MODULE 2 UNIT 4: LEUKOCYTOSIS Flashcards
are a heterogenous group.
Leukocytes
2 types of Leukocytes
granulocytes and agranulocytes
The granulocytes together with the monocytes share the (?) while the lymphocytes have their (?).
- same lineage with the red cells (CFU-GEMM)
- own (CFU-L)
pertains to the production and development of the three granulocytes.
Ganulopoiesis
Give the three granulocytes.
neutrophils, eosinophils and basophils
Give the three granulocytes.
neutrophils, eosinophils and basophils
The maturation sequence is almost similar for the three types of cells, except for the (?) that influence production and differentiation.
cytokines
Maturation Sequence of Neutrophil Development
I. Stem cell pool
II. Mitotic pool
III. Maturation pool
IV. Neutrophil
Pluripotential hematopoietic stem cell
Stem cell pool
Mitotic pool
Progenitors:
a. CFU-GEMM (Common Myeloid Progenitor)
b. CFU-GM (Granulocyte-Macrophage Progenitor)
c. CFU-G
Mitotic pool
Precursors:
d. Myeloblast
e. Promyelocytes
f. Myelocytes
Maturation pool
Precursors:
a. Metamyelocytes
b. Neutrophilic band
MYELOBLAST
Size (um)
N:C ratio
Nucleus Shape
Chromatin
Nucleoli
Staining
Granules
14 to 20
8:1 to 4:1
Round to oval
Homogenous, delicate, fine euchromatin
2 to 4
Slightly basophilic
No Granules
PROMYELOCYTE
Size (um)
N:C ratio
Nucleus Shape
Chromatin
Nucleoli
Staining
Granules
16-25
3:1 to 2:1
Round to oval
Heterochroma tin Slightly coarse
1-3
Basophilic
Formation of PRIMARY/ Azurophilic granules
PROMYELOCYTE
Size (um)
N:C ratio
Nucleus Shape
Chromatin
Nucleoli
Staining
Granules
16-25
3:1 to 2:1
Round to oval
Heterochroma tin Slightly coarse
1-3
Basophilic
Formation of PRIMARY/ Azurophilic granules
MYELOCYTE (“Dawn of Neutrophilia”)
Size (um)
N:C ratio
Nucleus Shape
Chromatin
Nucleoli
Staining
Granules
12-18
1:1
Oval or round
Coarser and condensed
NONE
Mixture of basophilic and acidophilic
Formation of SECONDARY / Specific granules “Dawn of Neutrophilia ”
METAMYELOCYTE
Size (um)
N:C ratio
Nucleus Shape
Chromatin
Nucleoli
Staining
Granules
15-18
1:1
KIDNEY-SHAPED
Coarse & clumped
NONE
Beige/ salmon
Formation of TERTIARY/ Gelatinase granules
BAND/STAB
Size (um)
N:C ratio
Nucleus Shape
Chromatin
Nucleoli
Staining
Granules
9-15
1:1 to 1:2
Elongate/ band (C or S)
Coarse & clumped
NONE
Beige/ salmon
Continuous formation of tertiary granules Formation of SECRETORY GRANULES (vesicles)
Cellular Activity of MYELOBLAST
0-3% of nucleated cells in BM
- Classification:
Type I blasts: No visible granules
“Granular blasts” Rare in normal marrow
Type II blasts: < 20 visible primary or azurophilic granules
Type III blasts: >20 visible primary or azurophilic granules
Cellular Activity of PROMYELOCYTE
1-5% BM Hof/ Paranuclear halo surrounding the nucleus
Cellular Activity of MYELOCYTE (“Dawn of Neutrophilia”)
6-17% BM
LAST STAGE CAPABLE OF MITOSIS
Cellular Activity of METAMYELOCYTE
3-20% BM
Formed during the promyelocyte stage
Last to be released (Exocytosis)
Primary (Azurophilic) Granules
Contain:
• Myeloperoxidase
• Acid-β- glycerophosphate
• Cathepsins
• Defensins
• Elastase
• Proteinase-3
• Others
Primary (Azurophilic) Granules
Formed during myelocyte and metamyelocyte stages
Third to be released
Secondary (Specific) Granules
Contain:
• β2- microglobulin
• Collagenase
• Gelatinase
• Lactoferrin
• Neutrophil gelatinase- associated lipocalin
• Transcobalamin I
• Others
Secondary (Specific) Granules
Formed during metamyelocyte and band stages
Second to be released
Tertiary Granules
Contain:
• β2- microglobulin
• Collagenase
• Gelatinase
• Lysozyme
• Acetyltransferase
Tertiary Granules
Formed during the band and segmented neutrophil stages
First to be released (fuse to plasma membrane)
Secretory Granules (Secretory Vesicles)
Contain (attached to the membrane):
• CD11b/ CD18
• Alkaline phosphatase
• Vesicle-associated membrane-2
• CD10, CD13, CD14, CD16
• Cytochrome b558
• Complement 1q receptor
• Complement receptor-1
Secretory Granules (Secretory Vesicles)
are also known as polymorphonuclear cells (PMNs) or segmenters.
Neutrophils
Neutrophils are the cells that respond to (?).
bacterial infection
Neutrophils average size ranges from (?) microns.
9 to 15 microns
The nucleus presents with (?) lobes with highly condensed chromatin.
2-5 lobes
The cytoplasm will contain continuously forming (?) secretory granules.
pink to rose-violet
- Normal values:
o Bone marrow:
o Relative value in peripheral blood:
o Absolute value:
o Bone marrow: 7-30% of nucleated cell population
o Relative value in peripheral blood: 50-70% of WBCs
o Absolute value: 1.7-7.5 x 109/ L
Neutrophil kinetics:
o Production:
o Mitotic pool:
o Maturation pool:
o Once in the peripheral blood, neutrophils are divided randomly into a (?) and a (?). The ratio of CNP and MNP is roughly equal.
o Majority of the MNP are in the (?) of the lungs.
o Production: 0.9-1.0 x 109 cells/ kg per day
o Mitotic pool: 2.11 x 109 cells/ kg
o Maturation pool: 5.6 x 109 cells/ kg
o Once in the peripheral blood, neutrophils are divided randomly into a circulating neutrophil pool (CNP) and a marginated neutrophil pool (MNP). The ratio of CNP and MNP is roughly equal.
o Majority of the MNP are in the capillaries of the lungs.
Transit time:
o HSC to myeloblast:
o Myeloblast to maturation pool:
o Neutrophil half-life in blood:
o It takes about (?) from the blast stage to the release of mature granulocytes.
o HSC to myeloblast: 6 days
o Myeloblast to maturation pool: 4 to 6 days
o Neutrophil half-life in blood: 6-8 hours
o It takes about 14 days from the blast stage to the release of mature granulocytes.
Neutrophil Function: a. Phagocytosis Steps
Chemical signals from damaged cells leading to chemotaxis → Margination (sticking to capillary endothelium) → Diapedesis → Recognition of pathogen→ Attachment (Toll-like receptor of phagocyte attaching to PAMPs) → Ingestion → Pathogen in phagosome → Formation of phagolysosome→ Digestion & killing
Respiratory burst through the activation of NADPH oxidase. H2O2 and peroxidase are produced
Oxygen dependent Digestion