Module 3 Section 6 (Gas Transport in Blood) Flashcards
Describe haemoglobin and why it is important for gas transport.
Haemoglobin plays a crucial role in permitting the transfer of large quantities of oxygen before blood equilibrates with the surrounding tissues.
Haemoglobin facilitates the exchange of oxygen between the alveoli and the lungs in the following ways:
1) No Hb Present:
- In the hypothetical situation in which no haemoglobin is present in the blood, the alveolar PˇO2 and the pulmonary capillary blood PˇO2 are at equilibrium.
2) Hb Partially Saturated:
- As the Hb starts to bind with oxygen, it removes oxygen from solution. Because only dissolved oxygen contributes to blood PˇO2, the blood PˇO2 remains below that of the alveoli, even though the same number of oxygen molecules are present in the blood.
- By binding some of the dissolved oxygen, Hb favours the net diffusion of more oxygen down its partial pressure gradient from the alveoli to the blood.
3) Hb Fully Saturated:
- Haemoglobin is fully saturated with oxygen and the alveolar and blood PˇO2 are at equilibrium again.
- The blood PˇO2 resulting from dissolved oxygen is equal to the alveolar PˇO2 despite the fact that the total oxygen content in the blood is much greater than in the case of no Hb.
Describe the oxygen-haemoglobin dissociation curve and explain the importance of the steep slope around PO2= 40 mmHg and the plateau around PO2= 100 mmHg.
The relationship between PˇO2 and % Hb saturation is described in what is called the oxygen dissociation curve.
This is a sigmoidal shaped curve that has a steep slope b/w 0 and 60 mmHg, and plateaus beyond 60 mmHg as it approaches 100 mmHg. This steep slope below 60 mmHg means that a small change in PˇO2 can have a large effect on % Hb saturation.
Plateau Portion of Curve:
- The plateau region of the curve, from 60 mmHg to 100 mmHg, represents the PˇO2 range found in the pulmonary capillaries where the Hb is collecting O2.
- When the blood is leaving the lungs with a PˇO2 of 100 mmHg, the dissociation curve shows that the Hb is 97.5% saturated. Therefore, blood leaving the lungs is normally always saturated.
- The low slope of this part of the curve also ensures that even if there was a drop in PˇO2 to 60 mmHg, Hb would still be 90% saturated.
- The plateau phase of the curve represents a margin of safety. This is important not only to persons with pulmonary disease, but also normal healthy persons under two circumstances:
1) At high altitude where PˇO2 of inspired air is reduced.
2) In oxygen-deprived environments at sea level. Ex: if a person was locked into an airtight room for a period of time, the plateau phase of the curve ensures that until their arterial PˇO2 drops below 60 mmHg, near normal amounts of oxygen can still be transported to the tissues.
Steep Portion of Curve:
- The steep portion of the curve between 0 and 60 mmHg corresponds to the range of PˇO2 that is found in the systemic capillaries.
- Blood arrives in the capillaries with a PˇO2 of 100 mmHg and is 97.5% saturated.
- By the time the blood is leaving the systemic capillaries the PˇO2 has dropped to 40 mmHg and is now 75% saturated. This means that 25% of the oxygen has been unloaded to support metabolism at rest.
- In metabolically active tissues where more oxygen is needed, a drop in PˇO2 to 20 mmHg can release an additional 45% of the total oxygen.
- The steep portion of the curve allows for larger amounts of O2 dissociation for small decreases in PˇO2.
Outline the factors that affect the dissociation curve.
During disease and exercise, the by-products of increased metabolism are heat, carbon dioxide, and lactic acid. All three of these shift the dissociation curve to release more oxygen. pH can also have a strong effect on the dissociation curve.
pH:
- The primary form that carbon dioxide is carried in the blood is as bicarbonate ion (HCO3-). As HCO3-goes through the anhydrase-carbonic acid cycle, a H+ ion is released.
- During exercise, lactic acid is produced. The combination of H+ and lactic acid can cause the pH to decrease, which enhances the dissociation of oxygen from haemoglobin in a phenomenon known as the Bohr effect.
BPG:
- Within the red blood cells themselves is 2,3-bisphosphoglyceate (BPG), which also affects the oxygen dissociation curve by shifting it to the right.
- When oxygen saturation in arterial blood is below normal, BPG production is increased. It kind of acts like an oxygen sensor such than in conditions of lower PO2, BPG enhances the unloading of oxygen.
- However, unlike H+ and CO2, the effects of which are reversed in the lungs, the BPG produced is not eliminated in the lungs so it persists in limiting oxygen binding to Hb, resulting in arterial blood to have a decreased % saturation.
CO2:
- Carbon dioxide (CO2) can also bind to Hb. When there is an increase in PˇCO2, the oxygen dissociation curve shifts to the right (decreased % saturation for a given PO2).
- This is another mechanism to increase oxygen unloading in metabolically active tissues where PˇCO2 is increasing such as the systemic capillaries. This is called the Haldane effect and leads to more oxygen unloading than a decrease in PˇO2alone could accomplish.
Hb and CO:
- Carbon monoxide (CO) is a toxic gas that is produced from the incomplete combustion of carbon-based products.
- CO competes with O2 for the same binding site on Hb and forms a product called carboxyhaemoglobin (HbCO). Why this is a problem though is that the binding affinity for CO is 240 times greater than O2 meaning that even low levels of CO can make a large number of oxygen-binding sites on Hb unavailable, and the % saturation is decreased.
- CO also shifts the oxygen dissociation curve to the left, requiring larger drops in PˇO2 to unload oxygen into the tissues. The consequences can be severe and cause death.
Describe how carbon dioxide is transported in the blood.
Physically dissolved:
- CO2 is 20x more soluble in solution than O2 so it makes sense that more CO2 is transported physically dissolved in the plasma.
- That said, only about 5-10% of total blood CO2 is freely dissolved but this small fraction accounts for the 46 mmHg partial pressure of CO2 when blood leaves the systemic capillaries.
Bound to haemoglobin:
- CO2 does not bind to the haem-O2 binding sites, rather it binds to the globin part of the molecule.
- Hb without oxygen has a greater affinity for CO2 so the unloading of O2 in the systemic capillaries enhances the uptake of CO2. That said, only another 5-10% of the total CO2 is transported in this manner.
As bicarbonate (HC O3-):
- Bicarbonate makes up 80-90% of circulating CO2 and can be represented by the equation: CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-
- CO2 combines with water to form carbonic acid.
- This reaction can occur slowly in the plasma but red blood cells have the enzyme carbonic anhydrase (C A), which accelerates the reaction.
- Carbonic acid spontaneously dissociates into hydrogen ions and bicarbonate.
The PˇO2 of arterial blood is 100 mmHg, which is around 200 ml O2/L. Oxygen, however, is poorly soluble in liquid such as plasma. How much of O2 can dissolve in plasma?
Only about 3 ml of O2 can physically dissolve into 1 L of plasma.
If freely dissolvable O2 was the only source for the metabolic needs of the body, the supply of O2 would clearly be lacking.
What is haemoglobin (Hb)?
Hb is an iron-bearing protein within red blood cells that can carry oxygen. In fact, 98.5% of circulating oxygen is bound to Hb.
Since O2 is poorly soluble in plasma, what is the solution to this problem?
The solution to this problem is haemoglobin (Hb). Once bound to Hb, oxygen no longer contributes to the PˇO2 meaning that the PˇO2 only represents the freely dissolved O2 in the plasma and the Hb-bound oxygen acts as a reserve.
True or false: in humans, haemoglobin is an assembly of four protein subunits.
True
Each subunit consists of a protein chain and a heme group, which contain the iron molecules to which oxygen binds.
Each of the four iron atoms in a Hb molecule can bind an oxygen molecule. What is the equation that represents this?
Hb + O2 ↔ HbO2 + O2 ↔ Hb(O2)2 + O2 ↔ Hb(O2)3 + O2 ↔ Hb(O2)4
The double arrows b/w each step mean that each of these reactions is fully reversible allowing Hb to bind oxygen for transport, then unbind oxygen for delivery.
Hb is fully saturated when all of the Hb present is carrying its maximum oxygen load. Hb saturation is expressed as a percentage. What is the most important factor for determining % Hb?
The most important factor for determining % Hb saturation is PO2.
According to the chemistry law of mass action, if you incr conc of one substance involved in a reversible reaction, the reaction is driven to the other side. The opposite is also true.
How is the steep portion of the curve also beneficial for persons breathing at altitude?
With a decreased atmospheric pressure, there is a decrease in alveolar PˇO2 and therefore a decrease in arterial PˇO2.
The decrease in arterial PˇO2 activates carotid chemoreceptors that causes an increase in ventilation. If the person is still at rest (no increase in metabolic activity) then this increased ventilation will result small decrease in arterial PˇCO2, which according to the arterial gas equation, means there will be a small increase in alveolar PO2.
On the steep portion of the curve, this small increase in alveolar PˇO2 can greatly increase % Hb saturation.
Check slide 5
Match the location in the body to the level of O2 attached to Hb into the boxes found on the curve.
Steep portion
-
Steep portion
- In the tissues
- Low O2 attached to Hb
Plateau region
- In the alveoli
- High O2 attached to Hb
Discuss the chloride (hamburger) shift.
In the systemic capillaries, as more CO2 enters the red blood cells, bicarbonate and hydrogen ions accumulate.
Red blood cells have a bicarbonate-chloride carrier that passively allows the exchange of these ions across the cell membrane.
- Consequently, bicarbonate leaves the cells and chloride enters the cell, down its electrochemical gradient.
- This inward shift of chloride, in exchange for bicarbonate, is known as the chloride (Hamburger) shift.
- Therefore, this shift facilitates the movement of CO2 from the tissues into the blood to be transported to the lungs and expired.
How is the reverse Haldane effect different from the Haldane effect?
The Haldane effect in which the binding of CO2 to Hb facilitates the release of oxygen at the tissue level, and results in a rightward shift of the oxygen dissociation curve.
There is also a phenomenon known as the reverse Haldane effect, which occurs when there are increases in arterial PˇO2, such as when breathing supplemental oxygen.
- The increased PˇO2 prevents the haemoglobin from binding carbon dioxide. This forces the CO2 to travel back to the lungs either dissolved in the plasma or as bicarbonate.
- As a result, blood acidity may rise, which might be the explanation for the increased ventilation rates associated with breathing supplemental oxygen.
- An increase in PˇO2 will prevent CO2 from binding to Hb, resulting in an increase of carbon dioxide that is transported as dissolved CO2 within the blood.
What are the 2 different forms of arterial PˇO2, in terms of abnormalities in arterial PˇO2?
Hypoxia: this condition is described as insufficient oxygen at the cellular level.
Hyperoxia: This is characterized by an abnormally high arterial PˇO2.
- This can never happen to a person breathing air at sea level but it can happen in someone breathing supplemental oxygen.
- The high oxygen content of the inspired gas raises arterial PˇO2 but the total oxygen content does not as Hb is essentially saturated with breathing normal air.
- This is not always good though as it can raise arterial PˇO2 to dangerous levels and cause oxygen toxicity.
- In some tissues, the increased dissolved O2 can cause the formation of reactive oxygen species that can damage cells.
- This can be the cause of brain and retina damage, causing blindness, in some patients breathing supplemental oxygen.
