L9: Pulmonary Gas Diffusion

Question 1

Factors affecting gas diffusion through respiratory membrane

Answer 1

Fick’s Law of diffusion:
Vg (rate of gas transfer) = D x A x (P1-P2) / T

1. Diffusion constant (D)
   - molecular weight: O2 lower: slightly faster than CO2
   - solubility coefficient: CO2 much higher —> much faster than O2
   - overall effect: CO2&raquo_space; O2 (therefore patient with impairment in gas diffusion usually only have problems with O2 diffusion)
2. Surface area (A)
   - total area of alveolar space in contact with capillary (50-100 m2)
   - emphysema, embolism, obstructive disease —> ↓SA
   - exercise: increase active circulating capillaries, dilatation of capillaries, increase functioning alveoli SA —> ↑SA
3. Distance for diffusion (T)
   - thickness of alveolo-capillary membrane (0.2-0.5 micron)
   - interstitial and alveolar oedema, thickened wall of capillary and alveolar wall ↑T (Alveolar capillary block)
4. Transmembrane pressure gradient (P1-P2)
   - Alveolar ventilation (higher Va —> alveolar gas more like inspired gas rather than venous composition —> increase gradient)
   - Capillary blood flow (higher Q —> capillary gas composition similar to venous composition —> increase gradient)
   - Chemical reactions with Haemoglobin (concentration, reaction rate: quick reaction (binding of O2 and unloading of CO2) from haemoglobin —> allow more gas to diffuse into blood for further reaction)

Question 2

Pulmonary Diffusing Capacity (DL)

Answer 2

DL = Vg / P1-P2 (ml/min/mmHg)

• Volume of gas diffuses through alveoli-capillary membrane per minute for 1mmHg pressure difference —> measure of lung functional integrity for gas diffusion
• DLCO used (since CO has high affinity to haemoglobin, can neglect CO in capillary blood + neglect blood flow —> all bind to haemoglobin)
• DLCO = rate of CO transfer / mean alveolar CO tension
• DLCO (17-25) x 1.23 = DLO2 (21-31)

Question 3

Factors affecting DL

Answer 3

1. Body size (↑body size —> ↑SA —> ↑DL)
2. Age
3. Lung volume (↑lung volume 50% —> ↑DLCO 10-25%)
4. Body position (standing to sitting to supine —> ↑DLCO due to less uneven distribution of ventilation and perfusion)
5. Exercise (↑DLCO)
6. Pathological condition (emphysema, embolism, obstructive disease —> ↓SA —> ↓DLCO)

Question 4

Oxygen transport

Answer 4

1. Dissolved form (2-3%)
2. Chemical bound form / Haemoglobin-binding (97%)
   - Oxygen content: total oxygen amount in blood
   - Oxygen capacity: maximum amount of O2 bind to haemoglobin
   - Oxygen saturation: Ratio of amount of O2 bind to Hb / maximum amount of O2 that can be bound to Hb (oxygen capacity)

—> PaO2: 19.7%, PvO2: 14.4%
—> body consumption of O2: 5.3%

Question 5

Oxygen dissociation curve (SaO2 - PaO2 relationship)

Answer 5

Sigmoid relationship
Low range of PaO2 —> steep curve —> HbO2 increases steeply with PaO2
High range of PaO2 —> flat slope —> HbO2 increase less with PaO2 (little change)

Question 6

Factors affecting oxygen dissociation curve

Answer 6

1. PCO2 (Bohr’s effect)
2. pH
3. Temperature
4. 2,3-DPG
5. Fetus (fetal haemoglobin have greater affinity for O2: curve on left of adult curve —> favour uptake of O2 from maternal haemoglobin)

↑PCO2, ↓pH/↑[H+], ↑temp, ↑2,3-DPG
—> favour oxygen unloading by haemoglobin
—> curve shift right and downwards

↓PCO2, ↑pH/↓[H+], ↓temp, ↓2,3-DPG
—> favour oxygen uptake by haemoglobin
—> curve shift left and upwards

Question 7

Carbon dioxide transport

Answer 7

1. Dissolved form (10%)
2. Chemically bound form
   - Bicarbonate ions (70%)
   CO2 + H2O ⇌ H2CO3 ⇌ HCO3- + H+
   —> HCO3- catalysed by carbonic anhydrase in RBC, 65% transported in RBC, 5% HCO3- moved into plasma coupled with chloride shift into RBC
   —> H+: favours unloading of O2 from Hb

• Carbaminohaemoglobin (20%)
• Plasma protein bound CO2 (<1%)

Question 8

Carbon dioxide dissociation curve (CCo2 - PaCO2 relationship)

Answer 8

Linear dissociation curve

- Amount of CO2 in blood directly proportional to PaCO2

Question 9

Factors affecting CO2 dissociation curve

Answer 9

Haldane effect (curve shift left)
- ↓ SaO2 —> curve shift left and upwards —> favour CO2 uptake —> larger content of CO2 at a given PCO2

Question 10

Interaction of O2 and CO2 transport mechanism

Answer 10

1. Bohr’s effect on O2 loading
2. Haldane effect on CO2 loading
   —> facilitate efficient exchange of gases in lungs and tissues

Tissue:
Bohr’s: increased PCO2 —> favour unloading of O2
Haldane: decreased PO2 —> favour loading of CO2

Lungs:
Bohr’s: decreased PCO2 —> favour loading of O2
Haldane: increased PO2 —> favour unloading of CO2