Canonical Question
Perfusion / Diffusion limiting
Master answer
Fick’s law of diffusion
- Describes Diffusion through tissues
- Rate of movement of solute across semi-permiable membrane J is
\[J\;={{D\;A\;\Delta C}\over{T}} \]
where
\[D=Diffusion\;constant\;\propto\;{{Solubility}\over{\sqrt{Molecular\;Weight}}}\]
C = concentration (or partial pressure for gasses)
A = cross-sectional area
T = thickness of the membrane or distance over which diffusion takes place.
The rate of diffusion of a gas through a tissue is:
Directly ∝:
- Surface area of the barrier
Affected by:- Parenchyma volume: Changes with Body size and in disease states
- V/Q mismatch: reduced in shunt and dead space
- Pulmonary Blood Volume: changed with vascular distension and recruitment
- Cardiac output: increased recruitment in high output states, decreased recruitment and increased V/Q mismatch in shock states
- Posture: Increased surface area while supine (compared to sitting or standing)
- Solubility of the gas
- CO2 is ~20 times as soluble as O2 in blood
- Concentration gradient (partial pressure difference)
- Rate of blood flow through lungs
- Transit time of blood across capillary (not part of Fick’s Equation) – based on HR
- alters total gas exchange across alveolus
- Can potentially change perfusion limited gas exchange to diffusion limited
- Alveolar partial pressure affected by:
- Atmospheric pressure
- Ventilation: Alveolar hypoventilation → ↑ PACO2 , ↓ PAO2
- Partial pressure in blood affected by:
- Binding of gas to protein:
- Rate of oxygenation of reduced Hb:
- Shift of oxygen dissociation curve (pH, temperature, PCO2, 2,3-DPG)
- Haematocrit
- Abnormalities of haemoglobin
- Formation of carbamino compounds
- Anaesthetic agents to plasma contents, e.g Albumin, cholesterol
- Enzymatic Action
- carbonic anhydrase (conversion of HCO3 to CO2)
- Rate of blood flow through lungs
Inversely ∝:
- Membrane thickness
- Increased thickness impedes gas exchange – Pathological states like pulmonary edema and cardiac failure
- Square root of Molecular Weight
- smaller substances diffuse more quickly
Diffusion vs. perfusion limited
Transfer of gases can be diffusion or perfusion limited dependent on the rate limiting step
Diffusion Limited
- Occurs in gases which do not reach equilibration of Pa and PA
- The rate of gas diffusion across the alveolar membrane limits its transport away from the lung
- Rate limiting step = rate of diffusion
- E.g. CO
- CO binds so avidly to Hb (250x that of O2) → virtually no CO dissolved in plasma → PaCO rises only slightly
- Even when RBC traversed entire length of pulmonary capillary, there is still substantial partial pressure difference across alveolar-capillary barrier → equilibrium of PaCO and PACO never reached
Perfusion Limited
- Characterized by complete equilibration i.e. Pa = PA
- amount of gas transferred between alveolus and capillary = dependent on amount of blood passing through the capillary
- rate limiting step = rate of blood flow
- E.g. N2O
- N2O rapidly diffuses across alveolar-capillary barrier
- Insoluble; does not bind to Hb; only carried in plasma in dissolved form
- PaN2O = PAN2O (<0.07sec); well before RBC has traversed pulmonary capillary
- ↑ diffusion rate will not ↑ blood transport away from the lungs → limiting factor = rate of blood flow / perfusion
- e.g. CO2 (ventilation limited i.e. perfusion limited in reverse)
Is the transfer of O2 perfusion or diffusion limited?
- Can behave as both perfusion and diffusion limited
- O2 diffusion takes 0.25s; pulmonary capillary transit time is 0.75s
- Normal conditions
- Transfer of O2 across the alveolar capillary barrier is perfusion limited
- Equilibrium is reached between alveolar and capillary PO2 before the RBC has traversed the pulmonary capillary
- Conditions where transfer of O2 may become diffusion limited
- Disease of the alveolar capillary barrier
- Pulmonary fibrosis: thickening of alveolar-capillary barrier → ↓ rate of diffusion
- Exercise: ↑ CO → ↓ RBC transit time
- Altitude: ↓ PaO2
- Disease of the alveolar capillary barrier
Diffusion of O2 and CO2
Oxygen
- Oxygen diffusion takes ~0.25s
- Pulmonary capillary transit time is 0.75s
- Therefore, under normal conditions oxygen is a perfusion limited gas
- However, oxygen may become diffusion limited in certain circumstances:
- Alveolar-capillary barrier disease
Decreases the rate of diffusion.- Decreased surface area
- Increased thickness
- High cardiac output
Decreases pulmonary transit time. - Altitude
Decreases PAO2
- Alveolar-capillary barrier disease
Carbon Dioxide
- Carbon dioxide is ventilation limited, rather than diffusion or perfusion limited
- This is because it is:
- 20x more soluble in blood than oxygen
- Rapidly produced from bicarbonate and carbamino compounds
- Present in far greater amounts than oxygen
1.8L.kg-1 exist in the body (though 1.6L-1 of this are in bone and other relatively inaccessible compartments).
- Impairment of diffusion capacity causes type 1 respiratory failure as oxygen is affected to a much greater extent than carbon dioxide
Kerr / JC 2020
Exam appearances
| Exam | Exact wording | Relationship | Success |
|---|---|---|---|
| 2016B Q22 | Outline the physiological factors that affect the diffusion of oxygen and carbon dioxide within the lung. | historical_member | — |
| 2021A Q15 | Explain perfusion limited and diffusion limited transfer of gases in the alveolus. | historical_member | — |
| 2023B Q06 | Explain perfusion limited and diffusion limited transfer of gases in the alveolus. | historical_member | — |