Respiratory Physiology Jim Pierce Bi 145a Lecture 17, 2009-10

Breathing and Ventilation How do we describe the normal flow in and out of the mouth, lung, and alveoli during a respiratory cycle? How do we get air in and out of the alveoli?

Breathing Exhale Inhale

Breathing

Breath Volumes Volumes that go through the mouth: Tidal Volume Vital Capacity Volumes that exist inside the mouth Residual Volume End Expiratory Volume (aka Functional Residual Capacity) End Inspiratory Volume Full Lung Capacity

Breathing The relationship between these volumes and breathing

Breathing and Ventilation We can subdivide the space from the mouth inside: Anatomically Upper Airways Lower Airways Alveoli Functionally Alveolar (Gas Exchanging) Physiologic Dead Space (Not) } Anatomic Dead Space

Alveolar Ventilation Anatomic Dead Space Physiologic Dead Space

Breathing

Breathing and Ventilation

Breathing and Ventilation

Breathing and Ventilation Flow: Tidal Volume through the mouth per breath Total Ventilation through the mouth per minute Alveolar Volume through the alveoli per breath Alveolar Ventilation through the alveoli per minute

Volumes and Gases We can use O2 and CO2 to Understand Volumes:

Volumes and Gases Fowler’s Method – Anatomic Dead Space If you inhale a pure gas, you will exhale: Pure Gas Mixed Gas Alveolar Gas

Volumes and Gases Fowler’s Method – Anatomic Dead Space Approximately 150 cc in a “regular man”

Volumes and Gases

Volumes and Gases Bohr Equation – Physiologic Dead Space All CO2 comes from alveolar gas (not dead space) Arterial CO2 is almost always equal to Alveolar CO2 There is conservation of mass.

Volumes and Gases Bohr Equation – Physiologic Dead Space PV = nRT PACO2 * VA = number of mols of exhaled CO2 PECO2 * VT = number of mols of exhaled CO2

Volumes and Gases Bohr Equation – Physiologic Dead Space So: PACO2 * VA = PECO2 * VT = number of mols of exhaled CO2

Volumes and Gases Bohr Equation – Physiologic Dead Space VA = PECO2 VT PACO2 VD = 1 - VA VT VT VD = 1 - PECO2 VT PACO2

Volumes and Gases Bohr Equation – Physiologic Dead Space

Alveolar Ventilation Flow takes Work We’ve already minimized work involved to move the chest and lung Why waste work opening alveoli?

Alveolar Ventilation What is the “Residual Volume?” The amount of air left in the lung after maximal exhale It’s purpose: Keep the Alveoli Open

Alveolar Ventilation At low volumes, alveoli would collapse by: Absorbing the last air left behind Emptying to a larger alveoli (Surface Tension experiment)

Alveolar Ventilation

Alveolar Ventilation Surfactants: Are amphipathic molecules that forms a phospholipid monolayer lining the alveoli The polar heads point at the alveolar wall, the lipophilic side chains point at the lumen

Alveolar Ventilation What is surfactant? Mainly dipalmitoyl phosphatidylcholine Protein B Protein D

Alveolar Ventilation Surfactant

Alveolar Ventilation At low lung volumes: In the small alveoli The lipophilic tails of surfactant are crowded and push each other away This keeps the alveoli open

Alveolar Ventilation At low lung volumes: In the large alveoli The viscosity of surfactant resist overdistension This keeps the alveoli from expanding

Alveolar Ventilation Thus, surfactant acts to 1) keep airways and alveoli open during end expiration. 2) cause even distribution of air during late inspiration.

Alveolar Ventilation Surfactant resists LaPlace

Alveolar Ventilation Another mechanism exists to prevent alveolar collapse: Without cartilage – bronchioles tend to collapse During inhalation, lung expansion opens bronchioles During exhalation, bronchioles can (and do) collapse

Alveolar Ventilation Another mechanism exists to prevent alveolar collapse: As the chest wall and lung recoil, the pressures in the lung increase These increased pressures start to start to force bronchioles closed By the end of exhalation, almost all bronchioles are collapsed

Alveolar Ventilation Another mechanism exists to prevent alveolar collapse: This is called: Small Airway Collapse

Hysteresis This gives lung a special property The pressure-volume curve is different during inspiration and expiration. This is known as Hysteresis

Hysteresis

Hysteresis

Hysteresis There are a variety of factors that influence the pressure-flow curve and cause hysteresis. There are TWO main factors: Surfactant Collapse of Airways

Hysteresis

Alveolar Ventilation Thus, surfactant causes the inspiratory portion of the hysteresis loop. And collapse of airways causes the expiratory portion of the hysteresis loop

Alveolar Ventilation Just as total muscle force is a function of average sarcomere length Alveolar Compliance and function is a function of average alveolar volume These same mechanisms lead preferentially to isovolumetric alveoli

Alveolar Ventilation So is alveolar ventilation even across different regions of the lung? No.

Regional Ventilation

Regional Ventilation Findings: Decreased flow to the upper lung Increased flow to the lower lung How do we explain regional differences in air flow to the lung?

Regional Ventilation

Regional Ventilation Thus, net differences in ventilation are based on differences in intrapleural pressure. These differences lead to different TRANSMURAL pressures, which lead to different flow rates.

Regional Ventilation

Alveolar Ventilation Atmospheric Air has mostly nitrogen Air that has been sitting in the nose, mouth, or trachea has water vapor Air that has been in the alveoli has water vapor, CO2, and less O2

Alveolar Ventilation One of the challenges is Mixing:

Alveolar Ventilation Thus – Alveolar Ventilation is affected by: Total Flow in and out Anatomic Dead Space Functional Dead Space Gas Mixing

Alveolar Ventilation To understand it you can: 1) Think about the gas composition at each level (mouth, trachea, etc) 2) Think about the gas content as it travels “down” its pressure gradient

Ventilation

Oxygen Atmospheric Pressure is 760 mmHg (at sea level) Atmospheric Fraction of Oxygen is 21%

Oxygen When Air goes through our upper airways, it becomes humidified and heated. The partial pressure of water rises to 47 mmHg

Alveolar Ventilation for Oxygen

Oxygen PIO2 = (760 mmHg - 47 mmHg) * FIO2 PIO2 = Inspired O2 Partial Pressure FIO2 = Fraction of Inspired O2 PIO2 = 713 * 21% = 150 mmHg

Alveolar Ventilation for Oxygen

Oxygen PAO2 = PIO2 – Pressure lost by displacement PAO2 = Alveolar O2 Partial Pressure The effect of mixing! Fortunately – CO2 Production is related to O2 Consumption

Carbon Dioxide The body uses oxygen to harness energy from reduced carbon. Depending on the carbon source (sugar, fat, protein) there are differing amounts of carbon dioxide produced

Carbon Dioxide The Respiratory Quotient, R, is the number of moles of CO2 produced per mole of O2 consumed. For a person eating a regular diet, it is approximately 0.8 It increases with fat metabolism It decreases with sugar metabolism

Oxygen PAO2 = PIO2 - PACO2 / R R = Respiratory Quotient PAO2 = 150 - PACO2 / 0.8 (just before mixing, arterial CO2 equals alveolar CO2) PAO2 = 150 - PaCO2 / 0.8

Alveolar Gas Equation PAO2 = (760 mmHg - 47 mmHg) * FIO2 - PartCO2 / 0.8

Carbon Dioxide In a similar fashion, we can watch Carbon Dioxide Pulmonary Artery brings in CO2 CO2 rapidly equilibrates with alveolar CO2 During exhale alveolar gas mixes with dead space gas displacing CO2 By end exhale, dead space gas is gone and CO2 is equivalent to alveolar CO2

Carbon Dioxide Capnogram = measurement of exhaled pCO2

Oxygen versus Carbon Dioxide Already we’re seeing one of the differences between these gases: Carbon Dioxide Equilibrates Quickly Oxygen Equilibrates Slowly

A-a Gradient When we start to look more closely at oxygen, we discover: The alveolar pO2 is higher than the arterial pO2 A-a gradient = PAO2 - PaO2

Alveolar Ventilation for Oxygen Atmosphere In Mouth

Alveolar Ventilation Thus, the things that reduce oxygen: Barometric Pressure Initial Inspired Fraction of Oxygen Humidification (before and after) Alveolar Mixing Diffusion Limits Mixing with Deoxygenated Blood Extraction by Tissue

Alveolar Ventilation The things that reduce carbon dioxide: Rate of Production of carbon dioxide Total Buffer of carbon dioxide Diffusion (not very limited) Alveolar Mixing Dead Space Mixing

Pulmonary Gas Exchange How does gas get from air to blood and back again? It must cross the membrane which divides the alveoli and the capillary.

Diffusion of Gases Is Described by Fick’s Law (yes, you’ve seen it before) Flow is proportional to Cross sectional area, Diffusion constant, Pressure gradient, The inverse of the thickness of the membrane.

Diffusion of Gases

Diffusion of Gases Thus, to maximize gas flow: 1) the lung increases cross sectional area by extensive branching 2) the lung makes the membrane as thin as possible 3) the blood has mechanisms to increase rates of uptake or removal of gas

Diffusion of Gases

Diffusion of Gases

Diffusion of Gases Each Gas (O2 , CO2 , CO, NO2 , N2O, Halothane) diffuses at a different rate. Blood flows by at a (relatively) constant rate. Thus, the total flow can be limited by either blood flow or diffusion.

Diffusion of Gases

Diffusion of Gases

Diffusion of Gases

Diffusion of Gases As a result, in general: Gases are PERFUSION LIMITED in health But can become DIFFUSION LIMITED in disease.

Carbon Dioxide versus Oxygen Gas flows down its pressure gradient. In general, the reservoir of gas will not be depleted. There will always be O2 in the air (atmospheric and both inhaled (21%) and exhaled (18%)) There will always be CO2 in the blood (arterial at about 40 mmHg, venous at about 45 mmHg) Furthermore, these pressures are relatively unchanged between pre and post exchange

Carbon Dioxide versus Oxygen The ability to maximize flow is the ability to make the recipient reservoir as empty as possible. As a result Oxygenation is based on PERFUSION Carbon dioxide excretion is based on VENTILATION.

Carbon Dioxide versus Oxygen When we use mechanical ventilation, we can only control ventilation. Thus, we can affect blood carbon dioxide with ease. Nevertheless, no changing in breathing will affect oxygenation

Carbon Dioxide versus Oxygen The ways we effect oxygenation by breathing is: Increase the inspired oxygen To increase the alveolar oxygen Which will increase the diffusion gradient Which will increase the flow of oxygen Fix the underlying problem (perfusion)

Questions?