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Respiratory Physiology and Importance of Respiration

This text provides an overview of respiratory physiology, including the processes of gas exchange, regulation of ventilation, and the importance of respiration in maintaining homeostasis and overall health. It also discusses the investigation of respiratory functions using non-invasive and invasive methods.

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Respiratory Physiology and Importance of Respiration

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  1.  Respirationphysiology P.Kučera,FBMIKladno,winter2014 incessantexchangesofO2andCO2 maintainingofacid-basebalance thermoregulation immunedefense respiration isessentialfor Importance: Arrestofrespirationleadstodeathinafewminutes Nakoncitétokapitolybychommělibýtschopni: 1. 2. 3. 4. 5. 6. 7. 8. 9. Popsatstavbudýchacíchcestaplic Popsatalveolo-kapilárníbariéru Porozumětventilačnímechanice Vysvětlitcojemrtvýprostor Vasvětlitcojekomplianceplicahrudníhokoše Vysvětlitpročjeintrapleurálnítlaknegativní Vysvětlitventilačnípráciarolisurfaktantu Vyjmenovatplicníobjemyapopsatmetodyjejichměření Vysvětlitmechanizmusadynamikuvýměnyplynůvplicích 10.Nakreslitakomentovatdisociačníkřivkuhemoglobinu 11.Srovnatkrevnítransportkyslíkuakysličníkuuhličitého 12.Definovatventilační-perfusnípoměr 13.Popsatprincipyregulacedýchání 14.Popsatjaksedýchánípřizpůsobujetělesnénámaze 16.Vysvětlitprincipyuměléhodýchání 17.Dokázat,žedýcháníovlivňujeacido-bazickourovnováhu 18.Umětvyužítfyzikálníchzákonůpřifyziologickýchvýpočtech 

  2.  PARAMETERSSTUDIEDINTHERESPIRATORYPHYSIOLOGY Parameter Symbol Unit Examples PB,PH2O VT Partialpressure Volumeofgas Flowofgaz,air P V V mmHg L L/min;mol/s… VE VO2 Qa :ventilation :oxygenuptake :arterialflow Flowoffluid Bloodconcentration Fractionalconc. Frequency solubilitycoefficienttempeatureviscosity Subsripts(gas):barometricinspired expiredalveolartidaldead Subsripts(sang):arterielvenous Q C FG f agaz T,t  L/min mLgaz/LsangCO2:VG/Vtot cycles/min capillaryconcentration FIO2 :O2fractionintheinspiredair mLgaz/mlH2O/760mmHg:@37°C:0.024pourO2,0.56pourCO2 °K,°C Ns/m2 Gaslaw:PV=nRT BIEATD av Dalton’slaw: pressureofagivengasinagasmixtureoccupyingagivenvolume=pressurethisgaswouldexertifitweretheonlyonetooccupythisvolume:PG=PB.FG.InpresenceofwaterPG=.FG(PB–PH2O);PH2O@37°C=47mmHg. Inamixtureofgasesinequilibriumwithafluid,partialpressuresofallgasesareequalinthebothphases. Henry’slaw:VGdissolved=PG. capillary c P1.V1P0.V0 = VSTPD VATPS VBTPS StandardTemperature(0°C)andPressure(760mmHg),Dry AmbientTemperature(t)andPressure(PB),SaturatedwithH2OVolumecalculus: BodyTemperature(37°C)andPressure(PB),SaturatedwithH2O T1 T0 PLAN Slides: INTRODUCTION -importanceandorganisationofrespiration,ambientatmosphere,physicallawsconcerninggases 1-2 AIRTRANSPORTBETWEENATMOSPHEREANDLUNGS -functionalanatomy,ventilation,passiveandactivepropertiesoflungsandthorax,ventilatorywork,investigationtechniques 3-13 OXYGENUPTAKEANDCARBONDIOXIDERELEASE -partialpressuregradients,alveolo-capillarydiffusion,bloodtransportofgases,haemoglobin, ventilation-perfusionrelationship 14-21 REGULATIONOFVENTILATION -controlbycentral&peripheralnervoussystem,linkbetweenrespirationandbloodcirculation,pHregulation 22-26 TECHNOLOGY -artificialventilation(positivepressure,negativepressure,highfrequency 27-30 

  3.  Respiration gasexchangebetweenorganismandambientatmosphere units:liters(moles)ofgas/min Withoutrespiration NOTENOUGHATP 2 ambientair OCO2 1)CONVECTION(ventilation) externalrespiration Lungs 2)DIFFUSION (alveolo-capillary) Hb bloodtransport 3)CONVECTION (carriertransport) H+ HCO3 4)DIFFUSION (capillary-cell) CO2+H2O+heat+ATP Glucose+O2 cell e.g.muscle internalrespirationmitochondrion FUNCTIONS Quantitatively:internalrespirationdeterminatesexternalrepiration Fractionalconcentrations(%)andpartialpressures(mmHg)of: inspiredair(STPD&BTPS),alveolarandexpiredair(BTPS)@760mmHg GASES DRYAIR ALVEOLARAIR EXPIRED AIR mmHg % mmHg % mmHg % Nitrogen 600.2 78.98 569.0 74.9 566.0 74.5 N2isneithertakenupnorproduced O2isconsumed Oxygen 159.5 20.98 104.0 13.6 120.0 15.7 Carbondioxide 0.3 0.04 40.0 5.3 27.0 3.6 CO2isproduced Airintheairwaysissatu-ratedwithwatervapour Watervapor 0.0 0.0 47.0 6.2 47.0 6.2 200 mmHg 150 PIO2 mmHg O CO2 Atmosphere Gradients(cascades)ofpartialpressures 1erssignsofhypoxia 100 MtBlanc 2 100 MtEv erest 50 0 5altitude 10km  amb.air alveoli blood tissue 

  4.  Macroscopy AIRWAYS:warming+humidification+cleaning d ead nose mouth mucussecretionciliarybeatingimmunecells trachea s pace bronchi respiratorybronchioli alveolarduct ALVEOLI gasexchange alveolus pulmonarycapillary pulmonaryartery pulmonaryvein  Microscopyofthelung:alveolo-capillarybarrier surfactant secretiondipalmitoyl-phosphatidyl-choline alveolus gas diffusion cellules waterlayersurfactant ↓T alveolus  

  5.  Surface tension! T (Laplacelaw) P= 2r ifT2=T1 P2<P1 alveolar collapsus P P 1 2 T surfactant ifT2<T1 P2=P1 no collapsus  INVESTIGATIONOFRESPIRATORYFUNCTIONS METHOD: PARAMETERSstudied: NON-INVASIVE spirometry volumesventilationpressures dynamics(dV/dt;dP/dt;airwaysresistanceoxygenuptake carbondioxideproductionlungdiffusioncapacity pneumotachography manometry gasanalysis INVASIVE bronchoscopy formdimensionskineticsmetabolism imaging(X-rays, CT,IRM,scintigraphie)  

  6.  VENTILATION -transportofairbetweentheambientatmosphereandthealveoles -realisedbythoracicpumping:alternativecontractionofinspiratoryandexpiratorymuscles restingconditions: PB P . VE=VTxfv ~7.5L/min . VA~5.25L/min B deadspaceVD~0.15L (doesnotparticipateingasexchanges) thorax +lung + alveolarspaceV~0.35L PA A (gasexchanges) -VA diaphragma +VA PA VT~0.5L diaphragma inhalation exhalation 15/min  Ventilatory mechanics cartilage sternum ribs axesof rotation vertebra joint sternum Inhalation(fulllines): diaphragme+externalintercostalmuscles ribs V&P Exhalation(interruptedlines): elasticrecoil+internalintercostalmuscles  

  7.  nasalcavity pharynxparietal larynxvisceral Lung-thorax relationship pleura secretionabsorption ofpleuralfluid pleural "space" trachea bronchi bronchioli Pintrapleural<O (canbemeasuredbyusingintra-oesophagealbaloon) ALVEOLI  PassivepropertiesofLUNG-THORAXsystem:relaxationcurve Pip~-20cmH2O V(liters) ↓V Pip~-5cmH2O Pip~-1cmH2OdV =C~0.1L/c dP air 5 ↑V 4 pneumothorax Pintrapleural<O 3 mH2O 2 1 Pintra–PB(cmH2O) pulm -40 0 +40 Pintrap–PB=Ptransthoracic Pintra pulm  

  8.  V Ventilatorywork static(elastic)~65% tissue~7% Normal dynamic(inhalation) R~28% dynamic(exhalation) P V V Increased resistance (asthma) Decreased compliance (fibrosis) P P  Spirometry determinationofpulmonaryvolumes time inspiratoryreserve vitalcapacity tidalvolume exspiratoryreserve functionalresidualcapacity residualvolume  

  9.  Dynamicventilatorytest(Tiffenau):OneSecondCapacity Measurement: -maximalinhalation -exhalationwithmaximaleffort . dV/dt=Vinstantaneous .. OSC VC V1–V3=f(effort&R) V4–V5=f(effort&R) .. Importance:OSC<80% -obstructionofairways -muscular OSC ≥80% VC  Alveolo-capillarydiffusion (partialpressuregradients) PAO2 2r alveoles d A h plasma PcapO2 D:diffusioncapacity PAO2:100 AO2T° .. (P A ). PCO:40 -P VO2~ O2capO2 A2 rO2 plasma d wherePO2=FAO2.(PB-PH2O) andr~√MW PvO2:40 PvCO2:46 PaO2:100 PaCO2:40  

  10.  Diffusionlimited&flowlimitedalveolo-capillarygasexchanges 100 O2 ↓diffusion 75cardiacfrequency 220180 120 CO2 50 PA(mmHg) EXERCISE R REST 0 0.2 0.4 0.6 0.8s timeofcontactblood-alveolus  Determinationoftheventilation,O2uptakeandCO2production . VE PNEUMOTACHOGRAPHY inout r4 ... 1 p ) (P1–P2 VE=  8 P1-P2(differential manometer) Gasanalysis: gasuptakeorproduction . . VO2 . VCO2 Vout . Vin . r =VE(FIO2-FEO2) . =VE(FICO2-FECO2) l . O2analyser: FEO2 VCO2 .=RQ(respiratoryquotient) VO2 FECO2 CO2analyser: 0.7<RQ<1.0  

  11.  BloodtransportofO2andCO2 Erythrocytes:haemoglobin(Hb)carbonicanhydrase(CA) Haemoglobinreactions LUNGS O2 Hb-(O2)4 4O2+Hb CO 2 TISSUES CO2-Hb H-Hb Hb+CO2 Hb+H+ HCO3 CO2 H2O CO2 CA H2O - - H++HCO3 CA Hb:transportofO2+transportofCO2+tampondeH+  Bloodtransportofoxygen WhatareFluorocarbons? 1)DISSOLVED 2)BOUNDtoHb 200 O2Hbbound Maximaltransportingcapacity: 1.39mLO2/gHb 150 Hbbloodconcentration: ♂160g/L♀140g/L 100 O2content(mLO2/Lblood ) PO2 50 Henry’s law . O2dissolved=760O2 0 PO2 0 0 10 75 20 150 30 225 40kPa 300mmHg  

  12.  Haemoglobinsaturation(dissociation)curve 100 ↑affinity ↓affinity:↑CO2 ↑H+ ↑2,°3DPG ↑T° lungs Hb+4O2Hb(O2)4 P50O2 %ofsaturation sigmoidcurve: increasing,thendecreasingaffinity(cooperativityamong4subunits) 50 tissues P50O2 0 0 0 3.65 2737.5 10 75 15kPa 113mmHg  . . I V/Q Inegalityoflungventilation- perfusionratioinstandingposture(rgh) .. MeanV/Q=0.9 .. V/Q II Heightoflungs .. V/Q III  Bloodflow 

  13.  . . DecreaseofVand/orQ→HYPOXEMIA(&hypercapnia) 57 43  RECEPTORS(transducers) inthecardio-vascularandrespiratorysystems Mechanoreceptors Chemoreceptors nerve P Glomuscells: O2sensitiveionchannels? O2 P T O2 out r in T=P.r K+ depolarisation: highrestingpotential:actionpotentials nosignalsignallingHYPOXIA: increasedventilation T T: nervefibredistensionopeningofionchannelsdepolarisation actionpotentialssensorysignal aboutthePRESSURE PCO2 Brainneurons: H+sensitiveionchannels (signallingacidosis) + ↑PCO2→↑H→depolarisation: increasedventilation  

  14.  + H O2 out in K+ depolarisation: APSIGNAL voluntarydecisions,emotions Centrogenicdrive(inhibition) Brain 4 3 Respiratoryrhythmogenesis 1 2 + Brainstem Spinalcord Respiratory movements Chemo-receptors Mechano- receptors brainstem ao&carot.bodies lung,thorax Nonfeedback afferents Ventilation  sensoryevents Principalstimuli ofventilation: ↑PaCO2 ↓PaO2 Whyintensivehyperventilation beforedivingcanleadtodeath?  

  15.  Adaptationtoexercise Respirationandbloodcirculationarecloselylinked: Duringphysicaleffort,theincreasedmetabolicdemandofmusclecellsmustbecoveredbyIncreasedflowsofsubstrates(glucose,fattyacids,O2)andproducts(CO2,lactate). ↑ofcardiacoutput ↑ofbloodflowtomuscles ↑ofventilation ↑ofO2extraction ↑ofthermaldissipation H+neutralisationsubstratemobilisation(liver,adiposetissue) Incaseofstrenuousexercise,thebloodflowtoheartincreases4x,toskeletalmuscle20x,doesnotchangetobrainanddecreasestoothertissues. ) in /m L ( t u p t u o c ia arterialblood) a-v-difference d Car mLO2/100mLblood mixedvenousblood Power(W) O2uptake(L/min)  O2uptake(L/min) Ventilation&pH(Davenport): - CO3 +B→ BH CO2+H2O→H2CO3→H++H thus [H+]x[HCO3]=K’[H2CO3] and -. - K’.[H2CO3] - [H+]= [HCO3] K’=10-6.1 - ]=CO2PCO2 [H2CO3 pH=-log[H+] [HCO3-] pH=6.1+log 0.03P CO2 VentilationcontrolsthebodypH!!!  

  16.  Arrestofrespirationleadstodeath! ARTIFICIALVENTILATION 1)@PositivePressure  PPventilationdecreasesvenousreturn: normalinspiration: -decreasedintrathoracicpressure -decreasedintracardiacpressure -increasedperipheraltoatrialpressuregradient -increasedbloodreturntotheheart P P heart +pressureinspiration: -increasedintrathoracicpressure(barotrauma!) -increasedintracardiacpressure -decreasedperipheraltoatrialpressuregradient -decreasedbloodreturntotheheart  

  17.  Artificialventilation:2)@negativepressure "iron"lung  Artificialventilation: 3)@highfrequency fV~12HzandVT<<VD!!! but ↑gasdispersionanddiffusion  

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