[Applause] [Music] hello this is Eric strong once again and this lecture will cover the mechanisms and ideologies of hypoxemia many of you have reached this lecture by progressing through this course on understanding abgs however some of you may have stumbled across it directly from a general YouTube search and may not be interested in a complete discussion of the interpretation of arterial blood gases if that's the case I think you'll still find this informative as a standalone lecture but if there are Concepts mentioned that are unfamiliar you may want to consider first watching lectures 16 and 17 for a more complete background the specific learning objectives of this lecture will be first to become familiar with the five basic mechanisms of hypoxemia and the second to know the differential diagnosis of hypoxemia to understand the mechanisms of hypoxemia you must be aware of two fundamental equations in respiratory physiology that were introduced in lecture 16 first is the calculation of the aa gradient this is the difference between the partial pressure of oxygen in Alvar gas minus the partial pressure of oxygen in the arterial blood the aa gradient is a measure of how difficult it is for oxygen to be exchanged across the Alvar capillary membrane in the lungs the larger the gradient the more severe the underlying pathology the pbig ao2 is estimated from the Alvar gas equation and the P little ao2 is directly measured from the ABG and here is the Alvar gas equation to remind you F2 is the fractional concentration of oxygen in inspired air Pi is the total pressure of inspired air pH H2O is the partial pressure of water vapor P little a CO2 is the partial pressure of carbon dioxide in arterial blood and RQ is the respiratory quotient which is determined by our metabolism the basic mechanisms of hypoxemia will become more obvious if we combine these two equations with some very simple algebraic rearrangement P little ao2 equals all this minus the aa gradient since hypoxemia is defined as low P little ao2 we can use this mathematical relationship to infer the possible mechanisms first there can be low pressure of inspired air essentially only seen at high altitude this is the entire focus of supplemental lecture number two of this course and given its Rarity in clinical practice we won't discuss it further here next the partial pressure of arterial CO2 can be high this is more commonly and succinctly known as hypoventilation and the specific ideologies of hypoventilation are the entire focus of lecture number 11 on respiratory acidosis finally there can be an elevated aa gradient there are three more specific mechanisms that fall into this category impaired diffusion something known as VQ mismatch and finally a shunt these will be the focus of this lecture before leaving the slide you might wonder about the three remaining variables on the right side of the equation and whether they can also lead to hypoxemia the basic answer is that they don't while F2 can be elevated and lead to a high p ao2 it is never abnormally low the partial pressure of water is a constant and finally while the respiratory quotient technically can vary in the setting of an extremely unusual diet the degree of possible variation is too slight to lead to hypoxemia the fundamental principle of gas exchange is that carbon dioxide returning from the systemic circulation via Venus blood diffuses out of the p pulmonary capillary bed and into the alveoli while oxygen diffuses out of the alveoli and into the capillaries before traveling to our vital organs and peripheral tissues via arterial blood the physical barrier these gases must cross during diffusion is known as the Alvar capillary membrane all causes of hypoxemia must somehow interfere with this process since the physical process of diffusion is key to gas exchange let's take a closer look at how that works diffusion can be mathematically described by fixed law this states that the rate of gas diffusion equals the diffusion coefficient times the surface area of the diffusing membrane times the partial pressure gradient of the diffusing gas all divided by the thickness of the membrane the diffusion coefficient for a given gas is dependent upon its molecular weight and its solubility thus although carbon dioxide is more massive a molecule than oxygen which should slow down its diffusion because it is much much more soluble than oxygen its overall rate of diffusion is faster although fixed law applies to all forms of hypoxemia the specific term impaired diffusion is generally reserved for pathologic States characterized by increased thickness of the Alvar capillary membrane such as pulmonary fibrosis let's take a closer look at how increased membrane thickness impairs gas exchange I'm going to reduce fix law but leave it visible so you can still refer to it if you like here's a graph of the partial pressure of oxygen within the pulmonary capillary as it flows along its length as a function of time I'm going to say that the left side of the graph represents the beginning of the capillary and the right side represents its end and here is the partial pressure of o in the alveoli with which the capillary blood is attempting to equilibrate normally this is what is seen the partial pressure of oxygen returning to the lungs from the systemic circulation often has a value of around 50 mm of mercury though this can be very variable as the deoxygenated blood moves through the capillary it reaches an equilibrium with the alular space very quickly such that the partial pressure of oxygen in the capillary is essentially equal to P big ao2 well before the blood reaches the end of the capillary with a condition such as pulmonary fibrosis the Alvar capillary membrane is thicker so diffusion proceeds more slowly thus the capillary oxygen tension doesn't reach that of the alvioli until much further along the capillary bed and may even fall short thus leading to systemic hypoxemia what I've shown here is essentially what happens under normal noral conditions that is at sea level with an otherwise healthy patient at rest what happens at high altitude at high altitude such as might be seen at the 2400 M of Mexico City the pbig ao2 may only be 75 mm of mercury thus there is a smaller pressure gradient driving diffusion so even in a person with normal lungs equilibrium between capillary oxygen tension and Alvar oxy tension will occur much further along the capillary bed in healthy individuals the consequences at a relatively modest elevation such as this is pretty small however in patients with fibrosis as you can see it is much more problematic next in states of high cardiac output such as exercise or sepsis the P big io2 is back to 100 but the more rapid circulation time results in less time elapsing between when blood enters and exits the capillary in other words the rate of diffusion is unaffected but the total amount of gas that diffuses is reduced because of less time for diffusion to occur once again for patients with normal lungs this isn't usually a problem however patients with fibrosis can find themselves getting quite hypoxemic the bottom line is that in states of impaired diffusion such as interstial lung disease and Pulmonary Fibrosis hypoxemia is particularly exacerbated by high altitude and high cardiac output you might be wondering how states of impaired diffusion impact carbon dioxide for comparison here is our graph for partial pressure of oxygen under normal conditions here is pbig a CO2 which would determine the pressure gradient driving the diffusion of carbon dioxide and here are the curves for the partial pressure of Co 2 in the capillaries as seen both in normal lungs as well as in fibrosis as you can see CO2 diffuses so quickly that even when it is slowed by fibrosis equilibrium with alveolar gas is still achieved with plenty of capillary length to spare thus diffusion of CO2 is almost never a clinically relevant problem provided adequate Alvar ventilation is occurring I am now going to move discussion away from a pair diffusion and onto ventilation profusion matching ventilation profusion matching is the process by which areas of the lung which are best ventilated also receive the highest blood flow this helps to maximize the efficiency of gas exchange it doesn't really make sense to discuss a perfect VQ ratio per se since there is no reason for alveolar ventilation in liters per minute to numerically match cardiac output in liters per minute but the normal VQ ratio if averaged over the entire lungs is about 0.8 that is normally 4 L per minute of alv ventilation matches 5 L per minute of cardiac output the VQ ratio is not constant in all parts of the lung even in normal individuals areas of the lung in which profusion is decreased out of proportion to ventilation have an increased VQ ratio areas of the lung in which ventilation is decreased out of to profusion have a decreased VQ ratio whenever the VQ ratios of the various parts of the lung average to something significantly different than 0.8 Physicians say that a patient is experiencing VQ mismatch the physiology of VQ matching is quite a deal more complicated but luckily most of its complexity is usually not clinically relevant at the bedside so therefore I will spare you most of the details and refer you to a physiology textbook if you want to know more about this process after the lecture you might also be wondering why Q stands for profusion I actually have no idea but unfortunately that's the confusing nomenclature that convention has stuck us with I understand you may be confused at this point but I think this concept of VQ mismatch will be clear with a few diagrams this would represent two different parts of the lungs I realize that it may look very much like one sphere is the right lung and the other is the left but it doesn't necessarily need to be so instead they represent two collections of alveoli with similar physiologic States in one situation each could represent one lung in another more common situation one sphere could represent both lung apes and the other sphere could represent both lung bases and here we have the blood flow to these regions de oxygenated blood comes to the lungs via the pulmonary artery filled with carbon dioxide when it reaches the alveolar capillary membrane CO2 diffuses into the alvioli and oxygen diffuses into the blood transforming the deoxygenated hemoglobin to oxygenated the Now red oxygenated blood recollects into the pulmonary veins where it will be sent to the left side of the heart and back into the systemic circulation what happens to cause the VQ mismatch that one might see with pulmonary edema one of the consequences in pulmonary edema is that some but not all alvioli will literally fill with an aquous Solution that's similar to salt water this will impair gas exchange in the affected alveoli thus blood leaving the capillaries adjacent to the flooded alvioli will not be fully oxygenated therefore when all of the blood collects in the pulmonary vein veins to go back to the body the overall resultant oxygenation of this blood will be reduced from normal let's go back again what if we have a situation where extrinsic compression from something like a tumor reduces the caliber of a large Airway which then reduces the amount of ventilation received by alvioli distal to that obstruction this partial collapse of alvioli known as atelectasis results in low oxygen within the infected alveoli this looks remarkably similar like the case with the pulmonary edema where there is incomplete oxygenation of blood leaving this lung unit to return to the pulmonary veins there's actually an Adaptive response within our lungs that helps to limit the negative impact on oxygenation it's called hypoxic basoc constriction in this normal process low oxygen tension is sensed by the local pulmonary vessels which then constrict The increased resistance to blood flow to these lung units diverts blood over to the rest of the normally ventilated lungs helping to mitigate systemic hypoxia a different form of VQ mismatch occurs with a pulmonary embolism often abbreviated PE in a PE a blood clot forms in a peripheral vein and is launched into the Venus circulation where it travels until reaching a vessel too small to allow it to pass through there it will completely obstruct the flow of blood alvioli that are adjacent to the now non- profused pulmonary capillaries are known as the alveolar Dead Space Dead Space is the part of ventilation that does not participate in gas exchange while it might be relatively easy to understand how increased pulmonary vascular resistance from a pe's physical obstruction to blood might Place significant stress on the right ventricle it is probably not initially obvious why this should result in systemic hypoxemia remembering back to fixed law diverting blood has two adverse effects first this will reduce the total surface area of the diffusing alv capillary membrane which will decrease the rate of diffusion second increased blood flow through a capillary bed of finite cross-sectional area will result in a greater velocity which will then result in decreased time that blood spends within the capillary during which oxygen can diffuse in therefore even if the Alvar capillary membrane in the remaining lung is perfectly normal blood exiting those lung units can still be incompletely oxygenated thus a PE can lead to both VQ mismatch as well as impaired diffusion the final and most straightforward mechanism of hypoxemia is shunt I introduced the idea of shunts in lecture 177 to remind you a shunt is a situation where blood bypasses the anatomic pathway it typically travels shunts are categorized as either right to left shunts in which either the Alvar capillary membrane or the entire lungs are bypassed or left to right shunts in which the systemic circulation is bypassed right to left shunts have a significant direct effect on arterial oxygenation while left to right shunts usually have minimal direct effect to help you better visualize what exactly a right to left shunt looks like I want to show just one example here is a diagram of a form of congenital heart disease known as tetrology of Pho it is the most common form of cytic heart disease in newborns affecting about 1 in 2500 live births the term tetrology refers to the fact that there are four distinct anatomic abnormalities seen in the heart the details of which are not actually important for this lecture I just want to point out that the overall consequence of these anatomic abnormalities is that de oxygenated blood in the right ventricle which normally travels to the lungs to be oxygenated via the pulmonary artery is instead diverted into the aorta via a defect in the ventricular septum now that we' reviewed three major mechanisms of hypoxemia it may be tempting to begin categorizing individual ideologies by mechanism for example since since I used pulmon fibrosis in the discussion of impaired diffusion it would seem natural to categorize it as so and I could continue with listing a bunch of diseases and pathologic problems in the mechanistic categories the problem with this process is that unlike the ideologies of acid-based disorders the ideologies of hypoxemia cannot be neatly categorized by mechanism because almost all ideologies result in hypoxemia via more more than one mechanism such as with a PE as we just saw a true categorization would look something more like this the only ideology that clearly falls into just a single mechanism is a right to left intracardiac shunt I'm going to go back now and talk a little bit more about VQ mismatch and shunting in order to demonstrate an important principle that can be used to different iate the more prominent of the mechanisms at work imagine that instead of two lung units like the prior schematic we now have three again these spheres obviously don't represent lungs but rather collections of alveoli that have similar physiologic States or properties and which I'll continue to refer to as lung units here's the blood supply traveling to each of the lung units and we'll start off by saying that each one has a normal VQ ratio if our patient has a cardiac output of 6 lers per minute and each of these lung units is identical that gives us 2 lers per minute to each one de oxygenated blood returning from the systemic circulation typically has an oxygen tension of somewhere around 35 and an oxygen saturation of somewhere in the neighborhood of 67% since ventilation and profusion are both intact and all of our lung units have normal VQ ratios the oxygen tension of blood departing the pulmonary capillary beds of each unit is the same in this case about 100 and with an O2 saturation of about 97% thus when the oxygenated blood is mixed in the pulmonary veins and left atrium the resulting P little a O2 is also 100 and O2 sat is also 97% that seems quite straightforward however what if these three lung units are not equal what if one of them for some reason has poor perfusion resulting in an elevated VQ ratio and another has some limitation of ventilation resulting in a decreased VQ ratio maybe a little hypoxic basil constriction kicks in diverting blood to the normal lung unit and minimizing how much incompletely oxygenated blood returns to the circulation let's add some hypothetical numbers in I'll start arbitrarily by assigning 1 lit per minute of cardiac output to the low VQ unit 4.5 L per minute to the normal unit and 0.5 lers per minute to the high VQ unit we'll say that our returning Venus blood looks the same as prior because ventilation is so poor in this first unit the P2 and O2 sat of blood leaving its capillary bed is only minimally increased over that of Venus return meanwhile the gas exchange in the normal unit is the same as before and in the high VQ unit since ventilation is in excess of profusion gas exchange is even better than normal resulting in a P2 of 140 and O2 sat of 99% what does the systemic arterial blood look like then when all of these are mixed together since the overwhelming majority of oxygen in blood is carried bound to hemoglobin systemic oxygenation is calculated by taking a weighted average of the oxygen saturations from each of the lung units and not from averaging the oxygen tensions in this particular example the weighted average results in a peripheral O2 set of 93% so despite one sixth of the cardiac output going to very poorly ventilated lung tissue the patient will suffer minimal adverse consequences what if that fraction of cardiac output is increased to 1/3 that is 2 lers per minute goes to poorly ventilated lung the weighted average changes resulting in an O2 sat which is lower possibly symptomatic but not necessarily dangerous and then let's change that fraction to 1/ half of the cardiac output or 3 L per minute O2 sat drops to 84% that's certainly not a healthy level of oxygenation but possibly not as severe as one might expect given how much blood is not participating in effective gas exchange now what if we take this patient with 3 lers per minute going to poorly ventilated lung and give him or her supplemental oxygen in this case 100% supplemental oxygen how does this change our numbers in that first lung unit although there is still a significant gradient between the partial pressure of oxygen in inspired air and the partial pressure of oxygen departing the pulmonary capillaries departing blood still has a very high oxygen content because the oxygen concentration is so high the same holds true for the other two lung units but even more so the final result is near maximumly oxygenated arterial blood but what if we take away that oxygen and then have our Airway obstruction progress from partial to complete this will result in the alveoli distal to the obstruction having no ventilation at all in other words a VQ ratio of zero this is in fact by definition a shunt if we take this patient with an equally large shunt and work out the numbers with him or her breathing room air the result is an O2 saturation of 83% which is very similar to what we saw if that first lung unit wasn't completely uded but only partially so however if we place this patient with a shunt on 100% oxygen what happens to the systemic arterial oxygen a almost no improvement even though there is Sky High oxygen tensions in the other two lung units while on 100% F2 remember that it's not the po2 in the capillaries that dictates the arterial oxygen tension but rather it's the weighted average of their O2 saturations so what exactly is the influence of the shunt fraction on response to changes in the fractional concentration of oxygen in inspired air here is a graph of arterial oxygen tension as a function of F2 when 10% of the cardiac output participates in a right to left shunt that bypasses gas exchange here is the relationship that is observed a normal pa2 of 100 can be achieved with only modest amounts of supplemental oxygen however if that shunt fraction is increased to 20% it requires a very high concentration of supplemental oxygen to achieve a p ao2 100 and once the shunt fraction reaches 30% depending upon the patient's cardiac output and other factors it may no longer be possible to achieve a p little ao2 100 at atmospheric pressures and finally once the shunt fraction has reached 50% that is when half of the cardiac output is bypassing either the alv capillary membrane or the lungs themselves in their entirety increasing F2 produces almost no change in P ao2 at all this leads us to important conclusions that will allow us to better differentiate which mechanism of hypoxemia predominates in a specific clinical scenario in shunts the oxygen saturation of arterial blood does not fully correct with 100% F2 unless the shunt is very small the oxygen saturation in situation of imper diffusion and VQ mismatch usually fully correct with 100% F2 unless the underlying pathology is very severe and or Advanced and although I have mentioned hypoventilation only in passing during this lecture I would like to note here that the O2 sat in hypoventilation always fully corrects with 100% F2 however the P little a CO2 which is the real problem in hypoventilation and Which is less L readily detectable is not helped by oxygen and can even be made worse this is why supplemental oxygen is never appropriate therapy by itself for hypoventilation so finally let me summarize a diagnostic approach to hypoxemia the first step is to compare the alv arterial gradients against normal adjusting for age and F2 if the aa gradient is normal you must be dealing with hypoventilation or low atmospheric pressure if it's elevated next check whether the O2 saturation completely corrects with 100% oxygen if not then the patient probably has a right to left shunt however if it does correct then the patient probably has either VQ mismatch and or impaired diffusion as the primary mechanism of hypoxemia as I have indicated already almost all caes of hypoxemia associated with an elevated aa gradient have more than one mechanism at work and there is no single algorithm to use at this point that will identify a specific diagnosis so instead you must review the history and exam and check a chest x-ray to help narrow down the possibilities if a shunt is present you should also consider getting an echocardiogram with a bubble study in a bubble study agitated saline is infused used into a vein to introduce small bubbles into the right side of the heart the echocardiographer can then observe whether or not these bubbles Bank their way to the left side of the heart which would confirm a shunt is present since the bubbles should not be able to pass through the very narrow pulmonary capillaries if bubbles do end up on the left side based on how quickly they appear there one can make an educated guess as to whether the shunt is present in the heart or the lungs even if the defect leading to the shunt is not directly observable I'm going to end this lecture on this next slide although I just said that there was no specific algorithm to use to determine a specific ideology of hypoxemia there are common patterns of radiographic abnormalities on chest x-ray that can help Focus the differential diagnosis uh this slide is actually adapted from Marini's solid intern level textbook Critical Care Medicine first the lungs on xray could appear completely normal this is what one might expect from a COPD or asthma exacerbation pulmonary embolism hypoventilation intracardiac shunt or pulmonary AVM next the lungs could have a single lobe that appears abnormal this most obviously suggests pneumonia but could also be seen with a pulmonary infar or collapsed lobe then with diffused involvement of just one lung one should consider a large plural affusion collapsed lung or mucus plug severe pneumonia reexpansion ponary edema occurring after a large Fusion has been drained or intubation of the opposite main bronchus finally with Theus bilateral abnormalities one should consider pulmonary edema ards or acute lung injury interstitial lung disease or atypical infections such as viral and fungal pneumonias that concludes this lecture on the mechanisms and ideologies of hypoxemia I hope you found this to be interesting and useful and I also hope it cleared up confusion on a topic that many people find it difficult to wrap their head around if you enjoyed it or have any questions please feel free to like the video or leave a comment the next lecture in the series we'll discuss carbon monoxide poisoning and met hemoglobinemia [Music]