Gas Transport Flashcards

1
Q

What is a hemoglobin structure?

A

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

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2
Q

What is the tense shape of hemoglobin?

A

Hemoglobin enters rel@Ced state which has a high affinity for O2

Hb is in ‘tense’ state and has a low affinity for O2

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3
Q

Why is the sigmoidal curve of hemoglobin important?

A

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
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4
Q

What is P50?

A

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

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5
Q

What can cause a rightward shift in the saturation curve?

A

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

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6
Q

What is the Bohr effects?

A

The effect of pH & PCO2 on Hb’s affinity to bind O2 is Bohr effect

Increased PCO2= low affinity and oxygen offloading
Decreased pH

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7
Q

What is 2,3-DPG?

A

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

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8
Q

How does anemia affect oxygen dissociation curve?

A

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

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9
Q

Does polycythemia improve tissue oxygenation?

A
  • 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
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10
Q

Why is carbon monoxide dangerous?

A
  • 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
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11
Q

What are the 2 types of gas movement in the lungs?

A

Bulk flow

Diffusionn

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12
Q

What is bulk flow?

A
  • 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
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13
Q

What does diffusion in the lung depend on?

A

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
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14
Q

Diffusion is governed by…

A

Fick’s law

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15
Q

Explain ficks law

A

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

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16
Q

Calculate the respiratory exchange ratio

A

Rate of O2 diffusion= 250 ml/min
Rate of CO2 diffusion= 200 ml/min

R= VCO2/vo2= 0.8

R- respiratory exchange ratio

17
Q

What substances make up the diffusion barrier for oxygen in order?

A
  1. Alveolar fluid
  2. Type 1 cell
  3. Interstitium
  4. Endothelial cell
  5. Plasma
  6. RBC
18
Q

How long does it take to get oxygen from alveoli to blood?

A

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

19
Q

How does blood flow affect uptake of gases?

A

Transit time never drops below 0.25s therefore blood PO2 is usually not affected (healthy Individuals )

20
Q

What is the impact of N2O?

A

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

21
Q

What is the impact of CO?

A

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

22
Q

Explain as a perfusion limited gas

A

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

23
Q

What happens of we increase barrier thickness and reduce rate of diffusion?

A

Diffusion limited

Pulmonary edema
Pulmonary fibrosis

24
Q

Explain carbon dioxide diffusion

A

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
25
Q

What are the differences in perfusion and diffusion limited gases?

A

Perfusion limited- there is equilibrate of gas between alveolar & pulmonary capillary

Diffusion limited- there is no equilobration of gas between alveolar & pulmonary capilkary

26
Q

How is diffusion capacity is used to evaluate?

A

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
27
Q

How do we measure DLCO?

A

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

28
Q

Explain the single breath method for assessing DL

A

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)

29
Q

What are the forms of CO2 in blood?

A

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
30
Q

Describe the creation of carbonic acid

A

Come back for image

31
Q

Summarize CO2 in blood

A

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

32
Q

What is the fate of CO2 in tissues?

A
  • 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
33
Q

Explain the fate of CO2

A

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

34
Q

How is incremental CO2 carried?

A

This 4mls is carried mostly in HCO3 form

35
Q

Describe the CO2 equilibrium curve

A

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
36
Q

Contrast the haldane effect and Bohr effect

A

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

37
Q

Compare O2 and CO2 dissociation curves

A
  1. CO2 content much higher than O2 content. 1 liter of blood can hold much more CO2 than O2
  2. For CO2- small change in PCO2 can load and unload > amount of CO2 as the gradient of the curve is steeper & linear