BLOOM & FAWCET T'S SECOND EDITIONChapter three Blood enrtnnocyTes 48 Eoshopic lukooyes L000 PLATELETS 44 Basophiticieukoores racine pate 44 GRANULAR LEUKOCYTES erate patoets 45 Maraytes LeuxocrTes: 4 Lymphocytes CGRAMULAR LEUKOCYTES 46 HeMOPOFESIS opi eakayies 446 BONE MARROW fed in a tid livid inte thtee major eat Blood is made up of several Kinds of cells susper matrix, the blood plas, Its ells cgories: erythrocytes (se blood cells), leukoeytes (white blood ‘el).and platelets, Unlike the cells of epithelia, the bland cells are unattached and make no enduring contact with one another flood circulates in the blvd vessels to maintain logistical support and commun tributes oaygen trom the lungs and nutrients from the on between all ther tissues ofthe body. It dis ustrvimestinal tract. It cartes carbon dioside from the tissue ‘exhalation, and nitrogenous wastes from the tissues tothe kslneys for excretion, It also playsan essential rae in integrating the functions of the orga from thei site of proxiuction to theie distant target tissues. hack wo the lungs . by carrying, hormones A knowledge of the normal fornt and number of the several kinds af blood cell is important to physicians, for no tissue is xamined more wlten for diagnostic purposes. Examination of stained blook-smears not any yields information abut diseases that primarily afte the blood, i also provides indirect evidence of viral, bacterial, a parasitic infections, and thus enables the physi ian to follow the course of the infection and evaluate the effectiveness of treatment ERYTHROCYTES: Enythrocytes are miinute anucleate corpuscles that impart a red color tothe blood! because they contain the oxygen-eareying 7 ment, hemoglobin. They number from 8.1% 10 ta S88 10" Frum inthe muae, and! from 4.3% 10" to 5.2% 10%omny in the female. In total, they present a surface area of 380m’ fabout the size of 47 Eaytneytpoiss se 29 Granoytopoess 88 50 Monocropresis 6 50 Thrombocytpesis 38 St Lyrptaetopies 20 52 HISTOPHYSIOLOGY OF BONE MARROW o 2 Football felt for gas exchange, The funetion ofthe erythrocytes is transport of oxygen (0) and carbon dioxide (CO). As blood passes through the capillaries of the lung, oxygen binds to the hemoglobin ofthe eeythracytes, converting it to oxyhemoglobin, which gives arterial blood its bright pink color. An erythrocyte contains about 250 million molecules of hemoglobin, each bine: ing fou -molecuks of oxygen, so each erythrocyte is able 10 transport about a billion molecules of oxygen, As they pass through the peripheral capillaries, Oi released and diffuses into the tisues. Concurrently, CO, ditfuses From the tissites into the ‘blood, combining with hemoglobin to form the carbaminohemo- globin, which imparts a bluish color to the senous blood, ta the Tangs, the CO. disgociates from the hemoglobin, dlflases into the air spaccsand is climinated in exhalation, Frythracytes develop in the bone marrow from mucleated pre: cursor cells, but before they enter the blood, the nuiclews and Songanelles are estraxed and they are reduced to membrane Tinted corpuseles, Hemoglobin accounts for 30% oftheir weight ‘Their shape is best deserihed as a biconcave disc 7.6-7. diameter. ‘Their thickness is 1.9yem near their periphery Somewhat ss at their center (Fig 3.1). This shape is well adapted to their function of gas exchange for it presents a surface area 20-30 In blaod-smears, the great major greater than that ofa sphere of the sime volume. of the erythroeyt pink, buta small number that have only recently entered the blood sain From the hone marrow have a bliish or greenish tint asa result of the hosophilie staining, of residual ribosomes in their cytoplasm. Such erthrocytes are commonly called reticulocytes, because, twhen stained with Brilliant Crest Vile, their ribosomes are pre Cipitated by the dye into a delicate basophiic nexwork in an ftherwise acidophilic cytoplasm. Within 24h of entering theFigure31 A scanning econ miro scat shape ob: ade), i basophilia. Inthe adult human, the number of reticulocytes averages about 8% ofthe total erythrocyte popula tion. The reticulocyte count is used clinically asa rough measure In patients with he rate of new erythrocyte production Anemia ste term apts a sgncantreustin inte ttl number of ajar, or nthe content of hamogbi, resulting in ceded onge- arming capcty of he bcd. Asien tary intake ofthe zon needed to ‘sjhesze hemoglobin may result an-deticlency anemia Deficiencies of ‘amin 8 o fe acd may lea Yo mogaloblastic anemia, n wich ther is 2 retarded producto of envectes ad hase poured ae of preter than ema :xamination of thin sections of erythrocytes under the electron microscope reveals the structural elements that maintain thei beneath the membrane made up af fil ith, bound together at their ends anusual biconc pe, Immediately here isa so-called membrane skeleton, a networ aments of spectrin 200 nm in le actin, Actin in erythrocytes does not form flamentsas it doesin the eytoskeleton of other cells. Instea, it forms very short poly. mers, only 7m in length, These bind to tropomyosin, forming nodal structures that join the ends of the spectein filaments together to form a network beneath the erythrocyte membrane ‘Near the middle ofeach spectrin filament theresa binding site for 1 phosphoprotein called ankyrin, which links the network to inte gral proteins ofthe cell membrane. This simple eytoskeleton helps to maintain the shape of the erythrocytes while, atthe same time giving them the resilience necessary to resist the frequent defor- ions to which they are subjected in thousands of passages wand 1 kinds of anemia, Those in which all erythrocytes anemias, ad those in which they are smaller than 64m are micro cyte anemias, The term anisocytosis is used to describe a finding of large numt ‘The membeal fof human erythrocytes contains certain inte- hese the basis of the immune response if transfused into another person). n B, and a he erythrocytes of some indi- antigen B, ace four are designated antigen A ABO blood- group typing system viduals have ‘and still others have neither, Thus, ther roups A, B, AB, and O, For reasons that are not ntibod- ‘occur on their own others have bo major blood ely clear, all individuals have in their blood plasm exythrocytes which antigens occur on the erythrocytes of the na of the to determin antibodies are pre donor, and in the p recipient. Failure to carry out this cross-matching may result ina massive intravascular agglutination and lysis of erythrocytes in the BLOOD PLATELETS Blood platelets are very small, eolorl ney are ovoid in surface view and fusiform in longi they number from 200000 to od. In stained blood smears, they exhibit two heh pale peripheral zone, lomere, and jon, the granulomere. The l small granules. Bl 1 the clotting ofthe blood limit bleeding after injury. Their numbers are regulated by a Inactive platelets Hectron micrographs of equatorial sections of platelet reveal ct ‘cumferential band of 10-15 microtubules inthe hyalomere imme: diately beneath the membrane. In cross-section, these appear asa ster of small circular profiles at ether end ofthe platelet (Fig,3.2).The hyalomere contains other vine clement, buat the presence bof aetinand myosin can hedemonstated by histachemical methods. ate activate in the i palymevizes into hlaments that are neces yin clot formation, I le aps, snall aggregations of ghyengen may be found lof secretory pronlicts of activate platelets. The mnt conspictots comp shes that respond tothe avaraphilic alpha grammes they ht microscope. They contain several substances that have important fanctions in loox! clotting: (1) platelet factor TV. whieh vounterauts the anticosgalantellect of heparin (2) won Willebrand's factor, glycoprotein that promotes theadhesion of plateletsto sites. injury in the wall of blood ves (3) platelet-derived growth faetor, which initiates the process of co kl vessel (2) thrombospondin, « glyeo in responsible for platelet aggregation and adhesion in the clotting process, The platelets af some species also contain beta granules, hic in and other molecules thal are potent promoters of platle Activated platelets Platelets in the Girsulting tk the vascular no to cletet any danse tothe ining of the blood vessels. The magnitude their mission is evident fromthe estimate that each ‘over 100K} of capillary 10" enulothelial cells They norrmllp shows no minute approsimately 19° platelen tendency to adhere to one another oF to the vessel wall, but iFany boeak inthe endothelial ining is detected, they adhere to it, and to vosnaees « | Fagure 3.218 econ meroorap of Patel, Te rows indicate rss: bund of excuntretal ‘cubes tht maint the at shape te plates) Coss-sctns ot ritroubues are moe cary wen Bait, 8 Courtesy of Dare Fin) allore to cllgen fibers af connective ssc exposed at the site wates the platelets, causing them to release a glycoprotein that is 3 wgeregation, resulting in adhesion of potent inducer of plate many more platelets to those already bound to the site of injury These events lea formation of platelet thrombus, a semis mass of platelets that partially acclides the famen of the blvd vessel (Fg, 8. sreont with platelet aggregation, other complex reactions fof the clotting pracess are set in motion, A complex called prothrombin activator and ather substances released hy injure! cells initiate a series of reactions in the blood plasma that convert prothrombin to thrombin. This, in ten, catalyzes conversion of © Fool (no) tov @ jo me Fe Figure 2.3 Schematic representation of eat events in fora! leo tn lod vessel Pall are the site and lease ADP ang aesve ‘ich resus in platelet aggregation. Tromboplsin om the of th esse! wal converts petirombe fo trombin, wich catalyzes ot Hoon Hom plasma fennoge. Fin laments nes plates forma gettin cot[Tee constituent of plasma called fibrinogen to fibrin, which polymer es to form a network of fibrils among the aggregated platelets (Fig 3.4). This binds the platelets together in gelatinous blood dot (or thrombus) that prevents further outflow of blood from the injured blood vessels. Pathological changes in the endo artery of the heart may cause platelet ad ot that oceludes its lumen, resulting in a heart attack.’ A number Of inherited diseases result from platelet abnormalities, oF from a deficiency of one of the plasma proteins that are involved in blood clotting, sion and formation of 2 emopila san inverts defect n factor Won of he ting factors, Devotrs of empha ee ceers andthe sons of such cars have a ‘Sone ctanc fering the eae. These patents ies ino uses, ts nd baoy cas fr days afer an injury Surgery and even deta exaron ste cared aut wih eee creo prevent excessive edo oe LEUKOCYTES Leukocytes (white blood cells) include several cell ypes involved in the defense of the body against invasi Figure 34 Scanning mirorag fa fein loa dat showing cenated rytrocyes and platelet ns reshwork of He. parasites, and foreign proteins. They are clasified as, granular sukocytes (granulocytes), oF or absence of specific granules visible in their sanular leukocytes, depending upon the presenc re three types of gran ‘lar leukocytes, neutrophils, eosinophils and basophils, and two types of agranular leukocytes, monocytes and. lymphocytes Fig: small faction oftheir life van in the circulation. Neutrophils and eosinophils spend no Frore than 2days in the blood, and lymphocytes less than day, ‘oss the wall of capillaries into the surrounding, cytoplasm in stained blood-smears. There Leukocytes spend relative! before migrating tissues. They are spherical and in: varying degrees of ameboid motility as they wander over the solid afforded by the collag number of leukocytes in the circulation ranges from 5000 This number varies somewhat with the age tive in the blood, but exhibit fibers ofthe connective tissues. subs Th to 9000/mm’ of blood tof the individual, and even with the time of day. The much larger fhumber in the tissues and organs cannot be quantified. Minor variations in the numbers of leukocytes are of little clinical sg scance, but if theze isan infection anywhere inthe body, the blood Teukocyte count may rise to 20000-40000/mm’ numbers ofthe several kinds of leukocytes, the so-called differen The relative ial leukocyte count, are normally fairly constant: neutrophils ssophils 020-0.79%; lymphocytes 96, Different diseases affect the number of 55-60%; cosinophils 1-3 25-3006; monocytes 3+ nore than others, and therefore the differential may be helpf leukocyte cou! in making a diagnosis. GRANULAR LEUKOCYTES Neutrophilic leukocytes (neutrophils), are the most They 3000 -6000/mmn’ and 20% 10" or more in the entire circulat ss and are easly recog: 1 lobules Polymorphonuclear leukocyte abundant of the granular leukocytes, number are 7um in diameter in blood:-sme A, 3.6). Neutrophil, bone nized by their unusual nucleus, which by narrow constrictions (Figs3. have only recently entered the circulation from t marrow, have a simple elongated nucleus with no cons ‘These are referzed to as band forms. An increase in the number of band forms in a differential leukocyte count suggests that the rhumber of neutropbils is inereasing n response to an infection. In the neutrophils of the human female, the chromatin representing, obule that is the X chromosome, {ditional minute drumstick’ because ofits characteristic nine the sex of an individual by ‘phils for the presence, o shape. Thus, iti possible to dete xamining 3 large aumber of 1 nce, ofthis nuclear appendage, A small Golgi complex is found between the lobules of the nucleus and there a Small clusters of glyco- rophil re not uncommon. The ¢ytoplasm of net Stippled with numerous small granules of two kinds: the specifi inch have little affinity for dyes, and the azurophilic igen granules granules, franules, which are slightly larger and stain more deeply.Pee Although the two kinds of granules are rather similar in appear- ance, they react differently to histochemical reagents, The specific ‘granules show a positive reaction for alkaline phosphatase, colla- genase, and lysozyme. The azurophil granules react positively for the enzymes peroxidase, acid phosphatase, and glucuronidase, ‘Neutrophils are in the front line of the body's defenses against bacterial infections. They rapidly gather atthe site and phagocytize and digest bacteria (Fig.3.7). Several factors contribute to their rapid mobilization. Changes in the membrane of endothelial cells lining capillaries inthe infected region cause neutrophils to adhere and migrate through their wall into the surrounding connective tissue. There they are exposed to low concentrations of bacterial products. Their cytoskeleton is reorganized and becomes pola ized for migration towards the source of Migration up the concentration gradient of a chemo: called chemotaxis. When they reach the souce they stop migr ing and become avidly phagocytic, taking in bacteria and destroying them with lysosomal enzymes (Fig. 3.7). Mobilization of circulating neutrophils is augmented by their release of ‘cytokines, which are carried inthe blood from the site of infection to the bone marrow, where they stimulate release of additional neutrophils into the blood to join those already a the site of bac- terial invasion, The inflammatory exudate (‘pus)) that accumulates at such a site consists mainly of dead and dying neu: trophils that have completed their mission, ose products Eosinophilic leukocytes Eosinophilic leukocytes (eosinophils) are 9 um in diameter in suspension and about 12 4m in diameter in blood-smears. They are easly distinguished from neutrophils by their larger specific granules, which stain pink with Wright's blood stain (Figs 3.58, 3.8). Their nucleus has two lobes, which are connected by a broad intermediate segment. Its chromatin pattern is less coarse than that of neutrophils. There is a small Golgi complex and a few mitochondria. The specific granules are the most conspicuous component ofthe cytoplasm. On electron micrographs, these vary inappearance in different mammalian species. Inthe human, they contain one or more dense crystals ina less dense matrix (Fig 3.8). ‘The granules of eosinophils contain several hydrolytic enzyme including aryl sulfatase, B-glacuronidase, acid phosphatase, and ribonuclease, They also contain three cationic proteins not found pes, major basophilic protein (MBP), eosinophilic in other cell cationic protein (ECP), and eosinophil-derived neurotoxin, osinophils circulate in the blood for only 6 to 10h before migrating into the connective tissues of the body, where they spend the remainder of their 8 to 10-day lifespan, They do not phagocytize and destroy bacteria. One of their functions isto take up and break down antigen-antibody complexes that are formed in allergic conditions, such as asthma and hay fever. Eosinophils. are especially numerous beneath the epithelium of the respiratory and gastrointestinal tracts where entry of foreign proteins is most likely to occur. They are attracted to sites of release of histamine. The enzymes in their granules are capable of degrading histamine, and other mediators of allergic reactions. Eosinophils play a more active role in certain parasitic infections of humans. The ionic proteins MBP and ECP are toxic to Schistosoma mansoni, and Trypanosoma cruzi, wo parasites that are common in the tropics. eosinophil Basophilic leukocytes Basophilic leukocytes, (basophils) are the east numerous of the of the total leukocyte Figue 37 Gecton meroqraoh oa reiopic lekocre engaged in pages of materia, Note several lage vacois nits eps, Jngested bacterinicragrapns, hasaphih have @ amtall Gal compensa few mito lls than in other leukocytes, Particles alycoger are often present in the cytoplasm, The rsa and 10,5 um in diameter. They ‘tain heparin aol histamine, but ne lysoscinal hydrases linger and have many swe granules, Rasaphils are short-lived and ingst cel fang lived, Mast vells are relatively sessile, whereas Dasphils are tile, yslusen by their assembly a sites oi ination, Both relesse histamine and epi anl they ee have similar actions, Whether they arise (rom the stme, or di Fever stem cells, is ot yo settled. They both contribute to the dis bin toone class of antibodies |immunoglobulin-E) and respond by rele histamine and heparin, Histamine causes dllatation of gl vessels which then leuk Hid constituents af the blood pasta inte The sno of Aransas: 0 | Figure 38 econ microarph fa arn eosinopic uate. Nate Ne lege speci grams. entarng dese whiely makes breathing dificult, The role of heparin in hypersen sitivity responses is less clear. It isan anticoagulant, slowing the clotting of blood, but it may have other less well known effects, AGRANULAR LEUKOCYTES hie apranular leukocytes include monocytes and lymphocytes, in which granules are nota prominent Feature ofthe eytaplasm, The alternative term in canininn use, mononuclear leukocytes, is ey leukocytes have more than one nucleus, Actually, all leukocytes havea single nucleus, but that ofthe granular Feukoeytes may have Monocytes out for S-4% of the circulating loukocytes. They Monocytes 3Figure 3.9 lector micomap “Te denge granules nocyte has a few short The cytoplasm contains a be up to 17qm in diameter in blood-smears. The nucleus is On clectron micrographs, the less deeply stained than lamelliform process kidney-shaped or bilobed, Its chromatin Scattered glycogen particles may also that of other leukocytes. The cytoplasm stains a pale blue color, id and, under the light microscope, appears to be devoid of granules nerous Figure 3.10 Becton mirograo money. has a dep nied sels, nd afew mtochondra and elteraeof endoplasmic retculum ina cytoplasm chin osoes. contains vo spect ransleukocytes u blood for I= ¢ body. There th Herentiate into tissue macrophages. Lymphocytes Lymphoeytes at the s specific granules hut there may be very few small azurophibic «110 .as small lymphocytes. Others, wth 9 Iymphoeytes, 10 maar categories, Heymphuxytes and lymphocytes. These diler in their development, Mespan, and Fite 3.1 Elecron morta» hmphocte thas 2 hetero ruses, surounded by thn yer a extopasm. Asma Gl compe, acetals saa mtacront ve sen ein is B lymphocytes. produce specie antibodies against invading T-lymph +: helper T-lymphocytes, which release signaling molecules to ita and sctivate B-lymphocytes, andl evtotoxie T-lymphocytes cells ar ell i adlition ty thelr eespectice toes in imammine responses Band TM Fumphocytes sevtete a dizen o more signaling molec lym phokines or cytokines) that inflence cach other's hebavia, and Lynuphiicytesane present in vast numbers the parenchyma the spleen and Iymph nodes, accessiry angans of the innnaune system The great majority of these are B Iymphoeyts, whit ha arisen (rn precursors in the bone marrow and hae best aie 1 these organs in the blood. Altera stay of varying uration in hese organs. they are returned tn the blow either directly ae via the Isinph, I-lymphocytey have a nermal fifeypan of many months. During this time, they recireulite through the blood Iymph nodes, spleen, ant Iymyph any tines iv est of a nnvxhin ic toorganisis. T aphex ytes havea very fleet history, The stom cells lestinea io give rye to Tym at inate in the bone marrow, but san alter bieth, they eater th blood and settle in the thymus, where they pruiferate. AS th progeny move through the cartes of the thymus and inte the medulla, they diferentiate, asin the surace markers and pplors characteristic of T-lymphocytes, Upon entering. the blood fiom the thymus, they join the continumusty recirculating population wf lymphocytes, They make apy 70% oF more of the Iymphoxytes of the blovwl, an! have a iespan, in huanans, th cells elle hemopoiesis. Beca the several kinds of blood cells have a very short lifespan, they must be continually replaced by new eels. The number of cells approximately 10" erythrocytes, an 4> 1? leukocytes are Formed cach day. The principal site of hemopwiesi, in the adult, is the bone marrow, whieh oceupies the medullary cavities of the long, bones and the spongiosa ofthe vertebrae, ribs and sternum, onic lt, when the skeleton is still entirely cai the earliest formation of inthe yolk sie blastic phase ood cells acct in small islands of precursor eel ; sis. Atahout 6 wceks of gestation, erythrocyte formapares: begins in the newly formed medullary cavities of the developing ‘bones, initiating the myeloid phase of hemopoiesis which contin tues throughout postnatal life Bone marrow occurs in two forms, distinguishable with the naked and yellow marrow, which is inactive and consists mainly of adipose cells that give it its yellow color, At birth, red marrow is found throughout years it is gradually placed by eye: red marrow, which is active in hemopoies the skeleton, but after the age of yellow marrow in many of the bones, By age 10 yeas, red marrow persists only in the vertebrac, ribs, elvis, and in the proximal ends of the humerus and femur. Active red marrow isa soft, highly cellular tissue consisting of| stem cells and precursors ofthe blood cells, supported by a loose stroma of reticular cells and reticular fibers (Fig 3.12). Is organi zation can best be de longitudin, 30%) netopis pesca (>SO%) Iympocyes ae que rare 10%) 2 Wien of ese statements best dessbes white oad cals? the primary function within lod vessels they eave bao vss to prtrm most of ther uncbons they uneton equal wel, no mater what her iacaion ‘ey remain inside lod vessels ‘heya possess a eund rious {5 Themacrophag ound in cance Uses of te body is derives tom monoeyts in te ccuaton aie rom mscroohage-foming clonal nt is phagocyt in susperson and when tached ta substrate a a bide mucous never has cyloplasmic granules 4 Whe of tese statements st descrteshasophis? » ‘ ‘hey leave te crulstion tohecome mast cols af the connective isu thay are ay ahagoyte ther ae aren soon ofa sutra thay contain histamine anaheparn ‘hey poses 3 urd suleus 5 Whicn of te followin blot grandoctes contains very age metachromatic ranses? basopni mast cot monocyte eutoohi lymphocyte 5 Croung ambos are produc by reutoois eosiopnis plasma cos mast cls moneys 7 10 " “ 6 "7 ~ Megakarycyts of te bone marow 12 are the source of ltl ound inthe ulation 'b_ undergo eytokiness watt benefit of Karyokiness (© ae haplot are sind {216 abot he sam sie a5 neutopis In heey sages ofan intarmatry response, wich athe foBowing el ‘ype wi predominate? a nacophaes 1b anocytes © basophis 4 neatopis plasma ces Cones such sinlereukn-1 ar esponse for 4 matwaton of entecbiass aifeenbaton a moneys to macrophages © actation of palts | praducton ot ertopaetn {© feeaseof neutrophils fam bone arrose Which statment est eseibes qraulonoies? (ges rset moras as well as granulocytes 1b sresuts in mature et tae cls © ipotucn od pata {6 en stimulates, produces enormous runes of proentrbsts © is ot mtnced by etoines Wot lod ce would be in tundance ding an ct paraiiintecton? What th most common nuceted cel inte cuter? hat the tags temogoetc cl inhuman oe maou? hat the component perighea oad provded by megakaryocytes? at the smatest wt os cl fours in ptinhera blood? nat cel the bone marow ste eariestrcogrizable stage of he red eos cet ine? a cal is th est ietiale precursor othe neuropil re? at cal ye has a ytroe sues that wie subsequent expels? at nematic i poll? nat a oes rect trom the yells?11 eosiapi 12 eutoh 13: mopakayocte 14 ates 18 ympnoce 16 proeytralast 17 pelts, 18 normalast 19 megkanoort 20 pronyeloote