Myelopoiesis and White Blood Cells 2009
May 5, 2009
- Circulating Blood
o The earliest recognizable myeloid cell is the myeloblast (10-20m diameter) with a large round to
oval nucleus. There is fine diffuse immature chromatin (without clumping), and a prominent
nucleolus. The cytoplasm is basophilic without or few granules. Although one may see a small
golgi area adjacent to the nucleus, granules are not usually visible or barely visible by light
microscopy. One should not see blast cells in the peripheral blood.
o The promyelocyte (10-20m) is slightly larger than a blast. Its nucleus, although similar to a
myeloblast shows slight chromatin condensation and less prominent nucleoli. The cytoplasm
contains striking azurophilic granules or primary granules. These granules contain
myeloperoxidase, acid phophatase, and esterase enzymes. Normally no promyelocyte are seen in
the peripheral blood. At the point in development when secondary granules can be recognized,
the cell becomes a myelocyte.
o At the point in development when secondary granules can be recognized, the cell becomes a
myelocyte. Myelocytes (10-18m) are slightly smaller than promyelocytes and have eccentric
round-oval nuclei, often flattened along one side. The chromatin is fine, but shows evidence of
condensation. Nucleoli may be seen in early stages but not in the late myelocyte. Primary
azurophilic granules are still present, but secondary granules predominate. Secondary granules
(neut, eos, baso) first appear adjacent to the nucleus. In neutrophils this is the “dawn” of
neutrophila. Myelocytes are not normally found in the peripheral blood.
o The neutrophilic myelocyte has a broad range of appearances when viewed by light microscopy
on a Wright-Giemsa stain. The earliest stage is characterized by the appearance of fine, pink
(neutrophilic) granules (secondary granules) in the Golgi area, and as a result this area appears
brighter. This stage has been referred to as the "dawn of neutrophilia".
o Myelocyte: At this early stage, most of the granules are still primary granules, most of the
cytoplasm is still blue, and nucleoli are still visible, but the nuclear chromatin is more coarse and
is starting to clump. From this stage the maturation progresses to a mature neutrophilic
myelocyte with the cytoplasm being all pink in appearance, and the primary granules having
been completely replaced with neutrophilic or secondary granules.
o Metamyelocytes (10-18m) are slightly smaller than myelocytes. They have kidney shaped
indented nuclei and relatively dense chromatin, especially along the nuclear membrane. The
cytoplasm is faintly pink with almost no blue background. Numerous secondary granules
(neutrophils, eosinophils or basophils) clearly outnumber primary granules. Zero to one percent
of the peripheral blood white cells may be metamyelocytes (juveniles)
o Bands, slightly smaller than juveniles, are marked by a U-shaped or deeply indented nucleus.
Opposite sides or lobes are of roughly equal size or diameter. There is no nuclear constriction >
than 1/2 the lobe diameter. The chromatin is heavily clumped and secondary or specific granules
either neutrophilic or basophilic predominate. Normal band counts vary but are usually in the
range of 0-6%.
o Segmented (segs) or polymorphonuclear (PMN) leukocytes (average 14 m dia) are distinguished
by definite lobation with thin thread-like filaments of chromatin joining the 2-5 lobes. The
chromatin of the segmented neutrophil is coarsely clumped and the cytoplasm is pink due to
large numbers of secondary granules. In practice when examining peripheral blood, neutrophils
are the only leukocytes to be divided into myelocyte, juvenile, band, and PMN stages. Eosinophils
and basophils of all stages are lumped together in most instances.
Normally approximately 45-75% of the peripheral blood white cells are segmented neutrophils.
Life span of 6-7 hours or up to 4 days in the connective tissue
- Blood cell count and blood smear
o Careful examination of the formed elements in the blood
Quantification of leukocytes
Quantification of the relative and absolute concentration of each type
Meticulous microscopic examination of morphology
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- WBC count and differential
o Total WBC count is measured; reference range varies
o Diff count is the relative concentration of the various leukocytes
o One of the most useful tests in the laboratory
Confirms a suspected hematological disorder (leukemia)
Demonstrates response to infection a/o inflammation
Monitors treatment
o Total and absolute numbers of each leukocyte
Alterations in the total numbers of leukocytes and in the relative proportions are
clinically significant
Left shifted maturation is clinically significant (more immature leukocytes)
o The most important information from the differential count is not the relative count (% of cells)
but the absolute count
o The absolute count for a specific leukocyte is the total WBC count multiplied by the % of that
leukocyte in the diff count
- Left shifted maturation
o Left shift
An increase proportion of immature cells
Band forms or younger are increased
Note: immature forms include: bands, metamyelocytes, melocytes
Early release from the bone marrow
Stress, acute infections, inflammation
o Bandemia
Increase in the fraction of band neutrophils
Bone marrow is responding to stress
Neutrophils are shifting from marginated pool to circulating pool
o Examples of immature cells
Blasts – lymphoblasts and myeloblasts, NOS
o Promeylocytes, myelocytes, and metamyelocytes
o Nucleated RBCs
o Band neutrophils > reference range
o The most significant left shift has the more immature cells.
Quantitative Abnormalites of leukocytes
- Cytopenia
o Leucopenia: decreased WBC count
o Neutropenia: reduced granulocytes
o Lymphocytopenia: decreased lymphocytes
Marked reduction in the peripheral blood lymphocytes
banded neutrophils>
myelocytes>myelocytes, promylocytes, and myeloblasts
Chronic Myelogenous Leukemia: Early myeloid cells such as myeloblasts, myelocytes,
metamyelocytes, and nucleated red blood cells are commonly present in the blood
smear, mimicking the findings in the bone marrow. The presence of the different
midstage progenitor cells differentiates this condition from the acute myelogenous
leukemias, in which a leukemic gap (maturation arrest) or hiatus exists that shows
absence of these cells.
o Acute leukemia: no maturation
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