2. Oxygen Transport & Cardiopulmonary Function Physiology and Pathophysiology RET 1613C Lecture 2 Dr. J.B. Elsberry Special Thanks to: Barbara L. Kenney, RRT and J. Steven Lytle, MS, RRT

3. You must look at O 2 transport’s 2 distinct pathways to understand pathology: RBCTransportDissolved in Plasma

4. Whole Blood Transport components You have done the Math mL Dissolved O 2 = 0.003 x Pa O 2 in mm Hg. mL. Bound O 2 = 1.34 x % SaO 2 x Hb (gms.%) + Total O 2 Content – CaO 2 in ml/dL

5. Oxygen Transport Mechanisms Revisited Dissolved in Plasma Dissolved in Plasma Henry’s Law - the amount of oxygen dissolved in plasma is directly proportional to the partial pressure or PO 2 that it is exposed to. Henry’s Law - the amount of oxygen dissolved in plasma is directly proportional to the partial pressure or PO 2 that it is exposed to. As P A O 2 increases - dissolved O 2 increases As P A O 2 increases - dissolved O 2 increases.003 ml/dl of dissolved oxygen per 1 mmHg of PO 2.003 ml/dl of dissolved oxygen per 1 mmHg of PO 2 At a P A O 2 of 100 the blood has.3 ml/dl of dissolved oxygen (100 x.003 =.3 ml/dl) At a P A O 2 of 100 the blood has.3 ml/dl of dissolved oxygen (100 x.003 =.3 ml/dl) ml/dl can also be expressed as vols % ml/dl can also be expressed as vols %

6. The O 2 Journey What could go wrong?

7. Bound to Hemoglobin Hemoglobin (Hb) - large protein molecule within a Red Blood Cell Hemoglobin (Hb) - large protein molecule within a Red Blood Cell molecular weight of 64,500 & 1/3 of RBC’s volume molecular weight of 64,500 & 1/3 of RBC’s volume consists of heme and globin consists of heme and globin heme is an iron containing pigment (Fe++) heme is an iron containing pigment (Fe++) globin is 4 linked amino acid chains called polypedtides globin is 4 linked amino acid chains called polypedtides heme, globin and Iron (Fe++) must be combined chemically in specific fashion for oxygen to bind heme, globin and Iron (Fe++) must be combined chemically in specific fashion for oxygen to bind variations changes Hb affinity for oxygen variations changes Hb affinity for oxygen

8. Each Hb has 4 heme groups each bonded with and enfolded in one of the globin molecule’s 4 polypeptide chains Each Hb has 4 heme groups each bonded with and enfolded in one of the globin molecule’s 4 polypeptide chains Each heme group can carry one oxygen molecule Each heme group can carry one oxygen molecule Thus each Hb carries 4 molecules of oxygen Thus each Hb carries 4 molecules of oxygen Oxyhemoglobin (HbO 2 ) - bound or saturated with O 2 Oxyhemoglobin (HbO 2 ) - bound or saturated with O 2 Deoxyhemoglobin - no O 2 Deoxyhemoglobin - no O 2

9. Hemoglobin Saturation not a measure of oxygen concentration Saturation - percentage of the total hemoglobin that is bound with oxygen Saturation - percentage of the total hemoglobin that is bound with oxygen Normal arterial saturation (S a O 2 %) is 97.5% Normal arterial saturation (S a O 2 %) is 97.5% reduced from 100% due to the anatomical shunt reduced from 100% due to the anatomical shunt Normal mixed venous saturation Normal mixed venous saturation (S v O 2 ) is 75% (S v O 2 ) is 75% can only be measured in the pulmonary artery can only be measured in the pulmonary artery otherwise expressed as venous saturation otherwise expressed as venous saturation Each gram (gm.) of hemoglobin can carry about 1.34* ml of oxygen Each gram (gm.) of hemoglobin can carry about 1.34* ml of oxygen *1.34-1.39 ml/gm may be cited in other texts

10. Oxygen Content Is a more accurate reflection of blood oxygen transport that takes into account: Is a more accurate reflection of blood oxygen transport that takes into account: total amount of circulating Hemoglobin total amount of circulating Hemoglobin anemia anemia polycythemia polycythemia saturation of Hb with oxygen saturation of Hb with oxygen amount of oxygen dissolved in plasma amount of oxygen dissolved in plasma adds both transport mechanisms adds both transport mechanisms P a O 2 = dissolved oxygen in plasma P a O 2 = dissolved oxygen in plasma HbO 2 = Oxygen bound to Hemoglobin HbO 2 = Oxygen bound to Hemoglobin

11. Ideal Transport C a O 2 = Hb x Sat% x 1.34 C a O 2 = Hb x Sat% x 1.34 Hb = 15g, S a O 2 = 97%, PO2 = 100 Hb = 15g, S a O 2 = 97%, PO2 = 100 15 x.97 x 1.34 = 19.5 ml/dl 15 x.97 x 1.34 = 19.5 ml/dl now we must add the amount of dissolved oxygen: now we must add the amount of dissolved oxygen: P a O 2 of 100 x.003 =.3 P a O 2 of 100 x.003 =.3 19.5 +.3 = 19.8 ml/dl or vols% 19.5 +.3 = 19.8 ml/dl or vols% What is the key transport vehicle? What is the key transport vehicle?

12. So---We Follow These Measurements: P a O 2 - partial pressure of oxygen in arterial blood P a O 2 - partial pressure of oxygen in arterial blood also referred to as oxygen tension also referred to as oxygen tension normally 80 - 100 mmHg normally 80 - 100 mmHg S a O 2 - % of Hb with oxygen bound to it S a O 2 - % of Hb with oxygen bound to it normally 97% normally 97% C a O 2 - content of oxygen in the blood C a O 2 - content of oxygen in the blood normally about 20 ml/dl or vols% normally about 20 ml/dl or vols%

13. HbO 2 Dissociation Curve relationship between plasma P a O 2 and S a O 2 Plasma P a O 2 Plasma P a O 2 horizontal axis horizontal axis S a O 2 S a O 2 vertical axis vertical axis shape of the curve reflects Hb’s change in O 2 affinity as each O 2 binds in succession shape of the curve reflects Hb’s change in O 2 affinity as each O 2 binds in succession *Assumes Hb of 15

14. SaO 2 of 90% corresponds with a PaO2 of 60 mmHg SaO 2 of 75% corresponds with a PaO2 of 40 mmHg SaO 2 of 50% corresponds with a PaO2 of 27 mmHg

15. Affinity of Hb for Oxygen P 50 - a measure of Hb’s affinity for oxygen P 50 - a measure of Hb’s affinity for oxygen normally P 50 is 27 mmHg normally P 50 is 27 mmHg at a PO 2 of 27 mmHg, 50% of Hb is saturated at a PO 2 of 27 mmHg, 50% of Hb is saturated Low P 50 - increased Hb affinity for O 2 (left shift) Low P 50 - increased Hb affinity for O 2 (left shift) less PO 2 (<27) is needed to bind O 2 to Hb less PO 2 (<27) is needed to bind O 2 to Hb binds easily but doesn’t release as well at the tissue binds easily but doesn’t release as well at the tissue High P 50 - decreased Hb affinity for O 2 High P 50 - decreased Hb affinity for O 2 high P a O 2 (>27) is needed to bind O 2 to Hb(right shift) high P a O 2 (>27) is needed to bind O 2 to Hb(right shift) doesn’t readily bind but readily releases at the tissue doesn’t readily bind but readily releases at the tissue

17. When the Curve Shifts: pH (H+), PCO 2, temp, 2-3 DPG Increased Affinity Increased Affinity left shift left shift decreased P50 (<27 mmHg) decreased P50 (<27 mmHg) greater S a O 2 for a given P a O 2 greater S a O 2 for a given P a O 2 Decreased Affinity Decreased Affinity right shift right shift increased P50 (>27 mmHg) increased P50 (>27 mmHg) decreased S a O 2 for a given P a O 2 decreased S a O 2 for a given P a O 2

18. Factors Affecting Curve Shifts: Left Shift Left Shift PCO 2 PCO 2 H+ ( pH) H+ ( pH) temperature temperature 2,3-DPG 2,3-DPG Right Shift Right Shift PCO 2 H+ ( pH) temperature 2,3-DPG Curve shifts affect O 2 release more than uptake

20. The Effects of pH When H+ concentration decreases in the lungs When H+ concentration decreases in the lungs curve shift’s to the left curve shift’s to the left facilitates loading of O 2 in the lungs facilitates loading of O 2 in the lungs When H+ concentration increases at the tissue bed When H+ concentration increases at the tissue bed curve shifts to the right curve shifts to the right facilitates the unloading of O 2 to the tissue facilitates the unloading of O 2 to the tissue

21. Effects of PaCO 2 (The Bohr Effect) The effect of an acid environment on hemoglobin The effect of an acid environment on hemoglobin H + ’s alter the structure of Hb H + ’s alter the structure of Hb increase the release of oxygen increase the release of oxygen important in active tissues producing carbon dioxide and lactic acid important in active tissues producing carbon dioxide and lactic acid most active in capillaries of active muscles most active in capillaries of active muscles

22. The Bohr Effect

23. Temperature Increased body temperature (exercise or infection) Increased body temperature (exercise or infection) curve shifts to the right curve shifts to the right facilitates the unloading of O 2 required for the increased metabolic demand facilitates the unloading of O 2 required for the increased metabolic demand Decreased body temperature (hypothermia) Decreased body temperature (hypothermia) curve shifts to the left curve shifts to the left unloading is impaired unloading is impaired lowered metabolic rate requires less O 2 lowered metabolic rate requires less O 2 reason for blue lips, ears, & fingers when swimming in cold H 2 O reason for blue lips, ears, & fingers when swimming in cold H 2 O

24. 2,3-Diphosphoglycerate Organic phosphate formed by RBC’s during anerobic glycolysis Organic phosphate formed by RBC’s during anerobic glycolysis Is an active RBC substance that alters the O 2 Dissociation curve to the right Is an active RBC substance that alters the O 2 Dissociation curve to the right (i.e. allows better tissue unloading of O 2 at high altitude) affects Hb affinity for oxygen affects Hb affinity for oxygen increased production occurs in: increased production occurs in: hypoxia hypoxia pH increases (i.e. during exercise) pH increases (i.e. during exercise) anemia anemia Stored blood has reduced 2,3-DPG Stored blood has reduced 2,3-DPG

25. a-v Oxygen-Exchange Ratio The difference b/w C a O 2 and C v O 2 The difference b/w C a O 2 and C v O 2 C a O 2 = 20 vols% C a O 2 = 20 vols% C v O 2 = 15 vols% C v O 2 = 15 vols% Systemic tissues at rest extract 5 ml of oxygen for each 100 ml of blood or 25% of C a O 2 Systemic tissues at rest extract 5 ml of oxygen for each 100 ml of blood or 25% of C a O 2 Calculation C(a-v)O 2 /C a O 2 Calculation C(a-v)O 2 /C a O 2 Ratio increases during Ratio increases during exercise, shivering, cardiac output, anemic states, exercise, shivering, cardiac output, anemic states, Ratio decreases during Ratio decreases during cardiac output, poisons, hypothermia, skeletal relaxation cardiac output, poisons, hypothermia, skeletal relaxation Difference is 5 vols%

26. Clinical Significance provides a view of an individual’s oxygen transport status, not readily available from other oxygen Normal O 2 ER Normal O 2 ER (20vols% -15vols%) (20vols% -15vols%) 20vols% 20vols% Abnormal O 2 ER Abnormal O 2 ER (10vols% - 5vols%) (10vols% - 5vols%) 10vols% 10vols% =. 25 or 25% =.50 or 50%

27. Oxygen Delivery DO 2 - oxygen delivery is: DO 2 - oxygen delivery is: a product of C a O 2 and Cardiac Output (Q) a product of C a O 2 and Cardiac Output (Q) (C a O 2 x 10) x Q = ml oxygen/min (C a O 2 x 10) x Q = ml oxygen/min normally ~1000 ml of O 2 /min normally ~1000 ml of O 2 /min affected by C a O 2 and Cardiac Output affected by C a O 2 and Cardiac Output C a O 2 = 20 ml/dl and Q = 5 l/m C a O 2 = 20 ml/dl and Q = 5 l/m (20 x 10) x 5 = 1,000 ml of oxygen/min (20 x 10) x 5 = 1,000 ml of oxygen/min Increasing cardiac output will significantly increase O 2 delivery especially during exercise and fever Increasing cardiac output will significantly increase O 2 delivery especially during exercise and fever

28. Oxygen Consumption(VO 2 ) VO 2 = Volume of O 2 used in one minute by the entire cell population VO 2 = Volume of O 2 used in one minute by the entire cell population normal is 250ml/min normal is 250ml/min assumed consumption assumed consumption » between 110 and 125 ml O 2 per min of time per square meter of BSA » VO 2 of 250 ml/min = 125 ml/min/m 2 with a BSA of 2m 2 (80kg/180cm)

29. Supply and Demand C(a-v)O 2 varies inversely with Cardiac Output-- the greater the blood flow, the less O 2 is removed per unit of blood and a smaller gradient of C(a-v)O 2 C(a-v)O 2 varies inversely with Cardiac Output-- the greater the blood flow, the less O 2 is removed per unit of blood and a smaller gradient of C(a-v)O 2 results… results… as blood flow decreases, O 2 removed by tissues increases so blood returning to the heart has less O 2 thus the wider the difference of C(a-v)O 2 as blood flow decreases, O 2 removed by tissues increases so blood returning to the heart has less O 2 thus the wider the difference of C(a-v)O 2

30. Arterial-venous O 2 Content Differences can be used in the ICU & the Cath Lab Fick equation for cardiac output: Fick equation for cardiac output: Q = (VO 2 )* (CaO 2 - CvO 2 ) x 10 (CaO 2 - CvO 2 ) x 10 *consumption of O2 at the tissue level (VO 2 ) divided by the amount of blood leaving the lungs (CaO 2 ) minus the amount of blood flowing into the lungs (CvO 2 ) x 10. *consumption of O2 at the tissue level (VO 2 ) divided by the amount of blood leaving the lungs (CaO 2 ) minus the amount of blood flowing into the lungs (CvO 2 ) x 10.

31. Cyanosis Desaturated Hemoglobin or deoxyhemoglobin hemoglobin without oxygen Cyanosis occurs when the blood has at least 5 gm of desaturated hemoglobin on board causes Hb to change shape takes on a deep purple color causes the skin to look blue or blue gray Two types peripheral - low cardiac output central - low S a O 2, inadequate lung function

32. Hemoglobin Abnormalities Carboxyhemoglobin (COHb) Carboxyhemoglobin (COHb) –carbon monoxide bound to Hemoglobin –binds 210 times greater affinity –shifts curve to the left impairing O 2 release at the tissue –created from cigarette smoking, inhalation of smoke from a fire, automobile exhaust  treated with 100% oxygen  hyperbaric oxygen chamber

33. Some Hemoglobin Variants Fetal Hemoglobin (HbF) Fetal Hemoglobin (HbF) –high O 2 affinity –decreased amount of 2,3-DPG and it doesn’t bind as well with HbF –enhances uptake of O 2 from the placenta Methemoglobin (metHb) Methemoglobin (metHb) –when O 2 binds it oxidizes the Fe++ –can’t unload it at the tissue bed –caused by nitrate poisoning or toxic reactions Sickle Cell Hemoglobin (HbS) Sickle Cell Hemoglobin (HbS) –crystallizes the RBC changing the shape to concave –can block small vessel passages causing ischemia

34. Shunts: perfusion without ventilation Normal anatomic shunt Normal anatomic shunt –2 - 5% of total cardiac output –thebesian veins, bronchial and pleural veins –abnormal anatomical shunt would be a VSD/ASD Capillary Shunt Capillary Shunt –blood passing alveoli that are not ventilated  edema - alveoli filled with fluid as in CHF  pus-like substances as in pneumonia Shunt like effects - mucous plugging, diffusion barriers like Pulmonary Fibrosis, bronchoconstriction, Shunt like effects - mucous plugging, diffusion barriers like Pulmonary Fibrosis, bronchoconstriction,

35. Venous Admixture Venous Admixture –Occurs when blood from normal alveoli mixes with blood from shunt areas Shunt Calculation Shunt Calculation –Qs/Qt = [C c O 2 - C a O 2 ]/[C c O 2 -C v O 2 ] –C c O 2 - pulmonary capillary blood  CcO 2 = {Hb x 100% x 1.34}+(P A O 2 x.003) Degrees of Shunt Degrees of Shunt –10% - still relatively normal –10 - 20% - higher than normal but not serious –20 - 30% - significant and may be life threatening –30% - extremely serious and likely to be life threatening

36. Oxygen is Transported in much the same way as Trains that carry passengers

37. Hypoxia vs Hypoxemia Hypoxemia - decreased oxygen tension (PO 2 ) in the blood Hypoxemia - decreased oxygen tension (PO 2 ) in the blood Hypoxia - decreased oxygen concentration at the tissue level. Depends on Hypoxia - decreased oxygen concentration at the tissue level. Depends on F i O 2 - F i O 2 - P A O 2 / PaO 2 P A O 2 / PaO 2 Hb concentration Hb concentration Blood flow / Cardiac Output Blood flow / Cardiac Output Four types - Hypoxic, Anemic, Stagnant, Histotoxic Four types - Hypoxic, Anemic, Stagnant, Histotoxic

38. Oxygen molecules are the passengers boarding the train

39. Hypoxemic Hypoxia Decrease in the alveolar PO 2 caused by Decrease in the alveolar PO 2 caused by hypoventilation hypoventilation drug overdose drug overdose high altitude high altitude lower barometric pressure, lowers PiO 2 lower barometric pressure, lowers PiO 2 shunt - perfusion w/o ventilation shunt - perfusion w/o ventilation mucous plugging, collapsed lung tissue mucous plugging, collapsed lung tissue V/Q mismatch - shunt and/or deadspace V/Q mismatch - shunt and/or deadspace pulmonary embolus, atelectasis pulmonary embolus, atelectasis

40. The Cars of the Train are like The Hemoglobin Molecules

41. Anemic Hypoxia Reduced amount of functional Hb caused by: Reduced amount of functional Hb caused by: hemorrhage hemorrhage decreased RBC production decreased RBC production anemia anemia abnormal Hb production abnormal Hb production met hemoglobin met hemoglobin impaired chemical combination of Hb with O 2 impaired chemical combination of Hb with O 2 carbon monoxide poisoning carbon monoxide poisoning

42. Stagnant Hypoxia Also called Circulatory or Hypoperfusion low blood flow or low cardiac output thus low oxygen delivery rate caused by cardiac pump failure (cardiogenic shock) reduced circulation greatly O 2 transport anaphylactic or septic shock

43. Histotoxic Hypoxia Poisoning of the cellular oxygen cyanide poisoning inactivates cellular enzymes necessary for oxidative metabolism ETOH (ethyl alcohol)

44. Diffusion Defects  Increase in the AC membrane –Pulmonary edema –interstitial Alveolar Fibrosis  transit time and equilibrium  Treat with supplemental oxygen –increases the P A O 2 /P a O 2 gradient

45. Physiologic Effects of Hypoxia Aerobic - with oxygen Aerobic - with oxygen Anaerobic - without oxygen Anaerobic - without oxygen generates lactic acid generates lactic acid lowers blood pH lowers blood pH Bodies response Bodies response increase Cardiac Output (increase HR) increase Cardiac Output (increase HR) increase minute ventilation increase minute ventilation increase red blood cell production increase red blood cell production

46. The Clinical Signs & Symptoms tachycardia tachycardia pulmonary vasoconstriction pulmonary vasoconstriction increased minute ventilation increased minute ventilation restlessness & irritability restlessness & irritability mild hypertension mild hypertension arrhythmias arrhythmias loss of muscular coordination loss of muscular coordination confusion confusion cyanosis cyanosis bradycardia bradycardia hypotension hypotension loss of consciousness loss of consciousness

47. Severity of Hypoxemia ClassP a O 2 S a O 2 % ClassP a O 2 S a O 2 % normal80 - 100 >95 normal80 - 100 >95 mild 60 - 7990 - 94 mild 60 - 7990 - 94 moderate 40 - 5975 - 89 moderate 40 - 5975 - 89 severe <40<75 severe <40<75 You must know the F I O 2 or P A O 2 to understand the severity of the hypoxemia You must know the F I O 2 or P A O 2 to understand the severity of the hypoxemia

48. The Threshold for Hypoxemia: P a O 2 decreases with age P a O 2 decreases with age 110 - 1/2 age 110 - 1/2 age 10 years of age 100 mmHg 10 years of age 100 mmHg 20 - 29 years of age 95 mmHg 20 - 29 years of age 95 mmHg 30 - 39 years of age 90 mmHg 30 - 39 years of age 90 mmHg 40 - 49 years of age85 mmHg 40 - 49 years of age85 mmHg 50 - 59 years of age 80 mmHg 50 - 59 years of age 80 mmHg 60 - 69 years of age 75 mmHg 60 - 69 years of age 75 mmHg 70 - 79 years of age 70 mmHg 70 - 79 years of age 70 mmHg 80 - 89 years of age 65 mmHg 80 - 89 years of age 65 mmHg

49. Hypoxemia continued: Altitude effects P a O 2 Altitude effects P a O 2 due to the drop in barometric pressure due to the drop in barometric pressure alters the P i O 2 alters the P i O 2 Barometric pressure < 24 mmHg / 1000 ft Barometric pressure < 24 mmHg / 1000 ft Expected P a O 2 = Expected P a O 2 = (> altitude Pb/760) x sea level P a O 2 (> altitude Pb/760) x sea level P a O 2

50. Oxygen Administration Oxygen Toxicity occurs F I O 2 >50% over 48 to 72 hours thickens the alveolar capillary membrane causing a diffusion defect destroys membrane walls

51. Let’s Review Hypoxia Types: Hypoxemic Hypoxia---Supply side Anemic Hypoxia---Transport Capacity Stagnant Hypoxia---Transport Failure Histotoxic Hypoxia---Delivery Obstacles

52. Let’s Review Important Oxygen Transport Equations Calculations Calculations CaO 2 = (Hb)(SaO 2 )(1.34) + (PaO 2 )(.003) = 20vols% CaO 2 = (Hb)(SaO 2 )(1.34) + (PaO 2 )(.003) = 20vols% CvO 2 = (Hb)(SvO 2 )(1.34) + (PvO 2 )(.003) = 15vols% CvO 2 = (Hb)(SvO 2 )(1.34) + (PvO 2 )(.003) = 15vols% SaO 2 associated with Hb vs dissolved in plasma = 97% SaO 2 associated with Hb vs dissolved in plasma = 97% Ca-vO 2 gradient = CaO2 - CvO2 = 5 vols% Ca-vO 2 gradient = CaO2 - CvO2 = 5 vols% PAO 2 = (Pb - 47)F I O 2 - PCO 2 /.8 = 100 mmHg PAO 2 = (Pb - 47)F I O 2 - PCO 2 /.8 = 100 mmHg A-aDO 2 = P A O 2 - PaO 2 = 5 – 15 mmhg A-aDO 2 = P A O 2 - PaO 2 = 5 – 15 mmhg DO 2 = (CaO 2 x 10)(C.O.) = 1000 ml/min DO 2 = (CaO 2 x 10)(C.O.) = 1000 ml/min O 2 ER = (Ca-vO 2 )/CaO 2 =.25 or 25% O 2 ER = (Ca-vO 2 )/CaO 2 =.25 or 25% VO 2 = (125ml/min/m 2 )(BSAm 2 ) = 250 ml/min VO 2 = (125ml/min/m 2 )(BSAm 2 ) = 250 ml/min

53. Your Questions ?