Benign

disorders
of white cells

CHAPTERS 8 AND 9
Benign disorders involving
white blood cells
Classification
Disorders of cell number
--cytosis (-philia)
- cytopenia
Disorders of function and morphology
White blood cells
Fig 9.2
Granulopoiesis

Post-mitotic
maturation
compartment
 Control of granulopoiesis
SCF, IL3, GM-CSF, G-CSF
G-CSF used following post
chemo-,radiotherapy or
stem cell/bone marrow
transplantation.
Speeds up granulocytic
recovery
 Neutrophils
2.5 - 7.5 x 109/L (Blacks and Middle Eastern individuals
often lower)
6-10 h in peripheral circulation then move into tissues (last
4-5 days)
Chemotaxis, phagocytosis
Morphology
contain granules primary (promyelocyte) secondary
(myelocyte)
primary contains myeloperoxidase and acid phosphatase
secondary contains collagenase, lactoferrin and lysozyme
Neutrophilia

Neutrophils > 7.5 x 109/L

Most often observed
change in blood count
analysis
Causes
 Clinical symptoms
Often associated with fever - release of
pyrogens
Other features
Generally neutrophilia is accompanied
by increase in total wbc count
Left shift - ie more band forms are seen
and occasionally other immature forms
Presence of toxic granulation and Dhle
bodies
 Neutropenia
Less than 0.5 x 109/L
May be selective or due to pancytopenia
Patient susceptible to recurrent infections
Causes (Table 8.4)
Drug-induced
anticonvulsants, antibacterial, anti-
inflammatory, antidepressants - many more
 Immune
antibodies to surface antigens either
facilitate destruction or impair prod. of
neutrophils
Infectious disease
hepatitis, influenza
typhoid
Congenital
Kostmanns syndrome
Presents in first year
Life-threatening infections
Mutation in the neutrophil elastase gene
 Clinical features of
neutropenia
Infections of mouth and throat
- ulceration
Normal flora may become
pathogenic (Staph, Strep,
Pseudomonas, E.coli)

Fig. 8.10
Diagnosis
Need to differentiate increased destruction
from decreased production - BM
Lack of release from BM stores
Depends on aetiology
BM examination often useful if aetiology is
unclear
Treatment
Drug induced - recovers spontaneously
Aggressive antibiotic, antiviral and
antifungal therapy
Use of G-CSF - stimulate neutrophil
production
Function/morphological
disorder of neutrophils
Chediak-Higashi syndrome
autosomal recessive
abnormal fusion of cytoplasmic granules -
giant granules
neutrophils less chemotactic and adherent
ingest foreign particles normally but
intracellular killing is defective
usually associated with neutropenia
assoc. with recurrent infections
Fig 8.8
Eosinophils
Refractile orange-red granules and
segmented nuclei (bilobed)
Granules (major basic protein (MBP),
hydrolytic enzymes, peroxidase
Function
first line of defense against parasites
modulate hypersensitivity reactions migrate to inflammatory sites
Eosinopenia
Rarely noted
Persistently low peripheral eosinophil count
- reason unknown
Aetiology
acute infections
administration of some drugs
 Eosinophilia >
0.4 x 109/L

Fig. 8.11
Hypereosinophilic
syndrome
above 1.5 x 109/L for over 6 months
assoc. with tissue damage (inapprop.
release of lysosomal enzymes)
heart valves, skin, lungs
therapy - steroids, cytotoxic drugs
 Basophils
Normal level is very low - 0.01-0.1 x 109/L
Purple-blue cytoplasmic granules (few and
large)
Functions
immediate hypersensitivity (asthma,
anaphylaxis)
 Basopenia not usually diagnosed since
normal level is very low (2% of wbc)
Basophilia (> 0.1 x 109/L)
Uncommon
common with myeloproliferative disorders
(CML)
sometimes associated with smallpox or
chickenpox infection and ulcerative colitis
Monocytes
Usually 1-6% of cells in peripheral blood (0.2-
0.8 x 109/L)
BM monocytes also give rise to macrophages
(lifespan months to years)
Nucleus slightly indented (cashew nut)
Granules
lysosomal group - fuse with phagosomes to form secondary
lysosomes
group of unknown function
 Monocyte functions
activated by stimuli - increase cell size and level of
lysosomal hydrolases
chemotaxis
phagocytosis
red cell removal
resistance to phagocytosis
tissue destruction
neoplastic cell destruction
 Monocytopenia
Usually due to generalized decrease in wbc
count
Autoimmune disorders, hairy cell leukaemia,
chemotherapy

Monocytosis
 Lipid storage diseases
Gauchers disease
Autosomal recessive
Abnormal accum. of lipids in monocytes and macrophages of
spleen, liver and BM
Defective lysosomal glucocerebrosidase
Gauchers cells secrete proteins which cause secondary
pathology
cholesterol gallstones, pulmonary hypertension.
Anaemia, leukopenia, thrombocytopenia
 Enzyme replacement therapy
Glucocerebrosidase made by
recombinant technology Cerezyme
Given fortnightly - intravenously
Shrinkage of spleen
Summary
Overview of function of the
white cells
Leukocytosis/leukophilia
versus leukopenia
Always be on the look out for
pancytopenia