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Leukocyte Disorders
Leucocytes differentiation
Granules in Neutrophils:
Primary granules: promyelocyte stage
Secondary granules: myelocyte stage and predominate therafter
Granulopoiesis
Neutrophil kinetics
Distribution of
Macrophages
Phagocytosis and bacterial
destruction1. Bacteria enter the
neutrophil surrounded by
invaginated cell
membrane
2. Fusion with primary
lysosome to form
phagosome.
3. Enzymes including
lactoferrin attack the
organism
Undigested bacteria
remains excreted by
exocytosis
Abnormal WBC
Toxic granules Dohle bodies Hypersegmented Basophilic inclusions
http://www.med-ed.virginia.edu/courses/path/innes/images/wcdjpeg/wcd%20leuko%20Eblastic%20x50.jpeg
Neutrophilia
>7.5 x 109/L
Other defining features:
1. Left shift
– Increased band forms
2. “toxic” cell
appearance
• Dohle bodies
• Vacuoles
• Intra-cellular
microbes
Causes of Neutrophilia
• Infections • Other
o (primarily bacterial) o autoimmune disorders
• Drugs/Hormones o stress
o severe physical activity
o epinephrine
o pregnancy
o corticosteroids
o smoking
o lithium
o acute hemorrhage
o venoms/poisons/toxins o post-splenectomy
• Tissue necrosis o myeloproliferative disorders
o acute gout • Metabolic
o burns o ketoacidosis
o trauma o uremia
o infarcts o eclampsia
o thyrotoxicosis
Graphic accessed URL http://www.med-ed.virginia.edu/courses/path/innes/wcd/leukocytosis.cfm, 2010.
Pathophysiology
Demargination of • Stress
marginated pool of cells (pseudoneutrophilia)
doubling of count
Release of BM-storage Acute Inflammation
pools
left shift
Increased cell production
• Chronic Infection
sustained neutrophilia
Eosinophilia
Absolute count >0.5 x 109/L
Causes:
parasites
Helminths
drug treatments
allergies
infections
neoplasms
Chronic myeloid leukemia
(CML)
autoimmune disorders
Basophilia
Absolute count >0.15 x 109/L
Causes:
CML
allergies
inflammatory
disorders
irradiation
viral infections
Monocytosis
Absolute count >0.8 x 109/L
Most commonly seen in
conditions with increased cell
damage -
Chronic infection [TB, syphilis,
protozoal infections, rickettsial
infections]
Recovery from agranulocytosis
Post-splenectomy
Strenuous exercise
Subacute bacterial endocarditis
Neutropenia
< 2.5 x 109/L
• Definition: less than the normal Causes
absolute count; greatly influenced • Reactions to Drugs
by patient age and race. – BM ablative therapy
– African and Middle Eastern
populations • Infections
– HIV/Hepatitis
• Subclasses include mild, moderate
and severe – Typhoid/ miliary TB
– Malaria
• Immune Disorders
– Systemic lupus erythromatous (SLE)
• Neoplasm
• BM Failure
– Megaloblastic Anemia
– Aplastic Anemia
• Hypersplenism
• Idiopathic (of unknown cause).
Neutropenia Pathophysiology
Defects inside or outside the Bone Marrow
Decreased proliferation [failure of cells - aplasia]
Decreased maturation [insufficient number of
precursors undergoing abnormal maturation]
Decreased survival [increased destruction and/or
rapid removal of cells]
Distribution [total body pools are normal,
circulating numbers are reduced]
Lymphocytosis
Absolute count >5.5 x 109/L
Normally: • Causes
60-80% circulating – Infections
• Viral
lymphs are T-cells – Infectious mononucleosis
[2:1 CD4/CD8] • Bacterial
– Pertussis
10-20% are B-lymphs – Thyrotoxicosis
5-10% are natural – Recovery from acute
killer or NK cells infections
– Neoplasm
• Leukemias
• Lymphomas
Infectious Mononucleosis
• Acute, self-limiting, febrile infection
of B-cells
• Circulating reactive lymphocytes are
primary CD8 T-cells
• Typically occurs in those age 10-25
years
Fever
Sore throat
Lymphadenopathy
Lethargy
Decreased production
Increased destruction
Changes in distribution
Lymphopenia
– Decreased production – Redistribution
SCID = severe Glucocorticoid
combined therapy
immunodeficiency
Anesthesia
Protein-calorie
malnutrition TB
Zinc deficiency Influenza
– Increased destruction Burns
HIV infection – Other
Radiation therapy Hodgkin’s
Neoplastic Myasthenia gravis
chemotherapy
SLE
Qualitative Think
Morphology
Alder Reilly
Chediak Higashi
Bordatella pertussis
• Whooping Cough
– BUTT CELL