Flashcards in L09 Pulmonary Gas Diffusion Deck (67):
What does continuous exchange of O2
and CO2 between blood and atmosphere involve?
Pulmonary ventilation + perfusion + alveolo-capillary gas transfer
State Fick's Law of Diffusion equation
V̇g = rate of gas transfer through a sheet
A= area for diffusion
D= diffusion constant, Molecular weight of molecule
P1-P2 = transmembrane pressure gradient
V̇g = DA(P1-P2)/T
What does DA/T ratio mean?
Pulmonary diffusion capacity
What three factors affect pressure gradient across membrane?
According to Fick's equation, what are the 4 factors that affect gas diffusion across a membrane?
Diffusion constant- D
Effective Surface Area -A
Diffusion Distance - T
Transmembrane pressure gradient (P1-P2)
What is the relationship between amount of gas transfer to molecular weight?
Vg ∝ 1/√MW
Amount of gas transfer (not rate because the V doesnt have a dot) is inversely proportional to the root of molecular weight
How do the Molecular weights of O2 and CO2 affect diffusion?
MW (O2) = 32
MW (CO2) = 44
O2 diffuses faster than CO2 due to lower MW
Which of the 4 factors does MW affect?
Diffusion constant- D
What else affects D?
Solubility coefficient (α) of gas
How does the solubility of CO2 compare to O2?
α(CO2) is 21 times higher than α(O2) at 38 degrees
so according to α only, CO2 diffuses much faster than O2
What is the overall combined effect of MW and α on D?
(MW + α): CO2 diffuses 20 times faster than O2
impairment in gas diffusion in patients would result in problem in the diffusion of which gas?
Since CO2 overall diffuses 20 times faster than O2
CO2 diffusion has no problems, but O2 diffusion has problems due to low α(O2)
In patient with impaired diffusion, what are the arterial pO2 and pCO2 values?
Very low Arterial pO2
What can happen to correct impaired diffusion physiologically? What happens to gases? Explain.
Ventilatory compensation, increase frequency of breathing
Improved but still low pO2 due to limitation of O2 loading to Hb
pCO2 would drop as increased alveolar ventilation means pCO2 decreases (inverse relationship)
The second factor affecting rate of diffusion is effective surface area. Define effective SA. and give typical SA in adult lungs
total area of alveolar space in contact with capillary blood. Requires ventilation and blood supply
What three factors cause decrease SA? (All patho-physiology)
Disruption of alveolar architecture (e.g. emphysema)
Decrease in functioning capillary bed (e.g. embolism: blood clot in vessel reaching
Partial block of airways (e.g. obstructive disease)
How can surface area be increase?
What physiological changes involved in increasing SA? (think how to increase perfusion and ventilation)
Increase in number of capillaries with active
circulation = more perfusion
Dilatation of capillaries already functioning = more perfusion
Increase in surface area of functioning alveoli (alveolo-capillary membrane) = more
Diffusion distance. Define and give normal alveolo-capillary membrane thickness.
= thickness of alveolo-capillary membrane
Name the four pathophysiological changes that can increase diffusion distance?
1. Intra-alveolar edema in septa (fluid accumulation)
2. Thickened alveolar wall (fibrosis)
3. Thickened capillary wall (fibrosis)
4. Interstitial edema within alveolar membrane
What is another way to increase T and decrease pulmonary gas diffusion?
Alveolar capillary block > longer pathway across alveolo-capillary membrane > decrease pulmonary gas diffusion
Alveolar ventilation and Blood flow are the main factors that affect transmembrane pressure gradient. For O2 and CO2 there are two proportionality to rate of gas diffusion. State.
for O2: V̇g ∝ PAg - PCg
for CO2: V̇g ∝ PCg - PAg
PCg is gas pressure in capillary
PAg is gas pressure in systemic arterial
(PVg is systemic venous blood)
Blood flow can alter PAg or PCg?
Increase pulmonary blood flow can cause what changes to transmembrane pressure grad.?
Increase blood flow > PCg becomes closer to PVg (systemic venous blood) due to less time for Hb loading > PcO2 drops and PcCO2 increases > increase pressure gradient for transfer
Low blood flow changes pressure grad. how?
Low flow > PCg becomes closer to PAg due to more time for Hb loading > PcO2 increase and PcCO2 drops > decrease pressure gradient for transfer
Another way to alter pressure grad. is change in ventilation. Which parameter does it change?
Ventilation changes PAg (unlike blood flow which changes PCg)
How does ventilation change PCg?
Increased Vent. > PAg exiting alveolar becomes closer to PIg (Atmospheric gas pressure) > Increased PAO2 and lower PACO2 > INCREASE GRADIENT
Decrease Vent. > PAg closer to PVg > Decrease PAO2 and increase PACO2 > DECREASE GRADIENT
What does Hb conc. change in transmembrane pressure grad?
like blood flow, change PCg
What does PCg depend on? Does it include gas bound to Hb?
Partial pressure of gas in medium depends on physically dissolved gas (O2 or CO2), NOT those combined with hemoglobin
But this partial pressure determines the amount of O2 and CO2 that can
combine with Hb (Bohr’s and Haldene effect)
How does Hb's characteristic change PCg? Explain for each gas.
Hb is a SOURCE of CO2 and a SINK for O2
HbCO2 > Hb + CO2
Give up CO2 into blood means increase PC(CO2)
Hb + O2 > HbO2
Take up O2 from blood means decrease PC(O2)
What is pulmonary diffusing capacity? Give formula
Dl ∝ A/T
Effective SA/ Diffusion thickness
Give word definition of Pulmonary diffusing capacity.
volume of gas that diffuses through alveolo-capillary membrane per minute when pressure difference = 1
mmHg (transfer factor)
What does pulmonary diffusing capacity measure?
measure of functional integrity of lung for gas diffusion / membrane for gas transfer
Dl = DA/T
Rearrange Fick's Law of diffusion give? Is D- diffusion constant- fixed (MW = solubility constant) for a partiucular gas?
Dl = V̇g/ (P1-P2)
Dlg = V̇g/ (PAg - PCg)
Yes fixed for particular gas
How is DlCO related to DlO2?
DlCO x 1.23 = DlO2
Formula and expected range of DlCO?
DlCO = rate of CO transfer / mean alveolar CO tension
Normal = 17- 25ml/min/mmHg
Expected range of DlO2?
since Dlg = V̇g/ (PAg - PCg)
Carbon monoxide is used to test for Dl and thus the functional integrity of lung for gas diffusion. Knowing CO bings irreversibly to Hb, what is the simplified formula?
PCg would be 0 because Co entering capillary would all immediately bind to O2
so formula is:
DlCO= V̇CO/ (PACO)
How is PAg or in this case PACO used clinically obtained? How much CO to give?
Alveolar gas measured: blow out air to RV. Last bit of breathe is alveolar gas.
Only administer a small amount of CO.
Why is CO used instead of O2 and CO2?
All rapidly diffuse across membrane
CO affinity for Hb is 240 times higher than O2
= negligible partial pressure / back pressure effect (= 0) in capillary blood
CO is also independent to blood flow compared to CO2 and O2 (see how Q changes transmembrane pressure gradient)
Dl depends on DA/T, where D is a constant. What 5 ways are there to change Dl via changing A?
(pathological conditions impacting above factors)
How does body size, sage and lung volume impact DlCO?
DlCO = SA x 18.84 - 6.8
Age: max DLO2 = 0.67 x height - 0.55 x age -40.9
so older means less SA
Lung vol: increase vol. by 50% increases DlCO by 10- 25%
Explain changes to DlCO due to posture.
gravity affects distribution of ventilation and perfusion (= blood flow))
Standing to sitting increase DlCo by 10-15%
Sitting to Supine increase DlCO by 15-20%
Exercise is the only way to increase SA. What levels of increase in DlCO are expected with moderate and intense exercise?
Moderate = increase by 25-35%
Severe= increase by 100%
State the distribution of O2 and CO2 in blood.
O2 dissolved in plasma= 2-3%
CO2 dissolved in plasma = 10%
Bicarbonate ions = 70%
Carbamino compounds = 20%
Oxygen dissociation is affected by which 4 factors>
CO2 dissociation is affected by what/
pO2- Haldene effect
What is CaO2, oxygen content?
Total amount of O2 present in blood
typical arterial O2 = 20 vol% (20mL of O2 in 100mL of blood)
What is Oxygen capacity?
Max. amount of O2 combined with Hb
1.34mlO2/ gram of Hb
What is O2 saturation?
% saturation of Hb with O2
Oxygen content (Hb)/ oxygen capacity (Hb)
SvO2 = 75%
O2 consumption in body is what vol%?
5.3 vol% = blood has to supply 5.3 vol% to tissues:
Arterial: 19.7 vol% (~100 mmHg) minus Venous: 14.4 vol% (~40 mmHg) = 5.3 vol%
pO2 60mmHg is a critical point in O2 dissociation. Why?
PO2 60 mmHg = intersection of flat and steep slopes on O2 dissociation curve due to positive cooperative binding.
pO2 higher than 60 mmHg indicates what? lower than 60mmHg indicates what?
At higher (PO2 >60 mm Hg):
- When PO2 changes = not much change in oxygen content (little change in amount of HbO2)= Does not affect metabolism considerably
At low range of (PO2 <60 mmHg):
-indicative of respiratory failure = When PO2 changes = considerable change in oxygen content (amount of HbO2 increases steeply
-Affects oxygen carriage: inadequate O2 may affect metabolism
How does fetal and adult Hb compare?
Fetal Hb can load O2 at much lower pO2
Fetal hemoglobin has greater affinity for O2
Compare fetal and adult O2 dissociation curve?
dissociation curve = left of adult curve (like myoglobin)
Saturate at pressure <100 mmHg
Give 4 factors that cause Bohr Shift.
increase Temp, pCO2, H+ ions conc., 2-3DPG from exercise
Explain Bohr shift and O2 unloading.
shift curve to right and down =favors unloading of O2 from Hb-O2
(E.g. oxygen saturation drops from 75% to 50% = favors unloading of O2)
Reverse changes - shift curve to left and up - favors uptake of O2 by Hb
CO2 transport. amount dissolved is 0.43vol%. Majority of CO2 is carried by what? How are these formed?
70% (mostly) = bicarbonate ions:
65% produced in RBC (fast), 5% produced in plasma (slow)
Give equation for CO2 becoming bicarbonate ions.
CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+
Enhanced by carbonic anhydrase in red blood cells
What other reaction is bicarbonate equation linked to?
Coupled with chloride shift: HCO3- ↔ Cl- (plasma)
Cl-migrates from plasma into red blood cells
HCO3- migrates from red blood cells into plasma
Maintain blood electrochemical grad.
How does CO2 > HCO3- + H+ lead to increased O2 unloading in Hb?
H+ + HbO2 >HHb (reduced) + O2(released)
More O2 unloaded
What are the two carbaminocompounds that account for 20% blood CO2?
CO2 combines to protein / NH2 group in:
20% = carbaminohemoglobin:
CO2 + Hb.NH2 ↔ Hb.NH.COOH > Hb.NH.COO- + H+
<1% = plasma proteins:
CO2 + ProtNH2 ↔ ProtNHCOO- + H+
How does blood CO2 relate to PaCo2? What does the CO2 dissociation compare to O2 diss.?
Amount of CO2 carried in blood proportional to PaCO2
CO2 dissociation = much more linear than O2 dissociation curve
within physiological range
State Haldene effect.
Haldane effect = effect of PO2 on CO2 dissociation curve:
For a given PaCO2, a drop in PO2 causes the curve to shift upward, favouring CO2 carriage
Interaction of O2 and CO2 transport mechanisms
What is this dependent on?
characteristics of hemoglobin
Facilitate efficient exchange of respiratory gases in tissues and lung
Explain how changes in tissue gases pressures change Hb loading / unloading characteristics.
Increase PCO2 > aids in unloading of O2 (Bohr’s effect)
Increase PO2 > aids in loading of CO2 (Haldene effect)