Blood gas transport week 5 Flashcards
Think about the OxyHb dissociation curve. What is the PO2 when O2sat is 50%? 75%? 95%?
Explain why the curve is sigmmoidal and how this is beneficial to metabolically active tissues.
Notice that the oxyhemoglobin dissociation curve is non-linear! This means that the amount of O2 in the blood is NOT directly proportional to the PO2. Yes, increasing PO2 increases the O2 content, but at high PO2, the curve saturates. This is due to the fact that most of the O2 in the blood is bound to hemoglobin. Each Hb molecule can bind four O2 molecules. When every Hb molecule has bound 4 O2 molecules, the blood is saturated and there is no room for more O2 –therefore, the curve is very flat at the top.
The sigmoid shape at the low end of the curve is explained by positive cooperativity. After one O2 molecule binds, the affinity (towards oxygen) of the remaining open sites increases. The slope becomes steeper after some O2 has bound, reflecting this allosteric effect.
What is the physiological significance of the shape of the curve? The flatness at the high end of the curve means that where PO2 is high (e.g. in the lungs), the blood becomes nearly saturated (filled) with O2. In addition, whether PA,O2 is 100 or 80 or 130 torr will not make very much difference in the O2 content because Hb is nearly saturated over this whole range.
The curve is steep at lower PO2 (e.g. in the tissues). This means that a lot of O2 is released due to a small change in PO2. That is, the amount of O2 released to the tissues will be very sensitive to the ambient PO2 of the tissues. For example, at a PO2 of ~25 torr (which would be observed in a very metabolically active tissue), O2 sat is 50%. This means that the affinity for O2 is such that at a PO2 of 25 torr, it will release 50% of its oxygen. Metabolically active tissues with high O2 consumption will have a low PO2 and therefore a lot more O2 will be released to them, which is a good thing!
Hb is 75% saturated at PO2 of 40 torr. Hb is 95% saturated at PO2 of ~80 torr.
Explain the oxygen content of blood when PO2 is above 100 torr.
As we know, at PO2 of 100 torr, almost all Hb is saturated. This means that any furhter increasei n PO2 will add mainlly to dissolved O2. The amount of dissolved O2 is directly proportionaly to PO2, and the graph becomes linear above PO2=100 torr.
What is O2 capacity of blood? How is it calculated?
See attached. Note that we must memorize the O2 cpacity (1.34 mlO2/gm Hb)
What is the O2 content of blood? How is it calculated?
As an example, calculate the CO2 (oxygen content) of venous blood which is 75% saturated at PO2= 40 torr.
Explain the differences in oxygen content btwn the 3 scenarios in the attached graph.
At PO2 of 100 torr, 100% saturation is achieved in all situations. O2 sat is not dependent on the amount of Hb because even if there is an increased or decreased amount of Hb, that amount will still be 100% saturated at PO2 of 100 torr. However, increasing or decreasing Hb does increase or decrease the O2 capacity. If there is more Hb in the blood, the capacity of the blood to carry O2 increases. The opposite is true for anemia.
What 4 things cause a right shift in the OxyHb dissociation curve? What is the effect of a right shift in this curve?
Increased temperature, H+, CO2, and DPG (byproduct of RBC glycolysis) all cause right shifts of the OxyHb dissociation curve. A shift to the right means lower affinity binding of O2 to Hb.
At any particular PO2, acidification of blood results in release of O2. Increasing PCO2 also shifts the curves to the right, most likely because of their effect on pH. (It is very difficult to separate the effects of PCO2 and of pH.) This is called the Bohr effect. Increases in temperature (as in working muscle) aid in unloading O2 from HbO2. The opposite case is also made – during hypothermia, hemoglobin has an increased affinity for O2.
What are the physiological consequences of a “right shifted” curve? In the lungs, a right shift reduces the O2 taken up by the blood, but only slightly, because the oxyhemoglobin dissociation curve is FLAT at the ambient PA,O2 (90-130 torr). But in the tissue capillaries, ambient PO2 is much lower and the curve is steep, so even a small shift to the right will significantly reduce the O2 capacity of Hb. Thus, more O2 is released to the tissues.
What are the 2 delterious effects of CO on the OxyHb dissociation curve?
CO is a colorless, odorless gas that has an Hb affinity 240x that of O2. CO has two deleterious effects on the oxyhemoglobin dissociation curve. First, by occupying sites on Hb, it prevents O2 from binding. The O2 capacity is therefore reduced. Secondly, it exerts an allosteric effect on the remaining sites, causing their affinity for O2 to be increased. This produces a leftward shift in the oxyhemoglobin dissociation curve, which means that at any given tissue PO2, less O2 will be released from the blood. This is bad news for your poor oxygen-starved cells.
How is CO poisoning treated?
Only about half of CO is removed after 5-6 ours when normal air is breathed. However, if a higher FI,O2 is breathed (e.g., 100% O2, called “1 atm” in the figure), 50% of CO is removed in an hour. If O2 is given at a higher atmospheric pressure of 2.5 atm, 50% of CO is competed off within 30 minutes.
What is hypoxia? What are the 3 possible outcomes of hypoxia? What is the difference btwn hypoxia and ischemia?
There are four classes of hypoxia. In each case, the lack of oxygen leads to one of three outcomes: reversible tissue injury, irreversible tissue injury, or death. Hypoxia should not be confused with ischemia (lack of blood flow), although certainly ischemia can cause hypoxia. Remember that gas transport from blood to tissues and vice versa occurs PASSIVELY by diffusion down the partial pressure gradient.
What are the 4 types of hypoxia? Give causes of each. Also, state whether or not increase FIO2 would help.
hypoxic hypoxia: An excessively low PA,O2 leads to a low Pa,O2. If Pa,O2 is decreased then the PO2 in the tissues will drop to very low levels, because the driving force will be reduced. Hypoxic hypoxia can occur from hypoventilation, diffusion impairment (fibrosis, pulmonary edema), shunts, V/Q mismatch, or high altitude.
anemic hypoxia: The O2 capacity of blood is too low (not enough Hb). Pa,O2 may be normal, but Ca,O2 is reduced, and the tissues still suffer! As O2 diffuses from systemic capillaries into the tissues, the capillary PO2 decreases faster than normal, and thus the driving force may drop to low levels before the tissues have enough O2.
hypoperfusion hypoxia (also called ciculatory hypoxia): Both O2 pressure and O2 content are normal, because the primary problem is not respiratory. The tissues may be deprived of O2 due to the slow flow of blood, because “all” of the available O2 is extracted before the blood has moved all the way through the capillary bed. Hypoperfusion hypoxia can occur in situations where there is low cardiac output (shock) or local arterial obstruction.
histotoxic hypoxia: Metabolic poisons affect cells by interfering with their utilization of O2 for mitochondrial respiration.
What are the 3 forms of CO2 transport? Which is the most common form?
What catalyzes the formation of bicarbonate? In what part of blood is this enzyme located?
HCO3- is produced by the enzyme Carbonic Anhydrase. Human CA-II (the isoform in RBCs) is the fastest known enzyme, with a turnover rate of 1,000,000 per second. CA-II is present inside RBCs, but is absent in plasma.
Describe the chloride shift and the Bohr effect as shown in the attached figure.
When HCO3- is formed, it leaves the RBC. Cl- comes in to balance HCO3 leaving. This is the chloride shift. Note that HCO3 is higher in venous blood and Cl is lower due to the chloride shift.
The conversion of CO2 to HCO3 also produces a H+ which may protonate hemoglobin (Hb ’ HHb). HHb has a lower affinity for O2 than Hb and therefore the addition of CO2 to the blood tends to promote the release of O2. This is the mechanism of the Bohr effect.
What is the Haldane effect? What 2 factors/properties of Hb contribute to the Haldane effect?
Like O2 content, CO2 content increases as PCO2 increases. However, CO2 content curves do not have the nice graceful shape of O2 curves. The key modulatory factor here is PO2. Consider blood in an alveolar capillary.
(1) When Hb is oxygenated, the pKa of amino groups that can bind protons decreases. This lower affinity results in the release of protons, which combine with HCO3 to form CO2 (which then diffuses from the blood into the alveolar air). Thus the total CO2 content is reduced AT ANY GIVEN PCO2. Despite all this intricate chemistry, after equilibration the blood Pa,CO2 always equals PA,CO2.
(2) The capacity of deoxygenated Hb to bind CO2 and form carbamino-Hb is greater than that of fully oxygenated Hb. More CO2 “fits” in deoxy-Hb.
These two factors contribute to what we call the Haldane effect: oxygenation of hemoglobin promotes dissociation of CO2 from hemoglobin.
Using the attached graph, explain how the Haldane effect impacts CO2 transport.
At the same tissue PCO2 btwn venous and arterial blood, significantly more CO2 is taken up than would have been taken up if not for the Haldane effect. Note this increase in CO2 content is due to decreases PO2 in venous blood. The Haldane effect is beneficial at the lungs as well as at the tissues.
