Chapter-1 / Physiological Foundations - WHNLive Public Library

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[Xeftt of,t"". Respiratorv... standstill117, 1 ~pHl210'"fr-..."f11JiJ1lppt6rtJITttfiaIItlttionpoltnfiIJ/.s in EeGE*11M\,~ r.. 37·C,\ pHA-imlor~ ~ '~sfiIItJf• 6.40\\\,69,76~,l I-.-....- -I1etut tr:'tWR" ""t- 430 405 JIK) "60 30 ominoto 1 2 3 4 5 6 7 8 9 10 11 " 13 14 15mint ..~pH·5,87finilimum)Fig. 108 Recording of the pH incerebral cortex of a rat in the pre-fiand final stage of prolonged etheranesthesia at a normal blood glucoselewl. Result: a spontaneous, rapiddrop of cerebral pH leads to exituslethalis within ~ 6 min(eg. flI19iTapet:lrrir)~myrxrutIitr irfurctJ1ysoso11KJ/ qloIytic t:IKtincytolySismJt'lion1KJI1-anl/uenftrunsitiontrJI1f1uent Q/'eosmimi •I'/flllalt:rJrtrr' smtlll-focus necroses Il11it:rocJrculotionrlisturbedififlfJisfatJe i tfJ/1 -f:&N,focliS t.crosis tlifh Copi rtJr.l doma~.....--.........,.......---~I1 10 10 2 10 3 '2,0' 10 5 10 6 10 7 'n:Iir l'tIs6.----..,....L.----r-.L-----r-...L---..,......L----r-...L---r-~-~..:i....:;£=:::.;:=-=.::::..imasinrJo'inhib Hail 'Y'T4 b;::---+----+----+----+----+------l-------l-------l---~~2 :::-+-----+-----+-------+-------+-------+-~ ~ fCfivtIiionol71---+----+-+--"----"'Il~~~~--+_----+---__l__-----+-____l 'I:Y::f1:~p1 1 ~--+---+-----+---+--6~--+----+---+---+---+--=-,~---+----+---+---+---+---+--'6 L---~J,.o.--~....--~.-----:+-.,...---+,---,.J.,O--....,,~OO---,00...L.-O",,-...J..Fig. 109 Guidelines for the dependency of the tissue pH on the size of volume V with total 02 deficiency. Meurements on cancer micro-metastases as models for glycolyzing tissue, with glass micro-electrodes under CMT cditions [2, 191]; V ~ volume with 02 utilization deficit•solid line in Fig. 109. We must allow for a normalblood glucose concentration for ourproblem (except for badly stabilized diabetic,ee below). Different fermentation capacity andupply ituation of the cell a well a oth rm tabolic exchange rate con tant are al 0
1000S! p.!!.. levelsmeasurtd inlerctlfli/lari/]79872f~XiOtlity oferythrocytes1 CMT • tumor tissue under cancer multistep therapy(CMT) conditions..iJ. g. metlSlUtd fisSIle -pHin OIT 1inforcl-I IV /.~ V 1/~ ~~~ ~ 'IV ~R·50 151""65 2 4 6 8 6 2 4 6 8 7pHR •Fig. 111 The pH at the venous end of capillaries (pHcv)in tissues under glycolysing conditions as function ofthe tissue pH at a given capillary distance R. Approximationaccording to [140]very small and very large volumes of O2 deficiencyin the myocardium, which are includedin Fig. 109. These measurements gave us thep values for the upper and lower boundarylevel of the transition curve for normal cellswith fermentation metabolism.ccording to our model, the followin~ as es ment should not be very far from reahty: the67472811,8oFig. 110 The pH as function of the distancefrom the capillary axis r in the venous capillaryarea of tissue volumes lJ ;;;. 10 mm 3 , underglycolysing conditions (lactic acid formation)of different intensity; calculated accordingto [140]. The lactic acid accumulation occurringin strongly inhibited microcirculation(e.g. case IV) is neglected. It brings about asignificant pH reduction in capillary andcapillary vicinitylactic acid formation in the space of the narrowglycolytic zone (cf. Fig. 99) of a single intercapillaryarea is not enough to lead to a considerablereduction of the mean pH level in theinterstitium (and at the venous end of thecapillary wall). Only when the glycolytic zonesof many intercapillary areas come together(V > 0.2 mm 3 ) can the reduction of the meanpH in the tissue exceed 0.5 pH units. pH reductionsof more than 1 unit in the tissue (andsevere pH reductions also at the venous endof the capillary walls), which finally trigger theblood microcirculation inhibition and capillarydamage, do not occur until the volume of theOrdeficient area exceeds 10 mm 3 .The consequences of an O 2 deficit in thevarious organs and tissues of the human areoften determined by the relation presentedhere. The connection between the size of thevolume affected by O 2 deficiency, and the levelof the pH reduction which occurs, is thus oneof the elementary pathophysiological bases ofO 2 deficiency diseases and conditions. It annow be understood why critical con equen e(e.g. large-area necrosis after a myo ardial infarction,tissue degradation in inflammati nprocesses) only occur when the aff t d ti uarea exceeds a certain volume (e.g. _ 10mm 3 ).pH profiles in the intercapillary spaccan be expected for the venouglycolysing ti u r gionmention d minimum volum[140), can be n in Fig. 110.
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Page 102 and 103: Exholationtubeloop aroundcmebroncll
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