Chapter 11 Gas Exchange & Transport Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Learning Objectives  Describe how oxygen & carbon dioxide move between the atmosphere & tissues.  Identify what determines alveolar oxygen & carbon dioxide pressures.  Calculate the alveolar partial pressure of oxygen (PAO 2 ) at any give barometric pressure & FIO 2.  State the effect that normal regional variations in ventilation & perfusion have on gas exchange. 2Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Learning Objectives (cont.)  Describe how to compute total oxygen contents for arterial blood.  State the factors that cause the arteriovenous oxygen content difference to change.  Identify the factors that affect oxygen loading & unloading from hemoglobin.  Describe how carbon dioxide is carried in the blood. 3Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Learning Objectives (cont.)  Describe how oxygen & carbon dioxide transport are interrelated.  Describe the factors that impair oxygen delivery to the tissues & how to distinguish among them.  State the factors that impair carbon dioxide removal. 4Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Introduction Respiration: process of moving oxygen to tissues for aerobic metabolism & removal of carbon dioxide  Involves gas exchange at lungs & tissues O 2 from atmosphere to tissues for aerobic metabolism Removal of CO 2 from tissues to atmosphere 5Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Diffusion  Whole-body diffusion gradients  Gas moves across system by simple diffusion  Oxygen cascade moves from PO 2 of 159 mm Hg in atmosphere to intracellular PO 2 of ~5 mm Hg  CO 2 gradient is reverse from intracellular CO 2 ~60 mm Hg to atmosphere where it = 1 mm Hg 6Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Diffusion (cont.) 7Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

8 There is a stepwise downward “cascade of partial pressures” from the normal atmospheric to the intracellular, for which of the following gases? A.CO 2 B.O 2 C.N D.H 2 O

Diffusion (cont.)  Determinants of alveolar CO 2  PACO 2 = (VCO 2  0.863)/V A  PACO 2 will increase with ↑VCO 2 or ↓V A  The relationship is expressed by:  PACO2 = arterial carbon dioxide tension (mm Hg)  V CO 2 = rate of CO 2 produced (in mL /min STPD)  V A = alveolar ventilation (mL /min BTPS).... 9Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Diffusion (cont.)  V CO 2 is expressed as flow of dry gas at 0ºC & 760 mmHg  V A reported as saturated gas at body temperature ambient pressure  Factor 863 is employed to correct measurement 10Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Diffusion (cont.)  Increase in deadspace (V D ) can also lead to increased P ACO 2  Portion of inspired air that is exhaled without being exposed to perfused alveoli  V A = alveolar ventilation  V T = tidal volume  V D = dead space volume  f = ventilatory frequency. 11Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

12Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. All of the following can lead to an increased Paco 2, except: A.↓ VD B.↓ VA C.↑ VCO 2 D.↑ VD

Diffusion (cont.)  Alveolar oxygen tensions (PAO 2 )  PIO 2 is primary determinant  In lungs, it is diluted by water vapor & CO 2  Alveolar air equation accounts for all these factors PAO 2 = FIO 2  (P B – 47) – (PACO 2 /0.8)  Dalton’s law of partial pressures accounts for first part of formula; second part relates to rate at which CO 2 enters lung compared to oxygen exiting Ratio is normally 0.8.  If FIO 2 > 0.60, (PACO 2 /0.8) can be dropped from equation 13Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Diffusion (cont.)  Changes in alveolar gas partial tensions  O 2, CO 2, H 2 O, & N 2 normally comprise alveolar gas N 2 is inert but occupies space & exerts pressure PAN 2 is determined by Dalton’s law PAN 2 = P B – (PAO 2 + PACO 2 + PH 2 O)  Only changes seen will be in O 2 & CO 2 Constant FIO 2, PAO 2 varies inversely with PACO 2 Prime determinant of PACO 2 is V A 14Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Diffusion (cont.) 15Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Diffusion: Mechanisms  Diffusion occurs along pressure gradients  Barriers to diffusion  A/C membrane has 3 main barriers Alveolar epithelium Interstitial space & its structures Capillary endothelium  RBC membrane  Fick’s law: The greater the surface area, diffusion constant, & pressure gradient, the more diffusion will occur 16Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Diffusion (cont.)  Pulmonary diffusion gradients  Diffusion occurs along pressure gradients  Time limits to diffusion: Pulmonary blood is normally exposed to alveolar gas for 0.75 second, during exercise may fall 0.25 second Normally equilibration occurs in 0.25 second With diffusion limitation or blood exposure time of less then 0.25 seconds, there may be inadequate time for equilibration 17Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Diffusion (cont.) 18Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Normal Variations From Ideal Gas Exchange  PaO 2 normally 5–1 mm Hg less than PAO 2 due to presence of anatomic shunts  Anatomic shunts  Portion of cardiac output that returns to left heart without being oxygenated by exposure to ventilated alveoli  Two right-to-left anatomic shunts exist Bronchial venous drainage Thebesian venous drainage These drain poorly oxygenated blood into arterial circulation lowering CaO 2  Regional inequalities in V/Q  Changes in either V or Q affect gas tensions... 19Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

20Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Which of the following choices accurately completes the statement, “anatomic shunts…” A.are a portion of cardiac output that returns to left heart without being oxygenated B.are exposed to ventilated alveoli C.cause the PaO to be normally 10–20 mm Hg less than PAO 2 D.are left-to-right shunts

Normal Variations From Ideal Gas Exchange (cont.)  V/Q ratio & regional differences  Ideal ratio is 1, where V/Q is in perfect balance  In reality lungs don’t function at ideal level High V/Q ratio at apices >1 V/Q (~3.3)  ↑PAO 2 (132 mm Hg), ↓PACO 2 (32 mm Hg) Low V/Q ratio at bases <1.0 (~0.66)  Blood flow is ~20 times higher at bases  Ventilation is greater at bases but not 20   ↓PAO 2 (89 mm Hg), ↑PACO 2 (42 mm Hg) See Table Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Normal Variations From Ideal Gas Exchange (cont.) 22Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Oxygen Transport  Transported in 2 forms: dissolved & bound  Physically dissolved in plasma  Gaseous oxygen enters blood & dissolves.  Henry’s law allows calculation of amount dissolved Dissolved O 2 (ml/dl) = PO 2   Chemically bound to hemoglobin (Hb)  Each gram of Hb can bind 1.34 ml of oxygen.  [Hb g]  1.34 ml O 2 provides capacity.  70 times more O 2 transported bound than dissolved 23Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Oxygen Transport (cont.)  Hemoglobin saturation  Saturation is % of Hb that is carrying oxygen compared to total Hb SaO 2 = [HbO 2 /total Hb]  100 Normal SaO 2 is 95% to 100%  HbO 2 dissociation curve  Relationship between PaO 2 & SaO 2 is S-shaped  Flat portion occurs with SaO 2 >90% Facilitates O 2 loading at lungs even with low PaO 2  Steep portion (SaO 2 <90%) occurs in capillaries Facilitates O 2 unloading at tissues 24Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Oxygen Transport (cont.) 25Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Oxygen Transport (cont.) 26Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Oxygen Transport (cont.)  Total oxygen content of blood  Combination of dissolved & bound to Hb  CaO 2 = (0.003  PaO 2 ) + (Hb  1.34  SaO 2 )  Normal is 16  20 mL/dL  Normal arteriovenous difference (~5 mL/dL) 27Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Oxygen Transport (cont.) 28Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Oxygen Transport (cont.)  Fick equation  C(a  v)O 2 indicates tissue oxygen extraction in proportion to blood flow (per 100 ml of blood)  Combined with total oxygen consumption (VO 2 ) allows calculation of cardiac output (Q t ) Q t = VO 2 /[C(a  v)O 2  10]  Normal adult Q t is 4  8 L/min.  VO 2 constant, changes in C(a  v)O 2 are due to changes in Q t ; i.e., ↑C(a  v)O 2 signifies ↓Q t Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Oxygen Transport (cont.)  Factors affecting oxygen loading & unloading  Besides shape of HbO 2 curve, many factors affect O 2 loading & unloading  pH (Bohr effect)  Describes affect pH has on Hb affinity for O 2  pH alters position of HbO 2 curve Low pH shifts curve to right, high pH shifts to left  Enhances oxygen transport At tissue pH is ~7.37 shift right, more O 2 unloaded Lungs pH ~7.4 shifts back left, enhancing O 2 loading 30Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Oxygen Transport (cont.) 31Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Oxygen Transport (cont.)  Body temperature (T) & HbO 2 curve  Changes in T alter position of HbO 2 curve Decreased T shifts curve left Increased T shifts curve right T is directly related to metabolic rate  When T is higher, right shift facilitates more oxygen unloading to meet metabolic demands  With lower metabolic demands, curve shifts left as not as much oxygen is required. 32Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Oxygen Transport (cont.) 33Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Oxygen Transport (cont.)  2,3-Diphosphoglycerate (DPG) & the HbO 2 curve  Found in quantity in RBCs; stabilizes deoxygenated Hb, decreasing oxygen’s affinity for Hb Without 2,3-DPG Hb affinity is so great that O 2 cannot unload  ↑2,3-DPG shifts curve to right, promoting O 2 unloading  ↓2,3-DPG shifts curve to left, promoting loading Stored blood loses 2,3-DPG, large transfusions can significantly impair tissue oxygenation 34Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Oxygen Transport (cont.)  Abnormal hemoglobins  HbS (sickle cell): fragile leads to hemolysis & thrombi  Acute chest syndrome (ACS), multiple causes Most common cause of death  Methemoglobin (metHb): abnormal iron (Fe 3+ ) cannot bind with oxygen & alters HbO 2 affinity (left shift) Commonly caused by NO, nitroglycerin, lidocaine Must frequently monitor for MetHb & weigh risk vs. benefit  Carboxyhemoglobin (HbCO): Hb binds CO, has 200 times > Hb affinity than O 2 Displaces O 2 & shifts curve left  O 2 which is bound cannot unload (left shift)  Treat with hyperbaric therapy 35Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Oxygen Transport (cont.)  Measurement of Hb affinity for oxygen 36Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

37Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. A factor that does not significantly affect oxygen loading & loading is: A.plasma oxygen content B.pH C.body temperature D.the amount of 2,3-Diphosphoglycerate (DPG) in RBC’s

Carbon Dioxide Transport  Transport mechanisms  Dissolved in blood: ~8% as high solubility coefficient  Combined with protein: ~12% binds with amino groups on plasma proteins & Hb  Ionized as bicarbonate: ~80% transported as HCO 3  due to hydrolysis reaction Majority of hydrolysis occurs in RBCs as they contain carbonic anhydrase—serves as catalyst HCO 3  diffuses out of RBCs in exchange for Cl , called chloride shift or hamburger phenomenon 38Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Carbon Dioxide Transport (cont.)  CO 2 dissociation curve  Relationship between PaCO 2 & CaCO 2  HbO 2 affects this relationship Haldane effect describes this relationship As HbO 2 increases, CaCO 2 decreases  Facilitates CO 2 unloading at lungs At tissues, HbO 2 decreases & facilitates higher CaCO 2 for transport to lungs 39Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Carbon Dioxide Transport (cont.) 40Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Carbon Dioxide Transport (cont.) 41Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Abnormalities of Gas Exchange & Transport  Impaired oxygen delivery (DO 2 )  DO 2 = CaO 2  Q t  When DO 2 is inadequate, tissue hypoxia ensues  Hypoxemia: Defined as abnormally low PaO 2 Most common cause is V/Q mismatch  Because of shape HbO 2 curve, areas of high V/Q cannot compensate for areas of low V/Q, so ↓PaO 2 Other causes: hypoventilation, diffusion defect, shunting, & low PIO 2 (altitude) Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Abnormalities of Gas Exchange & Transport (cont.) 43Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Abnormalities of Gas Exchange & Transport (cont.)  Physiologic shunt  Where perfusion exceeds ventilation, includes: Capillary or absolute anatomic shunts Relative shunts seen in disease states diminish pulmonary ventilation  Relative shunts can be caused by: COPD Restrictive disorders Any condition resulting in hypoventilation 44Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Abnormalities of Gas Exchange & Transport (cont.)  Shunt equation  Quantifies portion of blood included in V/Q mismatch  Usually expressed as % of total cardiac output: 45Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Abnormalities of Gas Exchange & Transport (cont.)  Shunt Equation:  Mixed venous oxygen content can be measured from pulmonary artery  End capillary content must be derived from additional calculation Using alveolar air equation & hemoglobin concentration  Deadspace Ventilation  Ventilation that doesn’t participate in gas exchange Waste of energy to move gas into lungs  Two types: alveolar & anatomic 46Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Abnormalities of Gas Exchange & Transport (cont.)  Alveolar Deadspace:  Ventilation that enters into alveoli without any, or without adequate perfusion  Disorders leading to alveolar deadspace :  Pulmonary emboli  Partial obstruction of the pulmonary vasculature  Destroyed pulmonary vasculature (as can occur in COPD)  Reduced cardiac output 47Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Abnormalities of Gas Exchange & Transport (cont.)  Anatomic Deadspace:  Ventilation that never reaches alveoli for gas exchange  Normal individuals have fixed anatomic deadspace  Becomes problematic in conditions where tidal volumes drop significantly Significant % of inspired gas remains in anatomic deadspace  Expressed as ratio to total tidal volume 48Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Abnormalities of Gas Exchange & Transport (cont.)  In face of increased deadspace, normal ventilation must increase to achieve homeostasis  Additional ventilation comes at cost:  Increase in WOB  Consumes additional oxygen  Further adding to burden of external ventilation 49Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Abnormalities of Gas Exchange & Transport (cont.)  Impaired DO 2 due to Hb deficiencies  Majority of O 2 is carried bound to Hb  For CaO 2 to be adequate, there must be enough normal Hb If Hb is low:  although PaO 2 & SaO 2 are normal, CaO 2 will be low Absolute low Hb is caused by anemia Relative deficiency may be due to COHb or metHb 50Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Abnormalities of Gas Exchange & Transport (cont.) 51Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

52Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc. Oxygen delivery to the tissues (DO 2 ) may be substantially impaired due to all of the following, except: A.Low Hb levels (anemia) B.V/Q matching C.abnormal cardiac output D.presence of Carboxyhemoglobin (COHb)

Abnormalities of Gas Exchange & Transport (cont.) 53Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Abnormalities of Gas Exchange & Transport (cont.)  Reduction in blood flow (shock or ischemia)  Hypoxia can occur with normal CaO 2 if Q t is low May be due to:  Shock –Results in widespread hypoxia –Limited ability to compensate  Prolonged shock becomes irreversible  Ischemia –Local reductions in blood flow may result in hypoxia & tissue death, i.e., myocardial infarction & stroke 54Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Abnormalities of Gas Exchange & Transport (cont.)  Dysoxia  DO 2 is normal but cells undergo hypoxia  Cells are unable to adequately utilize oxygen Cyanide poisoning prevents cellular use of O 2 In very sick individuals (sepsis, ARDS), oxygen debt may occur at normal levels of DO 2  If oxygen uptake increases with increased DO 2, then DO 2 was inadequate  Demonstrates low VO 2 /DO 2 (extraction ratio), thus dysoxia 55Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Abnormalities of Gas Exchange & Transport (cont.)  Impaired CO 2 removal  Disorders that decreases V A relative to metabolic need Inadequate V E  Usually result of ↓V T, ↓f rare (drug overdose) Increased deadspace ventilation (V D /V T ) caused by:  Decreased V T as in rapid shallow breathing or,  Increased physiologic dead space, as in pulmonary embolus Without compensation, alveolar is lowered per minute.. 56Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Abnormalities of Gas Exchange & Transport (cont.)  V/Q imbalance Typically, CO 2 does not rise; instead, increase V E. If patient is unable to ↑V E, then hypercarbia with acidosis occurs  Seen in severe chronic disorders, i.e., COPD.. 57Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.

Abnormalities of Gas Exchange & Transport (cont.) 58Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.