Slide 1BME 501 Lecture Notes – Feb 3Hypoxic Vasoconstriction & NOHypoxic Vasoconstriction & NOHypoxic Vasoconstriction & NOHypoxic Vasoconstriction & NOMeasuring Pulmonary Blood FlowMeasuring Pulmonary Blood FlowWater Balance in LungAdditional Lung FunctionsO2 Transport from Air to TissuesFour Causes of HypoxemiaFour Causes of HypoxemiaFour Causes of HypoxemiaFour Causes of HypoxemiaFour Causes of HypoxemiaFour Causes of HypoxemiaBME 501Advanced Topics in Biomedical SystemsSpring 2014Dr. KayBME 501 Lecture Notes – Feb 3Blood Flow and Metabolism•Hypoxic Vasoconstriction & NO•Measuring Pulmonary Blood Flow•Water Balance in Lung•Additional Lung FunctionsVentilation-Perfusion Relationships•O2 Transport from Air to Tissues•Causes of HypoxemiaHypoxic Vasoconstriction & NOActive Control of Pulmonary Circulation: Hypoxic VasoconstrictionMoudgil R et al. J Appl Physiol 2005;98:390-403Hypoxic Vasoconstriction & NORedox Theory of Hypoxic VasoconstrictionMoudgil R et al. J Appl Physiol 2005;98:390-403Hypoxic Vasoconstriction & NONitric Oxide VasodilationHypoxic Vasoconstriction & NOEffects of Inhaled NO•Primarily affects well-ventilated regions•High ventilation–High PA,O2–High perfusion•Increases Pa,O2•NO-induced dilation due to decrease in frequency of Ca2+ oscillationsMeasuring Pulmonary Blood Flow•O2 consumption per minute measured at mouth equals the amount of O2 taken up by blood in lungs per minute•Concentration of O2 entering lungs is mixed venous CO2; concentration of O2 leaving lungs is arterial CO2Fick PrincipleMeasuring Pulmonary Blood Flow•Dye or cold saline injected into right ventricle or pulmonary artery•Dye concentration or temperature measured further along pulmonary artery•Derivation of equation:Indicator-Dye or Thermal Dilution MethodWater Balance in Lung•Blood-gas barrier only 0.3 μm thick•Fluid exchange across capillary endothelium obeys Starling’s law of fluid exchange•Excess fluid called edema; affects gas exchange•Derivation of equation:Additional Lung Functions•Pulmonary circulation-Acts as reservoir for blood-Can take large volume of blood with only small rise in pulmonary pressure-Filters blood•Metabolic conversions–Many vasoactive substances metabolized by lung–Angiotensin I activated to angiotensin II (a potent vasoconstrictor) via ACE–Serotonin (5-HT) removed–Bradykinin (vasodilator) up to 80% removedO2 Transport from Air to Tissues•PO2 falls as gas moves from atmosphere to mitochondria•PI,O2 is approximately 150 mmHg•Maximum PO2 possible with perfect ventilation•Pa,O2 determined by O2 uptake by blood and O2 supply via alveolar ventilationFour Causes of Hypoxemia•Can result from drugs, damage to chest wall, paralysis of respiratory muscles, breathing dense gas•Causes PA,O2 to drop and PA,CO2 to increase•Relationship between PA,O2 and PA,CO2 is described by alveolar gas equationHypoventilationPA, O2=PI , O2-PA, CO2R+FFour Causes of Hypoxemia•In a perfect lung, arterial PO2 would be same as alveolar PO2•This is not actually the case•Difference normally very small, but stresses on system can increase alveolar-arterial PO2 differenceDiffusion LimitationFour Causes of Hypoxemia•Shunted blood enters arterial system without going through ventilated regions of lung•Normal shunts:-Some of bronchial artery blood is collected by pulmonary veins-Small quantity of coronary venous blood drains into left ventricle•Abnormal shunts:-Pulmonary arteriovenous fistula-Cardiac septal defectShuntFour Causes of HypoxemiaShunt•Shunted blood causes noticeable drop in PO2 at high starting levels of PO2 •O2 dissociation curve very flat at high PO2•PCO2 usually does not go up as a result of a shunt•Chemoreceptors sense higher PCO2 and increase ventilationFour Causes of HypoxemiaShunt CalculationFour Causes of Hypoxemia•Most common cause of hypoxemia•If ventilation and blood flow are mismatched in lung, gas-exchange is impaired•Ventilation-perfusion ratio determines efficacy of exchangeVentilation-Perfusion