Download - MLAB Hematology Keri Brophy-Martinez
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
Leukopenia
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
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, Dhle 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 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 Gauchers Disease Enzyme deficiency:
-glucocerebrosidase
Prevalent in the Ashkenazi Jewish population (eastern European)
Macrophage can not digest the stroma of ingested cells Results in
an accumulation of glucocerebroside Gauchers Cell Large histiocyte
(20-100 m)
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