Gas Transport Flashcards
Learning outcomes
- List the ways by which oxygen is carried in the blood
- Recognise what proportion of oxygen is carried in each form
- Describe the oxygen-haemoglobin dissociation curve
- Explain the physiological significance of the shape of the curve
- Describe the factors that cause the curve to shift to the right or to the left
- Calculate how much oxygen is carried in the blood
- List the ways by which carbon dioxide is carried in the blood
- Recognise what proportion of carbon dioxide is carried in each form
- Describe the role of the red blood cells in carbon dioxide carriage
- Describe how carbon dioxide is converted to bicarbonate
What are the primary functions of the resp and cardiovascular systems
- 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
- Both gases move by diffusion down their concentration gradients
Discuss oxygen transport
• Oxygen is transported in blood in two ways:
– Physically dissolved in plasma ~2%
– Combined with haemoglobin ~98%
Discuss O2 as it is found in plasma
- Amount of O2 dissolved in plasma depends on its solubility and partial pressure in blood (Recall Henry’s Law)
- Henry’s law states that at equilibrium for a given temperature
[O2]Dis = solubility O2 x PO2 (O2 sanscript)
- At 37oC the solubility of O2 in plasma is poor - only 0.03ml/L/mmHg
- Partial pressure of O2 in arterial blood is ~100 mmHg
- Therefore only 3ml O2/L of blood can be transported in solution
- Equates to 15ml O2/min delivery to tissues
- BUT our bodies consume 250ml O2/min
- So this mechanism of O2 transport is completely inadequate
Discuss the structure of haemoglobin
• Normal Hb (HbA) is a tetramer
• Four O2-binding heme groups each attached
to a polypeptide (globin) chain
• HbA consists of 2α and 2β chains
• In Fetal haemoglobin (HbF) the β- chains are replaced by γ-chains
• HbS causes sickle cell anaemia
– glutamate at position 6 in the β- globin is
replaced with a valine.
• Each haem group consists of a porphyrin ring surrounding an Fe2+ molecule
• O2 can only be bound in Fe2+ (ferrous state)
• If iron oxidised to ferric (3+) state leads to
methaemoglobin (~1.5% Hb is in this state)
– methaemoglobin reductase uses the NADPH chain to reduce metHb back to Hb
Discuss haemoglobin structural changes on oxygenation
- Deoxygenated Hb exists in a tensed state (T) compared with oxygenated Hb in a relaxed state (R)
- In the tensed state strong ionic bounds form between the 4 polypeptide chains – immobile and apart
• β-globins also bind 2,3 DPG
- The consequence of this is that the Fe lies deeper in the pocket and cannot bind O2
- As O2 binds the bonds break and the Fe moves to the plane of the porphyrin rings – relaxed state
- The colour of blood changes from dark blue to bright red
Discuss the haemoglobin oxygen dissociation curve
- Binding of one O2 molecule makes it easier for the subsequent ones to attach
- Haem-haem interaction – cooperatively. This accounts for the shape of O2-Hb dissociation curve
- The colour change is utilised clinically to measure the O2 saturation of blood using the pulse oximeter
Discuss maximal load of O2 in haemoglobin
- Amount of O2/L of blood attached to Hb, at full saturation, is called O2 capacity and depends on the Hb concentration in blood
- Each g of Hb, when fully saturated carries 1.35ml of O2
- Maximal O2 bound to Hb can be calculated as:
max 𝑂2 𝑏𝑜𝑢𝑛𝑑 𝐻𝑏 = 𝑂2 𝑐𝑎𝑝𝑎𝑐𝑖𝑡𝑦 ∗ [𝐻𝑏]
max 𝑂2 𝑏𝑜𝑢𝑛𝑑 𝐻𝑏 = 1.35𝑚𝑙/𝑔 ∗ 150𝑔/𝐿
=203ml O2/L blood
• Equates to 235ml O2/min delivery to tissues
• % 𝑠𝑎𝑡𝑟𝑛 𝐻𝑏
=
((𝑂2 𝑎𝑐𝑡𝑢𝑎𝑙𝑙𝑦 𝑏𝑜𝑢𝑛𝑑 𝑡𝑜 𝐻𝑏) OVER 𝑂2 𝑐𝑎𝑝𝑎𝑐𝑖𝑡𝑦 𝑜𝑓 𝐻𝑏) ∗ 100
Discuss myoglobin and foetal haemoglobin in comparison to adult haemoglobin interactions
- MyHb and HbF shift the curve to the left
- HbF Consists of 2 α-chains and 2 γ-chains
- HbF has higher O2 affinity than HbA due to special properties of γ-chains
- May take up to 2 years to convert all HbF to HbA
Discuss factors that affect haemoglobin affinity for O2
- CO2, H+ and 2,3 DPG affects the affinity of Hb for O2
- Left shift – high affinity
- Right shift – low affinity
- CO2, H+ and 2,3 DPG affect the globins
- In systemic capillaries increases in CO2, temperature and decrease in pH, move Hb to low affinity tensed state, so more O2 released (right shift)
• In pulmonary capillaries temperature is lower, Pco2 is lower and pH is higher, moves Hb to higher affinity relaxed state , so more O2 taken up by Hb
(left shift)
Discuss the Bohr effect (or shift)
• Bohr observed that respiratory acidosis shifted the Hb-O2 dissociation curve to right
• This respiratory acidosis has two components
– Decrease in pH (more acidic)
– Increase in Pco2
Effects of temperature and pH on the 02-Hb dissociation curve
Temperature affects the O2 capacity of Hb, by affecting Hb structure
• Changes in pH account for most of Bohr effect
• Metabolic acidosis
• Hb good buffer for H+, as [H+] increases conformational change in Hb structure and O2 affinity reduces
Discuss the effects of hypercapnia on the 02-Hb dissociation curve
- Small portion of the Bohr effect
- Pco2 increase – CO2 combines with unprotonated amino group on Hb – carbamino groups
- Carbamino haemoglobin
Discuss the effects of 2,3-diphosphoglycerate (DPG) on the O2-Hb Dissociation Curve
• RBC do not have mitochondria
– by-product of glycolysis
– decreasing PO2 of rbc’s stimulates glycolysis resulting in increased levels of 2,3-DPG
• 2,3-DPG interacts with β chains destabilising interaction of O2 with Hb
Affect of carbon monoxide (CO) on Hb affinity for 02
- CO, NO and H2S can also bind to Hb and snap it into relaxed state
- CO has a 200 fold greater affinity for Hb than O2
- maximal O2 capacity falls to extent that CO binds
- However, CO also increases O2 affinity of Hb and shifts dissociation curve to left
- Hb does not release O2 when it gets to tissue
