Diffusion of Gases in Lungs and Tissues Charles L

Diffusion of Gases in Lungs and Tissues
Charles L. Webber, Jr., Ph.D.

Learning Objectives: You should be able to:

Trace the pathways molecules of oxygen and carbon dioxide must traverse as pulmonary capillary blood become arterialized.
Contrast the diffusion constant for any gas versus diffusing capacity of the lung in mathematical terms of Fick's law of diffusion.
Plot as a function of time the change in blood P0₂ and PCO₂ as venous blood flows through the lungs.
List and explain four different causes of arterial hypoxemia found in abnormal human pathophysiology.

Rhoades & Tanner Text Readings: Chapter 21, Pages 386-391, 395-398

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Diffusion Pathway

Diffusion
- passive diffusion and catalytic action of carbonic anhydrase
- facilitated diffusion (cytochrome P-450 fixed site O₂ and CO carrier)
Respiratory Membrane and Barriers to Diffusion

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Diffusing Capacity of the Lung

Gas Fluxes Across a Resistive Barrier
- _gas = P_gas * (1 / R)
- _gas = P_gas * G
- where:
  - = diffusive gas flow (mL/min)
  - R = resistance to diffusive gas flow (mm Hg/[mL/min])
  - G = conductance to diffusive gas flow ([mL/min]/mm Hg)
  - P = (PP1_gas - PP2_gas) pressure gradient (mm Hg)
  - PP1 & PP2 = partial pressures of given gas species on either side of membrane
Expansion of Fick's Law
- _gas = P_gas * G
- _gas = P_gas * D_{L gas}
- _gas = P_gas * (area_mem/thickness_mem) * D_gas
- _gas = P_gas * (area_mem/thickness_mem) * (sol._gas/ mol. weight_gas)
  - D_{L gas} = diffusing capacity of the lung to the gas
  - D_gas = diffusion constant for the gas
Factors Favoring High Gas Conductance (D_{L gas})
- gaseous phase (1/ mol. weight_gas)
  - low molecular weight of gas
  - short diffusion path in gaseous phase
- respiratory membrane phase (area_mem/thickness_mem)
  - thin membrane (t = 0.2-1.0 µm)
  - large gas exchange area (A = 70 m² = 750 feet²)
  - high lipid solubility of gas
- aqueous phase (sol._gas)
  - high fluid solubility
  - fast reaction rate with hemoglobin
  - small pulmonary capillary diameter (8 µm)
  - large red blood cell diameter (5-8 µm)

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Alveolar Gas Partial Pressure

1. Dalton's Law of Partial Pressures

P_total = P₁ + P₂ + P₃ for a three-gas mixture
P₃/P_total = %P₃ present in total gas mixture
P_total = P_atm for dry air (e.g. atmosphere)
P_total = P_atm - P_H2O for 100% humidified air (e.g. trachea)
P_H2O = 47 mm Hg at 37°C
atmospheric %O₂= 20.9%

atmospheric %CO₂ = 0.03%

Physiologic Region	PO₂ (mm Hg)	PCO₂ (mm Hg)
inspired air	159	0.23
trachea	149	0.21
alveolus	100	40
pulmonary vein	95	40
pulmonary artery	40	46

important notes

pulmonary artery (high pressure) contains deoxygenated blood (from systemic veins)
pulmonary vein (low pressure) contains oxygenated blood (to systemic arteries)
P_AO₂ can be computed from the alveolar gas equation

2. Variations in Alveolar Ventilation

_A = f * (V_T - V_D) = (10/min) * (0.65 L - 0.15 L) = 5.0 L/min
mean P_AO₂ _Aand mean P_ACO₂ 1/ _A
_Aabove metabolic demand results in hyperventilation with P_AO₂ and P_ACO₂
_A below metabolic demand results in hypoventilation with P_AO₂ and P_ACO₂
such changes in ventilatory P_ACO₂ are important for maintaining acid/base balance

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Alveolar-Arterial Gradient

Red Blood Cell Transit Time
- T_transit = pulmonary capillary volume / cardiac output
- T_transit = (75 mL) * (60 sec/min) / (6000 mL/min) = 0.75 sec
- normally, gas equilibrations across the alveolocapillary membrane are complete in 0.25 sec
- the safety factor for gas equilibration is 0.5 sec or 2/3 of the cap length
- abnormal gas equilibrations
  - T_trans (< 0.25 sec) due to pulmonary capillary volume or cardiac output
  - respiratory membrane conductance (DL_gas)
Anatomical and Physiological Shunts
- systemic arterial gas tensions are not exactly matched to mean alveolar gas values
- P_aO₂< P_AO₂ by 5 mm Hg and P_ACO₂ > P_ACO₂ by 0.5 mm Hg (A-a gradient)
- A-a gradient is attributed shunt flow bypassing the gas exchange zone
  - anatomical shunts: post-pulmonary shunts, bronchial circulation, ventricular septal defects
  - physiological shunts: ventilation/perfusion inequalities
- clinically, PaO₂ > 85 mm Hg are considered normal

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Arterial Hypoxemia

Hypoventilation
- problem: V A PaO2 and CaO2 with no change in A-a gradient
  - nervous system defects (CNS, NM junction)
  - toxic drug effects (barbiturates, morphine)
- solution: V A with possible O2 supplementation
  - mechanical ventilation
  - respiratory stimulants
Diffusion Impairment
- problem: DLO2 PaO2 and CaO2 with A-a gradient
  - interstitial fibrosis ( thickness of alveolar capillary membrane)
  - interstitial pneumonia ( thickness of alveolar cap membrane)
  - pulmonary edema with alveolar flooding ( area gas exchange)
- solution: PAO2, but beware of oxygen toxicity
  - cute 100% O2 (< 2 days) induces pulmonary capillary permeability and alveolar edema
  - chronic 100% O2 (> 2 days) induces interstitial fibrosis & Clung
Anatomical Shunt
- problem: venous admixture PaO2 & CaO2 with A-a gradient
  - normal shunts: venous drainage from thebesian & bronchial circ
  - abnormal shunts: atrial or septal defects, patent ductus arteriosus
- solution: surgical repair of arterial-venous anastomosis
  - oxygen administration will not help (diagnostic test for shunt)
  - PaCO2 may not be raised above normal (40 mm Hg)
Ventilation/Perfusion Inequality
- problem: V A/Q PaO2 and CaO2
  - chronic obstructive pulmonary disease (COPD) (emphysema, bronchitis)
  - pulmonary embolism
- solution: PAO2 but be aware of induced physiologic shunt blood flow
  - very low V A/Q ratio alveolar units may become atelectic
  - PaO2 is still improved with oxygen supplementation

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