02-11-22 – Ventilation and Diffusion Flashcards
Learning outcomes
- Define the term “partial pressure” and know how to calculate a gas partial pressure
- Explain what factors determine how much gas dissolves in a liquid
- Explain what factors affect the diffusion of gases across the air-blood barrier, and the consequences of such factors on arterial blood gases
- State the normal partial pressures of nitrogen, oxygen, carbon dioxide and water vapour in atmospheric air and alveolar air (in mmHg and kPa)
- Describe the processes involved in an oxygen molecule moving from alveolar air to the blood
- Describe the processes involved in a carbon dioxide molecule moving from blood to the alveolar air
- State how different disease states can affect the diffusion of O2 and CO2 across the alveolar barrier
- Describe how altitude affects PO2
- Describe the effects of high pressure on blood gases
What is alveolar ventilation?
What is pulmonary ventilation?
What does pulmonary ventilation include?
How much of the air we breathe in is anatomical dead space?
Up to how many divisions of the respiratory system tree is anatomical dead space?
- Alveolar ventilation is the exchange of gas between the alveoli and the external environment
- Pulmonary ventilation is the process of air flowing into the lungs during inspiration (inhalation) and out of the lungs during expiration (exhalation) – about 500ml of air inhaled and expired on each breath
- Pulmonary ventilation includes the gas used in gas exchange, and the anatomic dead space air that fills up the respiratory system, but isn’t used in gas exchange
- 150ml of the 500ml of air we breathe in is anatomic dead space air
- Up to about 17 divisions/generations of the respiratory system tree can be anatomic dead space
What does the respiratory system tree consist of?
What are the conducting pathways of the respiratory system?
What do the respiratory divisions of the respiratory system extend between?
What is the structure of conducting airways like?
What is the structure of the respiratory bronchioles and alveolar ducts like?
Which airways are susceptible to collapse?
How many alveoli do humans have?
How much does this increase cross-sectional area?
- The respiratory system tree consists of continually dividing airways till we get to the alveoli
- The conducting pathways of the respiratory system extends between the nose and terminal bronchioles
- These pathways are filled with anatomic dead space
- The respiratory divisions of the respiratory visions extend between the respiratory bronchioles and alveolar sacs, as some gas transfer takes place on alveoli on the respiratory bronchioles and alveolar ducts, but most of it takes place in the alveoli in alveolar sacs
- The structure of conductive airways has cartilage with few smooth muscles, and collapse is very rare
- The structure of the respiratory bronchioles and alveolar ducts has no cartilage, lots of smooth muscle, and is susceptible to collapse
- Humans have ~ 300 million alveoli
- This increases cross sectional area from 2.5cm2 at trachea to around 100m2
At what number of airway generations/divisions does the velocity of airflow start to decline in the respiratory system?
Why does airflow velocity decrease?
At what number of airway generations/divisions does aggregate cross-sectional area start to rapidly increase?
Where will this area be around?
- At about 3 airway generations/divisions, the velocity of air flow in the respiratory system starts to decline
- Airflow velocity decreases to allow adequate time for diffusion once the air reaches the capillaries
- At about 12-14 airway generations/divisions, the aggregate cross-sectional area starts to rapidly increase
- The area will be around the respiratory bronchioles, as this area is where alveoli start to appear
What is one of the primary functions of the CVS?
Where is CO2 expired?
How are Oxygen and CO2 able to move by diffusion?
Where is Oxygen and CO2 partial pressure high and low?
How does partial pressure change affect diffusion of gas?
What is this principle the basis of?
- One of the primary functions of the cardiovascular systems is to transport O2 from the lungs to all tissues in the body and CO2 from the tissues to the lungs
- The lungs expire this CO2 to the atmosphere
- Oxygen and CO2 can diffuse (passive) as both gases move by diffusion down their partial pressure gradients (also down their concentration gradients)
- Oxygen partial pressure is high in the air, and low in the tissues
- CO2 partial pressure is high in the tissues and low in the air
- These both allow the gases to move down their partial pressure gradient
- If the partial pressure in the liquid becomes greater than in the air, the gas will diffuse out of the liquid, and vice versa, due to gases flowing down partial pressure gradients
- This is the basis for O2 moving into the blood from the lungs, whereas C02 moves out of the blood into the lungs
What are 2 reasons we use partial pressure instead of concentration?
- 2 reasons why we use partial pressure instead of concentration:
- Where there is exchange between a gas and a liquid, the partial pressure determines the chemical potential driving the diffusion from one phase to the other–not the concentration.
- So, one can more easily compare partial pressure values of a solute to determine the diffusion exchanges instead of concentration
- Also, since at a fixed temperature, the partial pressure is just proportional to the concentration of that gas, we can use a gas’s partial pressure as a stand-in for its concentration.
- Since most chemistry and biochemistry is done at a fixed total pressure, atmospheric pressure this works well.
What is total pressure of a mixture of gases?
What is the atmospheric pressure (barometric pressure) at sea level?
What are the partial pressures of the 4 gases that contribute to this?
What happens to these partial pressures when the atmospheric pressure changes?
What happens when the proportion of gas changes?
What are the partial pressures of oxygen in the lungs and tissues?
What is 1kPa equal to?
- Total pressure (PTotal) of a mixture of gases is the sum of their individual partial pressures (Px)
- Atmospheric Pressure (Barometric pressure - PB) at sea level is 760mmHg or 101.325 kPa, which is a sum of the partial pressure of the individual gases that make up the air
- 4 gases’ partial pressures that contribute to the atmospheric pressure:
1) Nitrogen (PN2): 78.09% x 760 mmHg = 593.48 mmHg
2) Oxygen (PO2): 20.95% x 760 mmHg = 159.22 mmHg
3) Carbon dioxide (PCO2): 0.030% x 760 mmHg = 0.23 mmHg
4) Argon (PAr): 0.930% x 760 mmHg = 7.07 mmHg
- If atmospheric pressure changes, then these partial pressure changes
- If proportion of gas changes its partial pressure changes
- The partial pressure of oxygen in lungs is 100mmHg / 13.3 kPa
- The partial pressure of oxygen in tissues is 40mmHg / 5.33 kPa
- 7.5mmHg = 1kPa
What does Henry’s law state?
What is the formula for concentration of O2 dissolved in water?
What is the solubility of oxygen in blood plasma at 37C?
What is the concentration of dissolved oxygen in arterial blood and mixed venous blood?
How does the difference in pKa then affect the concentration of gas in solution?
- Henry’s law states that the concentration of O2 dissolved in water ([O2]dis) is proportional to the Partial pressure (PO2) in the gas phase
- Formula for concentration of O2 dissolved in water:
- [O2]dis = s x PO2, where s = solubility of O2 in water
- For blood plasma s = 0.0013 mM/mmHg at 37C so:
- [O2]dis = 0.0013 x 100 mmHg = 0.13 mM of oxygen dissolved in arterial blood
- [O2]dis = 0.0013 x 40 mmHg = 0.05 mM of oxygen dissolved in mixed venous blood
- 10x more gas will go into solution if its partial pressure is 10kPa than if it were 1kPa based on these calculations
How soluble is CO2, O2, and N2 in blood at atmospheric pressure?
Why do we need haemoglobin?
- CO2 is the most soluble in blood plasma
- O2 is about 1/20th as soluble as CO2
- This means the blood can carry far more dissolved CO2 than O2
- This is why we need haemoglobin as a special oxygen carrier, otherwise we wouldn’t have enough oxygen in the blood
- N2 is barely soluble in blood at atmospheric pressure
What happens to alveolar air?
Why is this important?
How is this affected on a cold day?
How do we adjust our calculations for partial pressure of gases that make up atmospheric pressure?
What is the partial pressure of water vapour?
What is the adjusted partial pressure for the 4 gases when we breath them into the lungs?
How does this compare to the actual partial pressure of gases in the lungs?
Why are they different from calculated values?
- Alveolar air is warmed and humidified by adding water vapour to it
- This is important alveolar cells are sensitive to pressure/temperature
- When the air is cold, the humidity in the air is decreased, so the air becomes dry
- There is not enough time to warm this air, so it dries out the respiratory system
- Water vapour also has a partial pressure, so when we breath gases in and add water vapour, we have to subtract the partial pressure of water vapour from the partial pressure of these gases that make up atmospheric pressure
- The partial pressure of water vapour is 47mmHg
- Adjusted partial pressure for 4 gases when we breath them into the lungs:
1) Nitrogen (PN2): 78.09% x (760 – 47) mmHg = 556.78 mmHg
2) Oxygen (PO2): 20.95% x (760 – 47) mmHg = 149.37 mmHg
3) Carbon dioxide (PCO2): 0.030% x (760 – 47) mmHg = 0.21 mmHg
4) Argon (PAr): 0.930% x (760 – 47) mmHg = 6.63 mmHg
- O2 in lungs is actually lower (104 mmHg)
- CO2 is higher (40 mmHg)
- Water vapour is higher (as a consequence of this, N2 is lower)
- These pressures are different from the calculated values as alveolar air is made up of ‘fresh air’ plus the air that remains in the lungs after the last breath
What do gases have to do before diffusing across membranes?
What 3 things does O2 have to do in the body?
What is the partial pressure in the alveolus compared to the blood?
What is the formula for rate of diffusion/flow (in picture)?
- Before diffusing across membranes, a gas must first dissolve in fluid
- 3 things O2 has to do in the body:
1) Dissolve in an aqueous layer
2) Diffuse across the membranes
3) Enter the blood - The partial pressure of oxygen in the alveolus is higher than it is in the blood
- This leads to oxygen moving down its partial pressure gradient into the blood
What is the surface area of the lungs?
How many alveoli do we have?
How thick is the alveolar-capillary barrier?
What is the partial pressure gradient of oxygen at the areas of gas exchange?
Is molecular mass important?
Is solubility of the gas important?
- Surface area of lungs is large - 50 -100 m2
- Large number of alveoli (~500 million)
- The thickness of the alveolar-capillary barrier varies from 0.2 to 2.5 µm
- The partial pressure gradient of oxygen at the areas of gas exchange is large:
1) PO2 alveolar air is 100 mmHg
2) PO2 of venous blood is 40 mmHg, so diffusion rapid - Molecular mass is insignificant
- Solubility is very important, with CO2 diffusing 20 x more rapidly than O2, as it is 20x more soluble in blood plasma
How fast does blood pass through pulmonary capillaries at rest?
How long does O2 equilibrium take?
How fast does blood pass through pulmonary capillaries during exercise/respiratory distress?
- At rest, blood takes about 0.75 - 1 second for blood to pass through pulmonary capillaries (lower perfusion rate)
- O2 equilibrium only takes about 0.25 seconds, so at rest, oxygen saturation is not normally diffusion-limited
- During exercise/respiratory distress, blood flow time through the capillary can be reduced to as little as 0.3 seconds, so now oxygen saturation is diffusion-rate limited (perfusion rate too high)
- This can decrease how saturated each blood cell is with oxygen, leading to an incomplete O2 equilibrium.
What direction does CO2 move in?
What is the partial pressure gradient of CO2 at the areas of gas exchange?
How much faster does CO2 diffuse than oxygen?
How much oxygen and CO2 move in each direction?
- CO2 moves in the other direction from oxygen - from blood capillary into alveoli
- There is a smaller CO2 partial pressure gradient than oxygen at areas of gas exchange:
1) Alveolar PCO2 is 40 mmHg
2) venous PCO2 is 45 mmHg - CO2 solubility is 20x greater in blood plasma than oxygen, so it diffuses 20x more rapidly than O2
- The same amount of CO2 and oxygen move in each direction
In what 7 cases can the diffusion of gases across the alveolar-capillary barrier be affected?
How do they each affect this?
How do they each affect gas exchange?
- 7 cases diffusion of gases across the alveolar-capillary barrier can be affected
1) Oedema
* Thickness of barrier (T) increases
* Transit time through capillary may not be sufficient to complete full gas exchange
* Has exchange reduced
* More marked effect on O2 than CO2, due to greater solubility of CO2
2) Emphysema
* Breakdown of tissue and alveolar sacs
* Gas exchange reduced
3) Pulmonary fibrosis
* Thickness of barrier (T) increases due to deposition if fibrous tissue
* Gas exchange reduced
4) Mucus
* Gas exchange reduced
5) Inflammation of airways
* Gas exchange reduced
6) Tumours
* Gas exchange reduced
7) Reduced gas entry
* Gas exchange reduced
What happens to atmosphere pressure at high altitude?
What happens to PO2? Using Denver, Colorado as an example (1620m above sea level), how are the following factor affected:
* Atmospheric pressure (PB)
* Inspired PO2
* Alveolar PO2
* Alveolar PCO2?
At what inspired PO2 will we become hypoxic?
Where does this mark the highest human habitation level?
- At altitude, atmospheric pressure is reduced, hence, PO2 is reduced
- In Denver, Colorado, 1620m (5300 ft) above sea level the following values change:
1) PB is 632 mmHg (down from 760 mmHg)
2) Inspired PO2 – 125 mmHg (down from 149 mmHg)
3) Alveolar PO2 – 84 mmHg (down from 104 mmHg)
4) Alveolar PCO2 – 34 mmHg (down from 40 mmHg)
- Below 60mmHg inspired PO2, we start to become hypoxic
- This point will mark the highest human habitation level possible at about 6000m above sea level
What 3 acute physiological changes occur at altitude?
- 3 acute physiological changes that occur at altitude:
1) Hypoxia sensed by peripheral chemoreceptors in the carotid bodies and aortic bodies in the aortic arch
2) Ventilatory drive increases initially, but blunted by central chemoreceptors that respond to decreased PaCO2 due to increased ventilation
3) CO2 increases due to suppression of cardioinhibitory centre
What are 3 adaptive physiological changes that occur at altitude?
- 3 adaptive physiological changes that occur at altitude:
1) Central chemoreceptors adapt so ventilation rate continues to increase
2) PaCO2 drops leading to respiratory alkalosis
* Kidneys compensate by reducing acid excretion so blood pH normalises
3) Alkalosis stimulates 2,3 DPG production
* DPG is a product of glycolysis
* If we are going hypoxic, we increase the amount of glycolysis
* Only glycolysis, and not aerobic respiration, can occur in red blood cells
* DPG release leads to rightward shift of O2 dissociation curve, which causes the release of oxygen from haemoglobin to supply hypoxic tissues
What is the difference between acclimation and acclimatization?
What are 2 changes to do the blood from acclimation to attitude?
What is a change to the vasculature from acclimation to altitude?
What are 2 changes to the cardiopulmonary system from acclimation to altitude?
- Acclimation is the coordinated phenotypic response developed by the animal to a specific stressor in the environment
- Acclimatization refers to the coordinated response to several individual stressors simultaneously (e.g., temperature, humidity, and photoperiod).
- 2 changes to do the blood from acclimation to attitude:
1) Erythropoietin release Is stimulated to increase red blood cell production
2) Hb conc. increases to 200 g/L from 150 g/L - In the vasculature, hypoxia stimulates angiogenesis (formation of new blood vessels), leading to an increase in capillary density throughout the body
- 2 changes to the cardiopulmonary system from acclimation to altitude:
- Vascular and ventricular remodelling:
1) Smooth muscle growth increases vascular wall thickness
2) Right ventricle hypertrophies
How does depth affect atmospheric pressure?
How does depth affect partial pressure and volume of N2 and O2?
How does increase in atmospheric pressure affect gas exchange?
How soluble is N2 in blood at atmospheric pressure of sea level?
- Atmospheric pressure increases by 760 mmHg (1 atmosphere) every 10 m depth
- Depth leads to an increase in partial pressure and decreased volume of N2 and O2
- This increased atmospheric pressure can lead to N2 and O2 dissolving in the body at lethal excess
- An increase in atmospheric pressure also affects gas exchange by decreasing the ability of O2 and CO2 to cross the alveolar-capillary barrier
- At atmospheric pressure of sea level, N2 is barely soluble in the blood and sits in the lungs getting breathed in and out instead of entering circulation
In what 3 steps is N2 narcosis caused?
How can N2 narcosis be avoided?
- N2 narcosis steps:
1) At 40m of depth and below, the partial pressure of N2 rises, which leads to N2 dissolving into the blood and distributed into the circulation, preferentially partitioning in fat tissue
2) If we resurface too quickly, the high N2 partial pressure that forced N2 into the blood returns to normal, and the N2 comes out of the blood too quickly, which forms pure N2 bubbles
3) The presence of bubbles in the blood stream causes decompression sickness, or “the bends. – a painful process
- N2 narcosis can be avoided by resurfacing slowly, which allows N2 partial pressure to slowly equilibrate and N2 to move out of the blood slowly
What is oxygen toxicity/poisoning?
How is it normally caused?
How does it affect the lungs?
How soon can it appear?
How is O2 poisoning at depth caused?
- Oxygen toxicity/poisoning is organ system/tissue damage that occurs from breathing in too much extra (supplemental) oxygen
- Extended exposure to above-normal oxygen partial pressures, or shorter exposures to very high partial pressures, can cause oxidative damage to cell membranes, leading to the collapse of the alveoli in the lungs.
- Pulmonary effects can present as early as within 24 hours of breathing pure oxygen
- At higher atmospheric pressures due to depth, partial pressure of oxygen increases, which forces more oxygen to dissolve in the blood, causing hyperoxia
- This O2 dissolves in blood in excess of the buffering capacity of Hb, leading to blood alkalosis
How can N2 Narcosis and oxygen poisoning be avoided?
- N2 narcosis and oxygen poisoning can be avoided by replacing N2 with helium and tailoring the oxygen to reduce harm
- This mixture is known as Heliox (Helium and Oxygen)
- Helium (He) less readily dissolves in body tissues and is less narcotic
