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Author(s): John G. Younger, M.D., 2009

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Gas Exchange


                  John G. Younger, MD
                   Associate Professor
            Department of Emergency Medicine




Fall 2008
A Tour of the Lecture
•  Some perspective

•  Some physics and biochemistry
   –  Convection and Diffusion
   –  Hemoglobin
   –  Pressure, Content, and Transport

•  The lung as a gas exchanger
   –  Carbon dioxide handling and dead space
   –  Oxygen handling
          –  The four causes of hypoxia
   –  Quantifying gas exchange
Source Undetermined
Narayanese, WikiUserPedia, YassineMrabet, TotoBaggins (Wikipedia)
Rozzychan (Wikipedia)
Mitochondria are where
                      respiration occurs. The
                       respiratory system is really
                      a bulk transport system for
                      an incoming oxidizer (O2)
                      and outgoing gas (CO2) and
                      heat.



Source Undetermined
Bulk Transport:
         Getting Molecules from One Point to Another
•  Convection
    –    Bulk movement of gas due to pressure gradients
    –    Requires mechanical power input
    –    Transport from the environment to the terminal bronchioles
    –    Transport of erythrocytes between pulmonary capillaries and
         peripheral capillaries

•  Diffusion
    –  Transport based on random motion of thermally energetic particles
       situated in a concentration gradient
    –  Requires thermal input
    –  Transport from terminal bronchioles to erythrocytes
    –  Transport between erythrocytes and peripheral mitochondria
Source: NASA

                                 Diffusion


Convection
                        Spongy                           hv
                                       Chloroplasts
                       Mesophyll



                      Terminal                        Peripheral
   Atmosphere                        Circulation                    Mitochondria
                      Airways                         Capillaries




         Convection         Diffusion        Convection       Diffusion
         J. Younger
Transport by Convection

•    The movement of particles by convection is driven by:

      –  The pressure gradient between the atmosphere and terminal bronchioles
      –  Thus, this is in the realm of what s typically referred to as pulmonary
         mechanics


•    The mechanical work required to get this job done is a function of:

      –  Resistance of the transport path to air flow
           •  Itself a function of the effective cross-sectional area of the airways
      –  The viscosity and density of the air being moved
      –  The compliance of the lung and chest wall
Transport by Diffusion

•    The movement of particles by diffusion is driven by:

      –  Concentration gradient
           •  For physiological purposes, usually reported as differences in partial
              pressure
           •  Gradient may exist in either gas phase (e.g., bronchiole->alveolus) or liquid
              phase (e.g., plasma->RBC membrane)
           •  Note: Although concentrations are often reported in partial pressures, at it s
              heart this is a Brownian Motion based phenomenon!

      –  Diffusivity
           •  A measure of the tendency of a molecule to avoid getting hung up in the
              surrounding media
           •  Specific for solute, solvent, and temperature
           •  In part is a function of molecular mass
           •  E.g., the diffusivity of oxygen in air is different than in plasma, and the
              diffusivity of oxygen in plasma is different than the diffusivity of carbon
              dioxide
Diffusion is A Random Walk in Space




           Source Undetermined
Bulk Transport by Diffusion

•    The Brownian movement of
     particles over a distance is
     proportional to the square root
     of time                                                             5
                                                                       4.5




                                          Distance (arbitrary units)
                                                                         4

•    At scales more than 50 microns                                    3.5
                                                                         3
     or so, diffusion is a uselessly                                   2.5
     slow process!                                                       2
                                                                       1.5
                                                                         1
•    The keys to diffusing large                                       0.5
     amounts of gas (e.g., hundreds                                      0

     of milliliters per minute) are:                                         0           10            20   30
                                                                                          Time (msec)
      –  a very large surface area for
         gas particles to randomly walk                                          Source Undetermined
         across.
      –  A very short diffusion path
•  In adult humans, ~23
                                       generations of airway
                                       bifurcations

                                    •  2.5 – 7.5 x 106 alveoli

                                    •  Total surface area of ~ 130
                                       square meters

                                    •  Corresponding generations
                                       of both pulmonary arteries
                                       and pulmonary veins


Spencer, et al. Comp Bio Med 2001
•  Arthur Ashe Stadium
                               –  Each player brings a
                                  respiratory surface area
                                  comparable to the area
                                  of the court

                               –  At capacity, the stadium
                                  has a respiratory surface
                                  area of 2.8x106 m2 and is
                                  diffusing more than 4,400
Davidwboswell (Wikipedia)
                                  liters of O2 per minute
Exercise and Sport Science Review




                      Paolo Camera (Flickr)
Pulmonary Gas Diffusion in Health and Disease

•    Factors Adversely Affected by
     Illness
      –  Diminished concentration
         gradient between alveoli and
         pulmonary capillaries
          •  Due to convective failure
      –  Distance to be Traveled
          •  Membrane thickness
          •  Perivascular edema or fibrosis
      –  Surface Area
          •  Loss of alveoli, alveolar
             flooding

•    At some level, many therapies
     for lung disease strive to
     reverse these physical issues
     and enhance diffusive transport          Source Undetermined
Pressure, Content, and Transport
Pressure

Simple enough: Pressure is the force over an area applied perpendicular to that area s surface. Both gas
    diffusion and gas convection can exert pressure.

•    Two useful laws for today s discussion – One applies to gas phase only, both apply to gases dissolved in
     liquid

      –    Dalton s Law: The total pressure of a gas mixture is the sum of the partial pressures of its
           constituents:
                                                      Ptotal = ! Pi
                                                                 i


      –    Henry s Law: The partial pressure of a gas in equilibrium with a volume of liquid is proportional to
           the amount of gas dissolved in the liquid:
                                                        P = kc


           where k is a constant for a particular gas-solvent-temperature combination and c is the concentration
           of the gas.

           Beware: This is also often written as c = kP, where the relationship is the same, but the value of k is
           the reciprocal of the one noted above.
Consequences and Caveats about Dalton s
               and Henry s Laws


•    If total pressure is held constant (such as
     being held at atmospheric pressure), the
     partial pressure of one gas in a gas
     mixture or solution can only change if the
                                                                     John Dalton
     partial pressures of one or more other
     gases change                                                    1766-1844
                                                       Source Undetermined


•    Both Dalton s and Henry s Laws
     assume that the gases under discussion
     (either as gases or dissolved in liquid) are
     inert – they don t interact with one
     another or chemically with the media
     which they re in.
      –    Both of these are not true in the case of                     William Henry
           oxygen and carbon dioxide
                                                                         1775-1836
                                                       Source Undetermined
Content: Dissolved and Hemoglobin-Bound Oxygen
Implications and Limitations of Henry s Law


•    Henry s Law relates partial pressure of oxygen to concentration of
     dissolved oxygen in plasma as follows:

                            [O2] = 0.003 x PO2

     where [O2] is in ml/dl, PO2 is in mmHg and k is in ml/dl/mmHg, and
     physiological temperature (37oC) is assumed

•    For typical PO2 values (~100 mmHg or so), this is a very modest
     amount of dissolved oxygen and would require a tremendously high
     cardiac output to deliver enough oxygen per minute to the periphery.
The Only Way to Make Gas Transport Work in Large
        Creatures is with a Dedicated Oxygen Carrier
•    Some useful facts about hemoglobin*
      –  Concentration in blood is very high (~15 g/dl), constituting about a third of
         the mass of an erythrocyte, and about 15% of the mass of blood

      –  Each gram of hemoglobin can bind about 1.34 ml/g of O2**

      –  Always a tetramer, there are a variety of subunits that come to the fore at
         different points during development (including !, ", #, $, %, and &). In large
         part, these provide different tunings of the oxygen-hemoglobin
         dissociation curve

      –  A number of physical features of the local environment also serve to tweak
         the loading and unloading of oxygen from hemoglobin

      –  Hemoglobin is also an important carrier of carbon dioxide
           •  carbaminohemoglobin
                                                      * Byuseful, I mean of course testable.
                                                      **Note: This number is convention – it s
                                                      certainly an overestimate of the actual figure
Important Facts of O2 Binding by Hemoglobin

                               •  Binding is allosterically
                                  cooperative
                                   –  O2 binding to any heme
                                      group changes the structure
                                      of the entire molecule

                                   –  Each O2 bound promotes
                                      binding of the next O2

                                   –  The result is a very steep
     U.S. Federal Government
                                      Hgb-O2 dissociation curve in
                                      the physiologically useful
                                      range
Relationship Between Oxygen Tension and Hemoglobin Saturation


                                    •    Under resting conditions,
                                         hemoglobin leaves about 25%
                                         of its oxygen in the periphery

                                    •    With exercise, greater and
                                         greater amounts of oxygen are
                                         extracted, with progressively
                                         deoxygenated hemoglobin
                                         returning to the lungs

                                    •    Acidosis and increased
                                         temperature* tend to move the
                                         curve to the right, facilitating
     Arterial blood                      better O2 unloading
     Venous blood, at rest
     Venous blood, heavy exercise
        Source Undetermined
                                          *At heavy exercise, peripheral venous pH
                                          and temperature may reach 7.25 and 40oC
Conditions Affecting Oxygen-Hemoglobin Dissociation Kinetics

•    A shift to the right
      –  For a given PO2, hemoglobin will be less saturated
      –  For a given drop from arterial PO2, more oxygen will have been unloaded
      –  Useful for unloading hemoglobin

•    A shift to the left
      –  For a given PO2, hemoglobin will be more saturated
      –  For a given drop from arterial PO2, less oxygen will have been unloaded
      –  Useful for loading hemoglobin

•    Factors shifting to the right
      –  High Temperature
      –  High PCO2
      –  Low pH
      –  2,3 diphosphoglycerate
      –  Adult (versus fetal) hemoglobin

•    Factors shifting to the left
      –  The inverse of those above, plus
      –  Carbon monoxide
      –  Methemoglobinemia
An Important Application of a Curve Shifted to the Left



•  Maternal-fetal oxygen transfer
    –  The affinity for oxygen of
       hemoglobin on the fetal side of
       the circulation must, at a given
       PO2, be higher than the
       hemoglobin oxygen affinity on
       the maternal side



                                          Source Undetermined
•  Christian Bohr:
    –  Acidosis decreases affinity of
       hemoglobin for O2
                                                    Christian Bohr
                                                    (1855-1911)
                                        Source Undetermined




•  J. S. Haldane:
    –  Low PO2 increases the affinity
       of hemoglobin for CO2                        John S. Haldane
                                                    (1860-1936)

                                        Source Undetermined
Content and
                        Transport: The
                      link between the
                        cardiovascular
                       and respiratory
                           systems

Source Undetermined
Oxygen Content and Transport

•    Oxygen content is the total amount of oxygen within a volume of blood
      –  Determined by concentration of hemoglobin, its extent of saturation, and the partial
         pressure of oxygen
      –  Typically abbreviated as CxO2 (Arterial: CAO2 Venous: CVO2)
      –  Expressed in volume/volume (usually, clunkily, in ml/dl)

               Hemoglobin-Bound                                       Dissolved
               Oxygen                                                 Oxygen

 C=            ([Hb] x Saturation x 1.34)                           +         (0.003 x PO2)


        g/dl              %/100                   ml/g                ml/dl/mmHg
Oxygen Content and Transport

•  Oxygen transport is the rate at which oxygen is being moved by
   the circulatory system from the lungs to the periphery
   –  Determined by oxygen content and cardiac output
   –  Typically referred to as oxygen delivery, DO2
   –  Expressed in volume/minute or volume/minute/surface area



       DO2 =         Cardiac Output           x       CAO2

                    l/min                         ml/dl
                      or
                  l/min/m2
Oxygen Consumption

•  Oxygen consumption is the rate at which oxygen is utilized by
   the periphery
    –  Defined as the difference between the oxygen content in arterial
       blood and in mixed venous blood in the pulmonary artery.
    –  Expressed in volume/minute or volume/minute/surface area


     VO2 =          Cardiac Output             x     ( CAO2-CVO2)

                   l/min                           ml/dl
                     or
                 l/min/m2
Pressure, Content, and Transport



•    Ultimately, respiratory failure is an issue of reduced oxygen transport.

•    Clinical assessment of transport adequacy typically concentrates on pressure
     and content. Measuring blood flow requires more invasive methods than
     measuring hemoglobin saturation or the partial pressure of oxygen

•    Physiological compensation and medical therapy are directed against each
     element of the content and transport equations
      –  Increased PO2
      –  Increased hemoglobin concentration
      –  Increased cardiac output
Nonrespiratory Situations May Have Large Impact on
                 Oxygen and CO2 Transport



•    Anemia
      –  Decreased oxygen content regardless of the extent of saturation


•    Congestive heart failure
      –  Decreased blood flow regardless of content


•    Living at altitude or in artificial atmospheres
      –  Low ambient oxygen tension
The Lung as a Gas Exchanger
The Human Lung as Gas Exchanger: System
                  Requirements


•  Oxygen uptake
   –  Measured as volume of oxygen consumed per minute (VO2)
   –  At rest, VO2 ~ 200 ml/min
   –  At exercise, VO2 ~ 3 l/min for 8 minute mile

•  Carbon dioxide clearance
   –  Commensurate with amount of oxygen consumed

•  Extensive reserve
   –  In health, for exercise
   –  In illness, for wiggle room
The Human Lung as Gas Exchanger: System
                        Requirements

•    The basic idea
      –  Bring deoxygenated blood and well-ventilated alveoli as close to one another as you
         can. This is called ventilation:perfusion matching

      –  Ventilation is controlled globally by CNS respiratory regulation in conjunction with the
         chest wall and diaphragm

      –  Perfusion is controlled globally by regulation of cardiac output, and locally by hypoxic
         pulmonary vasoconstriction

•    How efficiency is lost
      –    Malfunctioning alveoli are not appropriately ventilated
      –    Local blood flow regulation fails to re-route blood around hypoxic alveoli
      –    Diffusion distance is increased
      –    Diffusion surface area is reduced
Highest VO2 Measured in Human:
      VO2: 6.61 l/min
      Respiratory Rate: 62
      Tidal Volume: 3.29 l




    John Slade (Wikipedia)
CO2 Handling in the Lung
Carbon Dioxide Handling in the Lung



•  CO2 is ~ 20x more soluble than O2 in plasma

•     CO2 transfer is therefore much less susceptible than oxygen
     transfer to changes in disease-related loss of diffusion ability

•  For the sake of discussion, if CO2 rich venous blood gets to an
   alveolus, the PCO2 in blood and gas will quickly equilibrate
Changes in arterial PCO2 are, practically
speaking, a result of changes in CO2
production by tissues or changes in
alveolar ventilation
Functional Compartments in the Lung:
                     Anatomic Dead Space

•    Only a portion of the respiratory system participates in gas exchange
     (i.e., diffusion)

      –  Respiratory Bronchioles -> Alveoli

•    A portion of the system is only needed to move tidal breaths (i.e.,
     convection)

      –  Pharynx -> Bronchioles are conducting airways
      –  Anatomic dead space
Functional Compartments in the Lung:
                 Physiologic Dead Space


•  Anatomic dead space, plus…
•  Ventilated areas receiving no blood flow
Ventilation

•    Ventilation is the movement of fresh gas from the environment down to the
     alveoli and, conversely, the movement of hypoxic, hypercarbic gas from the
     alveoli back to the environment

•    Typically categorized into 3 component rates, each described as volume per
     time, derived from 3 anatomic compartments in the lung:
      –  Minute ventilation: Tidal volume x Breaths per minute
      –  Dead space ventilation: Dead space x Breaths per minute
      –  Alveolar ventilation: (Tidal volume – Dead space) x Breaths per minute
Why Dead Space is Important


•  To move air requires power
   –  (i.e., work over time)


•  To meet oxygen delivery and CO2 removal demands, a certain
   amount of fresh gas must be moved per minute

•  As dead space increases, more air has to be moved to maintain
   the same alveolar ventilation

•  Therefore, increased dead space means decreased efficiency
   and increased work of breathing
Conditions Associated with Increased Dead space

•  Chronic obstructive disease
   –  Obliteration of capillaries

•  Pulmonary embolism
   –  Occlusion of vessels to ventilated alveoli


•  Endotracheal incubation
   –  Length of tube beyond the lips represents additional anatomic
      dead space
Conditions Associated with Changes in Minute
                          Ventilation

•  Hyperventilation
    –    Compensation for hypoxia
    –    Compensation for metabolic acidosis
    –    Anxiety
    –    Intoxication (e.g., salicylates, pretty uncommon)

•  Hypoventilation
    –    Obstructive Sleep Apnea
    –    CNS and Peripheral Neuromuscular Disease
    –    Intoxication
    –    Airway Obstruction
    –    COPD
Oxygen Handling
The Problem with Oxygen


•    Transfer into the plasma from the alveoli by diffusion is less rapid
      –  Oxygen is less soluble
      –  Diffusion is more strongly impacted by distances and surface area

•    A lot of oxygen must be transferred, so the time required to load up
     becomes important
Significant Time is Needed to Fully Oxygenate Blood Entering the
                              Lung




          Source Undetermined
Diffusion of Gas from an Alveolus into Capillary Blood




                     Source Undetermined
Diffusion into capillaries: Impact of Short Transit Time




                     Source Undetermined
Impact of Supplemental Oxygen



                            •    Supplemental oxygen increases
                                 the oxygen gradient from alveoli
                                 to capillaries

                            •    Flux into capillary blood
                                 increases
                                  –  Plasma and hemoglobin load
                                     more quickly
                                  –  Blood can become fully
                                     oxygenated despite diffusion
                                     limitation

Source Undetermined
The Four Riders of the Apocalypse:
     The Causes of Hypoxia



•    Hypoventilation
•    Diffusion Block
•    Shunt
•    V/Q Mismatch
A Quick Diversion: Normal Partial Pressures of Various
             Gases in the Lung and Blood

                                 •    Arterial Values (at Rest)
                                       –  PO2        ~90-100 mmHg
•    Alveolar Values                   –  PCO2       ~35-45
      –  PH2O      ~47 mmHg
      –  PO2       ~150 mmHg
      –  PCO2      ~35-45 mmHg   •    Mixed Venous Values (At Rest)
                                       –  PO2        ~40 mmHg
                                       –  PCO2       ~45 mmHg
I. Hypoventilation



•    Failure to bring fresh gas
     into the lung will decrease
     the arterial pO2.

•    Hypoventilation causes
     hypoxia by displacing
     alveolar O2 with CO2 -- the
     alveolar-capillary partial
     pressure gradient goes
     down, so diffusion is
     reduced
                                   Source Undetermined
II. Diffusion Block

•  Direct impairment of gas transfer across the alveolar
   membrane

•  Seen in any disease that lengthens the gas diffusion
   path
   –  Fibrotic disease
   –  Lung edema

•  Or that significantly reduces surface area
   –  COPD
III. Venous Admixture (Shunt)




   Source Undetermined
Venous Admixture and Arterial Oxygen Tension




•  Key fact #1: The higher the proportion of flow through
   the shunt to the total flow in the lung, the lower the
   PaO2.
Venous Admixture and Arterial Oxygen Tension




•  Key Fact #2: Hypoxia caused by shunt cannot be
   overcome with supplemental oxygen. A portion of
   blood passing through the lung never encounters a
   ventilated alveolus.
More on Venous Admixture

•  Physiologic
   –  Bronchial veins -> drain to pulmonary vein
   –  Thebesian veins -> drain to left ventricle

•  Pathologic
   –  Intracardiac, R->L shunts
   –  Intrapulmonary AV malformations
   –  Totally unventilated alveoli
       •  e.g., Collapsed lobe due to obstructing endobronchial cancer
IV. Ventilation-Perfusion Inequality


•    Pure dead space and pure shunt are not commonly seen clinical

•    Some blend of these phenomena is the most common cause of
     hypoxia

•    A mix of dead space and shunt physiology

•    Requires thinking in a multi-alveolar way
Multiple Alveolus Model




   Source Undetermined
Character of Pulmonary
                            Venous Blood

               The Dead Space Alveolus. In theory, no blood leaves
               this unit. As V/Q approaches !, in pulmonary
               venous blood:
                          PaO2 -> (Patm-PH2O) x FiO2
                          PaCO2 -> 0 mmHg

              The Ideal Alveolus. V/Q ~ 1. In pulmonary venous blood:
                      PaO2 -> [(Patm-PH2O) x FiO2] - (PCO2/RQ)
                      PaCO2 = 40 mmHg



              The Shunt Alveolus. No fresh gas is delivered to blood.
              As V/Q approaches 0, in pulmonary venous blood:
                      PaO2 -> PvO2
                      PaCO2 -> PvCO2

Source Undetermined
Source Undetermined
Diseases Associated with V/Q Inequality




•  Pretty much everything except pure shunt or pure
   hypoventilation will produce V/Q inequality

   –    Pneumonia
   –    Obstructive disease
   –    Fibrotic disease
   –    Pulmonary embolism
Diffusion        Hypo-
 Block         Ventilation




                  V/Q
 Shunt
               Inequality


  J. Younger
Fibrosis

               Hypo-
Diffusion    Ventilation
 Block




 Shunt          V/Q
             Inequality


J. Younger
COPD


                Hypo-
              Ventilation
Diffusion
 Block

               V/Q
      Shunt Inequality

 J. Younger
The 5th Cause: Low Inspired Oxygen Concentration



•  Altitude
•  Commercial air travel
    –  Cabin pressurized to ~ 8,000 ft altitude
•  Errors regarding supplemental oxygen
Thinking Clinically about Gas Exchange

•    Clinically, quantifying gas exchange is used to evaluate the function of the lung

•    If you know:
      –  Gas partial pressures (tensions) in the alveoli
      –  Gas tensions in the blood

•    Then you can calculate the A-a gradient
      –  This allows you to make some good guesses about:
           •    Ventilation, perfusion, and diffusion phenomena across the alveolar membrane.

•    In critical care and research settings, you can get fancier
      –  PaO2/FiO2 ratio
      –  Oxygenation Index
           •    (Paw x FiO2) / PaO2
The Alveolar Gas Equation


•    The basis for calculating the alveolar-arterial O2 difference (A-a
     gradient)

•    The A-a gradient is a really useful way to ask the general question:
     How effectively is oxygen brought into the lung making it into the
     bloodstream?

•    Simply pregnant with testing possibilities
To Evaluate the Performance of the Lung as a Gas
 Exchanger, Begin with the Gas Tensions in The Alveoli


•    Measuring alveolar gas concentrations is not simple and is usually not
     done except in pulmonary function or research laboratories

•    Guessing about alveolar gas concentrations usually suffices

•    The guess that is used is the alveolar gas equation
Nitrogen
                  Oxygen
                  Water Vapor
                  Carbon Dioxide
                  Trace Gases




Source Undetermined
The Alveolar Gas Equation

Water Vapor:    47 mmHg


Everything else entering the lung :   (Patm - PH2O)


Oxygen entering the lung:             (Patm – PH2O) x FiO2


Oxygen in the alveoli:                [(Patm - PH2O) x FiO2] - PaCO2/RQ


Carbon dioxide in the alveoli:        Assumed equal to arterial PCO2
The Respiratory Quotient

•    The ratio of the amount of CO2 produced to the amount of O2
     consumed

•    Typical values range from 0.7 to 1.0

•    Obviously dependent on relative consumption of carbohydrate, protein,
     and lipid substrates

•    For many calculations, a value of 1.0 is reasonable

•    Assumes metabolic equilibrium
      –  Vigorous exercise is a great example of disequilibrium
      –  During exercise beyond the anaerobic threshold, the value can take on
         values greater than 1.
The alveolar-arterial (A-a) oxygen gradient


•  The difference between the oxygen partial pressure in alveoli
   and the pressure in blood

•  Higher gradients mean worse performance
A-a Gradient and the 4 Causes of Hypoxia


 •    Hypoventilation
       –  A-a Gradient should be normal
       –  Hypoventilation simply increases the PCO2 term in the alveolar gas
          equation

 •    A-a Gradient will not differentiate:
       –  Diffusion block
       –  V/Q inequality
       –  Shunt
Figuring Out Which of the 4 Causes Affects a
                 Given Patient

•  History and Physical
    –  i.e., the rest of the respiratory sequence
•  Evaluate for obstructive physiology
•  Test for diffusion abnormalities (DLCO)
•  Intervene and see what happens
    –  Supplemental oxygen
    –  Augmented ventilation
        •  Bronchodilators
        •  Mechanical support
A Teaser for Next Week: Oxygen Delivery versus
                 Mitochondrial Accessibility


•    DO2 is a global, gross measure of a patient s ability to delivery oxygen to tissues

•    Relying on DO2 clinically assumes that downstream vascular plumbing is working
     appropriately
      –    Regional vascular autoregulation


•    Shock states (e.g., sepsis, trauma) are associated with dysfunctional autoregulation at the
     tissue level, making DO2 an imperfect parameter

•    Sometime in our lifetime, practical tissue O2 sensors will be available to monitor oxygen
     delivery at the tissue or cellular level
Important Things to Walk Away With


•  Differences between convection and diffusion
•  Meaning of tension, saturation, and content and associated
   calculations
•  Impact of alveolar ventilation and dead space on carbon dioxide
   handling
•  The 4 primary causes of low arterial PO2 and the physiology of
   each
•  The alveolar gas and A-a gradient equations
Question to Ponder Tonight:

Which would most adversely affect arterial oxygenation?

    1.    An acute pneumonia completely involving the left lower lobe such that no
          gas exchange could occur
    2.    Surgically removing a normal left lower lobe
Question to Ponder Tonight


At altitude, some degree of hypoxia is a common occurrence. If
someone were hypoxic at a given altitude, how could you tell whether
or not there lungs were exchanging gas properly?
Question to Ponder Tonight

For each measurement, which would take longer to reach equilibrium
following a change?

  –  Arterial oxygen content, following a sudden decrease of atmospheric FiO2
     from 0.21 to 0.16

  –  Arterial carbon dioxide tension, following a sudden decrease in minute
     ventilation by 15%?

  –  Hint: At this moment, which gas are you carrying around more of, oxygen
     or carbon dioxide? Where do you store those gases?
Question to Ponder Tonight

Some seals, walruses, and whales can stay submerged for extended
periods of time (approaching an hour). How is this possible?
Additional Source Information
                                    for more information see: http://open.umich.edu/wiki/CitationPolicy
Slide 5: Source Undetermined
Slide 6; Narayanese, WikiUserPedia, YassineMrabet, TotoBaggins (Wikipedia),
      http://commons.wikimedia.org/wiki/File:Citric_acid_cycle_with_aconitate_2.svg CC: BY-SA 3.0
      http://creativecommons.org/licenses/by-sa/3.0/
Slide 7: Rozzychan (Wikipedia) http://commons.wikimedia.org/wiki/File:Mitochondrial_electron_transport_chain.png
CC: BY-SA 2.5 http://creativecommons.org/licenses/by-sa/2.5/
Slide 8: Source Undetermined
Slide 10: John Younger
Slide 13: Source Undetermined
Slide 14: Source Undetermined
Slide 15: Spencer, et al. Comp Bio Med 2001
Slide 16: Davidwboswell (Wikipedia), http://commons.wikimedia.org/wiki/File:Arthur_ashe_stadium_interior.jpg CC: BY-SA 3.0
      http://creativecommons.org/licenses/by-sa/3.0/
Slide 17: Paolo Camera (Flickr), http://www.flickr.com/photos/vegaseddie/3309223161/ CC: BY 2.0 http://creativecommons.org/licenses/by/2.0/
Slide 18: Source Undetermined
Slide 21: Source Undetermined; Source Undetermined
Slide 25: U.S. Federal Government
Slide 26: Source Undetermined
Slide 28: Source Undetermined
Slide 29: Source Undetermined; Source Undetermined
Slide 30: Source Undetermined
Slide 39: John Slade Wikipedia http://commons.wikimedia.org/wiki/File:GB_Pair_at_Henley_2004.JPG
Slide 51: Source Undetermined
Slide 53: Source Undetermined
Slide 54: Source Undetermined
Slide 57: Source Undetermined
Slide 59: Source Undetermined
Slide 64: Source Undetermined
Slide 65: Source Undetermined
Slide 66: Source Undetermined
Slide 68: John Younger
Slide 69: John Younger
Slide 70: John Younger
Slide 75: Source Undetermined

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09.12.08(a): Gas Exchange

  • 1. Author(s): John G. Younger, M.D., 2009 License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution–Share Alike 3.0 License: http://creativecommons.org/licenses/by-sa/3.0/ We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, and adapt it. The citation key on the following slide provides information about how you may share and adapt this material. Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions, corrections, or clarification regarding the use of content. For more information about how to cite these materials visit http://open.umich.edu/education/about/terms-of-use. Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about your medical condition. Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers.
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  • 3. Gas Exchange John G. Younger, MD Associate Professor Department of Emergency Medicine Fall 2008
  • 4. A Tour of the Lecture •  Some perspective •  Some physics and biochemistry –  Convection and Diffusion –  Hemoglobin –  Pressure, Content, and Transport •  The lung as a gas exchanger –  Carbon dioxide handling and dead space –  Oxygen handling –  The four causes of hypoxia –  Quantifying gas exchange
  • 8. Mitochondria are where respiration occurs. The respiratory system is really a bulk transport system for an incoming oxidizer (O2) and outgoing gas (CO2) and heat. Source Undetermined
  • 9. Bulk Transport: Getting Molecules from One Point to Another •  Convection –  Bulk movement of gas due to pressure gradients –  Requires mechanical power input –  Transport from the environment to the terminal bronchioles –  Transport of erythrocytes between pulmonary capillaries and peripheral capillaries •  Diffusion –  Transport based on random motion of thermally energetic particles situated in a concentration gradient –  Requires thermal input –  Transport from terminal bronchioles to erythrocytes –  Transport between erythrocytes and peripheral mitochondria
  • 10. Source: NASA Diffusion Convection Spongy hv Chloroplasts Mesophyll Terminal Peripheral Atmosphere Circulation Mitochondria Airways Capillaries Convection Diffusion Convection Diffusion J. Younger
  • 11. Transport by Convection •  The movement of particles by convection is driven by: –  The pressure gradient between the atmosphere and terminal bronchioles –  Thus, this is in the realm of what s typically referred to as pulmonary mechanics •  The mechanical work required to get this job done is a function of: –  Resistance of the transport path to air flow •  Itself a function of the effective cross-sectional area of the airways –  The viscosity and density of the air being moved –  The compliance of the lung and chest wall
  • 12. Transport by Diffusion •  The movement of particles by diffusion is driven by: –  Concentration gradient •  For physiological purposes, usually reported as differences in partial pressure •  Gradient may exist in either gas phase (e.g., bronchiole->alveolus) or liquid phase (e.g., plasma->RBC membrane) •  Note: Although concentrations are often reported in partial pressures, at it s heart this is a Brownian Motion based phenomenon! –  Diffusivity •  A measure of the tendency of a molecule to avoid getting hung up in the surrounding media •  Specific for solute, solvent, and temperature •  In part is a function of molecular mass •  E.g., the diffusivity of oxygen in air is different than in plasma, and the diffusivity of oxygen in plasma is different than the diffusivity of carbon dioxide
  • 13. Diffusion is A Random Walk in Space Source Undetermined
  • 14. Bulk Transport by Diffusion •  The Brownian movement of particles over a distance is proportional to the square root of time 5 4.5 Distance (arbitrary units) 4 •  At scales more than 50 microns 3.5 3 or so, diffusion is a uselessly 2.5 slow process! 2 1.5 1 •  The keys to diffusing large 0.5 amounts of gas (e.g., hundreds 0 of milliliters per minute) are: 0 10 20 30 Time (msec) –  a very large surface area for gas particles to randomly walk Source Undetermined across. –  A very short diffusion path
  • 15. •  In adult humans, ~23 generations of airway bifurcations •  2.5 – 7.5 x 106 alveoli •  Total surface area of ~ 130 square meters •  Corresponding generations of both pulmonary arteries and pulmonary veins Spencer, et al. Comp Bio Med 2001
  • 16. •  Arthur Ashe Stadium –  Each player brings a respiratory surface area comparable to the area of the court –  At capacity, the stadium has a respiratory surface area of 2.8x106 m2 and is diffusing more than 4,400 Davidwboswell (Wikipedia) liters of O2 per minute
  • 17. Exercise and Sport Science Review Paolo Camera (Flickr)
  • 18. Pulmonary Gas Diffusion in Health and Disease •  Factors Adversely Affected by Illness –  Diminished concentration gradient between alveoli and pulmonary capillaries •  Due to convective failure –  Distance to be Traveled •  Membrane thickness •  Perivascular edema or fibrosis –  Surface Area •  Loss of alveoli, alveolar flooding •  At some level, many therapies for lung disease strive to reverse these physical issues and enhance diffusive transport Source Undetermined
  • 20. Pressure Simple enough: Pressure is the force over an area applied perpendicular to that area s surface. Both gas diffusion and gas convection can exert pressure. •  Two useful laws for today s discussion – One applies to gas phase only, both apply to gases dissolved in liquid –  Dalton s Law: The total pressure of a gas mixture is the sum of the partial pressures of its constituents: Ptotal = ! Pi i –  Henry s Law: The partial pressure of a gas in equilibrium with a volume of liquid is proportional to the amount of gas dissolved in the liquid: P = kc where k is a constant for a particular gas-solvent-temperature combination and c is the concentration of the gas. Beware: This is also often written as c = kP, where the relationship is the same, but the value of k is the reciprocal of the one noted above.
  • 21. Consequences and Caveats about Dalton s and Henry s Laws •  If total pressure is held constant (such as being held at atmospheric pressure), the partial pressure of one gas in a gas mixture or solution can only change if the John Dalton partial pressures of one or more other gases change 1766-1844 Source Undetermined •  Both Dalton s and Henry s Laws assume that the gases under discussion (either as gases or dissolved in liquid) are inert – they don t interact with one another or chemically with the media which they re in. –  Both of these are not true in the case of William Henry oxygen and carbon dioxide 1775-1836 Source Undetermined
  • 22. Content: Dissolved and Hemoglobin-Bound Oxygen
  • 23. Implications and Limitations of Henry s Law •  Henry s Law relates partial pressure of oxygen to concentration of dissolved oxygen in plasma as follows: [O2] = 0.003 x PO2 where [O2] is in ml/dl, PO2 is in mmHg and k is in ml/dl/mmHg, and physiological temperature (37oC) is assumed •  For typical PO2 values (~100 mmHg or so), this is a very modest amount of dissolved oxygen and would require a tremendously high cardiac output to deliver enough oxygen per minute to the periphery.
  • 24. The Only Way to Make Gas Transport Work in Large Creatures is with a Dedicated Oxygen Carrier •  Some useful facts about hemoglobin* –  Concentration in blood is very high (~15 g/dl), constituting about a third of the mass of an erythrocyte, and about 15% of the mass of blood –  Each gram of hemoglobin can bind about 1.34 ml/g of O2** –  Always a tetramer, there are a variety of subunits that come to the fore at different points during development (including !, ", #, $, %, and &). In large part, these provide different tunings of the oxygen-hemoglobin dissociation curve –  A number of physical features of the local environment also serve to tweak the loading and unloading of oxygen from hemoglobin –  Hemoglobin is also an important carrier of carbon dioxide •  carbaminohemoglobin * Byuseful, I mean of course testable. **Note: This number is convention – it s certainly an overestimate of the actual figure
  • 25. Important Facts of O2 Binding by Hemoglobin •  Binding is allosterically cooperative –  O2 binding to any heme group changes the structure of the entire molecule –  Each O2 bound promotes binding of the next O2 –  The result is a very steep U.S. Federal Government Hgb-O2 dissociation curve in the physiologically useful range
  • 26. Relationship Between Oxygen Tension and Hemoglobin Saturation •  Under resting conditions, hemoglobin leaves about 25% of its oxygen in the periphery •  With exercise, greater and greater amounts of oxygen are extracted, with progressively deoxygenated hemoglobin returning to the lungs •  Acidosis and increased temperature* tend to move the curve to the right, facilitating Arterial blood better O2 unloading Venous blood, at rest Venous blood, heavy exercise Source Undetermined *At heavy exercise, peripheral venous pH and temperature may reach 7.25 and 40oC
  • 27. Conditions Affecting Oxygen-Hemoglobin Dissociation Kinetics •  A shift to the right –  For a given PO2, hemoglobin will be less saturated –  For a given drop from arterial PO2, more oxygen will have been unloaded –  Useful for unloading hemoglobin •  A shift to the left –  For a given PO2, hemoglobin will be more saturated –  For a given drop from arterial PO2, less oxygen will have been unloaded –  Useful for loading hemoglobin •  Factors shifting to the right –  High Temperature –  High PCO2 –  Low pH –  2,3 diphosphoglycerate –  Adult (versus fetal) hemoglobin •  Factors shifting to the left –  The inverse of those above, plus –  Carbon monoxide –  Methemoglobinemia
  • 28. An Important Application of a Curve Shifted to the Left •  Maternal-fetal oxygen transfer –  The affinity for oxygen of hemoglobin on the fetal side of the circulation must, at a given PO2, be higher than the hemoglobin oxygen affinity on the maternal side Source Undetermined
  • 29. •  Christian Bohr: –  Acidosis decreases affinity of hemoglobin for O2 Christian Bohr (1855-1911) Source Undetermined •  J. S. Haldane: –  Low PO2 increases the affinity of hemoglobin for CO2 John S. Haldane (1860-1936) Source Undetermined
  • 30. Content and Transport: The link between the cardiovascular and respiratory systems Source Undetermined
  • 31. Oxygen Content and Transport •  Oxygen content is the total amount of oxygen within a volume of blood –  Determined by concentration of hemoglobin, its extent of saturation, and the partial pressure of oxygen –  Typically abbreviated as CxO2 (Arterial: CAO2 Venous: CVO2) –  Expressed in volume/volume (usually, clunkily, in ml/dl) Hemoglobin-Bound Dissolved Oxygen Oxygen C= ([Hb] x Saturation x 1.34) + (0.003 x PO2) g/dl %/100 ml/g ml/dl/mmHg
  • 32. Oxygen Content and Transport •  Oxygen transport is the rate at which oxygen is being moved by the circulatory system from the lungs to the periphery –  Determined by oxygen content and cardiac output –  Typically referred to as oxygen delivery, DO2 –  Expressed in volume/minute or volume/minute/surface area DO2 = Cardiac Output x CAO2 l/min ml/dl or l/min/m2
  • 33. Oxygen Consumption •  Oxygen consumption is the rate at which oxygen is utilized by the periphery –  Defined as the difference between the oxygen content in arterial blood and in mixed venous blood in the pulmonary artery. –  Expressed in volume/minute or volume/minute/surface area VO2 = Cardiac Output x ( CAO2-CVO2) l/min ml/dl or l/min/m2
  • 34. Pressure, Content, and Transport •  Ultimately, respiratory failure is an issue of reduced oxygen transport. •  Clinical assessment of transport adequacy typically concentrates on pressure and content. Measuring blood flow requires more invasive methods than measuring hemoglobin saturation or the partial pressure of oxygen •  Physiological compensation and medical therapy are directed against each element of the content and transport equations –  Increased PO2 –  Increased hemoglobin concentration –  Increased cardiac output
  • 35. Nonrespiratory Situations May Have Large Impact on Oxygen and CO2 Transport •  Anemia –  Decreased oxygen content regardless of the extent of saturation •  Congestive heart failure –  Decreased blood flow regardless of content •  Living at altitude or in artificial atmospheres –  Low ambient oxygen tension
  • 36. The Lung as a Gas Exchanger
  • 37. The Human Lung as Gas Exchanger: System Requirements •  Oxygen uptake –  Measured as volume of oxygen consumed per minute (VO2) –  At rest, VO2 ~ 200 ml/min –  At exercise, VO2 ~ 3 l/min for 8 minute mile •  Carbon dioxide clearance –  Commensurate with amount of oxygen consumed •  Extensive reserve –  In health, for exercise –  In illness, for wiggle room
  • 38. The Human Lung as Gas Exchanger: System Requirements •  The basic idea –  Bring deoxygenated blood and well-ventilated alveoli as close to one another as you can. This is called ventilation:perfusion matching –  Ventilation is controlled globally by CNS respiratory regulation in conjunction with the chest wall and diaphragm –  Perfusion is controlled globally by regulation of cardiac output, and locally by hypoxic pulmonary vasoconstriction •  How efficiency is lost –  Malfunctioning alveoli are not appropriately ventilated –  Local blood flow regulation fails to re-route blood around hypoxic alveoli –  Diffusion distance is increased –  Diffusion surface area is reduced
  • 39. Highest VO2 Measured in Human: VO2: 6.61 l/min Respiratory Rate: 62 Tidal Volume: 3.29 l John Slade (Wikipedia)
  • 40. CO2 Handling in the Lung
  • 41. Carbon Dioxide Handling in the Lung •  CO2 is ~ 20x more soluble than O2 in plasma •  CO2 transfer is therefore much less susceptible than oxygen transfer to changes in disease-related loss of diffusion ability •  For the sake of discussion, if CO2 rich venous blood gets to an alveolus, the PCO2 in blood and gas will quickly equilibrate
  • 42. Changes in arterial PCO2 are, practically speaking, a result of changes in CO2 production by tissues or changes in alveolar ventilation
  • 43. Functional Compartments in the Lung: Anatomic Dead Space •  Only a portion of the respiratory system participates in gas exchange (i.e., diffusion) –  Respiratory Bronchioles -> Alveoli •  A portion of the system is only needed to move tidal breaths (i.e., convection) –  Pharynx -> Bronchioles are conducting airways –  Anatomic dead space
  • 44. Functional Compartments in the Lung: Physiologic Dead Space •  Anatomic dead space, plus… •  Ventilated areas receiving no blood flow
  • 45. Ventilation •  Ventilation is the movement of fresh gas from the environment down to the alveoli and, conversely, the movement of hypoxic, hypercarbic gas from the alveoli back to the environment •  Typically categorized into 3 component rates, each described as volume per time, derived from 3 anatomic compartments in the lung: –  Minute ventilation: Tidal volume x Breaths per minute –  Dead space ventilation: Dead space x Breaths per minute –  Alveolar ventilation: (Tidal volume – Dead space) x Breaths per minute
  • 46. Why Dead Space is Important •  To move air requires power –  (i.e., work over time) •  To meet oxygen delivery and CO2 removal demands, a certain amount of fresh gas must be moved per minute •  As dead space increases, more air has to be moved to maintain the same alveolar ventilation •  Therefore, increased dead space means decreased efficiency and increased work of breathing
  • 47. Conditions Associated with Increased Dead space •  Chronic obstructive disease –  Obliteration of capillaries •  Pulmonary embolism –  Occlusion of vessels to ventilated alveoli •  Endotracheal incubation –  Length of tube beyond the lips represents additional anatomic dead space
  • 48. Conditions Associated with Changes in Minute Ventilation •  Hyperventilation –  Compensation for hypoxia –  Compensation for metabolic acidosis –  Anxiety –  Intoxication (e.g., salicylates, pretty uncommon) •  Hypoventilation –  Obstructive Sleep Apnea –  CNS and Peripheral Neuromuscular Disease –  Intoxication –  Airway Obstruction –  COPD
  • 50. The Problem with Oxygen •  Transfer into the plasma from the alveoli by diffusion is less rapid –  Oxygen is less soluble –  Diffusion is more strongly impacted by distances and surface area •  A lot of oxygen must be transferred, so the time required to load up becomes important
  • 51. Significant Time is Needed to Fully Oxygenate Blood Entering the Lung Source Undetermined
  • 52. Diffusion of Gas from an Alveolus into Capillary Blood Source Undetermined
  • 53. Diffusion into capillaries: Impact of Short Transit Time Source Undetermined
  • 54. Impact of Supplemental Oxygen •  Supplemental oxygen increases the oxygen gradient from alveoli to capillaries •  Flux into capillary blood increases –  Plasma and hemoglobin load more quickly –  Blood can become fully oxygenated despite diffusion limitation Source Undetermined
  • 55. The Four Riders of the Apocalypse: The Causes of Hypoxia •  Hypoventilation •  Diffusion Block •  Shunt •  V/Q Mismatch
  • 56. A Quick Diversion: Normal Partial Pressures of Various Gases in the Lung and Blood •  Arterial Values (at Rest) –  PO2 ~90-100 mmHg •  Alveolar Values –  PCO2 ~35-45 –  PH2O ~47 mmHg –  PO2 ~150 mmHg –  PCO2 ~35-45 mmHg •  Mixed Venous Values (At Rest) –  PO2 ~40 mmHg –  PCO2 ~45 mmHg
  • 57. I. Hypoventilation •  Failure to bring fresh gas into the lung will decrease the arterial pO2. •  Hypoventilation causes hypoxia by displacing alveolar O2 with CO2 -- the alveolar-capillary partial pressure gradient goes down, so diffusion is reduced Source Undetermined
  • 58. II. Diffusion Block •  Direct impairment of gas transfer across the alveolar membrane •  Seen in any disease that lengthens the gas diffusion path –  Fibrotic disease –  Lung edema •  Or that significantly reduces surface area –  COPD
  • 59. III. Venous Admixture (Shunt) Source Undetermined
  • 60. Venous Admixture and Arterial Oxygen Tension •  Key fact #1: The higher the proportion of flow through the shunt to the total flow in the lung, the lower the PaO2.
  • 61. Venous Admixture and Arterial Oxygen Tension •  Key Fact #2: Hypoxia caused by shunt cannot be overcome with supplemental oxygen. A portion of blood passing through the lung never encounters a ventilated alveolus.
  • 62. More on Venous Admixture •  Physiologic –  Bronchial veins -> drain to pulmonary vein –  Thebesian veins -> drain to left ventricle •  Pathologic –  Intracardiac, R->L shunts –  Intrapulmonary AV malformations –  Totally unventilated alveoli •  e.g., Collapsed lobe due to obstructing endobronchial cancer
  • 63. IV. Ventilation-Perfusion Inequality •  Pure dead space and pure shunt are not commonly seen clinical •  Some blend of these phenomena is the most common cause of hypoxia •  A mix of dead space and shunt physiology •  Requires thinking in a multi-alveolar way
  • 64. Multiple Alveolus Model Source Undetermined
  • 65. Character of Pulmonary Venous Blood The Dead Space Alveolus. In theory, no blood leaves this unit. As V/Q approaches !, in pulmonary venous blood: PaO2 -> (Patm-PH2O) x FiO2 PaCO2 -> 0 mmHg The Ideal Alveolus. V/Q ~ 1. In pulmonary venous blood: PaO2 -> [(Patm-PH2O) x FiO2] - (PCO2/RQ) PaCO2 = 40 mmHg The Shunt Alveolus. No fresh gas is delivered to blood. As V/Q approaches 0, in pulmonary venous blood: PaO2 -> PvO2 PaCO2 -> PvCO2 Source Undetermined
  • 67. Diseases Associated with V/Q Inequality •  Pretty much everything except pure shunt or pure hypoventilation will produce V/Q inequality –  Pneumonia –  Obstructive disease –  Fibrotic disease –  Pulmonary embolism
  • 68. Diffusion Hypo- Block Ventilation V/Q Shunt Inequality J. Younger
  • 69. Fibrosis Hypo- Diffusion Ventilation Block Shunt V/Q Inequality J. Younger
  • 70. COPD Hypo- Ventilation Diffusion Block V/Q Shunt Inequality J. Younger
  • 71. The 5th Cause: Low Inspired Oxygen Concentration •  Altitude •  Commercial air travel –  Cabin pressurized to ~ 8,000 ft altitude •  Errors regarding supplemental oxygen
  • 72. Thinking Clinically about Gas Exchange •  Clinically, quantifying gas exchange is used to evaluate the function of the lung •  If you know: –  Gas partial pressures (tensions) in the alveoli –  Gas tensions in the blood •  Then you can calculate the A-a gradient –  This allows you to make some good guesses about: •  Ventilation, perfusion, and diffusion phenomena across the alveolar membrane. •  In critical care and research settings, you can get fancier –  PaO2/FiO2 ratio –  Oxygenation Index •  (Paw x FiO2) / PaO2
  • 73. The Alveolar Gas Equation •  The basis for calculating the alveolar-arterial O2 difference (A-a gradient) •  The A-a gradient is a really useful way to ask the general question: How effectively is oxygen brought into the lung making it into the bloodstream? •  Simply pregnant with testing possibilities
  • 74. To Evaluate the Performance of the Lung as a Gas Exchanger, Begin with the Gas Tensions in The Alveoli •  Measuring alveolar gas concentrations is not simple and is usually not done except in pulmonary function or research laboratories •  Guessing about alveolar gas concentrations usually suffices •  The guess that is used is the alveolar gas equation
  • 75. Nitrogen Oxygen Water Vapor Carbon Dioxide Trace Gases Source Undetermined
  • 76. The Alveolar Gas Equation Water Vapor: 47 mmHg Everything else entering the lung : (Patm - PH2O) Oxygen entering the lung: (Patm – PH2O) x FiO2 Oxygen in the alveoli: [(Patm - PH2O) x FiO2] - PaCO2/RQ Carbon dioxide in the alveoli: Assumed equal to arterial PCO2
  • 77. The Respiratory Quotient •  The ratio of the amount of CO2 produced to the amount of O2 consumed •  Typical values range from 0.7 to 1.0 •  Obviously dependent on relative consumption of carbohydrate, protein, and lipid substrates •  For many calculations, a value of 1.0 is reasonable •  Assumes metabolic equilibrium –  Vigorous exercise is a great example of disequilibrium –  During exercise beyond the anaerobic threshold, the value can take on values greater than 1.
  • 78. The alveolar-arterial (A-a) oxygen gradient •  The difference between the oxygen partial pressure in alveoli and the pressure in blood •  Higher gradients mean worse performance
  • 79. A-a Gradient and the 4 Causes of Hypoxia •  Hypoventilation –  A-a Gradient should be normal –  Hypoventilation simply increases the PCO2 term in the alveolar gas equation •  A-a Gradient will not differentiate: –  Diffusion block –  V/Q inequality –  Shunt
  • 80. Figuring Out Which of the 4 Causes Affects a Given Patient •  History and Physical –  i.e., the rest of the respiratory sequence •  Evaluate for obstructive physiology •  Test for diffusion abnormalities (DLCO) •  Intervene and see what happens –  Supplemental oxygen –  Augmented ventilation •  Bronchodilators •  Mechanical support
  • 81. A Teaser for Next Week: Oxygen Delivery versus Mitochondrial Accessibility •  DO2 is a global, gross measure of a patient s ability to delivery oxygen to tissues •  Relying on DO2 clinically assumes that downstream vascular plumbing is working appropriately –  Regional vascular autoregulation •  Shock states (e.g., sepsis, trauma) are associated with dysfunctional autoregulation at the tissue level, making DO2 an imperfect parameter •  Sometime in our lifetime, practical tissue O2 sensors will be available to monitor oxygen delivery at the tissue or cellular level
  • 82. Important Things to Walk Away With •  Differences between convection and diffusion •  Meaning of tension, saturation, and content and associated calculations •  Impact of alveolar ventilation and dead space on carbon dioxide handling •  The 4 primary causes of low arterial PO2 and the physiology of each •  The alveolar gas and A-a gradient equations
  • 83. Question to Ponder Tonight: Which would most adversely affect arterial oxygenation? 1.  An acute pneumonia completely involving the left lower lobe such that no gas exchange could occur 2.  Surgically removing a normal left lower lobe
  • 84. Question to Ponder Tonight At altitude, some degree of hypoxia is a common occurrence. If someone were hypoxic at a given altitude, how could you tell whether or not there lungs were exchanging gas properly?
  • 85. Question to Ponder Tonight For each measurement, which would take longer to reach equilibrium following a change? –  Arterial oxygen content, following a sudden decrease of atmospheric FiO2 from 0.21 to 0.16 –  Arterial carbon dioxide tension, following a sudden decrease in minute ventilation by 15%? –  Hint: At this moment, which gas are you carrying around more of, oxygen or carbon dioxide? Where do you store those gases?
  • 86. Question to Ponder Tonight Some seals, walruses, and whales can stay submerged for extended periods of time (approaching an hour). How is this possible?
  • 87. Additional Source Information for more information see: http://open.umich.edu/wiki/CitationPolicy Slide 5: Source Undetermined Slide 6; Narayanese, WikiUserPedia, YassineMrabet, TotoBaggins (Wikipedia), http://commons.wikimedia.org/wiki/File:Citric_acid_cycle_with_aconitate_2.svg CC: BY-SA 3.0 http://creativecommons.org/licenses/by-sa/3.0/ Slide 7: Rozzychan (Wikipedia) http://commons.wikimedia.org/wiki/File:Mitochondrial_electron_transport_chain.png CC: BY-SA 2.5 http://creativecommons.org/licenses/by-sa/2.5/ Slide 8: Source Undetermined Slide 10: John Younger Slide 13: Source Undetermined Slide 14: Source Undetermined Slide 15: Spencer, et al. Comp Bio Med 2001 Slide 16: Davidwboswell (Wikipedia), http://commons.wikimedia.org/wiki/File:Arthur_ashe_stadium_interior.jpg CC: BY-SA 3.0 http://creativecommons.org/licenses/by-sa/3.0/ Slide 17: Paolo Camera (Flickr), http://www.flickr.com/photos/vegaseddie/3309223161/ CC: BY 2.0 http://creativecommons.org/licenses/by/2.0/ Slide 18: Source Undetermined Slide 21: Source Undetermined; Source Undetermined Slide 25: U.S. Federal Government Slide 26: Source Undetermined Slide 28: Source Undetermined Slide 29: Source Undetermined; Source Undetermined Slide 30: Source Undetermined Slide 39: John Slade Wikipedia http://commons.wikimedia.org/wiki/File:GB_Pair_at_Henley_2004.JPG Slide 51: Source Undetermined Slide 53: Source Undetermined Slide 54: Source Undetermined Slide 57: Source Undetermined Slide 59: Source Undetermined Slide 64: Source Undetermined Slide 65: Source Undetermined Slide 66: Source Undetermined Slide 68: John Younger Slide 69: John Younger Slide 70: John Younger Slide 75: Source Undetermined