Document ZRwkZ7dEpJLv96yB1QnY03ad

' hagocytosis, Mucous Flow, and iv Oft |iliary Action "t t>(C. HILDIXO, XD, nJ5.. DCICTH. MINN. Prt.{ JThe following presentation is a discussion turbinates, then'ardring back and down into 4 the physiology of the defense of the respir- the nasopharynx and larynx. and \r> {iry tract against inhaled particulate matter, 1C).* Along the flow way there areanum " * jSether living or nonliving. The physics uf ber of eddies and changes otdiroetioowtoere nir r/position in the tract has been described by special impact occurs. preturbinal areas, the antes Wft0rtion)of 'nra^fy Moae the turbinates, the nasopharyn3^hfct>ase:of "Vryv Anatomy.--This defense begins in the nose wd. htch acts to prepare the inspired air for the tongue; and the^pyrifotm'fOSU*^:^ Ait-Flow * * * Fir fveptance into the hmgs. The nose is about. through a Manj. cm. long and 5 cm. high. The entrance byers<one layer next to tfa*L at the nsres which lie practically horizon- .1 \V ion lr I!v and are very narrow. The exit is at the ataGonaiy'and tU*^luoa(pb^d|j X. Ar. ^janae, which are larger than the nares each easunng about 2J> cm. in height by 1.25 an. roimiWi r. E. eccK-rr mu ( Jo>" sorta i width. The roof is arched; the floor is* onaW/ ju{wn>uiy)w *t. The nose is narrower anteriorly and ntttwK>tu .ill Hteriorty and wider in the middle. In cross TO Dc nnuMICUU>l,IBI Vm anon, it is triangular m shape, being wider standpohu.ofedepusitionffi? dow and narrower above. Most of the space . Franr - filled with the turbinates which, with the 'MWtt U Pan- <T*um. form narrow flues through which the .yts'dK A, t flow*. (Fig. M). These floes are normally . jostheM&L hes sr site narrow and cause the air to flow in flat feet* in such manner thrt no portion of the *. iMtncam b very far from the mot* mocous J ISSL bnbet lming the air spaces. The width of **. 5 V air spaces b adjustable by virtue of sweO changeaW 1939. olies m the septum and turbinates. Pre- depoiMdit* amably the siaa of the air-flow is adjusted to tHe AlWnPT unluOt W aO^m UK i . Patkoi (Oct L: Dhboo O do Jour Frown. wet varying atmospheric conditions. the pyriform fossae, and inareeS^TOundi Physiology.--Inspired air flow* in a jet- %e stream through the nostril*, upward and where there b 'nek. posting above (he level of the middle Rttsinooxr Iknat^ jmofjr w ,M I'memtd * ih* Skyteg, Pa, Conference on Ret* structure which uumiauodfa tfoatytagtir* <n*wy OtaMt b Isdawry, May 14.11 1952. Fnwi M flw tssnt Laboratory, St Lbn`i .fpnmnm oI. A Pennr Manrf. "-V mroorwd tr Its Lobs W. '< KMdHIFMr of St Past flu *d C Ceagdow Memorial Camdan sad The Wrmm's Service GoB4 " * Ufce' HtofttoL DV9Ki^QnywlRKj*w wtw* 4 layers of lapfaemsam^egaand then The ^ elongated luiuumareeBawhichuxteDd to dm **' %' 4l \V** ' f iHKHH'ILi <JI- ISVIRONUESTAL In ! anrhtee. The cnfamnar eefls are bjr dib 5 to 7 mm. m length over whfchfltei tWo,. layer of wscoos blanket. However, this typical foetn I ) mm luunuwrjwwff* inuvcnmnoro--ru Ol vBc BQM WnfrC me Bopsci OI r (94 vm r#a^ixg# mi cpumiOT (h4ubvqqmi His many cells deep and Is layered fifce akin. Farther back-on the tmbiaataa aeptum, and spaces non exposed to air.ftw te epithelium becomes >eoh--ar nd4ih,'h u- m-j-ut.kk. *1n- e c ur-a---m--- r oea,-m. u- e .-mA---. - . *1 cw iff will nnTwpRi Mi wncfw posed, are apt to appear with team. ^Tatha more protected areas voder the huthi--> T *,' HI:.H 7 H.HSOCYTOSIS c I--"<4, liriu showing the n.thing eham* N , c ncee. TV .in. t the right outfit r ^tmyi i Gr [` Dr. SVtwmi. Mid Jkallmfcn.j id Dr. Arthur \\ *) ; 5, pTO^lf rm rm of >iwp*m<r\ . Not* the chain* -eebon high *r tetior partxir M te Mid again r jpfcarynx--lv> tV to the orot>Vr m joyhorynx (Com : Dr. Arthur H i ; C. partem i/i itory air How i the pharynx j oit behind (Com f Dr. Arthur W ). * to deep nor anr od the cilia art Wtrwl In (hr each u m thr ally only 2 Urn* oeSeand 1 larr berrane to than vidal. They art yrj air does m< i I cefl*, the epithr and become* I endothelium ir tury bronchi* lie* TSe air flow of expiration follow* a ome* flow takes place through ciliary action. In .Sai different pattern and, for our purposes, the anterior third of the now:, where there , of lew importance. are no cilia, secretions seem to be removed Ciliary Action--Cleansing Mcchanum,-- through traction by the cilia farther back, rv nose prepares the inspired air for the The flow is relatively slow, 1 to 2 nxa. in jtr(. Much particulate matter is deposited hour. In the posterior two-thirds of the nose, , the nose, especially in the anterior third, the rate of flow is 8 to 10 mm. a minute. Vnce it is carried down and back into the The direction of flow from the anterior, noo- , jiynx and eventually into the stomach. The dilated areas is into the meatuses under the turbinates. From the medial walls of the turbinates the.fourtends to be down and back and is apt to s!ide<ui*der the margin of the turbinates into the meatuses (Fig. 2).' From the septum the flow tends to go bade and. on the way, to cross the floor laterally, winding up also underthrinferior turbinate. At the posteriorends^^thehurbinates, the streams flow across flu. laU. t tl phar/ngemfwwB, <fivide around theeastaduan'tnbe, and are earned by mtacntaryactioovdowTi rate the csophs- ,. ..y; --* V * _7 Temptratmt Adjustment.--The tempera- v^ture of the*airis^adjusted/upHK^dciwn,'*c- confiny to drcnmstance*. By 'theJtime The air reaches the (pharynx,' it *Unpractically at v body temperature,-even if the reatfing at the tip of the^noae4s^20F. ' Hnmii is -air readsmetherpharyme/^is ptwctkaDy^satu- ratetWSince webreatheatieastlO/XD liters each day, ttris/means^that* a conriderable amount of heatnmafbeaadiated fronrthein* tenor saracet,of^henose and a considerable amount oi waterevaporated lluuugh'fhe mu* cotta blankeU. Ati ordinary room ..tempera* tores, aodatwsuaT&unidity, the air is said to evaporate 1,000 tnlawh 24 hows.41 >y " ; *< I-- Pacstra of diary framing in the nose. 7* wre of low of macua on the lateral nasal " tV arthrs areaa; B. the coarse of flow of 1 '** w the lateral ami wall in the inactive "**v*ri C\ the coarse of flaw of macas on the T* V rate~ or-*er*--th.e* ftraA c--tiIv. e FtWre<eUp(vs<t*iwppVled) . -ir Anatomy, Tbe cruaa sectional area of the trachaobroochial tree at different levels is aboot-the same." In other words, the com bated crosa-sectionil area of the 2 mam bron chi it about theme as the croaa sectional area-of the trachea,-and, if one proceeds to mptequem cnyttiOM im nn rcsnortsnips seem to hold true, at least down to bronchi about 1 mm. in diameter. Distal to those, the M ARCHIVES OF ESVIRQSMENTAL Hi FI. X -- Oi' the 10-fold ionv4> turn of the dbn*. the bronchi thr, branchings Thr arm wctiooal ir, maim about the mil of these levc?. toy of Tram. Am OtoiaryTtf.) cross-sectional area begins to widen rapidly will beat if tom away from the cell, [mr , and eventually becomes very large. The area it has its rootlet and a bit of cytoj | 01 the lining mucosa, on the other hand, in attached. Some believe that ciliary act*, c creases with each subsequent division. The controlled by acetylcholine and choliiv. * trachea is about 5 cm. in circumference. The ase u others 7 attribute it to serotonin. F 2 main bronchi together are about 7.5 cm. in method of stimulation and control ha. $ circum ference and, with each subsequent divi been established. In isolated bits of ol. t sion, the combined circumferences increase, epithelium in vitro the ciliary beat or *: as does the area of the lining mucosa. By the slowed or stopped by cooling. It is p>-- time one reaches the respiratory bronchioles, actually to freeze respiratory _epith p or terminal bronchioles, where the cilia begin, briefly and have the cilia revive and beat - -*r or end, (depending upon the direction), the thawing. Movement of the raucous blank v total combined circumferences of all the tubes very susceptible to drying, i.e., it slow* : C at that level is very great; probably meters excessive dryness, and the alb eventv : in extent (Fig. 3). stop beating. An increase in pH to ahe J Lining Epithelium.--The lower tract, like the upper, is lined by ciliated columnar epithe lium, surmounted by a mucous blanket. The alia beat in coordinated, ware-like move ments, about 1,000 times a minute and move the blanket, like an endless escalator, upward toward the larynx and pharynx. Here, the blanket turns downward toward the stomach. seems to stimulate the rate of ciliary beat <-* a decrease to below 6 tordecrease thet^- However, in vivo it is doubtful that an; these factors aHernormal'function. Evrt|i the hottest, driest, -orfcoklek^ynethet^^ unlikely that 'there^is^any^zsotioeaWe^tCs^ on ciliary streaming in the!tndnobron( tree, since the air-conditionings^function Cilia.--The cilia beat with a purpoaeftd stroke, something like that of a swimmer's arm. From a more or less rigid, straight up right position, the cilia sweep forward through an arc of 30 or 35, and then bend to make a stroke of recovery. The rhythm is about 1:3, i.e., the effective stroke takes only one-third as long as the recovery stroke. The cilia are not under nervous control. the normal nose is so^effectaal. No ma' what the temperature nf^aspited air tip of the nose- whether 300 For --<*> I by thetkne thsak^reacfaM^i^haTym^^ practically at body temperature and satun> ' with moisture. Great extremes of dryne" < temperature-might conceivably have - -r effect in theaaiddle portion.of the nose. I am unaware of any determinations ' How they are stimulated to beat and how they are coordinated is unknown. When bits As the amoous blanket flows alone of epithelium are tom loose from their posi forms a sort of upside down river. Begin'' tion, and kept moist and warm, the cilia in the respiratory broochiotes, it mmr - continue to beat. The cells may be separated upward and ever into a progressively - one from another, but the cilia of a single rowing streambed. It begins in s strenn rJ1 will <-! Fr*n a irtrrV rilrtlfTt nerhans meters in extent and, by the t"1 c.vr.-it. m .iu ucocrrosfs 7 1 -- DUcram O-foW incrrav n, of the diamxtir. bronchi (hnn^i himrt. Tv I,.. lectioroi arvn . i aboat the wnx : thne level* ( C..r of Tran*. Am. Ac., lrynf.) -iche* the trachea, the itreambed is only ) mm. witle--the circumference of the ichea. During its progress, just as a georaphic river meets obstructions so doe* this ocous-flow riser. When it encounters the ^rnings of tributary bronchi, these openings ccome obstructions, like islands, and the jow must |ss around them. (Figs, 4, SA <ml SB ami 6A and 6B). At the upstream nargin of each bronchial opening, there it a \ the cell, pro\ i>lr'' bit of cytopta'-: it ciliary action . : and cholirvoter to serotonin. TU '1 control has tv: ed bits of ciliated liary beat can ! ing. It is possible ratory epithelium vive and beat after mucous blanket t i.e., it slo^s fnsii * cilia eventually in pH to about ' of dliary beat and decreaae the rate, nbtfal that any of function. Even iu lest weather, it is ' noticeable effect s tracheobronchial ximg function of ecttaJ. Vo matter nspired air at the OOF or --40F-- the pharynx, it is tore and saturated me* of drynew or vrbly hare some n of the note, but rmnation* which t flow* along, ft n nrer. Beginning ' les. it more* ever >rogre**iT<ly nar* as in a streambed i la the cUbry 4-way split of the mucous blanket*1 (In todies with radioeettve polonium, Caaarctt * found that accumulation* occur it beonehtobr branch point* when the material ha* been * inhaled.) In the area just upstream from this * margin, (he cilia change their tfireetkw-.ofa-su blet from an axial one to an oblique ooe ao ->y; / that the blanket i* steered around das opening. In otherwise normal bronchial trees, it is not m.icom.mo.n t.o find areas of 1sq7uam-_o_u.s _Fie. 55--Di_a_g_ra_m__o.f th. e k*.r...:.t.e.n. i o.f .S_o_ar. fc* r -- ,f^ro SIT no cilia. Such (Courtesy of Acta Ootaryng.) M ARCHIVES OP ENVIRONMENTAL in areas might be likened to shallow sand bars under a flowing geographic nver. The mocous blanket does not necessarily stop upon them bat is dragged across by the alia surrounding, the area. From the standpoint of physics,'it would seem that there would hare to be slow-' ing at such points. Squamous metaplasia in the trachea does not seem to be as commotr as in the main bronchi, although it does occur/. There are, of course, no branches or tributary bronchi acting as obstructions. TBe wext J stroction encountered by the mucous river is : at the transversely placed vocal cords," the*^prSrr carina ta'a margins of which are composed of squamousOs - - V --V'W-V ' ii-.---vVr'V ~ -V "Ivn.r- ,so'Vehv^at- m. ( wm^uVuCNI^K\1BviH_i *C'nff 'rt^ inacus mustincrease or the rate of flow W^mcKfla^A^number' of attertipts h*x m%. ^stwdeby myselfand others',to, measur /of the mucous bbni 1*+* f4aeS ./xy fW >^<^.<4'' . .. Fig. 7--Patternedciliary'flow (broach the L of a ealt TbedUarr stnaai flowing up tfcr " ie>dyed'viti! Iada ink It flowed j rV'asDdit cords-wore rwM oirf thn 2 at tiu aattrlnr BBiwiQfiiorV O.iwr M tnafctw Fig. 6A.--Dksm of tatters of flew foaodas^] (Courtesy of Acta Otolorya.)^ epithelium. The mocns does not flow across the cords but ascends the tncheal wall passing between the tr and out into the pharynx. The mucous on the anterior tracheal watt-passes up to the vocal cords where, at the commissure, it splits into 2 parts, oachof which passes posteriorly under the. corre* ipwwipf oora I>M| BWWf pm or oftr Ai^ioMQi no ovt tnco nn pw7nx* flow on the side walls tala* an oblique course WDCn It divert uv mTjtKX mOd pIMv Upwlftl and poeeeriorly. It . ia > interesting that the1-/, dfiary beat in the larynx also seems to change^1 direction inferior to the eord*-Instead'of^ Dcnf ixw hm airmen upvinif tM aiitfjrc* beat is directed more posteriorly, aiding in' *** ,l'* I'l.nW m An* ft!wr*!ow inwH 'i.^l.Tr iUCOCYTOMS 91 s. icr of iSr of Acta nver of cver-narh of the rkrrr rmJ ve been isure the blanket ai e rates of n hr taryw the awouiu rH axia/K >rf thm tjim w been nM The tlnta are very unsatisfactory, but, According to Morrow,4* the factors coo rtt-h a they are, they indicate that there is trolling deposition of particulates from an , |.n>trressi\r increase in rate of flow from air-stream are gravity, inertia, velocity, diffu Se small l*mnchi toward the trachea and that sion, and the viscosity of the medium. The He mucous blanket also increases in depth. density and the nature of the particles are Rate of Flow.--In the trachea it is about also involved A very denae particle is more )0 mm.. [>*sibly aa high as 15 mm., per susceptible to the effects of gravity and ninute, whereas in the smallest tubes meas- inertia. Hatch's work indicates that practi v/ml it is only 1 mtn. or less per minute. It cally 100% of dust particles, 10* or larger emu almost impossible that such a rate of and 80% of particles at 5* are deposited tn W as 15 mm. can be attained by 1,000 the upper respiratory tract. (Hatch considers .-vrles per minute. Even if the cilia were the upper tract to extend down to the respira -fective for their full length of 5* or 6*, tory bronchioles, stating, "As a minimum, thi would account for only 5 or 6 mm. per we may distinguish between 2 significantly minute, and the cilia are by no means effec- different cooes of deposition: along the tipper m\c for their full lengths. The effective stroke respiratory tract, down to and including the ir probably only 2ft to 3* in length. Tbe terminal bronchioles; and within the pulmo mswer seems to lie in the fact that the blanket nary lobule." The latter is, of course, below ' moved by the effective stroke only (not the the ciliary stream.) Then the retention drops .iroke of recovery), which uses only one- off to reach a minimum of 20% to 30% at f iurth of the time of the cycle. Also, during 025* to 0.50*, below which it increases again. be effective stroke, it is likely that the blanket returning to 60% or better for tubmtero- i* in contact only during the peak velocity of scopic (less than0.10*) particles. The reason die active phase and not so much during the . for then changei.iics in the fact that gravity federation and deceteratkju of the cilia. The^Cacta^oirtbeilafger'perticlerand diffusion on~._ mucous blanket Is tossed from crest to crest '^ffw snwiler^partk^rbelowO^wThai lowest ^ <f the waves, so to speak, and is in contact pcobebflityrfor deposition'inthe*respiratory- vitk the underlying cilia only at the brief tractoccurs at 02S^to<X50* whercthecoro- SAr period of peak velocity, when they give the^bined*foreea^of|pfeopitation,rgraTky, and^ and moat rapid "kick." The hi--****$2^1 tho^P: QWinWWHy M <XX| OCX wpift^OKWHii imLHUIwWlI jO** . and start (like a cinema film) with the thrust^not^yet^taibw^oi^fDiffuiiontTiaCraaia and recoveiy of the cilia (Fig. 8.) the partklnsiiedropabefaw Deposition.--Although most inhaled par- ` Cipor*tt*Smok*.--Cif9r4at smoke,proh*-v fieuiale matter b deposited normally in die ably the grmteat.pofiututfnf aS, bypasses the ; of it gets past the nose and into noee. ItJbtahen undilatedWo tbemouth and; respiratory tract as evidenced by ^'.then fod miotb^nexf^kiaxning^fkjw^ff m~- particles in the hmgs of all aduhs. "spired air~throMghythenose.` ts^k1*passes-'- through- the- pharynx. Some smokers inhale smoke in concentrated form without diluting V* it with the next incoaung sir. Theywill take a ycQncnurww gnowtrmbk wm bctpi Wf 'Opening tfomouth* will gulp > deep breath The upe arrow Indkuw dw UUacttun ^ *-<--------- ^. hr towrr arrow tha dimtkai of the wave- "f *' * hr ciia. Tho muram Mm it*V ofimoke -'---- hiftimWi'h ton_ntinr * ^wwtfion seems to be a little greater ARCHIVES OP ENVIRONMENTAL HEa in the proximal part of the tract, the larynx, still others that both sources five n and around the carina,4 but the total amount ptaforyttt.si.as4i.4t In the lunp, for deposited it probably much prater diitally Macklin believes that the so-called pneuni where the surface area is prater. Also, the cytes (dust cells, macrophages) origma initial deposit is probably more concentrated epithelium on (he walls of the alveoli, f in the distal portions than it is in the trachea, he describes 3 type* of cads. Maddia m. because the depth of mucus on which it is that the poeumonocytes never leave the deposited is so very much less, i.e., the passages and are not to be confused mucous blanket is so very much thinner. For phagocytic histiocytes that originate in ah this reason, as the ciliary stream flows up lar septa and may enter lymphatics. ward, carrying the deposited material with fie that as-it may, the process of enpl*ri it, the concentration of this material, unless - meat is agreed upon. The surface tnemhr. it has been absorbed, may become very much of a phagocyte is of an undulating nature; greater in the main bronchi and the trachea forms indentations, folds, and ruffles.*3 WH than the initial deposit there. contact is made with material to be engtrii Air Pollutants In discussing air pollutants, it is essential to consider their solubility, toxicity, and other physiochemical characteristics. Chemical compounds which are promptly --dostparticles, for instance anmdcntati forms to accommodatrthe particles/and fold develops thatfeoversfthe'indentation fuses with the cetTmembrane on the far sil. The indentation-plnchtt off ~and^bccomer vesicle or vacuole within the cefl'The wafif absorbed perhaps may not return to the ciliary fupfonndifly'the- vacuoles 'and vesicles'sho stream or may return in reduced amounts. the same: strueturetaa the cdl walls and Those which do come back may dissolve composed'of*3 layers," Tdenser roo with slowly or act slowly on the underlying cells. less denseone between, " ' ' This situation is postulated for carcinogenic Phagocytic action? may be blocked compounds. A wide spectrum of known certain xtmaustances. For instance, materials have a slowing effect on the ciliary - bacilli ate teat readily pickedup by phagocj action,4 so that, in addition to natural ob aftr o<haripartkt<atinaitey har'bMff < structions to the mucous flow, the stream it gdfed.7oynarB**Uaed^ number of^fferer] self might be slowed in certain areas or its ubatances*andfound* trypan^ blue* entire extent by the action of contained silica, coal dust/ and'India' ink^effective. chemical compounds. Long ago we demon that order, in blocking the uptake of'tuberek] strated that blowing a little cigarette smoke over a solution containing aliated epithelium caused the cilia to cease beating.1* This ob servation has been confirmed by other workers who carried the studies even fur ther.1-* Phagocytosis Phagocytosis has been studied extensively.* On* throther hand/Heppleston ** recentlyj reported that single macrophages might tain assintimate mixture of coal and hemat dustv afthooglr these had been*: inhaled otuei--cn.r n.1i--nes. . , Ptdmonmry Pkmgoeytojit.--When parties-j late matter it deposited in the lungs, some r In General.--It is defined as the engulfing eliminated via the air ways and some v of microorganisms, other celts, or other sub interstitial tissue and the lymphatics. Mo- stances by phagocytes. Phagocytes may be texts on pathology maintain that all dimiiu fixed endothelial cells or free, wandering tion is carried out by phagocytes. The gen cells. The origin of the wandering cells has rally accepted concept seems to be that the not been determined to everyone's satisfac phagocytes leave the capillaries or intent itii tion* Some believe they are mesodermal in tissue to enter the air spaces, where the' origin,3 others that they are ectodermal, and pick up foreign material and reenter the in Ref. bV. 1 1 *. in Vi t? u .i:.ut 41 it 44 ter*tirial ti*i*e, and nrocrod :J mnph th* Kir fI Hi.A H.UjOCYTOSIS s^ve pk % S.itu.-s to the lymph nodes, Macklin and pbston 14 such inert particles continue to for in*Uru> ll(n lake exception to this concept. The move in and out of fibrotk nodules via 3 pneunKm., ,niter describes small pores or "sumps'* phagocytes. originate n ,nxich which particulate matter may enter Summary veoli, wher, icklin sU(r rave the ,v: i fused wit}ate in alve.,. ICS. of enguW e mfmhrnrv r nature an. ^."When be engulfe-! indentation icles, and i ntition arvl :he far skk ^ becomes 3 . . The wall, sides show ills and art :>nes with a t eked under ' ce, tubercle phagocytes s been entf different je, cement, ffectrve, in of tuberde . ..ues. Gross sutes that the basis fur the The nose acts as an efficient air-deaning nmcratkxt-immigration concept is far from and air-conditioning mechanism. Much, per .murtdng. He has demonstrated experi- haps most, particulate matter is caught in the v-ntally that dust particles may leave the air nose and escalated back and down on the .;ocr5 and enter the intercellular spaces with- mucous blanket by ciliary action to the "in mt the agency of phagocytes. Macklin cinerator" in the stomach. The character aintains that the "pneumooocytes" origi- the lining epithelium varies with its exposure v.ic from the epithelium and never leave to the inflowing air. The mucous blanket is he air spaces and passages. He thinks produced by the epithelium and varies in ` hat particulate matter may be carried into the viscosity and probably, general chemical nvmes by phagocytes but that these are histio- nature according^otircurostances^The dense .yte< of mesodermal origin and are not to be pollutant rigarette-smoke, unlike most other''*. o in fused with pncumonocytes. * pollutants, bypasses thenose entirely. There is no doubt that much particulate The physiologxrdrainage of tbribroochial 'T matter is removed by phagocytes wandering tree is accomplished by the mucous blanket,*;,-. up from the alveoli to the respiratory bron- ; whichr ntotivatediby anderiying eflia* con-^; hides. LaBdle and Briegeru developed a > stitutes the'ciliary'stream.iFrom respiratory^ icthod by which the number of free -hago-Ri' broochioles tofesophagus* the streambed-nar-A' Mrs in experimental rats could be estimated. rows markedly,`and probably the eetoaty of'f TVy found that the amount of dust elimi mucous flow increaaes as the streambed nar nated was proportional to the number of rows. The ciliary stream encounters a number - ;hagocytes present They concluded that of naturaQj^occttrriiig* obstructions in the', transport of partides by phagocytes is the- form of^squamousioslands, broochiaiopen- primary mechanism by which inhaled dust ings, *-xi t^vocai 'cords. ,Retardation of the*?' (articles are eliminated from the lungs. dKary'streazmmayioccur at such areas and yj* When the phagocytes reach the headwaters may be enhanced byedgarette smoke or other^ >f the ciliary stream, many disintegrate** air polhitants whkhtknror temporarily stop?. depositing their load to be carried away on anary acitoa,. taemtansg protongea- acuon he escalator nrucous blanket. Many phago- -v. ot my ctfunOfar n&cair ' recently . might conid hematite , eytes do not disintegrate but are carried out intact The fate of particulate matter depends upon its nature and the reaction of the en- >(M__I_C_S__po,-*t*!**; Probably most- of the- particulate matter that gains'access to the alveoli and alveolar ducts is removed byphagocytic actioa and inhaled 9 j * suiting cells. Particulate matter may be carried out the tracheobronchial tree into the*; *n particu- broken down and destroyed by Intraceflular^ esophagus^ Some gates access to the^intent! rozymes or, conceivably, be changed to more Hal tissue, lymphatics, and lymph nodes. rs. some i* some via tics. Most ill elimma* The gen ' j * Hr*ic compounds.4* If relatively insoluble, Whether this isalways accomplished by particulate matter may be carried unchanged - phagocytic action1 isaiaoofrpomt. * - bring the cell's life-time. The situation so A. C HIkfing, HD. PMX Research Labora br as the tissues and inhaled materials are tory, St Luka's HmpHal'Dohrth U. Mhm. rn*wttied, depends upon the nature of the ie that the k*tr and the reaction of the former. ' RtmtNcn interstitial here they er the in* h the Ijrm- ( ^ The concept that insoluble material in the "woes lies enclosed either in lymph nodes or *n fibrertic- nodules unchanged and static is 1. Ballanger, J. A: Experimental Effect of Qtarette Smoke on Homan Respiratory dim. New EagL Med 2U:2-S3S, I960. 2. Battaglia, F.: Phagocytosis in the Fetal Long. *** necessarily true. According to Hep- . RJv. Pac-Sper. 6 J08,1990L 7 ARam-iis or lsvirqsmlstai. n 3. CxMrctl, L- J.: Some Finical and Phyuologi- 18 Hilding, A. G: On Ggarette cxl Factor* Controlling ibe Fate of Inhaled Sub Bronchial Carcinoma, and Gliary Action: b stances: Retention, Health i'hys. 2:J79-J86i, 1960, mental Study on the Filtering Action of 4. Dalhalm, T.: Mucous Flow and Ciliary Longa, The Deposition of Tar n the Rn- Activity in the Trachea of Healthy Rat* and Rata Tree and Removal by Ciliary Action, New Exposed to Respiratory Irritant Gaaea (SO* H*N\ J. Med. 2S4:1155-11601 1956 HCHO): A Functional and Morphologic (Light 19. Hilding, A G: On Ggarette So Microscopic and Electron Microscopic) Study, with Bronchial Carcinoma, and Gliary Action: A Special Reference to Technique, Acta PhysioL lation of Ggarette Tar Upon Artificially Pn, ScantL 36:(SuppL 123) 1-161, 1956. DecQiated Islands in the Respiratory Epith 5. Daihahn, T.: The Effect of Girarette Smoke Ana OtoL 65:116-13011956 on Gliary Activity in the Upper Respiratory Tract, 20. Hikfing, A G : On Gguette So . AMA Arch. Otoiaryng. 70:166-168, 1959. Bronchial Carcinoma, and diary Action: C 6. Ermaia, P, and Hoiiti, L. R.: Distribution and Streaming' Through the Larynx and Dritribos Absorption of Tobacco Tar in the Organs of the Laryngeal Epithelium, Ann. OtoL 65:736-746.: Respiratory Tract, Cancer 8 -67J, 1955. 2L HOdfaig, A G: diary Streaming 7. Gosselrn, R. E: The Glioexritatory Activity Bronchial Tree and . the - Tune Element m i of Serotonin, J.Ofl Comp. Physiol. 58:17-26, 196L ciiwgtneais. New EngUJ. Med. 2S6:<34-6I0.: 8. Gross, P, and Westridc, M.: The Permeability 22.'Hiking;: A. G: Experimental Stud*- of Long Parenchyma to Particulate Matter, Amer. Some Little Understood Aspects of the Phyw J. Path. JO.195-213, 1954. of the Respiratory^ Tract and Their- O - 9. Hatch, T. F.: Distribution and Deposition of Importance, Trans.' Amer. Acad. OphthaL i- Inhaled Particles in the Respiratory Tract Baet laiym. 65 .-473-95. 196L Rev. 25.237-401 1961. 23. Hikfing, A G: .The Respiratory Epithr 10. Heppleston, A G.: The Disposal of Dost in u a Vital Organ and Same Pathological -On- the Langs of Silicotic Rats, Amer. J. Path. 40: in it Due to Common Diseases, Acta Otohr 49J-506V 1962. Stockh. 37:138-152. 1949. 11. Hilding, A. C: Histologic Changes in Kasai 24. Hiking, A G:. Air-Flow as m Eh4 Mucosa Following Experimental Variations in Factor in Metaplasia in the Trarhrobrooddsi 1 Ventilation and Exposure, Proc. Mayo CGn. 6:772- Arch. Path. 70:556-561, 196a 774, J931. 25. HDdiag, A G: Ggarette Smoke sad 12. Hilding, A G: Experimental Surgery of Physiologic Drainage, of the Bronchial Trcr, I the Nose and Sinuses: Changes in the Morphology Chest J9JS7, 196L of the Epithelium Following Variations in Venti 26 Hikfing, A G: Possible Relation of lation, Arch. Otoiaryng. 16:9-18, 1932. Manner of Deposition and Disposition of Gm-` LI Hikfing. A C: The Physiology of Drainage Smoke in the Bronchial Tree to Carcinowai. of Nasal Mucus: Flour of the Mucus Currents Special Reference to the Pattern of Gliary Str Through the Drainage System of the Nasal Mucosa ing m the Branchial .Tree, :Acta Otoiaryng. Saw. and Its Relation to Gliary Activity, Arch. Oto- 48:2M0( 1957. . laryng. 15.92-100, 1932. 27. Hilding. A G: Cffiary Streaming in ' 14, Hilding, A G: The Physiology of Drainage Lower Respiratory Tract, Amer. J. PhysioL ! of Nsssl Mucus: Glia and Mucin in the Mechanical 404-416 1957. Defense of the Nasal Mucosa; A Motion Picture 28. HOdk-g, A G: Gliary Streaming Thn-- Demonstration, Ann. OtoL 41:52-58, 1932. the Larynx and Trachea: Relation to Direct** 15. HUdtng, A G: The Physiology of Drainage CBiary Beat and Significance la Sites of IUipii of Nasal Mucus: Experimental Work on the Disease, /. Thor. Carthor. Sarg. 37:208-117. 1* Accessory Sinuses. Amer. J. Physiol. 100:664-670, 29. Ingdstedt, S, and Toremalm, N 1932. Aerodynamics Within the Larynx and Trid 16 Hik&ng, A C: Four Physiologic Defenses of Indfcmtioaa for Vapour Therapy in Acme Lair- the Upper Part of the Respiratory Tract: Gliary Tracheitis, Acta Otoiaryng. Stockh. SnppL 1M' Action, Exchange of Mucin, Regeneration and 92, 1966 Adaptability. Aim. Intern. Med. 6 -227-234, 1932. 36 Joyner, J. \V,, and Calhoun, G L. L.: 1 17. Hilding. A G, and Hilding. D.: The actuations on In Vitro Behavior of AH*' Volume of the Bronchial Tres at Various Levels Mononuclear Phagocytes Following Expnmn and Its Possible Physiologic Significance. Am Tubercle BadIH. Proc. Soc. Exp. BioL Mol OtoL 57 J24-J42. 1948, 210-213, 1957. 17a. Hikfuig, A G: On Ggarette Smoking, 31. Kajha, A.; Makamurcfc, K.,- Taya. S. Bronchial Carcinoma and Ciliary Action: Smoking Tesheitra, T.: The Electron Microscopic Habits k Measurement of Smoke Intake, New tions on the Pulmonary Alveolar Pimenov -- - ->-< the Vnttw. Tobohu J. Exp. Med. 70:JIM8 : I I H.acocytosis n Sniotj, tx(T- *( Cm Brood,. n r. Smokn-- AcconProduc- pithciu* Smoicw. o: Glijf nbuboo -746, iOi wr m h 't in G>: MWO. [V: Studies . Physiclor ir Qraio ithaL Oa> , ( Epithdiw Chancy Otoiarj-^ in Etioloo ochdj Tftv # Ae and th- i I Tree. D* inon of rV of Clfxm* nnoma, wnt cary Strew Stoctk ; mmir m n.* j PhysioL 191 nrt Throw* > Direction ^ Rnpmtor <*117, 1959 hn. x. c utd Tenches cote Lnrynao , mppL 1*i i : U: ? of AIten'il 1 Expowre **ol. Meet to S eTava, S* ,, . f' -npic Oh*m J I'hatncvyrt <rt "< 11 1 .1 1 <HO d Karrer, H E.: Electtor Microscopic Study i<c Phagocytosis Procesa m Lane. J. Biophys. < IiTTTV Crd. 7 J5746. I960. ;i Kordik. P : Burn. J. H, end Bdbrieac. E-: un Morerent end Acctytehoine. Brit. /. 5, Karaoesky, U. L.: oi Phnfocytic AdMty 42Mym,. 1962. & LaBefle, G W, awl Brief*. H.: Sywrpesuc ESscts oi Aerosols: Elects on Rate of Oceranc* irmcol 7-67. 1952. ii LaBeOr, G W,, and Brietrer, Hemnch: The if of Inhaled Pertkiea the Early PosSexposur* from the Lm*. Arch. Iadns. 195*. 7. Morrow, P. E.: - F rrv.l: The Role of Pulmonary Phagnrytneie. al Factor > - ii Environ. HmWh 1423-Z7, 19601 tv Macklin. C G: 1-onx Field. Alveolar Dust :>ntt and Initial Leeiom of Disen i MmL MeA Ass. J. 72464465. 1951 * Markfin. C C: Pain--ry Swaps. Dm* stones* US^Aton*. Enarg,, 113-36, 195*. L Mattnra. G: and Sikes oi Dm* IaA Mod. 9 *54*i NSZ^ \nmmoteioM. Aheotar Fluid, and Lymph Veetda. J:. R SpaeatUn, H.> '.a Amt (Basel) 23:1-23. 1951 .: Mackfin. G G: The Dm CeOt a the Lanp&wintotr TVwh t the Afteno Mourn: Their Structure. Rduhm.^dW-H IW^ l .) Mode of Action Lancet 1 432-4JS, 1951. A .MadtSe. G G: The Puhuonary Ahwahr Uaroid F3ai and.the-Pmuawocytev Itwtil me-iKK 1954. A Mcflort. R. C : Mkroecopie r.tarro Smoke Product* in the Animals Exposed to Ogarcrte \mrr. Am Cancer Res. 2J25, I95B. . Morrow, P. G: Some Physical <Jnrical Factors ContrelTinc the Fate of I; ' ffiHrTi. ixyoMioi^ nCwui nyv 6 II. Peace. R. J.: The Role of the. ' ie Cefls in Reaction to Lamp lxjury, MnL ,!. S3 49045L. i960. G. Praeta. Arthur XV.: Essays au the nir*eh>jr at the Nose. FA 2. St ihMWdn* CA mi-'H kk Rohertsou, O. 3L: Phaocyto4of Material in the- Lm^Physiol. Res. 2t:llM TNI. 44. Stihefa. fL; Suaer. E, aud--------------------^ , I -; StwSes on the Interaction Detween PhapecyhI . "** d Takertie HarilS: Ohaervathm on the lletalin '* of Guinea Pip Leucocytes and the Isfluencs of Mtoha after the '^mfjtusia. ;. Exp. MeA 104:121-196, 1954 aaraaanvaa ,,.. a * SecKcmfy CM hut Used m Buchpround^ I Ikmt, F. B.: MucodHaty Fsnctkm aa Pro- Mrrtnlmi in Upper Respirutorr Trac^t r^i Vr. 2S*2Jh 1*M. I Camnut L. j.; Mathanhm of Owm of/ !sN*rd Parrlrutsiu from the Lm, U.S. Comm. Wash. 1923:137-51 1994 * CVnwma J. A.: Surface Tsmkm of UUM'.* ---- Lm^yT. *'*1* PrrK' ** BM. MeA 95:170-174 sma 4 Grtsheueff, It A.: O ftinairnii ? A Hhto ^ Cnntrhutten to the Sahdfan of Seme 1 *mbI Proll--a. London. Perpmnon Praa. ^ 1> 149-150. sealarsptfhehmR. Such of a hum uufls ft ARCHILLS OP ESr iKu.'iM^.'* . seen a Ur that al*>t on vrtei* or bronchi, and it ocrun without Da. Fuctts : Hare you made any ob*r, the aid o( phagocytic csll*. on fibrosis ? Da. Mcon: I would like to aik Dr. lidding if he can help tn out with the situation in the vestilwle of the nose which it supposed to be the place of elective localization of Staphylococcus nuretn in the carrier. Can you tell tn a little hit about the histology of the region and whether or not it U reasonable to suppose that any sort of treatment with antibiotica might have acceas tn the staphy lococci which seem to be do* in in the vestibule of the none? Da. A. C Hiumno : I have no special information on this. The vestibule of the nose ia lined by skm and staphylococci being on the surface and in the surface cells. I think they would not be reached by antibiotics taken mtemaQy. Da Hiuukc Va, l have only had on-, make one tingle measurement in a human in a nurse who had a laryngectomy tony before. One could not know if tiu is the : volume. Over a period. I think, of 12 hoc made collections in Kleenex that had been * wore AM IJTWlUBllfUjf poc UKO petluC Dftf> she produced at the rate of 10 ml fat 24 boon Da. Muse: Although Dr. Briefer far evidence of any selectivity in phagocytosis h- oxide and etlky if you go into the of bacteria, there is tremendous <Sf<between bacteria which have a film of phagoev promotlng antibodies and those that do i*< the ato Da. Moan: What about immunisation? The drainage, I take it. is back away from the vestibule. Da. R Bmnc*,^Jff*rsoa' Uedieml Coflru Da. Hclmko: N'o, by the vestibule we mean just this little skin-lined area in front that we blow out to dean. Farther poweriorty. of course, alt BWCnil fOCI QSCX. trv IWK IT RM KT1I (XpOHvCCn Pennsylvania. Philadelphia: This is e r . mow compmx pFoomv i fncviDuucu uo mr ' no CsmBBGV nw uc uKUAcu cottotix*v in^, ^ vrao|iin numui ommeo pvnMlocjv^K. . *. onteas it is absorbed, it is reaihr still outside the Da. Kasa, Th^Botoou QtyWospital. Mfl Hwg^' y[ body. It is on its way to the stonurh. where it acta Are, Boston: There b-en aapeet that lms iw^t^|^ into the body only if it is abwwbed. Da. S. Mubo, Chief, Mlcrobtoiogk Reward* Program. Veterans Administration Hospital. Uni versity and Woodland Avenues, Philadelphia: A serum would hare dffiealty in gaining access to cehred as much coosidemtioo hi the yuhnoasiy., 1 at it has hi other work and that is that it ha* ` 4' himii ttyoBwy torn tie tmimr 01 woicn por are taken up by the i etkulueintotbcUum is a*1 by a variety of. materials that may < VI CnV VTBDOH^ aVC^ Da. Hawise: In the vestibule rtsdf, in this dry, T agree wfthyou. ' ^ *J skin-lined ares, yes. Farther back, it might, but Da. FAtuemta: 1 would dice to iSrect a even there I doubt it to either Dr. Brieptr or Dr. Gross, and ped Da. R. E. Foasrsa, Professor and Chairman, Department of Physiology. The Graduata School of Medkfcw, University of Pennsylvania: I would Hke to ask Dr. HTkfiug what he thinks Is the normal flow of the mucous sheet up the trachea in a normal man. Da. Htuoso: The volume of mucous flow is also mow difficult to measure. The few available data iudkatt a total volume m a iwniuJ brondua) tree in 26 hour* of the order of 10 mL I <fid some experimeta* on chickens which consisted essentially Dr. Hndbg can abed some light on this too. M is the nature of oil film, that is. inhalation of o particles? Wt have dime a little bit of work < uva mo Tr/l^fO ottr psnoiQ|m----oran. mm. q_ 9VKNHt TOO pomDAnJ Onat wwMSv_Bl.omcvpst might be made up of this dL Do either sf' know of a work whkb would show whether actually get a layering effect in the tracheobrow tree aa a result of Mrnflag oBsl Da. Bemcn: t have no personal hnowfcAr till*. - - - in the creation of a harrier to the ciliary stream Da. HttMno: I tfid Just one expevkueM triers: without interrupting air flow. At the end of the an exenw ipiuvuviv m w an m penw** operation, the akin was doeed and the bird breathed normally, but all of the e menus flow collected at the barrier. These tilichens went operated on in pain and, at the aid of the operation, one was kmnadbariy Wiled. The experiment was terminated mucous bbmket If it were mwdpelMsd h*m way that It were mode to penetrate, it gwun*^ the cilia badhr. That's all the fight I cna kri the question. Da. Gaoas: From dWcai experience tt ^ i at the end of an hour and the collected mucus max iM toiiowmf ht pfinraBi/ nv iin < recovered and weighed. The live birds produced that all placed in the aa average of 2J mg. In an hour, a rate of half a membrane wQI gravitast gram in 24 hours. For some reawn which is not mucous blanket down to the alveoli; (2) riser, the dead ones avs raged exactly twice as on the alveolar surface K is apt to remain much, 46 mg. <J> that it (a not auweptlble to rleuranrv Vd. 6. Jm., mi Ur .' !> iwn- "V ITlc1 C. ; V unri . Vtxf. *rv-~ ffrrrrt cyrrxj not I irrtihr.' Ik*** < mw there \ of :f iv fsrrixi i*nC t ary an- tew hrrparticV ` pert nay cm: pci fun o. \VT*b f oil-fm*' oric inf* ficnlfy yen fte r of ther y i with el ftrate rt m wsrh i owned w i shed lets: <P I irruroo- <-icr ite oner it i* ..ia rrosts Tt .ibfr nwttrr The (True- why oil i* re*itnt to time, and many of them are not resolved as yet Let - vr,4jr clraranrr mecHamwn It not known. its consider the amount of dost ultimately rrtained , llaireiJt: In kjctic personal experiment*! ex- in the lung and its action on the lung. The amount r> | have note*! that liquid material in par* taken out of the lung by the ipntuw is of interne. r ,t*m it unable to ttimatate phagocytosis, Once it is in the ipotum, U is of relatively bttie i it may be phaeocytized. interest Retention of dust is determined by a variety MttJt.xo: All liquid* in * particle--in other |,irtcte*ti*eil liquids, retard!el* of tire? I'.tttm : Liquid particles, ye*, i. * ix Mittixc: Are they ttill cleared? . i Italian: I have no reliable data on clearance, I Imm that they do not ftmrolate phagocytosis. , marks referred to insoluble or only slightly 1 , -olid parttries The fate of soluble particles ..,i, iKfferent. Father they cfisaolee and enter the ..i stream, or they combine with cell fluid, and nr have the interesting phenomenon that wch ojI may be identified in the longs much longer i. Mitel material. of factora which relate not only to the inhaled 1 concentration of the dust particulate but is tremen dously related to the use of the particles. TWa thouki he kept in mind when speaking of response! to phagocytosis ami particulate material. Another parameter to be considered is the inherent biological toxicity of the partid** -li a particle has a low level of biological activity, its ability to dear from the lung is much more rapid, perhaps, than that of the particle which has a high level. There are other variable factors mch as length of retention in what I call the rtratogic segmer* of the respiratory tract In some of our recent Hudic a. we have observed rather rapid drainage of radhmetive particulates of i * \ l*i anACH : I would like to direct the quea- different rarer dements, m ll of them, out of i.i luth Dr. Driecer and Dr. Gross, and perhaps the hmga into the tracheobronchial lymph - \ orwald would also say something. About JO and into other tisanes of the body. It would irar* ago in South Africa, Great Britain, aid that many of these very small inorganic particulate i nitcd State* there were a number of experi- agents penetrate vessels to a surprising degree. So, i.il nhe* on the production of silicosis in in silicosis, in so-called benign pneumoconiosis. we` --iU carried out In these studies, basically dif- find relatively early deposition in the tracheobrow- . 1 animals were exposed to different fibrosis- dual lymph nodes. It is dswk, for example, to lost dusts, and the results were almost uniform observe in human pathology thait if an itffivhhssl J countries. They were attempting to anawar is subjected to fragKut of small partidea-:c;* - ii rrgxrting the size of the particles, length which gain access to the <- i rotore. and the crystal and chemical character* lymph nodes relatively himy^.HV <h of the dust They came to the conduaicn that re of the dost was important and that the duet *`i iwg pfnRmr tmoc mr ruiHT um tiie anon -rid the duets. The duet was inhaled, tha '*Jar phagocytes reacted and. if the dust particles * wuall enough, they were absorbed by the "Aw phagocyte> after which elimination would *nr If the inhalation was equivalent to the dimi- moons cXfOKRDF sen pnmn^ non o on ijopi nodes irst ktmat<llg]rin,((lBi>fmtp. dfcstors of-whet iwhappoaiug. . WHh respect to eoluMa'partkfies, i 1 It is an acrosoL or la a uat amrc.or leaa rriH and they gain access try the pajamas r, example, as Dr. nrirgrr a--tionwl. in vv nr the etimination kept pace with the inhaia* certain onaaic tolabla partidea, they nothing would happen; However, if the station of particles was great, and the rate of ~matina couM not keep ap with the rate of to- u,a*. the wwa partidea were carried by way > ,fw lymphatics to the lymph nodes. One Lrgrrts* - * l asimd from this was that there was an early marten of foci, that lymphatic invasion occurred M 'wriy. The dlflrnvtee bitneen a fibrosis pro mg dust and an Innocuous duet eras that the *'pnaharlitg dust was capable of preatrving 'rr*- Thrrrfore, as this dust eras deposited along *nnr of the lymphatics. It would, through ehwti* I ardinm muwIsmm nDnRM. --*iSl-a--g fv--mpTC--MiI-O-fl JI |MRQii '* "hqt H that the action seemed to he pride* t mnued. ' * V#wwato: Of course, the problems that were tariaL Let as be vary that the subsaanes found in carclaonea of the ksng, a soBsoom wiocn m vm oooNm iiuui s on* Turng/ OOSOOn Offr OS OOBW IO% BOK US mw oow rapossoo tor on cocoooi or qmk ' ***** up this morning are problem* which many been there to produce the cancer--itot e word of n" have hern interested in for a long period of