Leukocytes Be Be nign Disorders Normal Peripheral Peripheral Blood Blood
Format ion of Phagocytes Phagocytes in Bone Bone Marrow
Leukocytes Leukocytes Diff erential Counts Counts Leukocytes (4-11 x /L /L)) Neutrophils Eosinophils
Absolute (x /L) /L) 2.5 - 7.5 0.04 - 0.4
Relative (%) 34 – 75 0–5
Basophils Lymphocytes Monocytes
0.01 - 0.1 1.5 - 3.0 0.2 - 0.8
0 -3 20 - 45 3 - 10
White Blood Cells Neutrophils Neutrophils
Eosinophils Eosino phils
Basophils Basophils
Monocytes Monocytes
Lymphocytes Lymphocytes
2-5 Lobes o f dense dense Nucleus
Bi-lobed Nucleus
Occasionally Occasionally seen
Largest WBC Nucleus Nuc leus 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 overlyi ng nucleus nucleus (contain (contain Hepari n, Hista mine)
Cytoplasm is abundant Sky Clue in colour colour Contains many fine vacuoles & granules
Scanty bluish cytoplasm
Many azurophilic granules 1° gr anules (promyelocyte) (promyelocyte)
Role in Aller gic responses responses Defence Defence against par asites Removal of fibri fibrin n forme forme d during inflammation
Become mast cells in tissues Have Ig E attachment attachment sites & degranuatlion associated with histamine release
↑ associated with Aller gic reaction reaction Parasite infections infections Chronic skin Infections Cancers
↑ associated with Cancers Allerg ic reactions reactions Infections Radiation exposure
↑ seen in Most v iral infections infections Bacterial infections infections Cancers Graves’ disease
↓ associated with Stress Steroid exposure exposure Anything – suppress WBC prod.
↓ associated with Stress reactions Allerg ic reactions reactions Hyperthyroidism Prolonged steroid exposure
↑ associated with Recovery from acute infection Viral illness illness Parasitic infections infections Collagen disease Cancers ↓ associated with HIV infection infection Rheumatoid Rheumatoid arthri tis (RA) Steroid exposure exposure Cancers
Myeloperoxidase, Acid Phosphatase, Phosphatase, Hy drolases 2° granules (specific granules) Collagenase, Lactoferin, Lactoferin, • Lysozyme Lifespan in Blood – 6-10h 1° defence against infection ↑ in response to Bacterial infection/ infection/ inflammatory inflammatory disease BM disorders (eg. CML) •
↓ as a result of Severe infection infection Response to medications (chemotherapy)
Variations of Neutrophils Neutrophils
↓ seen in Steroid exposure exposure Cancers Immunodeficiency Renal failure Lupus
Qualitative Benign Disorders
Quantitative Quantitative Disorders Disorders
Morphologic changes Functional defects in ≥ 1 WBC types
Total Leukocytes Leukocytes ↑ (Leukocytosis)
Description Description of cells ↑ (Philia)
↓ (Leukopenia)
↓ (Penia)
Leukocytosis ↑ Leukocytes ( >11 x 10 /L) Physiologic
Pathologic
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 Deficiency of Antimicrobial proteins Disordered in Degranulati on/ Chemotaxis Chemotaxis
Stres Exercise Epinephrine ≥ 1 Leukocytes can be responsible
Diseas Disease e Tissue Damage
Often due to ↑ Neutrophils Mechanism of Leukocytosis (due to ↑ in) Neutrophil count (Neutrophilia) Lymphocyte count (Lympho cytosis cytosis)) Monocyte count (Mono cytosis cytosis)) Eosinophils Eosinophils count (Eosinoph (Eosinophilia) ilia) Basophils count (Basophilia)
Other Causes of Benign Leukocytes Disor der Eosinophilia Eosinope Eosinop e nia
Pelger-Huet Pelger-Huet Anomaly Inherited Morphological Abnormalitie Benign Autosomal Dominant Bi-Lobe Bi-Lobe d Neutrophil s
May-Hegglin Anomaly Inherited Morphological Abnormalitie Rare, A utosomal utosomal Dominant Dominant
Allerg ic disorders (Asthma, (Asthma, Hay Hay Fever) Fever) Tissue parasite infection infection Dermatoses (Eczema) Drugs
Str ess (Release (Release of of Epinephrine) Epinephrine) Aftermath of Acute Inflammation Inflammation
Basophilia Hyperlipidemia Small Pox/ Pox/ Chicken Chicken Pox
Basopenia Hyperthyroidism Acute Stres
Chronic Chronic Si nusitis Ulcerative Coliti Monocytosis (↑ Cell Damage cases) Recovery Recovery from Acute Infection Infection Tissue Trauma Bacterial Endocarditis TB Collagen Disorders (RA, SLE) Post Splenectomy (Monocytes busy cleaning up Neutrophils) Inflammatory Inflammatory Bowel Disease
Monocytopenia Prednisone Prednisone Therapy
Neutrophil contain large Basophilic inclusions of RNA similar: Dohle bodies Monocyte Disorders Inherited Abnormalities of Neutrophils are also seen in Monocyte (Originate from Common Stem Cell) Chronic Chronic Granulomatous Disease (Defective Respirat Respirat ory Buss) Buss) Chediak Higashi (Abnormal Lysosomes caused by Fusion of 1° Granules) Alder Reilly Anomaly Anomaly (Large (Large Purple-Blue Purple-Blue Granules) Lymphocytes Disorders Wiskott-Aldrich Sy ndrome ndrome Severe Combined Combined Immunodeficiency Immunodeficiency S ystem (SCIDS) Neutrophil Neutrophil Hypersegmentation Morphological Morphological A bnormaliti bnormaliti es Rare Autosomal Dominant condition Neutrophil Neutrophil function function is essentially Normal Normal Seen in Megaloblastic Anaemi
DiGeorge Sy ndrome ndrome X Linked Agammaglobulinemia Agammaglobulinemia Ataxia Telangiactasi Macrophage Disorders Lipid Storag e Diseases (cells unable to digest phagocytosed phagocytosed material complete) complete) Gaucher’s Gaucher’s Disease Niemann-Pick Diseases Tay Sachs & Sandhoffs Diseases
Neutrophilia Neutrophilia/ Neutrophilia/ Neutrophilic Neutrophilic Leukocytosis Leukocytosis > 7.5 x10 /L Pathophysiology Pathophysiology 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 Occur 4-5h after pathologic stimulus ↑ Cells Flow (BM (BM → Peripheral) Bands, Bands, Met amyelocytes seen
Follows acute neutrophili neutrophili Left Left shift shift (BM (BM release younger cells)
1° Hereditary Chronic Chronic Idiopathic Familial Myeloproliferative Diseas
2° Infection Str es Chronic Chronic inflammation
Leukaemoid Leukaemoid reactions associated wit h congenital congenital anomalies Leukocytes Adhesion Deficiency (LAD) (LAD)
Drugs Non-Haematological Neoplasms Asplenia, Aspleni a, Hyposplenism
Familial cord Urticaria, Urticaria, Leukocytosis 2° Neutrophilia Bacterial Bacterial Infections Infections (most common) Usually A bsolute Neutrophilia Neutrophilia (10-19 x 10 /L) Morphological changes Left shift Vacuolation Dohle Bodies Toxic Toxic gra nulation
Eosinophilia > 0.5 x10 /L Causes Allergic Diseases Parasitic Diseases Recovery from Acute Infection Ski n Diseases (Psoriasis, (Psoriasis, Dermatitis, Urticaria) Urticaria) Drug Sensitivity Graph Versus Host Disease HyperEosinophilic HyperEosinophilic Syndrome (>1.5 x 10 /L) Treatment w ith GM-CSF Lymphocytosis Acquired, Quantitativ Self-Limited Both B-cells, T-cells Affected Function – Normal Morphology – Het erogenous Absolute Absolute ( >3x /L) /L) Vir al Infections Infections May/ May Not Accompany Leukocytosis
Relative (>40%) 2° to Neutropenia Neutropenia
Causes Infections •
Vira l Infections (Infe (Infectious ctious Mononucleosis, Mononucleosis, CMV, Rubella, Rubella, Hepatitis, Adenoviruses, Chicken Pox, Dengue)
Bacterial Infections (Pertussis, (Pertussis, Healing TB, Typhoid Fever ) Protozoal Infections Infections ( To xoplasmosis) xoplasmosis) Allerg ic Drug Reactions Reactions Hyperthyroidism Splenectomy Serum Sickness • •
Infectious Infectious Mon onucleosis onucleosis ( 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 Bordetella Pertussis Infectio n Leukocytosis (with Absolute Lymphocytosis) Due to redistribution of T Lymphocytes (Tissues → Circulation) Lymphoc Lymphocytes ytes are Small, Normal Normal appearing Lymphocytes Lymphocytes
Leukaemoid Leukaemoid Reaction Reactiv Reactiv e, Excessive Excessive Leukocytosis Leukocytosis Characterized Characterized by Presence Presence of Im mat ure cells Many Bands, Metamyelocytes, Myelocytes (Left-shift) Promyelocytes, Promyelocytes, Myeloblasts (occasionally (occasionally seen) Resem bles CML but can be excluded No Philadelphia chromosome Transient (Temporary (Temporary ) Elevat ed Leukocyte Alkaline Phosphatase Phosphatase score score No Basophilia
Lymphocytic Lymphocytic Leukaemoid Leukaemoid Reaction Peripheral smear shows ↑ Lymphocytes with Younger Lymphocytes seen Can occur occur wi th TB, Chicken Pox, Pox, B ordetella Pertussis
Neutropenia < 1.8 x10 /L Can be due to Impaired production by BM Shift from circulating circulating pool to marginat ed pool ↑ Peripheral destruction <0.5 x /L Likely to have have recurrent infections infections 1° Inherited (Kostmann’s (Kostmann’s syndrome syndrome ) Acquired (Drug induced) Cyclical Neutropenia Neutropenia (Inherited Autosomal Dominant) (Several days of Neutropenia Neutropenia with infection followed by asymptomatic) Familial (Benign, Chronic, Mild with rare symptoms) symptoms) Infantile Infantile Genetic Agranulocytosis (Rare, (Rare, Congenital, Congenital, Fat al disorder) disorder)
<0.2 x /L
Very serious serious risk 2° (↑ common) Drug Therapy Infection (Adult – common) Immunologic Disorders Idiopathic Neutropenia Autoimmune Neutropenia
Lymphocytopenia Response Response to S tress, Corticosteroids Corticosteroids Immune Immune Deficiency Disorders – A IDS, S LE After exposure exposure t o physical agents – Radiation Administration of Cytotoxic Drugs Infectious Infectious Hepatiti s
