Gas diffusion and transport

Question 1

What is the drive for the diffusion of gases across the alveolar-capillary membrane?

Answer 1

1) Partial pressure gradient

2) Pulmonary capillary blood flow

3) The diffusion properties of the alveolar-capillary membrane

Question 2

How to calculate the partial pressure of oxygen?

Answer 2

• Dalton’s law:

Po2 (about 21%) = Pb (barometric pressure) * Fo2 (Fractional concentration of O2)

• Pb is the sum of partial pressures of all gases in a mixture

Question 3

Describe the changes in oxygen tension “PO2” with altitude

Answer 3

As we move to higher altitudes, the atmospheric pressure decreases, while the oxygen concentration stays the same, however, the partial pressure of oxygen (Dalton’s law: PO2 = PB x FO2) decreases.

Question 4

What happens to the diffusion when we increase our lung volume (inspire)?

Answer 4

Inspiration will increase the lung volume, increasing the area for diffusion and decreasing the thickness of the alveolar-capillary membrane which will ultimately lead to more diffusion

Question 5

What is the partial pressure of O2 and CO2 in the lung and the systemic circulation?

Answer 5

Oxygen partial pressure in the air is 160 mmHg, while in the alveoli it is 100 mmHg, and in the vein, it is 40 mmHg

• Diffusion gradient across the alveolar-capillary membrane is 60 mmHg

On the other hand, CO2 is 0 mmHg in the air, 40 mmHg in the alveoli, and 46 mmHg in the veins

• The diffusion gradient is 6 mmHg

Question 6

What is meant by the transit time?

Answer 6

It is the time required for RBC to move through the capillary (0.75 sec)

Question 7

What are the two factors that limit diffusion?

Answer 7

1) Perfusion-limited

2) Diffusion-limited

Question 8

What is meant by perfusion-limited?

Answer 8

• Once equilibrium is reached there is no partial pressure difference between the alveoli and the blood
• Limitation to diffusion due to the blood flow, so for example N2O reaches the equilibrium faster than 0.75 seconds (it reaches it by 0.15 seconds) which means that the limit to their perfusion is the pulmonary blood flow (perfusion)

Question 9

What is meant by diffusion-limited?

Answer 9

• Once equilibrium is reached there is no partial pressure difference between the alveoli and the blood
• How much the lung can let the substance pass (limited by the permeability of the alveoli)
• For example, CO diffuses readily across the alveolar-capillary membrane, and binds to Hb quickly thus equilibrium is almost never reached as only free gases cause a partial pressure and thus it is diffusion-limited

Question 10

Describe the oxygen diffusion at sea level and high altitude in a normal person

Answer 10

At sea level:

• In the lungs of a normal person oxygen perfusion at rest is perfusion-limited PA02 is constant at 100 mmHg, and PAO2 will reach equilibrium at 1/3 of the time taken for the blood to perfuse

At high altitudes:

• At high altitudes, the barometric pressure is reduced with the same O2 fraction in the inspired air the partial pressure of oxygen in the alveoli will also be reduced, this reduction in oxygen partial pressure means that the diffusion of O2 will be reduced, and more slowly taking 2/3 of the time instead of 1/3

Question 11

Describe the oxygen diffusion in a person with a fibrosed lung

Answer 11

In fibrosed lungs and during strenuous exercise oxygen diffusion becomes diffusion-limited as

• For example in fibrosis, the alveolar wall thickens increasing the diffusion distance for gases, slowing the rate of O2 diffusion preventing the equilibration between the oxygen in the alveoli and the pulmonary capillary
• In such cases, equilibrium is not met between the alveoli and capillary and thus decreased oxygen pressure in the systemic circulation

Question 12

What happens to the capacity of diffusion during exercise?

Answer 12

• During exercise, Vt (tidal volume), increases dramatically, increasing the alveolar surface area and decreasing the alveolar-capillary membrane
• Increased pulmonary blood flow due to recruiting closed ones and dilating the ones already open
• Both the alveoli and blood side of the alveolar surface area are increased (aiding diffusion)
• During exercise the uptake of O2 is determined by the amount of blood flow (perfusion limited)
• During rest and exercise CO has the highest diffusing capacity, and O2 and CO have the same capacity

Question 13

What is Fick’s law of gas diffusion?

Answer 13

Vgas (volume of gas diffusing per minute) = As (membrane surface area) * D (diffusion coefficient of the gas) * partial pressure difference / T (membrane thickness)

• Volume of gas diffusing is directly proportional to the membrane surface area, partial pressure difference, and diffusion coefficient
• And the volume of gas diffusing is indirectly proportional to the thickness of the membrane

Question 14

What is meant by the diffusion coefficient?

Answer 14

How soluble the thing is the greater its solubility the greater the coefficient, on the other hand, the higher its molecular weight the lower its solubility

Question 15

If the alveolar surface area is decreased by 50% and the pulmonary thickness is doubled what is the diffusion rate compared to normal?

Answer 15

75% decreased

Question 16

What is meant by lung diffusion capacity?

Answer 16

• It is a measure of how easy a gas can diffuse across the entire lung
• Lung diffusion capacity is a combination of diffusion coefficient, surface area of the membrane and the thickness of the membrane

Dl (lung diffusion capacity “ml/min/mmHg”) = Vgas / (P1-P2)

Question 17

What are the different clinical applications of lung diffusing capacity?

Answer 17

1) In emphysema Dl decreases (due to decreased SA as the alveoli are destructed)

2) In fibrosis or pulmonary edema the Dl decreases (due to the increased membrane thickness)

3) During exercise the Dl increases as additional capillaries are perfused, which increases the SA for gas exchange

4) Decreased blood Hb decreases the Dl

5) Capillary blood volume, the lower the lower the Dl

Question 18

If we want to measure the diffusion capacity of a subject which air molecules would be the most suitable one to use?

Answer 18

CO

• Because it is limited by the diffusion capacity and thus we can determine the DL with a single breath from a container that has CO

Question 19

What are the two forms by which oxygen is carried in the body?

Answer 19

1) Dissolved (2% of the total O2 content)

2) Bound to Hb (98% of total O2 content)

• Dissolved O2 is the only form of O2 that produces a partial pressure

Question 20

What is Henry’s law?

Answer 20

It measures the concentration of dissolved gas (ml gas/100 ml blood)

• Cx (concentration of a dissolved gas) = Px (partial pressure of a gas) * Solubility (solubility of a gas in blood)
• O2 has a Cx of 0.3ml/100 ml blood
• Partial pressure of oxygen is a force that is created by the dissolved O2 which acts to keep O2 bounded to Hb

Question 21

What are the factors that oxygen depends on to remain bounded to Hb?

Answer 21

1) Affinity of Hb binding to O2

2) PO2

Question 22

What is meant by the positive cooperativity of oxygen to Hb?

Answer 22

Whenever an O2 binds to one of the four Hb molecules in a RBC it makes it easier for the one after it to bind

Question 23

How to calculate the saturation of Hb with O2 (SO2)?

Answer 23

• Oxygen carrying capacity: maximum amount of O2 that can be carried (20.1 ml O2/100 ml blood “this is the standard”)
• HbO2 content: this is the actual amount of O2 bound to Hb
• SO2 = (HbO2 content / HbO2 capacity) * 100

Question 24

How to calculate the O2 content?

Answer 24

• O2 content is the actual amount of O2 per volume of blood
• O2 content (ml O2/100 ml blood) = oxygen bound to Hb (oxygen binding capacity “this is the maximum capacity of O2 binding which is usually 15g/100 ml” * Saturation “the actual percent of O2 bound to Hb”) + Dissolved oxygen (usually 0.3)

Question 25

What is the relationship between Hb saturation and the PO2?

Answer 25

• PO2 determines the percentage if saturated Hb
• Due to the positive cooperativity as the PO2 increases the Hb saturation will increase till around a PO2 of 60 where after that 80% of Hb is saturated and a plateau phase is reached
• P50 where 50% of Hb is saturated is when the PO2 reaches 25 mmHg
• In the lungs, High PO2 which means Hb will load with oxygen, while in the peripheral tissue where the PO2 is low, there is oxygen Unloading, In the tissues, PVO2 is approximately 40 mm Hg, much lower than it is in the lungs. At a PO2 of 40 mm Hg, hemoglobin is only 75% saturated and the affinity for O2 is decreased. O2 is not as tightly bound in this part of the curve, which facilitates the unloading of O2 in the tissues.
• It produces a sigmoidal graph

Question 26

What is meant by the Bohr effect?

Answer 26

It is the effect of PCO2 and pH on Hb saturation

Question 27

What are the factors that increase the affinity of Hb to oxygen (decreases the P50)?

Answer 27

• Basically, all of the factors correlate to decreased body metabolism:

1) Decreased Pco2

2) Decreased temperature = Decreased metabolism = decreased O2 demand (when you exercise your temp increases)

3) Decreased levels of 2,3-DPG (a by product of glycolysis, where 2,3BPG binds the b-chains of deoxyhemoglobin and reduces its affinity towards oxygen, increase during exercise and hypoxia)

4) Increased pH

5) Hb-F

• Opposite will decrease the affinity including exercise (except for Hb-F “ما خصه”)

Question 28

What is the effect of carbon monoxide on the oxygen dissociation from the Hb?

Answer 28

• Reduces the sites available for O2 carrying, as it binds to Hb with a greater affinity to Hb than O2 and it shifts the graph to the left which makes it a nasty gas, decreasing the unloading of O2 in the peripheral tissues
• In CO poisoning - not only is there reduced O2-binding capacity of hemoglobin, but the remaining heme sites bind O2 more tightly. (يعني مافي مكان للأوكسوجين ولو في الكرياتالحمرة بدهاش تتخلص منهم)

Question 29

What is the effect of anemia on oxygen dissociation from the Hb?

Answer 29

In anemia, there is a reduced amount of RBC, thus less Hb and less O2 shifting the graph to the right as O2 must be unloaded due to the decreased amount of O2

Question 30

What is the effect of CO poisoning and how to treat it?

Answer 30

It induces brain tissue damage causing blurred vision and unconsciousness, to treat it you must use 95% O2 and 5% CO2

Question 31

What are the different forms by which CO2 is transferred in the body?

Answer 31

1) Dissolved CO2 (5%)

2) Carbamino compound (3%)

3) Bicarbonate (>90%)

Question 32

What controls the partial pressure of PaCO2?

Answer 32

• The Va and the metabolic production of CO2 control it
• PACO2 = CO2 production / Va

Question 33

How to calculate the dissolved CO2 using Henry’s law?

Answer 33

Paco2 = 40 mmHg

• Dissolved CO2 = solubility (0.06 * 40 = 2.4 ml/100 ml blood)

Pvco2 = 45 mmHg

• Dissolved CO2 = 0.06 * 45 = 2.7 ml/100 ml blood

Question 34

What are the steps of CO2 transport?

Answer 34

1) CO2 produced by the tissues

2) Carbonic anhydrase (on the RBC) catalyzes the hydration of CO2 to form H2CO3

3) RBC will dissociate H2CO3 into H+ and HC03-

4) HC03- will be exchanged with Cl- in the plasma

5) In the lungs HCO3- will be exchanged with Cl- through a band-3 protein where the reverse reaction will occur to form CO2 and for it to diffuse out of the alveoli

Question 35

What is meant by the Halande effect?

Answer 35

Higher partial pressure of oxygen will shift CO2 equilibrium to the right and downwards allowing the blood to load more CO2 in the tissue and unload more CO2 in the lungs

• Basically high Po2 more unloading of CO2 less PO2 more loading of CO2