symptoms are rare with the neutrophil count above 1 x 109/L
Bacterial infections are the commonest.
Fungal, viral and parasitic infection are relatively uncommon.

16. (NEUTROPENIA) contd. Causes of Neutropenia Racial Congenital
Marrow aplasia
Marrow infiltration
Megaloblastic anemia
Acute infections
Typhoid, Miliary TB, viral hepatitis
Drugs
Irradiation exposure
Immune disorders
HIV
SLE
Neonatal isoimmune and autoimmune neutropenia
Hyperslplenism

17. The causes of eosinophilia can be considered under following headings
Increase in the eosinophil count must prompt for further investigation (>0.6 x 109/L)
The causes of eosinophilia can be considered under following headings
Allergy
Atopic, drug sensitivity and pulmonary eosinophilia
Infection
Parasites, recovery from infections
Malignancy
Hodgkin’s disease, NHL and myeloproliferative disorders
Drugs
Skin disorders
Gastrointestinal disorders
Hypereosinophilic syndrome

18. Hypereosinophilic syndrome
(EOSINOPHILIA) Contd.
Hypereosinophilic syndrome
Criteria of diagnosis
Peripheral blood eosinophil >1.5 x 109/L
Persistence of counts more than 6 months
End organ damage
Absence of any obvious cause for eosinophilia
Organ most commonly involved
Heart
Lung
Skin
Neurological

19. Absolute monocyte count is age dependent
(MONOCYTOSIS)
Absolute monocyte count is age dependent
Count rarely exceeds >1.0 x 109/L
Have no marrow reserves
Causes of monocytosis can be grouped as
Infections
Chronic infection (TB, typhoid fever, infective endocarditis)
Recovery from acute infection
Malignant disease
MDS, AML, HD, NHL
Connective tissue disorders
Ulcerative colitis, Sarcoidosis, Crohn’s disease
Post splenectomy

20. (BASOPHILIA) Basophils are least common of the granulocytes
Reference range for adult is 0 – 0.2 x 109/L
Most commonly associated with hypersensitivity reactions to drugs or food
Inflammatory conditions e.g RA, ulcerative colitis are also sometime associated with basophilia
Myeloproliferative disorders
Chronic myeloid leukemia

21. (LYMPHOCYTOSIS)
The blood contain only few percent of total body lymphocytes
The most consistent variation is seen with age
Alteration of lymphocyte counts can result from
The redistribution of lymphocytes
Absolute increase of lymphocyte number
Loss of lymphocytes
Combination of these

22. Non-malignant causes of lymphocytosis
Infections
Viral infections
Infectious mononucleosis
CMV
Rubella, hepatitis, adenoviruses, chicken pox,dengue
Bacterial infections
Pertussis
Healing TB, typhoid fever
Protozoal infections
Toxoplasmosis
Allergic drug reactions
Hyperthyroidism
Splenectomy
Serum sickness

23. Infectious Mononucleosis
(LYMPHOCYTOSIS)
Infectious Mononucleosis
Epstein-Barr virus
Saliva from infected person is the main contagion
Virus infect epithelial cells and B cells
Infection in children under the age of 10 does not cause illness and result in life long immunity
Clinical features
Fever, malaise, fatigue, sore throat, splenomegaly
Blood picture shows leucocytosis ( 10 – 20 x 109/L) due to absolute increase in lymphocytes
Diagnosis is by serological tests
There is no specific treatment

24. Qualitative changes (MORPHOLOGY) Congenital acquired Pelger-Huet anomaly Toxic granulation Neutrophil hyper-segmentation Dohle bodies May-Hegglin anomaly Pelger cells Alder’s anomaly Hypersegmented neutrophils Chediak-Higashi syndrome

25. LEUCOCYTES BENIGN DISORDERS Qualitative changes (MORPHOLOGY)
Congenital
Pelger-Huet anomaly
Bilobed and occasional unsegmented neutrophils
Autosomal recessive disorder

26. LEUCOCYTES BENIGN DISORDERS Qualitative changes (MORPHOLOGY) contd.
Neutrophil hyper-segmentation
Neutrophil function is essentially normal
May-Hegglin anomaly
Neutrophils contain basophilic inclusions of RNA
Occasionally there is associated leucopenia, Thrombocytopenia and giant platelet are frequent

27. LEUCOCYTES BENIGN DISORDERS Qualitative changes (MORPHOLOGY) contd.
Alder’s anomaly
Granulocytes, monocytes and lymphocytes contain granules which stain purple with Romanowsky stain
Granules contain mucopolysaccharides

28. LEUCOCYTES BENIGN DISORDERS Qualitative changes (MORPHOLOGY) contd.
Chediak-Higashi syndrome
Giant granules in granulocytes, monocytes and lymphocytes
Depressed migration and degranulation
Recurrent pyogenic infections
Lymphoproliferative syndrome may develop
Treatment is BMT

29. LEUCOCYTES BENIGN DISORDERS Qualitative changes (MORPHOLOGY) contd.
Acquired
Toxic granulation
Dohle bodies
Pelger cells
Hypersegmented neutrophils

30. Homework
(1) Case : A 20-year-old student presented with a 7-day history of fever, sore throat, lethargy and tender enlarged glands in the neck. Physical examination reveals fever, mild jaundice, inflamed pharyngeal mucosa and cervical adenopathy. Blood results
Hb; 12.5 g/dl, wbc 18.0x109/l , differential 30% neutrophils 40% lymphocytes 30% abnormal lymphocytes. Platelets 100 x109/l. Throat swab: No bacterial growth
HIV test negative
Does the student has Neutrophilia OR Lymphocytosis?
Explain your answer in Q1
What is the probable diagnosis?
(2) Design a table containing the 5 types of leucocytes with their normal ranges in adults.