4. Gas Transport and Exchange Flashcards
What do the following symbols stand for: • P • S • A • a
- P - partial pressure
- S - Hb saturation
- A - alveolar
- a - arterial
What does Dalton’s Law state?
Partial pressure of a [total] gas mixture is equal to the SUM of the partial pressure of [separate] gases in the mixture
What does Fick’s Law state?
Molecules diffuse from regions of high concentration to low concentration at a rate:
• proportional to the concentration gradient, exchange SA and diffusion capacity of the gas
• inversely proportional to the thickness of the gas exchange surface
What does Henry’s Law state?
• Constant temperature
• Amount of a given gas
- dissolves in a given type and volume of liquid
• Directly proportional to the partial pressure of that gas
- in equilibrium with that liquid
(bigger solubility coefficient - dissolves more easily)
What do Boyle’s and Charles’ Law both state?
Boyle’s Law
• Constant temperature
• Volume inversely proportional to pressure
Charles’ Law
• Constant pressure
• Volume directly proportional to temperature
What do you change if you are supplementing oxygen to someone with a diffusion problem?
Steepen the diffusion gradient
How do gases change at a greater altitude?
- Pressure decreases
- Smaller volume
- Proportions of gases remain the same
What is the PO2 of oxygen in dry air?
21.3 kPa
How does the PH2O change down the conducting airways?
Increases as dry air gets warmed, humidified, slowed and mixed with air already in the lungs
What is the PO2 at the respiratory airways?
- 13.5 kPa
* This is 100% saturation
Why can’t we rely on solely dissolved oxygen to keep us alive?
- 0.32mL/dL => 16mL/min
- Can only dissolve 17mL of oxygen
- Oxygen consumption (VO2) is around 250mL/min
Describe the structure of haemoglobin
- Monomer has Fe2+ (ferrous iron) at the centre of the tetrapyrrole porphyrin ring
- Connected to a protein chain (globin)
- Covalently bonded at the proximal histamine residue
- Tetramer with 2 alpha and 2 beta chains - HbA
- HbA2 - normal variant (2%) with 2 alpha and 2 delta chains
- Foetal (HbF) - trace levels, 2 alpha and 2 gamma chains
Describe the binding of oxygen to haemoglobin
- Haemoglobin has a low affinity for oxygen when not bound
- Oxygen binds - conformational changes (allosteric), greater affinity
- Each haem binds one molecule of oxygen
- Affinity for 4th oxygen is 300x that of the first oxygen
- Conformational change also occurs in the middle - becomes a binding site for 2,3-DPG (glycolytic by-product, reflective of metabolism)
- 2,3-DPG decreases the affinity of haemoglobin for oxygen
- Oxygen can be squeezed out where metabolism is high, so more is available for respiration in these places
What is cooperativity?
Describes how haemoglobin changes shape and affinity based on how much oxygen is bound
What is methaemoglobin?
- Fe2+ (ferrous iron) is oxidised to its ferric form (Fe3+) - becoming MetHb
- Doesn’t bind to oxygen
- Methaemoglobinaemia can cause functional anaemia (normal Hct but impaired O2 capacity)
What can oxidise Hb into MetHb, and what can be used to correct his?
- Nitrites - oxidise
* Methylene blue - correction
Why is the oxygen dissociation curve not linear?
- HbO2 saturation changes by a proportion that is not large enough in systemic circulation (lower PO2)
- Little scope for unloading
- HbO2 saturation changes by a large proportion in pulmonary circulation (high PO2)
- This causes a large variation in oxygenation in the lungs
Why is a sigmoid oxygen dissociation curve better?
- Can go from 76% to 8% saturation in tissues
- Very high unloading capacity
- Small change and very high HbO2 saturation in pulmonary circulation
- Effectively 100% saturation across a big range of alveolar PO2
What is P50?
Partial pressure of oxygen when haemoglobin is 50% saturated
What chemical changes in the respiratory system occur during exercise?
- Increase in temperature
- Acidosis (lactic acid and excess CO2)
- Hypercapnia (elevated CO2)
- Increase in 2,3-DPG
How does high energy consumption e.g. exercise, change the oxygen dissociation curve?
- Shifts right
- Greater unloading of oxygen
- Therefore lower HbO2 saturation at lower PO2 (systemic)
(hyperventilation decreases CO2 so causes a shift to the left)
How does anaemia change the oxygen dissociation curve?
- Downwards shift
- The HbO2 concentration remains ‘the same’ as y-axis just becomes smaller
- Comparing the oxygen carrying capacities
- Pulse oximetry can’t compare the Hct, only saturation of the total
How does polycythaemia (increased Hct) change the oxygen dissociation curve?
- Upwards shift
- More erythrocytes - higher oxygen capacity - larger y-axis
- Thicker blood - slower blood flow - oxygen delivery impeded
How does Carbon Monoxide poisoning change the oxygen dissociation curve?
- Downwards and leftwards shift
- Decreased oxygen capacity - smaller y-axis
- Increased affinity (for CO than O2)
- Reduces available haemoglobin or holds onto oxygen tighter
How is the oxygen dissociation curve different for foetal haemoglobin and myoglobin?
Foetal
• Sharper increase
• Greater affinity than adult HbA to extract oxygen
Myoglobin (monomeric protein)
• Hyperbolic curve
• Very sharp increase, reaching 100% saturation at a low PO2
• Present for when the muscle needs oxygen rapidly
How oxygenated is blood arriving in the pulmonary circulation?
- Mixed venous blood
- Not deoxygenated
- Around 75% oxygen bound
- Arrives at the exchange surface at around 5.3 kPa
Describe the oxygen gradient in the red blood cell
- Plasma > intraerythrocytic oxygen concentration
- Oxygen moves into the red blood cell
- Occupies the final binding spot in haemoglobin
What is the oxygen saturation of the blood when it reaches the tissues?
97%
Why is the blood diluted in the pulmonary system?
• Pulmonary system has 2 circulations:
- own blood supply (to stay alive)
- pulmonary blood supply for oxygenation
• Circulation of own blood supply drains into the pulmonary circulation before returning to the left atrium
How does the concentration and saturation of oxygen change at the tissues?
- 20.3 - 15.1 mL/dL
* 97 - 75%
What is oxygen flux?
- Overall amount of oxygen being deposited
- -5 mL/dL
- This equals a consumption of 250 mL of oxygen per minute in the body
What happens to CO2 when it enters circulation?
- CO2 is more soluble than oxygen - dissolves in plasma easily
- CO2 + H2O => H2CO3 (carbonic acid)
- H2CO3 => H+ + HCO3- (dissociates into proton and bicarbonate - slow as there are no enzymes)
- Same reaction occurs in red blood cells
- Rate of bicarbonate production is 5000 times greater - carbonic anhydrase catalyses formation of carbonic acid
- Chloride shift - as bicarbonate ions leave, chloride ions enter to maintain the resting membrane potential (AE1 transporter)
- Chloride entering draws water in with it, which is used to react with CO2
- Water needed to prevent dehydration too
(process also acts as a pH buffer)
How does CO2 interact with proteins in the blood
Binds to the amine end of haemoglobin => Carbaminohaemoglobin (HbCO2)
How do proteins control red blood cell pH
- Excess protons
* Negatively charged amino acids e.g. histidine are good proton acceptors
How does CO2 production compare to O2 consumption?
- +4mL/dL net increase in CO2 concentration
- 200mL of CO2 produced a minute
- Not equal to the 250mL oxygen consumption
- Some water produced is lost in metabolic water production
Describe the CO2 dissociation curve
- As PCO2 increases, blood CO2 content increases (more linear than oxygen)
- As blood loses oxygen, haemoglobin carries more CO2 - allosteric behaviour
What is the Haldane Effect?
Describes how the amount of CO2 that binds to the amine end of haemoglobin protein chain changes depending on how much oxygen is bound
What is the respiratory membrane?
Areas where the alveolar cells and endothelial cells of the capillaries are close enough for exchange to take place
What is the pulmonary transit time?
- Time during blood cells are in contact with the respiratory membrane
- Total - 0.75s
- Gas exchange complete - 0.25s
- CO2 reaches equilibrium - 0.1s
Why can exercise lead to hypoxaemia?
- Increased CO and pulmonary blood flow
- Blood not in contact with respiratory membrane for long enough
- Not enough time to reach 100% oxygen saturation
(CO2 crosses the membrane much more easily and faster)
How does ventilation in the apex compare to the base of the lungs?
Apex • Less ventilation • Less blood perfusion (gravity) • Ventilation outweighs perfusion • V/Q (ventilation/perfusion) tends towards infinity
Base • More ventilation • Better perfusion • Perfusion outweighs ventilation • V/Q tends towards zero
How does alveolar pressure, venous pressure and arterial pressure compare in the apex, middle and base of the lungs?
- Apex - alveolar pressure > arterial pressure > venous pressure
- Middle - arterial pressure > alveolar pressure > venous pressure
- Base - arterial pressure > venous pressure > alveolar pressure