Download MLAB 1315- Hematology Fall 2007 Keri Brophy

MLAB 1415- Hematology
Keri Brophy-Martinez
Chapter 19:
Granulocyte and Monocyte Disorders
Review: Neutrophil Function
The contents of primary,
secondary and tertiary
granules in neutrophils are
enzymes which are involved
in killing and digesting
bacteria and fungi.
Review: Neutrophil Function
 Primary function is phagocytosis
which occurs in three stages.
 Stage 1: Migration and diapedesis
 Chemotaxis is the process of directional
migration which occurs under the guidance
of chemoattractants which are produced by
the site of injury.
 The neutrophil transforms from smooth and
round to rough and flat.
 Diapedesis is the movement of the
neutrophil through the vessel wall.
Review: Neutrophil Function
 Stage 2: Opsonization and
recognition
 Opsonization is the mechanism
which facilitates recognition and
attachment to the organism to be
ingested.
 After the bacteria is coated by
immunoglobulin and complement, it
is referred to as an opsonin.
Review: Neutrophil Function
 Stage 3: Phagocytosis: Ingestion,
killing and digestion
 The cytoplasm of the neutrophil forms
a pseudopod which surrounds and
envelops the microorganism forming a
vacuole called a phagosome.
 Cytoplasmic granules migrate to the
vacuole and release their lytic
contents which kill and digest the
organism.
Disorders
 Affects granulocytes and
monocytes
 Response to various
nonmalignant disease states
and toxic changes
 Changes can be qualitative or
quantitative
Terms
 Leukocytosis
 Total leukocyte count is more than 11.0
x 109/L in adult
 Most commonly caused by increase in
neutrophils
 Leukopenia
 Decrease in leukocytes below 4.5 X 109/L
 Most commonly caused by decrease in
neutrophils
Disorders of Neutrophils:
Quantitative
 Causes
 Malignant
 Neoplastic transformation of
hematopoietic stem cell (discussed
later)
 Benign
 Acquired
 Neutrophilia: increase in total
circulating absolute neutrophil
concentration
 Neutropenia
Neutrophilia


ANC > 7.0 x 109/L
Occurs as a result of a reaction to a pathologic or
physiologic process (reactive neutrophilia)



Immediate
 Increase lasts about 20-30 minutes
 Redistribution of neutrophils from marginal pool to circulating pool
 Neutrophils are mature
 Seen in acute exercise, anxiety
 “shift neutrophilia” or “pseudoneutrophilia”
Acute
 Occurs 4-5 hours post-pathologic stimulus (i.e bacterial infection)
 Increase in flow of neutrophils from the bone marrow pool to the blood
 Immature neutrophils numbers may increase
Chronic
 Follows acute neutrophila, if the stimulus continues beyond a few days
 Storage pool in bone marrow depletes
 Bone Marrow show increased numbers of early neutrophil precursors
 “shift to the left”
Conditions Associated with
neutrophilia
 Reactive Chronic
neutrophilia
 Leukocytes< 50 x 10 9/L
 Shift to the left
 Presence of toxic granulation,
DÖhle bodies and cytoplasmic
vacuolization
Dohle bodies
Toxic granulation
Neutrophilic Conditions



Bacterial Infection
 Most common cause of neutrophilia
 Seen with staphylocci and streptococci infections
 Bone marrow increases output of storage neutrophils to peripheral
blood, see shift to the left
Physiologic leukocytosis
 No shift to the left
 Birth to the first days of life
 Childbirth
 Extreme temperatures
 Emotional stimuli
Tissue destruction/Injury, Metaboloic disorders
 Neutrophil input is increased from the bone marrow to the tissue
 Examples include: Rheumatoid arthritis, burns, gout, uremia,
trauma
Neutrophilic Conditions
 Leukoerythroblastic reaction




Presence of nRBCs
Shift to the left
Poik, tear drops, aniso
Associated with chronic neoplastic myeloproliferative
conditions
Neutrophilic Conditions
 Leukemoid reaction






Leukocytes> 50 x 10 9/L
Advanced degree of leukocytes in
the blood that is not a result of
leukemia
Transient; leaves when stimulus is
removed
Many circulating immature
leukocyte precursors seen
Seen in chronic infections,
carcinoma of certain organ systems
Blood picture similar to chronic
myelocytic leukemia(CML)
 Leukocyte Alkaline
Phosphatase, is used to
differentiate leukemoid reaction
from CML
 LAP increased in leukemoid
reaction, decreased in CML
Neutropenia
 ANC <1.5 x 109/L
 Causes
 Increased cell loss
 Increased neutrophil diapedesis (Tissue egress)
 Bone marrow can not keep up with cell utilization
 Examples: immune neutropenia, hypersplenism
 Megaloblastic Anemia
 Hypeplastic bone marrow
 Abnormal myeloid cells destroyed
 Decreased bone marrow production
 M:E ratio decreased
 Myeloid hypoplasia
 Storage pool in bone marrow decreased, as is
circulating and marginal pool
 Examples: stem cell disorders, aplastic anemia,
chemicals/drugs
Cytoplasmic Inclusions
Inclusion
Characteristic
Composition
Conditions
Döhle body
Light gray-blue oval near
periphery
Rough endoplasmic
reticulum (RNA)
Infections,
burns, cancer,
inflammatory
states
Toxic granules
Large blue-black granules
Primary granules
Same as above
Cytoplasmic
vacuole
Clear, unstained circular area
Open spaces from
phagocytosis
Same as above
Bacteria
Small basophilic rods or cocci
Phagocytized
organisms
Bacteremia or
sepsis
Fungi
Round or oval basophilic
inclusions, larger than bacteria
Phagocytized
organisms
Fungal
infections
Morulae
Basophilic, granular, irregular
shape
Clusters of Ehrlichia
rickettsial organims
Ehrlichiosis
Nuclear Abnormalities
Anomaly
Description
Conditions
Pelger-Huët
•Neutrophil nucleus is bi-lobed or
has no lobes
• May have a “pince-nez”
appearance
• clumped chromatin
•Can be real or pseudo
caused by drug ingestion
or leukemia
Hypersegmentation
•larger than normal neutrophils
with 6 or more nuclear lobes.
•Megaloblastic anemia
Pyknotic nucleus
•Degenerating nucleus
•Dying neutrophils
PelgerHuët
Pyknotic
Inherited Functional
Abnormalities
Condition
Morphologic or
Functional Defect
Clinical Features
Alder-Reilly
•Large, dark cytoplasmic
granules in all leukocytes
•Cells function normally
Associated with
mucopolysaccharidosis
Chediak-Higashi Syndrome
•Giant fused granules in
neutrophils and lymphs
•Cells engulf but do not kill
microorganisms
Often fatal due to recurrent
pyrogenic infections
May-Hegglin
•Blue, Döhle-like
cytoplasmic inclusions in
granulocytes
•Cells function normally
•Bleeding tendency from
thrombocytopenia
•Giant platelets
Chronic granulomatous
disease
•Defective respiratory burst
•Cells engulf but do not kill
microorganisms
•Recurrent infections, esp.
in childhood
•Prognosis poor
Myeloperoxidase deficiency
•Low or absent
myeloperoxidase enzyme
•Cell morphology normal
benign
Monocyte/Macrophage
Disorders
Quantitative
Monocytes only
Qualitative
Monocytes and
macrophages
Quantitative
 Monocytosis
 AMC > 0.8 x 109/L
 Seen in inflammatory
conditions and malignancies
 Monocytopenia
 AMC < 0.2 x 109/L
 Seen in stem cell disorders
Qualitative
 LIPID (LYSOSOMAL)STORAGE
DISEASES
 Inherited disorders
 Accumulation of unmetabolized material
in the lysosomes of various cells. They
are caused by various enzyme defects
(inborn errors) in lipid metabolism linked
to an enzyme deficiency
 Three main disorders
Disorder #1
 Gaucher’s Disease
 Enzyme deficiency: βglucocerebrosidase
 Prevalent in the Ashkenazi Jewish
population (eastern European)
 Macrophage can not digest the stroma
of ingested cells
 Results in an accumulation of
glucocerebroside
Gaucher’s Cell
 Large histiocyte (20-100
µm)
 Displaced nucleus which
contains one or more
round nucleoli
 Cytoplasm is faintly
blue/white with
characteristic “crumpled
tissue paper” appearance
which is probably the
result of glycolipid
deposition
Disorder #2
 Niemann-Pick Disease
 Enzyme deficiency: sphingomyelinase
 Increased incidence in the Jewish population
 Causes an accumulation of unmetabolized
sphingomyelin and cholesterol
 Classic form presents with jaundice at birth,
hepatosplenomegaly, enlarged lymph nodes,
neurological symptoms, retarded physical
and mental development. Death occurs by
age 3.
Niemann-Pick Cell
 Lipid-laden giant
foamy cell found in
BM, tissues and
other organs
Disorder #3
 Tay Sachs Disease
 Enzyme deficiency: hexosaminidase A
 Higher incidence in Ashkenazi Jewish population
 Severity of the disease correlates with residual
enzyme activity.
 The buildup of unmetabolized GM2 ganglioside
in the tissues has devastating effects in the
central nervous system and eye.
 Physical and mental deterioration occur along
with seizures and paralysis. Death comes by
age 4.
Tay Sachs Disease
 Foamy lymphocytes are present but are not
diagnostic
 The blue cells seen here are abnormally
enlarged neurons