Leukocytes Be nign Disorders

Normal Peripheral Blood Formation of Phagocytes in Bone Marrow Leukocytes Differential Counts

Leukocytes

(4-11 x���/L)

Absolute

(x���/L)

Relative

(%)

Neutrophils 2.5 - 7.5 34 – 75

Eosinophils 0.04 - 0.4 0 – 5

Basophils 0.01 - 0.1 0 - 3

Lymphocytes 1.5 - 3.0 20 - 45

Monocytes 0.2 - 0.8 3 - 10

White Blood Cells

Neutrophils Eosinophils Basophils Monocytes Lymphocytes

2-5 Lobes of dense Nucleus Bi-lobed Nucleus Occasionally seen Largest WBC

Nucleus slightly indented with

clumped chromatin

Smallest WBC

Large condensed nucleus

Pale cytoplasm with irregular

outlines

Coarse cytoplasmic granules

(More deeply red staining)

Dark cytoplasmic granules

overlying nucleus

(contain Heparin, Histamine)

Cytoplasm is abundant

Sky Clue in colour

Contains many fine vacuoles

& granules

Scanty bluish cytoplasm

Many azurophilic granules

1° granules (promyelocyte)

• Myeloperoxidase, Acid

Phosphatase, Hydrolases

2° granules (specific granules)

• Collagenase, Lactoferin,

Lysozyme

Role in

Allergic responses

Defence against parasites

Removal of fibrin forme d during

inflammation

Become mast cells in tissues

Have IgE attachment sites &

degranuatlion associated with

histamine release

Lifespan in Blood – 6 -10h

1° defence against infection

↑ in response to

Bacterial infection/

inflammatory disease

BM disorders (eg. CML)

↑ associated with

Allergic reaction

Parasite infections

Chronic skin Infections

Cancers

↑ associated with

Cancers

Allergic reactions

Infections

Radiation exposure

↑ associated with

Recovery from acute infection

Viral illness

Parasitic infections

Collagen disease

Cancers

↑ seen in

Most viral infections

Bacterial infections

Cancers

Graves’ disease

↓ as a result of

Severe infection

Response to medications

(chemotherapy)

↓ associated with

Stress

Steroid exposure

Anything – suppress WBC prod.

↓ associated with

Stress reactions

Allergic reactions

Hyperthyroidism

Prolonged steroid exposure

↓ associated with

HIV infection

Rheumatoid arthritis (RA)

Steroid exposure

Cancers

↓ seen in

Steroid exposure

Cancers

Immunodeficiency

Renal failure

Lupus

Variations of Neutrophils

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Qualitative Benign Disorders

Morphologic changes

Functional defects in ≥ 1 WBC types

Chediak-Higashi Syndrome

Inherited Morphological & Functional Abnormalities

Rare Autosomal Recessive disorder

Giant Granules (in cytoplasm)

Neutrophils

Eosinophils

Monocytes

Lymphocytes

Accompanied by Neutropenia

Thrombocytopenia

Hepatosplenomegaly

Netrophils have Deficiency of Antimicrobial proteins

Disordered in Degranulation/ Chemotaxis

Pelger-Huet Anomaly

Inherited Morphological Abnormalities

Benign Autosomal Dominant

Bi-Lobe d Neutrophils

May-Hegglin Anomaly

Inherited Morphological Abnormalities

Rare, Autosomal Dominant

Neutrophil contain large Basophilic inclusions of RNA similar: Dohle bodies

Neutrophil Hypersegmentation

Morphological Abnormalities

Rare Autosomal Dominant condition

Neutrophil function is essentially Normal

Seen in Megaloblastic Anaemia

Quantitative Disorders

Total Leukocytes Description of cells

↑ (Leukocytosis) ↑ (Philia)

↓ (Leukopenia) ↓ (Penia)

Leukocytosis

↑ Leukocytes ( >11 x10�/L)

Physiologic Pathologic

Stress Disease

Exercise Tissue Damage

Epinephrine

≥ 1 Leukocytes can be responsible

Often due to ↑ Neutrophils

Mechanism of Leukocytosis (due to ↑ in)

Neutrophil count (Neutrophilia)

Lymphocyte count (Lymphocytosis)

Monocyte count (Monocytosis)

Eosinophils count (Eosinophilia)

Basophils count (Basophilia)

Other Causes of Benign Leukocytes Disor der

Eosinophilia Eosinope nia

Allergic disorders (Asthma, Hay Fever) Stress (Release of Epinephrine)

Tissue parasite infection Aftermath of Acute Inflammation

Dermatoses (Eczema)

Drugs

Basophilia Basope nia

Hyperlipidemia Hyperthyroidism

Small Pox/ Chicken Pox Acute Stress

Chronic Sinusitis

Ulcerative Colitis

Monocytosis (↑ Cell Damage cases) Monocytope nia

Recovery from Acute Infection Prednisone Therapy

Tissue Trauma

Bacterial Endocarditis

TB

Collagen Disorders (RA, SLE)

Post Splenectomy

(Monocytes busy cleaning up

Neutrophils)

Inflammatory Bowel Disease

Monocyte Disorders

Inherited Abnormalities of Neutrophils are also seen in Monocytes

(Originate from Common Stem Cell)

Chronic Granulomatous Disease (Defe ctive Respiratory Buss)

Chediak Higashi (Abnormal Lysosomes caused by Fusion of 1° Granules)

Alder Reilly Anomaly (Large Purple-Blue Granules)

Lymphocytes Disorders

Wiskott-Aldrich Syndrome

Severe Combined Immunodeficiency System (SCIDS)

DiGeorge Syndrome

X Linked Agammaglobulinemia

Ataxia Telangiactasia

Macrophage Disorders

Lipid Storage Diseases (cells unable to digest phagocytosed material complete)

Gaucher’s Disease

Niemann-Pick Diseases

Tay Sachs & Sandhoffs Diseases

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Neutrophilia

Neutrophilia/ Neutrophilic Leukocytosis

> 7.5 x10�/L

Pathophysiol ogy

Reaction mediated by

• Growth Factors (eg. G-CSF, GM-CSF, C-Kit Ligand)

• Adhesion molecules (eg. CD11b/ CD18)

• Cytokines (eg. IL-1, IL-3, IL-6, TNF)

Acute Chronic

Occur 4-5 h after pathologic stimulus Follows acute neutrophilia

↑ Cells Flow (BM → Peripheral) Left shift (BM release younger cells)

Bands, Metamyelocytes seen

1° 2°

Hereditary Infection

Chronic Idiopathic Stress

Familial Myeloproliferative Disease Chronic inflammation

Leukaemoid reactions associated with

congenital anomalies

Drugs

Non-Haematological Neoplasms

Leukocytes Adhesion Deficiency (LAD) Asplenia, Hyposplenism

Familial cord Urticaria, Leukocytosis

2° Neutrophilia

Bacterial Infections (most common)

Usually Absolute Neutrophilia

(10-19 x10�/L)

Morphological changes

Left shift

Vacuolation

Dohle Bodies

Toxic granulation

Leukaemoid Reaction

Reactive, Excessive Leukocytosis

Characterized by Presence of Immature cells

Many Bands, Metamyelocytes, Myelocytes (Left-shift)

Promyelocytes, Myeloblasts (occasionally seen)

Resembles CML but can be exclude d

No Philadelphia chromosome

Transient (Temporary)

Elevated Leukocyte Alkaline Phosphatase score

No Basophilia

Neutropenia

< 1.8 x10�/L

Can be due to

Impaired production by BM

Shift from circulating pool to marginated pool

↑ Peripheral destruction

<0.5 x���/L <0.2 x���/L

Likely to have recurrent infections Very serious risks

1° 2° (↑ common)

Inherited (Kostmann’s syndrome ) Drug Therapy

Acquired (Drug induced) Infection (Adult – common)

Cyclical Neutropenia

(Inherited Autosomal Dominant)

(Several days of Neutropenia with

infection followed by asymptomatic)

Immunologic Disorders

Idiopathic Neutropenia

Autoimmune Neutropenia

Familial (Benign, Chronic, Mild with

rare symptoms)

Infantile Genetic Agranulocytosis

(Rare, Congenital, Fatal disorder)

(Defective BM production of

Neutrophils)

Eosinophilia

> 0.5 x10�/L

Causes

Allergic Diseases

Parasitic Diseases

Recovery from Acute Infection

Skin Diseases (Psoriasis, Dermatitis, Urticaria)

Drug Sensitivity

Graph Versus Host Disease

HyperEosinophilic Syndrome (>1.5 x10�/L)

Treatment with GM-CSF

Lymphocytosis

Acquired, Quantitative

Self-Limited

Both B-cells, T-cells Affected

Function – Normal

Morphology – Heterogenous

Absolute (>3x���/L) Relative (>40%)

Viral Infections 2° to Neutropenia

May/ May Not Accompany

Leukocytosis

Causes 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

Infectious Mononucle osis (IM)

Lymphocytosis

Accompanied by Leukocytosis

Caused by EBV (Epstein-Barr Virus) infecting B

Lymphocytes

Cytotoxic T cells Kill Infected B cells

Reactive Lymphocytes (Cytotoxic T cells) seen in

peripheral smear

Cytomegalovirus Infection

Leukocytosis (with Absolute Lymphocytosis)

Bordetella Pertussis Infection

Leukocytosis (with Absolute Lymphocytosis)

Due to redistribution of T Lymphocytes (Tissues → Circulation)

Lymphocytes are Small, Normal appearing Lymphocytes

Lymphocytic Leukaemoid Reaction

Peripheral smear shows ↑ Lymphocytes with Younger Lymphocytes seen

Can occur with TB, Chicken Pox, Bordetella Pertussis

Lymphocytopenia

Response to Stress, Corticosteroids

Immune Defi ciency Disorders – AIDS, SLE

After exposure to physical agents – Radiation

Administration of Cytotoxic Drugs

Infectious Hepatitis

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