Chapter 2 Blood cell morphology and development

2.3 ORIGIN AND DEVELO !EN" O# RED BLOOD CELL$
There are three types of cellular elements in the blood - erythrocytes ( red cell%), leukocytes &'h(te cell%), and thrombocytes (platelet%). Each has its own functions and differs clearly from the others. In health, destruction is balanced by production and the quantity of circulating cells remain remarkably constant. ost of the blood cells are formed in the bone marrow. !onsequently, e"amination of marrow specimens often pro#ides information of great #alue in the diagnosis and treatment of hematologic disorders.

2.3.* !+ELO OIE$I$,
The prefi" -myelo-. generally refers to all aspects of bone marrow acti#ity and is not limited to granulocytic elements alone. The only e"ceptions to this rule are the terms myeloblast, myelocyte, and metamyelocyte, which refer to specific stages in granulocyte maturation. !onsists chiefly of erythropoiesis, granulopoiesis, and thrombopoiesis. onocytes appear to be formed in the marrow as well as elsewhere. $ymphopoiesis occurs largely in e"tramedullary sites such as the spleen, thymus, and lymph nodes. There is little doubt that a primiti#e, pluripotential reticulum cell or %stem cell% can undergo differentiation into a specific blast cell. The marrow reticulum cells are those from which the differentiated blood cell precursors arise. The reticulum cells in a &right's stained preparation are relati#ely large &2/.3/ 0 (n d(ameter) with abundant, light blue, opaque cytoplasm. The cell borders are typically irregular. These cells ordinarily ha#e one to two nucleoli with the nucleus being round to o#al, with a finely to coarse reticulated chromatin pattern. Figure II.1 lists the steps in the de#elopment of the #arious blood cells from the marrow reticulum cell.

7 Erythrocyte . Immature cells are generally larger and become smaller as they mature. if there is a question whether a cell is a rubricyte or a metarubricyte.4. *s the cell matures. #(g0re II.2.3.3.4 ER+"1ROC+"E !A"2RA"ION $E32ENCE.6 Ret(c0locyte or polychromatoph(l(c cell 2. call it the latter.4. many cells are in transition from one named cell type to another. cells in transition are classified towards the more differentiated cell type.3.3.3 !A"2RA"ION $E32ENCE *s cells de#elop.4. These morphologic alterations occur gradually+ therefore. any names ha#e been used for the de#elopmental stages of an erythrocyte.2 ER+"1RO OIE$I$.4.3. (istinct morphological and functional stages can be recogni)ed in the de#elopment of an erythrocyte and ser#e as a useful outline of erythropoiesis.* R05r(5la%t 2. fine and stippled.3 illustrates these maturation changes.3.4. their morphology changes. all of the immature and mature erythrocytes in the body are designated the erythron. the chromatin becomes coarse. . 2. The nonnucleated red cells in the peripheral blood are deri#ed from nucleated precursors in the bone marrow. *s a general rule.4 !etar05r(cyte 2.3.3. *s a group. Thus.3 R05r(cyte 2. The chromatin of the nucleus in immature cells is delicate.2 ror05r(cyte 2.2 illustrates the relationship of cell si)e to maturation and di#ision. 2.3.ucleoli are found in the nucleus of immature cells. The nuclei of the immature cells are relati#ely large in relation to the amount of cytoplasm and become smaller with maturity. #(g0re II.4. 2. The terminology used in this syllabus is preferred since accurate definitions are a#ailable. clumped and compact.

1 "he Relat(on%h(p o8 Cell $(9e to !at0rat(on and D(v(%(on .* Figure II.#(g0re II.

3 !orpholog(c Change% Occ0rr(ng D0r(ng Red Blood Cell !at0rat(on R2BRIBLA$". .FIGURE II.

. but remnants of the nucleoli may still be present. . &hen obser#ed in peripheral blood.• • • • • -irst recogni)able cell in the erythrogenic series. The cytoplasm stains similarly to the mature erythrocyte. * deficiency of hemoglobin in the cell can result in e"tra di#isions and smaller cells. pyknotic. This cell can be further subdi#ided according to the amount of hemoglobin in the cytoplasm into basophilic. • • • • • • !ell is smaller than the /rorubricyte. • • • • • !ell is similar to the . it denotes a response to an anemic condition of at least 01-23 hours duration.uclear chromatin material is coarsely clumped separated by light streaks gi#ing the so-called cartwheel appearance. . The nucleus contains one to se#eral nucleoli. The e"ception is the horse in that this species does not release nucleated red cells into the peripheral blood under any circumstances. .ucleus is round and stains #ery dark. R2BRIC+"E. * perinuclear clear )one may be obser#ed. and appears as a dark blue homogeneous mass without any distinct chromatin structure. The nucleus is small. The cytoplasm stains basophilic. The chromatin material is somewhat coarser. !ell di#ision stops when a critical hemoglobin concentration is reached.ubriblast but smaller in si)e. !ytoplasm stains #ery basophilic in the early rubricyte stage. The cytoplasm is somewhat scanty and stains #ery basophilic. The nuclear chromatin is delicate and stippled.) !E"AR2BRIC+"E. (E:A! LE: Iron deficiency results in microcytes. polychromatophilic and normochromic rubricyte. but the blue color is diluted out by the pink color of hemoglobin as it matures toward the ne"t stages. * large round cell which contains a large round nucleus with a thin rim of royal blue cytoplasm. The cell is the last cell in the erythrocytic series capable of cell di#ision under normal cond(t(on%. ROR2BRIC+"E. The cell is not found in the peripheral blood of normal healthy animals.ucleoli are usually absent.

7ranulocytes are readily differentiated from the nucleated erythrocytes by their fine. !ells are not found in health in the peripheral blood of the horse. reticulated chromatin structure and bluish cytoplasm. • • These are the mature non-nucleated red blood cells. sheep.3. cow. This means that the reticulocyte ripens in the bone marrow in these species. The cell does not participate in normal rouleau" formation or pathologic agglutination+ is more resistant to crenation and lysis+ is less susceptible to mechanical trauma+ has a great e"cess of membrane in relation to its contents. 4owe#er. ER+"1ROC+"E. thyroid. !ell may contain a small round nuclear remnant called a 4owell-5olly body. and goat. Endocrine glands such as the pituitary.Its release is determined by tissue o"ygen le#els. !ell stains buff or reddish color. and gonads affect erythropoiesis. Erythropoietin also causes an increased release of reticulocytes into the circulation &ret(c0locyto%(%). reticulocytes in the peripheral blood. adrenals.*. These glands are responsible for general metabolic acti#ity and cellular o"ygen requirements. • • • • • • This cell is larger than the mature erythrocyte and is non-nucleated..6. 2. !ytoplasm stains slightly basophilic with &right's stain. but is able to synthesi)e hemoglobin. when stained with a %0prav(tal.* (reticulum) can be demonstrated within the cell.RE"IC2LOC+"E OR OL+C1RO!A"O 1ILIC CELL.6 CON"ROL O# ER+"1RO OIE$I$ Erythropoietin is accepted as the fundamental erythropoietic stimulus. . 2.It is produced by the kidney and6or li#er in most species.4 ORIGIN AND DEVELO !EN" O# GRAN2LOC+"E$ 7ranulocytes de#elop in the bone marrow from undifferentiated stem cells. (ogs and cats may normally ha#e *.%ta(n such as new methylene blue or brilliant cresyl blue. precipitated ribrosomal .

2.2 rogran0locyte 2.4.* !+ELOBLA$" • • • • • The first cell that can be recogni)ed in the granulocytic series. Ba%oph(l< eo%(noph(l< ne0troph(l 2.6 !etamyelocyte .2.4.4.. It is the most immature granulocytic precursor..granules.4. therefore.* !A"2RA"ION $E32ENCE aturation of the granulocytic series of cells is characteri)ed by the de#elopment of granules.4.2 GRAN2LOC+"E !A"2RA"ION $E32ENCE 8e#eral distinct de#elopmental stages of granulocytes can be recogni)ed morphologically.. !ells which ha#e granules with an affinity for blue or basic dye are identified as basophils+ cells that are stained reddish-orange with the acid dye eosin are called eosinophils+ and the cells with granules which do not stain intensely with either dye are called neutrophils.Basophil eosinophil.3 !yelocyte .7 Segmented Cell -. . The stages are9 2. the myelocyte stage is characteri)ed by the appearance of %specific% or secondary granules that persist throughout the maturation process. The cell possesses a relati#ely large. 2.2. *s the maturation sequence continues.2. These granules are pero"idase positi#e and de#elop from fusion of small proteinaceous material by the 7olgi comple". will not stain with &right's stain. the primary or a)urophil granules lose their acid mucopolysaccharide and. The chromatin material of the nucleus is finely stippled or has a light ground glass appearance.4. and does not contain granules. round to o#al nucleus.2.4.4. 7ranules are initially formed in the progranulocytes and are called -pr(mary or a90roph(l.* !yelo5la%t 2. Ba%oph(l< eo%(noph(l< ne0troph(l 2.7 Band Cell .2.4.2. basophilic. with one to se#eral nucleoli. The cytoplasm is somewhat scanty. Ba%oph(l< eo%(noph(l< ne0troph(l 2. neutrophil 2.2. 4owe#er.

7 $EG!EN"ER CELL . The nucleus is indented and often resembles a kidney bean.ucleoli are not present and the nuclear chromatin material is coarser and clumped. 2.or specific granules that are identified by their staining properties as neutrophils. !ytoplasmic granules are also present. eosinophils. Therefore.2. and basophils.2.2. 2.2.2. The opposite sides of the nucleus are more or less parallel. These granules are pero"idase negati#e.emnants of the nucleoli may still be present.4.2 ROGRAN2LOC+"E • • • The nuclear chromatin material is coarser and slightly more clumped than that of a myeloblast.will not take the &right's stain.6 BAND CELL • • • • This cell has a horseshoe shaped nucleus. eosinophils and basophils. This cell may be differentiated from the metamyelocyte by the nuclear shape and the tendency for the nuclear sides to become parallel. The cytoplasm is less basophilic than the myeloblast and contains darkly stained non-specific granules called -pr(mary or a90roph(l(c gran0le%. The nuclear chromatin material is markedly clumped.2. the myelocyte and all subsequent cells of the granulocytic series should be characteri)ed as neutrophils. .4. *s maturation of the granulocytes continue. 2.4. This cell contains -%econdary. . si)e and concentration in domestic species.4 !E"A!+ELOC+"E • • • • This cell closely resembles the myelocyte.4. The myelocyte stage is the last stage of cell di#ision and the first cell capable of phagocytosis. the -%pec(8(c gran0le%.will increase and the -a90roph(l(c gran0le%. These granules #ary greatly in shape.3 !+ELOC+"E • • • • • • The nucleus of the myelocyte remains somewhat round to o#al and the chromatin material is more closely clumped.% These granules are pero"idase positi#e.4. 2.

The nucleus contains one or two nucleoli. The nucleus does not become segmented and specific granules do not de#elop. or may consist of se#eral lobes separated by constrictions or by filaments. /rimary granules (a90roph(l gran0le%) contain acid phosphatase. It is round or o#al. These cells generally originate in the lymphatic system.4. &hen leukocytes phagocyti)e. acid hydrolytic en)ymes. basic protein and one-third of the lyso)yme.* L+! 1OBLA$" o o o o !ell is similar to other blast cells. lactoferrin and two-thirds of the lyso)yme.6. 2. The stages in lymphocytic de#elopment are9 • • • $ymphoblast /rolymphocyte $ymphocyte 2. #ery large.2 ROL+! 1OC+"E .*. The cytoplasm is bluish and nongranular and forms a thin rim around the nucleus. This series includes the lymphocytic and monocytic groups.6. 2. with a large round to o#al reddish-purple nucleus. but like the granulocytic series. lymphocytes are -pero>(da%e negat(ve-. $ymphocytes are the most undifferentiated of all blood cells normally found in the peripheral blood. The nuclear chromatin material is fine and well distributed but perhaps more coarse than in myeloblasts.6.*. 2. they may be produced elsewhere in the body. The cytoplasm stains #ery faintly.* L+! 1OC+"IC !A"2RA"ION $E32ENCE The lymphocytic series refers to the de#elopment of the lymphocytes. 8econdary granules (%pec(8(c gran0le%) contain alkaline phosphatase.6 ORIGIN AND DEVELO !EN" O# AGRAN2LOC+"E$ The agranulocytic series is comprised of leukocytes de#oid of specific granulation. The lymphocyte cytoplasm does not de#elop past the blue stage. there is a release of lysosomal contents. The cells arise mainly from the reticular tissue of the lymph nodes and lymphoid tissue from which they deri#e their name. 2.3 LE2=OC+"E L+$O$O!E$ The term lysosome is used to describe intracellular membranous sacs containing acid hydrolytic en)ymes.The nucleus may be mono-lobed with clumped chromatin material. Therefore.

The cytoplasm is grayish blue and may contain non-specific granules.6.ucleoli are absent. .2 !ONOC+"IC !A"2RA"ION $E32ENCE The monocytic series refer to the stages of de#elopment of the monocyte.6.2. 4owe#er. The cells are easily distorted and often appear in irregular shapes in stained preparations. The nuclear chromatin material is fine and well-distributed. medium or large. The nuclear chromatin is condensed to form large.ucleoli or remnants of nucleoli may be present.3 L+! 1OC+"E This is the mature cell of the lymphocytic series and the only cell form found in the peripheral blood in health.E cells. .6. The nuclear chromatin is coarse and slightly clumped. There is an abundant amount of light blue cytoplasm around the nucleus. $ymphocytes #ary greatly in si)e and may be classified as small. 2.o o o o The nucleus is round or o#al in shape but smaller than the lymphoblast.* !ONOBLA$" The cell is large with a round or o#al nucleus. there may be a few a)urophilic granules in the cytoplasm. *lso. with thickening of the nuclear membrane.The nuclear chromatin material is fine and spongy. There are no granules present in the cytoplasm. 2. discrete almost solid clumps. There is a thin rim of clear blue cytoplasm around the nucleus.on specific granules may be obser#ed in the cytoplasm of these cells. There may be a nucleolus or a remnant of the nucleolus present. :ne of the most important sites of origin is the spleen. si)e does not determine age of these cells.2. * nucleolus is present. These cells may be formed from .*.2 RO!ONOC+"E The cell is somewhat smaller than the monoblast with the nucleus being irregularly-shaped. . The stages in the monocytic de#elopment are9 • • • onoblast /romonocyte onocyte 2.6. . 2.

7. thus producing giant polyploid cells.* !EGA=AR+OBLA$" The cell is large. but may be deeply indented or ha#e two or more lobes connected by narrow bands. culminating in platelet differentiation and liberation. nongranular cytoplasm.7.2.6. . 2. The cytoplasm undergoes maturation changes characteri)ed by the de#elopment of granules and membranes.7 ORIGIN AND DEVELO !EN" O# "hrom5ocyte%?platelet% !ells of the megakaryocytic system are peculiar in that the nucleus undergoes multiple mitotic di#isions without cytoplasmic separation.2. The stages in thrombocyte de#elopment are9 • • • • egakaryoblast /romegakaryocyte egakaryocyte Thrombocyte & latelet) 2.7. irregularly shaped with a single or se#eral round or o#al nuclei and with a blue. They are frequently mistaken for immature neutrophils and large lymphocytes.3 !ONOC+"E The cell is larger than a neutrophil in the thin portions of a smear. The shape of monocytes is #ariable. The multiple nuclei usually remain attached to each other and are often superimposed gi#ing a lobular appearance.ucleoli are usually present.The nuclei are usually round or kidney-shaped.2 RO!EGA=AR+OC+"E This cell differs from the megakaryoblast in that there are bluish granules in the cytoplasm ad<acent to the nucleus. onocytes are most difficult to identify and to differentiate from other cells. blunt pseudopods and the brain-like con#olution of the nucleus. .The three most characteristic features of the monocytes and the most helpful in diagnosis are the dull grayish-blue color of the cytoplasm. 2.3 !EGA=AR+OC+"E .lunt pseudopods and digesti#e #acuoles may be present. The nucleus in this second stage of maturation has usually di#ided one or more times and the cell has increased in si)e. 2.

.4 "1RO!BOC+"E?platelet /latelets are fragments of the cytoplasm of megakaryocytes. 2. and multiple nuclei.The cell is #ery large with relati#ely large amounts of cytoplasm. The cytoplasm contains numerous small. They #ary in si)e and shape from a barely #isible structure to masses larger than red cells or leukocytes. uniformly distributed granules that are reddish-blue in color.7. The cytoplasm stains a light blue and contains #ariable numbers of small blue granules (a90roph(l(c).