1. Unit I Oxygen Delivery: Heart, Lungs and RBCs Michel Désilets

2.  Trace the oxygen delivery system from ambient air to the cellular level.  Define oxygen content, oxygen saturation and partial pressure of oxygen.  Describe the mechanisms of hypoxemia and relate them to their position in the alveolar O 2 equation.  Compare the effects of methemoglobin and sulfhemoglobin on oxygen delivery and content as a method to understand oxygen delivery.  Outline the methods of clinical and laboratory assessment of cyanosis, hypoxemia and tissue hypoxia. Objectives

3. Oxygen delivery system Rhoades & Bell. Medical Physiology. Principles for Clinical Medicine, 3 rd Ed., 2009 P IO 2 = 150 P ICO 2 = 0.3 Inspired tracheal air (humidified) P O 2 = 160 P CO 2 = 0.3 P AO 2 = 102 P ACO 2 = 40 P EO 2 = 116 P ECO 2 = 32 Pa O 2 = 95 Pa CO 2 = 40 Pv O 2 = 40 Pv CO 2 = 45 Symbols P =partial pressure (mm Hg) I = in inspired air (humidified) E = in expired air A =in alveolar air a =in arterial blood v =in venous blood

4. Oxygen delivery system Symbols P =partial pressure (mm Hg) atm = in atmospheric air I = in inspired air (humidified) E = in expired air A =in alveolar air c = in end pulmonary capillary a =in arterial blood v =in venous blood The oxygen cascade P atmO 2 http://www.prognosis.org/physiology/index.php (Also, for more details: http://www.altitude.org/oxygen_delivery_model.php)http://www.altitude.org/oxygen_delivery_model.php

5. Oxygen delivery system 1. Pulmonary ventilation: from atmosphere to alveoli Dry air in atmosphere (barometric pressure) = 760 mm Hg  P O 2 + P N 2 Patm O 2 = F IO 2 x 760 = 0.21 x 760 = 160 mm Hg (F IO 2 = Fraction of O 2 in inspired dry air) In trachea: air saturated with water vapour: P IO 2 = F IO 2 x (760 – P H 2 O ) = 0.21 x (760 – 47) = 150 mm Hg

6. Oxygen delivery system 1. Pulmonary ventilation: from atmosphere to alveoli In alveoli: O 2 partly absorbed by capillary blood and replaced with CO 2 Alveolar gas equation: P AO 2  P IO 2 − [P ACO 2 / RQ]  100 mm Hg RQ= Respiratory quotient = rate of CO 2 production (V CO 2 ) / rate of O 2 consumption (V O 2 ) = V CO 2 / V O 2  0.8 Symbols P =partial pressure (mm Hg) atm = in atmospheric air I = in inspired air (humidified) E = in expired air A =in alveolar air c = in end pulmonary capillary a =in arterial blood v =in venous blood

7. Oxygen delivery system In a perfect lung: Pa O 2 = P AO 2 In practice: Pa O 2 < P AO 2 3 causes: i.Ventilation-perfusion mismatch (50%):  Low V A / Q ratio at the base of the lungs ii. Anatomic shunts (50%):  Bronchial arteries to pulmonary veins (1% of cardiac output)  Coronary venous blood (Thebesian veins) to left ventricle (<1% of cardiac output) iii. Diffusion block (normally small):  Incomplete equilibrium through the respiratory membrane Definitions: Physiological shunt: Ventilation-perfusion mismatch + anatomic shunts Venous admixture: Mixing of oxygenated blood with unoxygenated blood 2. From alveoli to blood Partial pressure (mm Hg)

8. Oxygen delivery system P atmO 2 PaO 2 2. From alveoli to blood Alveolar-arterial oxygen gradient (AaDO 2 ): 5% shunt  AaDO 2 ≈ 10 mm Hg AaDO 2

9. Oxygen delivery system Alveolar-arterial oxygen gradient (AaDO 2 ): Difference between alveolar (P AO 2 ) and arterial (Pa O 2 ) partial pressures of O 2 AaDO 2 = P AO 2 – Pa O 2 Normal A-a O 2 gradient: 5-15 mm Hg A-a O 2 gradient increases with age Quick estimate:AaDO 2  (age + 10) / 4 E.g.: AaDO 2  10 mm Hg at age 30 A-a O 2 gradient increases with increasing F IO 2 Quick estimate: about 5 to 7 mm Hg per 10% increase (  6 mm Hg / 10%)

10. Oxygen delivery system A-a O 2 gradient increases with shunt AaDO 2

11. Oxygen delivery system 90% block A-a O 2 gradient increases with diffusion block

12. Oxygen delivery system A-a O 2 gradient increases with increasing FIO 2 (FIO 2 = Fraction of O 2 in inspired dry air) FIO 2 = 0.5

13. Oxygen delivery system P atmO 2 3.From blood to cells

14. Oxygen delivery system % Hb saturation (S O 2 ) O 2 content (mL/ dL blood) CaO 2 CvO 2 PaO 2 PvO 2

15. Oxygen delivery system P atmO 2 O 2 content (mL O 2 / dL blood) CaO 2 CvO 2 C(a-v)O 2 3.From blood to cells

16. Oxygen delivery system O 2 delivery (mL O 2 / min): amount of oxygen delivered to the tissues per minute D O 2 = Cardiac Output x Ca O 2 = 5 L/min x 20 mL O 2 /dL x 10 dL/L = 1000 mL O 2 / min O 2 content (mL O 2 /dL blood) = O 2 bound to Hb + O 2 dissolved O 2 bound to Hb = O 2 capacity of Hb x Hb content x % Hb saturation In arterial blood: 1.34 x 15 x 97.5% = 19.6 mL O 2 /dL blood In mixed venous blood: 1.34 x 15 x 75% = 15.1 mL O 2 /dL blood O 2 dissolved = Solubility of O 2 x P O 2 In arterial blood: 0.003 x 100 = 0.3 mL O 2 /dL blood In mixed venous blood: 0.003 x 40 = 0.1 mL O 2 /dL blood Ca O 2 = Arterial blood oxygen content = 19.6 + 0.3  20 mL O 2 /dL blood Cv O 2 = Venous blood oxygen content = 15.1 + 0.1  15 mL O 2 /dL blood (mL O 2 /g Hb) x (g Hb/dL blood) x % (mL O 2 / dL blood mm Hg) x (mm Hg) A decrease of O 2 delivery could be caused by a decrease in: 1) cardiac output, 2) Hb content, 3) % Hb saturation 3.From blood to cells: Transport of oxygen

17. Oxygen delivery system 3.From blood to cells: Oxygen extraction C(a-v)O 2 = (CaO 2 – CvO 2 ) = (20 – 15) = 5 mL O 2 /dL An increase in O 2 consumption would lead to one or more of the following : 1)A decrease in Cv O 2 (i.e. an increase in O 2 extraction) 2)An increase in cardiac output 3)An increase in Ca O 2 (long term adaptation) O 2 consumption (mL O 2 / min): amount of oxygen consumed by the tissues per minute V O 2 = Cardiac Output x (Ca O 2 – Cv O 2 ) = 5 L/min x (5 mL O 2 /dL) x 10 dL/L = 250 mL O 2 / min O 2 extraction: fraction of O 2 removed from the blood O 2 extraction = (CaO 2 – CvO 2 ) / CaO 2 = 5 / 20 = 0.25

18. Example 1. Cardiogenic shock A decrease in cardiac output increases C(a-v)O 2 gradient, with little effect on CaO 2 Cardiac Output Oxygen delivery system O 2 content (mL/dL blood)

19. Example 2.Anemia A decrease in Hb reduces CaO 2 with little effect on C(a-v)O 2 gradient Oxygen delivery system C aO 2 C vO 2 O 2 content (mL/dL blood)

20. Mechanisms of hypoxia and hypoxemia Hypoxia: Inadequate oxygen delivery to the tissues Hypoxemia: Reduced Pa O 2

21. Hypoxemic hypoxia I.Oxygen deficit in inspired air (e.g. high altitude) II.Alveolar hypoventilation (e.g. neuromuscular disease) III.Ventilation/perfusion mismatch (e.g. severe asthma, COPD) IV.Problems with diffusion (e.g. interstitial lung disease) V.Right to left shunt (e.g. cyanotic congenital heart defects) Mechanisms of hypoxia and hypoxemia

22. Hypoxia without hypoxemia VI.Hypoxia of transport (anemia) (e.g. anemia, CO poisoning, MetHb) VII.Ischemic hypoxia (stagnant) circulatory shock (e.g. CV Collapse) VIII.Troubles with diffusion at the interstitial level (e.g. interstitial oedema) IX.Histotoxic hypoxia (e.g. cyanide poisoning) X.Cellular overuse of oxygen (e.g. muscular rigidity, fever, chills, intense exercise)

23. Mechanisms of hypoxia and hypoxemia HypoxiaPa O 2 AaD O 2 Ca O 2 C(a-v) O 2 A Low P IO 2 (low inspired O 2 ) LowN N BHypoventilationLowN N CV/Q mismatchLowHighLowN D Decreased diffusion LowHighLowN E Cardiovascular (stagnant) NNNHigh FAnemiaNNLowN GHistotoxicNNNLow Symbols PAO 2 = partial pressure of O 2 in alveolar air PaO 2 = partial pressure of O 2 in arterial blood AaDO 2 = PAO 2 – PaO 2 CaO 2 = total content of O 2 in arterial blood CvO 2 = total content of O 2 in venous blood C(a-v)O 2 = CaO 2 - CvO 2

24. Mechanisms of hypoxia and hypoxemia ConditionPa O 2 AaD O 2 Ca O 2 C(a-v) O 2 ECardiogenic shockNNNHigh CSevere asthmaLowHighLowN AHigh altitudeLowN N BHypoventilationLowN N CTetralogy of FallotLowHighLowN DPulmonary fibrosis LowHighLowN GCN- toxicityNNNLow FCO poisoningNNLowN Would hypoventilation and tetralogy of Fallot respond the same to O 2 therapy? Symbols PAO 2 = partial pressure of O 2 in alveolar air PaO 2 = partial pressure of O 2 in arterial blood AaDO 2 = PAO 2 – PaO 2 CaO 2 = total content of O 2 in arterial blood CvO 2 = total content of O 2 in venous blood C(a-v)O 2 = CaO 2 - CvO 2

25. Hypoventilation (50% V T ) and O 2 therapy (FIO 2 = 0.9) O2O2 O 2 content (mL/dL blood)

26. Shunt (50%) and O 2 therapy (FIO 2 = 0.9) O2O2 O 2 content (mL/dL blood)

27. Effects of methemoglobin and sulfhemoglobin on O 2 delivery and content - Methemoglobin (metHb): Oxidation of the iron ions in hemoglobin. Hb (Fe 2+ )  metHb (Fe 3+ ) metHb reductase (Treatment: methylene blue, a “redox dye”) Oxidant - Sulfhemoglobin (sulfHb): addition of a sulfur following oxidation of the porphyrin ring in hemoglobin Hb + -S  sulfHb (irreversible)

28. The affinity of Hb for O 2 (left and right shifts) directly affects oxygen extraction by altering Cv O 2  affinity   O 2 extraction  affinity   O 2 extraction

29. Effects of methemoglobin and sulfhemoglobin on O 2 delivery and content Normal blood 60% metHb Anemia (40% of normal) Properties of metHb: Decreased O 2 binding capacity (mimics anemia) Increased affinity for O 2 (left shift)  May lead to severe decrease in O 2 delivery and extraction

30. Effects of methemoglobin and sulfhemoglobin on O 2 delivery and content Properties of sulfHb: Decreased O 2 binding capacity (mimics anemia) Decreased affinity for O 2 (right shift)  Effects much less severe than metHb Normal blood 60% metHb Anemia (40% of normal) 60% sulfHb

31. Clinical and laboratory assessment of cyanosis, hypoxemia and tissue hypoxia. Main laboratory assessments: Pulse oximetry Measures Hb saturation (not Pa O 2 ) Inaccurate in the presence of abnormal Hb or dyshemoglobins (carboxyHb, metHb, sulfHb) Arterial blood gases: Measures of Pa O 2, Pa CO 2, pH From calculation, allow estimates of AaDO 2, Ca O 2 (with Hb measurement)

32. CBC News 08/06/2007 [SHb]: 2g/L Drug used: Sumatriptan (a sulfonamide)

33. Clinical and laboratory assessment of cyanosis, hypoxemia and tissue hypoxia. Main clinical assessments of cyanosis: Cyanosis: blue coloration of the skin as a result of poor saturation of hemoglobin (detectable with deoxyhemoglobin > 40 g/L) Assessment: Cyanosis Response to O 2 Yes No Continued cyanosis PaO 2 Low High metHb level high, response to methylene blue Yes No Respiratory disease Heart failure Pulmonary shunt (ARDS) Cyanotic heart defect (newborn) Exposure to oxidants (drugs, nitrates) Severe acidosis Hereditary defects SulfHb Methylene blue overdose