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Leukocytes Be nign Disorders

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

Leukocytes Absolute Relative


(4-11 x૚૙ૢ/L) (x૚૙ૢ/L) (%)
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 Nu cleus Bi-lobed Nu cleus Occasionally seen Largest WBC Smallest WBC
Nucleus slightly indented with Large condensed nu cleus
clumped chromatin
Pale cytoplasm with irregular Coarse cytoplasmic granules Dark cytoplasmic granules Cytoplasm is abundant Scanty bluish cytoplasm
outlines (More deeply red staining) overlying nucleus Sky Clue in colour
(contain Heparin, Histamine) Contains many fine vacuoles
& granules
Many azurophilic granules Role in Become mast cells in tissues
1° granules (promyelocyte) Allergic responses
• Myeloperoxidase, Acid Defence against parasites Have IgE attachment sites &
Phosphatase, Hydrolases Removal of fibrin forme d during degranuatlion associated with
2° granules (specific granules) inflammation histamine release
• Collagenase, Lactoferin,
Lysozyme
Lifespan in Blood – 6 -10h
1° defence against infection
↑ in response to ↑ associated with ↑ associated with ↑ associated with ↑ seen in
Bacterial infection/ Allergic reaction Cancers Recovery from acute infection Most viral infections
inflammatory disease Parasite infections Allergic reactions Viral illness Bacterial infections
BM disorders (eg. CML) Chronic skin Infections Infections Parasitic infections Cancers
Cancers Radiation exposure Collagen disease Graves’ disease
Cancers
↓ as a result of ↓ associated with ↓ associated with ↓ associated with ↓ seen in
Severe infection Stress Stress reactions HIV infection Steroid exposure
Response to medications Steroid exposure Allergic reactions Rheumatoid arthritis (RA) Cancers
(chemotherapy) Anything – suppress WBC prod. Hyperthyroidism Steroid exposure Immunodeficien cy
Prolonged steroid exposure Cancers Renal failure
Lupus
Variations of Neutrophils
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Qualitative Benign Disorders Quantitative Disorders

Morphologic changes Total Leukocytes Description of cells


Functional defects in ≥ 1 WBC types ↑ (Leukocytosis) ↑ (Philia)
↓ (Leukopenia) ↓ (Penia)
Chediak-Higashi Syndrome
Inherited Morphological & Functional Abnormalities Leukocytosis
Rare Autosomal Recessive disorder ↑ Leukocytes ( >11 x10ଽ /L)
Giant Granules (in cytoplasm) Physiologic Pathologic
Neutrophils Stress Disease
Eosinophils Exercise Tissue Damage
Monocytes Epinephrine
Lymphocytes ≥ 1 Leukocytes can be responsible
Accompanied by Often due to ↑ Neutrophils
Neutropenia
Thrombocytopenia Mechanism of Leukocytosis (due to ↑ in)
Hepatosplenomegaly Neutrophil count (Neutrophilia)
Netrophils have Deficiency of Antimicrobial proteins Lymphocyte count (Lympho cytosis)
Disordered in Degranulation/ Chemotaxis Monocyte count (Mono cytosis)
Eosinophils cou nt (Eosinophilia)
Basophils cou nt (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

Pelger-Huet Anomaly
Basophilia Basope nia
Inherited Morphological Abnormalities
Hyperlipidemia Hyperthyroidism
Benign Autosomal Dominant
Small Pox/ Chicken Pox Acute Stress
Bi-Lobe d Neutrophils
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)
May-Hegglin Anomaly Inflammatory Bowel Disease
Inherited Morphological Abnormalities
Rare, Autosomal Dominant
Neutrophil contain large Basophilic inclusions of RNA similar: Dohle bodies

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 Immunodeficien cy System (SCIDS)
Neutrophil Hypersegmentation DiGeorge Syndrome
Morphological Abnormalities X Linked Agammaglobulinemia
Rare Autosomal Dominant condition Ataxia Telangiactasia
Neutrophil function is essentially Normal
Macrophage Disorders
Seen in Megaloblastic Anaemia
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 Eosinophilia
Neutrophilia/ Neutrophilic Leukocytosis > 0.5 x10ଽ /L
> 7.5 x10ଽ /L Causes
Pathophysiol ogy Allergic Diseases
Reaction mediated by Parasitic Diseases
• Growth Factors (eg. G-CSF, GM-CSF, C-Kit Ligand) Recovery from Acute Infection
• Adhesion molecules (eg. CD11b / CD18) Skin Diseases (Psoriasis, Dermatitis, Urticaria)
• Cytokines (eg. IL-1, IL-3, IL-6, TNF) Drug Sensitivity
Acute Chronic Graph Versus Host Disease
Occur 4-5 h after pathologic stimulus Follows acute neutrophilia HyperEosinophilic Syndrome (>1.5 x10ଽ /L)
↑ Cells Flow (BM → Peripheral) Left shift (BM release younger cells) Treatment with GM-CSF
Bands, Metamyelocytes seen
Lymphocytosis
Acquired, Quantitative
1° 2°
Self-Limited
Hereditary Infection
Both B-cells, T-cells Affected
Chronic Idiopathic Stress
Familial Myeloproliferative Disease Chronic inflammation Function – Normal
Morphology – Heterogenous
Leukaemoid reactions associated with Drugs
Absolute (>3x૚૙ૢ/L) Relative (>40%)
congenital anomalies Non-Haematological Neoplasms
Viral Infections 2° to Neutropenia
Leukocytes Adhesion Deficiency (LAD) Asplenia, Hyposplenism
May/ May Not Accompany
Familial cord Urticaria, Leukocytosis
Leukocytosis
Causes
2° Neutrophilia
Infections
Bacterial Infections (most common )
• Viral Infections (Infectious Mononucleosis, CMV, Rubella, Hepatitis,
Usually Absolute Neutrophilia
Adenoviruses, Chicken Pox, Dengue)
(10-19 x10ଽ /L)
Morphological changes • Bacterial Infections (Pertussis, Healing TB, Typhoid Fever)
Left shift • Protozoal Infections ( Toxoplasmosis)
Allergic Drug Reactions
Vacuolation
Dohle Bodies Hyperthyroidism
Toxic granulation Splenectomy
Serum Sickness

Leukaemoid Reaction Infectious Mononucle osis (IM)


Reactive, Excessive Leukocytosis Lymphocytosis
Characterized by Presence of Immature cells Accompanied by Leukocytosis
Caused by EBV (Epstein-Barr Virus) infecting B
Many Bands, Metamyelocytes, Myelocytes (Left-shift)
Promyelocytes, Myeloblasts (occasionally seen) Lymphocytes
Cytotoxic T cells Kill Infected B cells
Resembles CML but can be exclude d
Reactive Lymphocytes (Cytotoxic T cells) seen in
No Philadelphia chromosome
Transient (Temporary) peripheral smear
Elevated Leukocyte Alkaline Phosphatase score Cytomegalovirus Infection
No Basophilia 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

Neutropenia
< 1.8 x10ଽ /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) Lymphocytopenia
Response to Stress, Corticosteroids
Inherited (Kostmann’s syndrome ) Drug Therapy
Acquired (Drug induced) Infection (Adult – common ) Immune Defi ciency Disorders – AIDS, SLE
Cyclical Neutropenia Immunologic Disorders After exposure to physical agents – Radiation
(Inherited Autosomal Dominant) Idiopathic Neutropenia Administration of Cytotoxic Drugs
(Several days of Neutropenia with Autoimmune Neutropenia Infectious Hepatitis
infection followed by asymptomatic)
Familial (Benign, Chronic, Mild with
rare symptoms)
Infantile Genetic Agranulocytosis
(Rare, Congenital, Fatal disorder)
(Defective BM production of
Neutrophils)