Gas Transport Flashcards
What is a hemoglobin structure?
Tetramer (made of 4 units)
- each monomer contains a heme group (porphyrin ring with Fe held in the center) & a polypeptide (globin) which is either a or B in form
- Adult hemoglobin (HbA) consists of 2a & 2B units
- Fetal hemoglobin (HbF) - 2a & 2Y units
In sickle cell HbS- 2a &2 abnormal B units
Hb is in ferrous state, If oxidized to ferric state cannot bind O2 -is mown as methoglobin
What is the tense shape of hemoglobin?
Hemoglobin enters rel@Ced state which has a high affinity for O2
Hb is in ‘tense’ state and has a low affinity for O2
Why is the sigmoidal curve of hemoglobin important?
The shape of the curve reflects several physiological advantages
- Plateau portion of the curve is also known the loading phase in which O2 content & O2 saturation remain fairly constant over a wide range of partial pressures- occurs in lungs
- Steep portion of the curve known as unloading phase allows release of O2 at tissue level where there is low PO2
What is P50?
From the curves -can see that it is the steep art most affected by a change in P50
Therefore, since alveolar PO2 is in 80-100 mmHg range- only minor 9xygem loading problems occur if the P50 changes
However, a rightward short, increased P50 decreases Hb affinity for oxygen making it easier to unload oxygen
A leftward shift, decreased P50 and increases Hb’s affinity for O2 making it more difficult to unload oxygen- but easier to load oxygen
What can cause a rightward shift in the saturation curve?
A working muscle heats up, produces CO2 and becomes acidic
Increased temperature, decreased pH, increased CO2, increased 2,3-DPG, results in right shift and increased P50
Lower the affinity for O2 easy oxygen unloading
What is the Bohr effects?
The effect of pH & PCO2 on Hb’s affinity to bind O2 is Bohr effect
Increased PCO2= low affinity and oxygen offloading
Decreased pH
What is 2,3-DPG?
Is end product of RBC metabolism is present in increased quantities in RBC’s
Chronic hypoxia- e.g., COPD, high altitude, chronic lung disease
Stored blood may be depleted of 2,3-DPG, so it may be difficult to off load O2
How does anemia affect oxygen dissociation curve?
Anemic patient has decreased Hb and therefore, can carry less O2(100% saturation is at a lower plateau)
Saturation will not fall- all the available O2 binding sites are full (SaO2 normal)
PaO2 remains normal- PaO2 depends on PAO2 and diffusion not Hb
It is just that there are fewer binding sites in total-therefore the O2 content falls - but the saturation is not affected
Does polycythemia improve tissue oxygenation?
- Increased in the concentration of RBCs
- Therefore, more Hb per 100 ml blood
- Increased oxygen carrying capacity of blood
- No change in the affinity- just more binding sites for O2
It increases blood viscosity-fatigue, poor exercise tolerance
Patients do better when bled
O2 content is so low causing tissue anoxia to a lethal level
-1st organ to be affected is brain
- Symptoms include
- slow reaction time
- blurred vision
- coma
Why is carbon monoxide dangerous?
- Has 210x the affinity of O2 to Hb
- is colour less & odorless so undetectable
- PaO2 is normal but O2content low
- No physical signs to indicate O2 content is low, when CO binds Hb- blood is cherry red & not cyanotic
O2 content is so low causing tissue anoxia to a lethal level
1st organ to be affected is brain
Symptoms include
- slow reaction time
- blurred vision
- coma
Rx-remove person from the source
- administer 100% O2
- O2 mixed with 5% CO2 increases alveolar ventilation
What are the 2 types of gas movement in the lungs?
Bulk flow
Diffusionn
What is bulk flow?
- all gas molecules move as one unit
- that’s how gas moves from trachea to alveoli
- Driving pressure is the pressure gradient between Patm (at the mouth)-PA
What does diffusion in the lung depend on?
That’s how gas moves from alveoli to blood or from blood to tissues
Depends on:
- pressure gradient
- thickness of the membrane
- surface area
- diffusion coefficient
Diffusion is governed by…
Fick’s law
Explain ficks law
Rate of diffusion is inversely related to the thickness of the membrane
- If you double the thickness the rate of diffusion would be halved
- It is directly proportional to surface area
- If you double the surface area the rate of diffusion will double
Diffusion coefficient(D)= solubility/ sqrt(Mol wt)
More soluble the gas& the < the molecular weight > the d8ffusiom
Calculate the respiratory exchange ratio
Rate of O2 diffusion= 250 ml/min
Rate of CO2 diffusion= 200 ml/min
R= VCO2/vo2= 0.8
R- respiratory exchange ratio
What substances make up the diffusion barrier for oxygen in order?
- Alveolar fluid
- Type 1 cell
- Interstitium
- Endothelial cell
- Plasma
- RBC
How long does it take to get oxygen from alveoli to blood?
Time required for RBC to move in the alveolar capillary is 0.75 secs at rest
This is time the blood or RBC. has to equilibrate with alveolar gas tension
Is known as transit time can vary with CO- during exercise transit time is decreased due rapid blood flow
Amount of O2 uptake is limited by pulmonary capillary blood flow
How does blood flow affect uptake of gases?
Transit time never drops below 0.25s therefore blood PO2 is usually not affected (healthy Individuals )
What is the impact of N2O?
Is a dental anaesthetic
-doesn’t bind to Hb
-it equilibrates in 1/10th seconds
Once it equilibrates it’s partial pressure gradient is zero, that means no more gas can diffuse unless there is new blood flow
This is perfusion limited
What is the impact of CO?
CO binds avidly to Hb > O2
-Rate of diffusion through the capillary barrier is slower
- It takes > 0.75 secs for Hb to be fully saturated
- So, there is constant partial pressure gradient between PACO & PaCO (pulmonary capilllaries)
This is a diffusion limited gas
Explain as a perfusion limited gas
O2 diffuses rapidly across the barrier has affinity for Hb but < CO
the rate of this reaction is slower than CO, however it’s diffusion across the barrier allows it to equilibrate quickly in 0.25 secs
It has 0.5 secs reserve time
Oxygen is therefore perfusion limited, normally
What happens of we increase barrier thickness and reduce rate of diffusion?
Diffusion limited
Pulmonary edema
Pulmonary fibrosis
Explain carbon dioxide diffusion
CO2 is perfusion limited
- Takes 0.25s to equilibrate which same as O2, even though it is more soluble
- That is because 🔼P is only 5-6 mmHg
CO2 retention -Severe diffusion impairment
Mild to moderate diffusion impairment
- can still equilibrate
- due to 0.5 reserve time
What are the differences in perfusion and diffusion limited gases?
Perfusion limited- there is equilibrate of gas between alveolar & pulmonary capillary
Diffusion limited- there is no equilobration of gas between alveolar & pulmonary capilkary
How is diffusion capacity is used to evaluate?
Is used to assess the lung function
-To measure DL, you use a single breath test with carbon monoxide (CO)
- Carbon monoxide is chosen because it is
- PCO is diffusion limited only
- none in venous blood
- it avidity to binding Hb maintains PACO near zero
How do we measure DLCO?
By simplifying Fick’s law & using CO
Since DL is hard to measure , you can use rearrange equation the below for measuring DL
P2= PaCO(pulmonary capillaries) which is near 0 therefore
DL= VCO/ PACO
VCO= CO uptake in mm/min
PACO= alveolar partial pressure of CO
DL= combined term for diffusion characteristics
Explain the single breath method for assessing DL
Breath out to residual volume
Take maximal inspiration with 0.3% CO/10% He mix with gas
Hold breath for 10s
Breath out- at end of breath measure CO and He
Measure the difference between the concentration of He in inspired and expired air -this gives a dilution factor and can bu used to calculate lung volume (since no He is taken up by lung)
Measure the difference between the concentration of CO in inspired and expired air (corrected for the He dilution ) & this will give you the amount of CO taken up by the lung in 10s
Then the equation DL= VCO/PACO
Normal value is 20-30 ml CO min/mmHg
Decreased with pulmonary fibrosis, edema or loss of alveolar membrane (emphysema)
What are the forms of CO2 in blood?
Bicarbonate -60%
Dissolved CO2- 8-10%
CO2 is mostly carried in HCO3 form
Carbamino compounds-30%
Carbonic acid- minor
Carbonate (CO3^2-)
- only 1/1000th
- formed when HCO3 dissociates
Describe the creation of carbonic acid
Come back for image
Summarize CO2 in blood
CO2 actually has a larger solubility in water than O2
[PCO2] dissolved= PCO2 x s
At PCO2 of 45 mmHg there is 3.4 ml/100 ml (compare 0.3 ml/mm/100 ml
But fate of CO2 is more complex
What is the fate of CO2 in tissues?
- Increased PCO2 in tissues drives CO2 into blood
- Only small portion dissolves
- The bulk of it diffuses into RBCs
- In RBCs it is converted to HCO3^- - H+ by an enzyme carbonic anhydrase
Explain the fate of CO2
Majority of HCO3^- moves out of the cell
-Cl- moves in to maintain the electrical neutrality . Thus is known as chloride shift
H+ remains in the cell as the membranes impermeable & is buffered by the following reaction
H+ + HbO2 HHb + O2
CO2 reacts with free amine groups NH2
Either in plasma proteins or importantly in hemoglobin
Hb-NH2 + CO2 Hb-NHCOO-
Accounts for 20%-30% of the CO2 carried in the blood
How is incremental CO2 carried?
This 4mls is carried mostly in HCO3 form
Describe the CO2 equilibrium curve
CO2 curve is relatively linear- what it means as you increase the PCO2 content it can carry more CO2
- This curve is also showing the Haldane effect (effect or O2 on CO2 equilibrium curve
- In arterial blood there is less CO2 content for the same given partial pressure than venous blood
Contrast the haldane effect and Bohr effect
The inverse relationship between CO2 & PO2 on CO2 dissociation curve is haldane effect
Haldane effect-more CO2 to load in tissues allows- unload more CO2 load in lungs
Bohr effect- Shift in curve in either direction 2 degrees to PCO2 changes is Bohr effect
Compare O2 and CO2 dissociation curves
- CO2 content much higher than O2 content. 1 liter of blood can hold much more CO2 than O2
- For CO2- small change in PCO2 can load and unload > amount of CO2 as the gradient of the curve is steeper & linear
