Leukocyte Development, Kinetics, and Functions Flashcards
Two categories
- Granulocytes
- Mononuclear cells
are a group of leukocytes whose cytoplasm is filled with granules with differing staining characteristics and whose nuclei are segmented or lobulated.
Granulocytes
categorized into MONOCYTES and LYMPHOCYTES. These cells have nuclei that are not segmented but are round, oval, indented, or folded.
Mononuclear cells
The number of circulating leukocytes vary depending on:
• Sexandage
• Activity andethnicity
• Timeofday
• Differs according to whether or not the leukocytes are reacting to stress, being consumed, orbeing destroyed, and whetheror not they are being produced by the bone marrowinsufficient numbers.
NormalValues:
Adult:
Children:
Newborn:
Adult: 3.6– 10.6 x 10³/µL or 3.6 x10.6x10⁹/L Children: 5.0– 17.0 x 10³/µL or 5.0–17.0x 10⁹/L Newborn:8.0–24.0x10³/µL or 8.0–24.0x10⁹/L
Overall function of leukocytes is in mediating immunity:
• Innate
• Adaptive
Neutrophils in two forms:
Segmented
Band shape
Major cytokine responsible for the stimulation:
Granulocyte Colony-Stimulating Factor (G-CSF)
also known as colony-forming units granulocyte, erythrocyte, monocyte and megakaryocyte(CFU-GEMMs)
CMP
consists of HSCs that are capable of self-renewal and differentiation.
Stem cell pool
consists of cells that are dividing
Proliferation pool
consists of cells undergoing nuclear maturation that form the marrow reserve and are available for release
Maturation pool
(Maturation pool)
Releases:
metamyelocytes, band neutrophils, and segmented neutrophils
Proliferation pool releases
Myeloblast
Promyelocytes
Myelocytes
is characterized by:
• A high N:C ratio of 8:1 to 4:1;
• Slightly basophilic cytoplasm;
• Fine nuclear chromatin; and
• Two to four visible nucleoli.
• It has no visible granules when observed under light microscopy with Romanowsky stain.
Type 1 myeloblasts
Shows the presence of dispersed primary (azurophilic) granules in the cytoplasm which does not exceed 20 per cell
Type II Myeloblast
• Have a darker chromatin and a more purple cytoplasm
• Rare in normal bone marrows, but they can be seen in certain types of acute myeloidleukemias
Type III myeloblasts
It has been proposed to combine Type II and Type III blasts into a single category of
granular blasts
• Comprise 1% to 5% of the nucleated cells in the bonemarrow.
• Relatively larger than the myeloblast cells and measure16 to25 µmindiameter.
Promyelocyte
• Nucleus: round to oval and is often eccentric.
• A paranuclear halo or “hof” is usually seen in normal promyelocytes but not in the malignant promyelocytes of acutepromyelocytic leukemia.
• Chromatin clumping may be visible, esp. around the edges of the nucleus.
• One to three nucleoli may be seen but may be obscured by thegranules
Promyelocyte
• The cytoplasm is evenly basophilic and full of primary (azurophilic) granules. These granules are the first in a series of granules to be produced during neutrophil maturation
Promyelocyte
• Make up 6% to 17% of the nucleated cells in the bone marrow
• Final stage to whichmitosis occurs
• Cell begins to manufacture secondary (specific) neutrophil granules.
Neutrophil myelocytes
may look very similar to the promyelocytes in size and nuclear characteristics except that patches of grainy pale pink cytoplasm representing secondary granules begin to be evident in the area of the Golgi apparatus, referred to as “dawn of neutrophilia”. The granules eventually turn more lavender-pink than blue.
Early myelocytes
measures 15– 18 µm, and the nucleus has considerably more heterochromatin. Nucleoli are difficult to see by light microscopy.
Late myelocytes
• Consists of 3% to 20% of nucleated marrow cells.
• The nucleus is indented (kidney bean shaped or peanut shaped), and the chromatin is increasingly clumped.
• Synthesis of tertiary (gelatinase) granules may begin during this stage.
• Cytoplasm contains very little residual RNA and therefore little or no basophilia
Neutrophil metamyelocytes
• Makes up 9% to 32% of nucleated marrow cells and 0% to 5% of the nucleated peripheral blood cells.
• Evidence of basophilia is absent
• Secretory granules, also known as secretory vesicles, may begin to be formed during this stage.
• Nucleus is highly clumped and nuclear indentation that began in the metamyelocyte stage now exceeds one half the diameter of thenucleus.
Neutrophil band
• Make up 7% to 30% of nucleated cells in the bone marrow.
• Secretory granules continue to be formed • The only morphologic difference between segmented neutrophils and bands is the presence of between two and five nuclear lobes connected by threadlike filaments. • Present in highest numbers among the leukocytes in adults.
Segmented neutrophils
• Formed during the promyelocyte stage
• Last to be released through exocytosis
PRIMARY (AZUROPHILIC) GRANULES
• Formed during the myelocyte and metamyelocyte stage
• Third to be released through exocytosis
SECONDARY (SPECIFIC) GRANULES
• Formed during metamyelocyte and band stages
• Second to be released
TERTIARY GRANULES
• Formed during band and segmented neutrophil stages
• First to be released (fuse toplasma membrane)
SECRETORY GRANULES (Secretory Vesicles)
Involves the movement of neutrophils and neutrophil precursors between the different pools in the bone marrow, the peripheral blood, and tissues.
Neutrophil kinetics
The transit time from myeloblast through myelocyte has been estimated to be roughly _____, and the transmit time through the maturation pool is approximately _____.
- 6 days
- 4-6 days
Half-life of neutrophils:
approximately 7 hours
Onceinthe peripheral blood, neutrophils are divided randomly into a
CNP and MNP
_____ ______are of significant importance in allowing neutrophils to marginate as well as exit the blood and enter the tissues by the process known as ______
- Integrins and selectins
- diapedesis