 According to Dalton's law, partial pressure of any gas is determined by the percentage composition of that gas in a mixture of gases. So, when we calculate partial pressure of oxygen in atmospheric air, we know that the percentage composition of oxygen is around 21% and we multiply this 21% with the total atmospheric pressure which at sea level is 760 millimeter So, basically it is given by a percentage composition of the gas multiplied by the total atmospheric pressure. Now, as we ascend to high altitude, what happens that there is decline in this total atmospheric pressure? Percentage composition of the gas remains the same. Remember this. Okay, so this percentage composition or the percentage of oxygen which we inhale that is also known as FiO2 that is fraction of inspired oxygen. So, that will be how much it will be? 21% or if we put it in fraction, it will be 0.21. Now, at high altitude, this percentage composition or FiO2 is same only. Only the total atmospheric pressure is dropping. But since partial pressure of oxygen is determined by both, what will happen? Partial pressure of oxygen is going to decrease and when this inhaled partial pressure of oxygen decreases in the alveoli, the partial pressure of oxygen is going to decrease. So, obviously less oxygen will be able to cross to the blood and hence partial pressure of oxygen in the blood vessels is also going to drop. Now, because oxygen content depends on this partial pressure of oxygen and the amount of oxygen which is bound to hemoglobin. So, that determines the total content and if you remember that oxy hemoglobin dissociation curve for which I have another video also. So, what happens that on x-axis, there is partial pressure of oxygen and on y-axis, there is percentage hemoglobin saturation. So, you see this percentage hemoglobin saturation is directly dependent on the partial pressure of oxygen. So, when partial pressure of oxygen will decrease, less oxygen will be bound to hemoglobin. So, obviously, total content of oxygen is going to fall in the blood and what is this? This is hypoxia because less auto content, that means less auto will be delivered to tissues also. So, this ascent to high altitude leads to hypoxia and because it is due to decrease in the partial pressure of oxygen, this is known as hypoxemia, hypoxemia. So, hypoxemia is leading to hypoxia and that is known as hypoxic hypoxia. So, at high altitude, what is the main problem? Main problem is hypoxic hypoxia. Okay. So, what happens that as we ascent to high altitude, body responds to this hypoxic hypoxia and make some changes and these bodily changes which occur at high altitude help us sustain that environment and these changes are known as acclimatization. So, what is acclimatization? Bodily changes which occur which help us adapt to the high altitude environment. So, what are these changes which occur in acclimatization? Let us see. For this one fundamental you should remember that all changes are such that body is better able to supply oxygen to the tissues and they are able to use whatever oxygen is available in a better way. So, first changes which occur they are in pulmonary system. So, you see there is decrease in partial pressure of oxygen in blood and this partial pressure of oxygen is detected by peripheral chemoreceptors and what happens when this peripheral chemoreceptors are detected low partial pressure of oxygen they will increase the rate and depth of ventilation, right. So, that is the first change which occurs but remember when there is increase in rate and depth of the ventilation more oxygen is going in. But with increase in ventilation you see oxygen comes in but carbon dioxide moves out of the body and because of that what happens that there will be decrease in the partial pressure of carbon dioxide in blood and this decreased partial pressure of carbon dioxide will cause increase in the pH thus leading to respiratory alkalosis, okay. And you see that fall in partial pressure of carbon dioxide tends to inhibit this rate and depth of ventilation because fall in partial pressure of oxygen will increase ventilation but fall in partial pressure of carbon dioxide will decrease ventilation. So, you see what is happening that this response of increasing in ventilation is getting blunted it is not that effective. So, now what to do? Well body has other mechanisms to cope with this. So, kidneys now start working for correction of this pH how they will do? They will cause more excretion of bicarbonate ions in urine thus causing correction in pH. So, what is the point of all this thing? Well the point is that decrease in partial pressure of oxygen is not that effective initially in causing increase in ventilation. This increase in ventilation is maximum only by 4th to 7th day of ascent to higher altitude, okay. Only when this pH is getting corrected by the kidneys. So, that is why it is very important that we slowly ascent to high altitude and should not be like we land up at a very high altitude on day one. Though sometimes it is not possible say suppose there are rescue operation going on or there is a war going on. So, basically the military people who are posted there it will not be possible for them to have a slow ascent to high altitude. So, we will see that what can be the problems and how to deal with that. But you remember this that the maximum ventilator response occurs by 4th to 7th day of ascent to high altitude. So, that is the first change which occurs in respiratory system. Second what happens that because of decrease in the partial pressure of oxygen the metabolism in RBC changes such that there is increase in 2-3 BPG and this 2-3 BPG you can recall from oxy hemoglobin dissociation curve that this 2-3 BPG shifts the curve to the right, okay. And when this curve shifts to the right what happens that there will be increase in release of the oxygen, right. So, this is partial pressure of oxygen this is percentage hemoglobin saturation and this curve is shifted to the right. So, you see that at higher partial pressure of oxygen the percentage hemoglobin saturation actually is much lesser. So, in the original graph it will be somewhere here, okay. But when there is shift to the right percentage hemoglobin saturation decreases such that there is increase in delivery of oxygen to the tissues. Again you remember that this respiratory alkalosis what does it do? It is causing increase in pH and when we apply this increase in pH to oxy hemoglobin dissociation curve it tends to shift the curve to the left, right. So, again you see that this maximum effect will take some time when there is correction of the alkalosis also the effect of 2-3 BPG is somewhat more causing ultimate a little shift to the right only. So, that causes more delivery of oxygen to the tissues. Then there is increase in diffusion capacity as well. So, there is increase in diffusion capacity to understand this we have to understand first the cardiovascular changes which are happening. See in hypoxia what happens there is increase in the sympathetic activity and whenever sympathetic activity increases what will be the effect on heart? It causes increase in the heart rate and increase in the contractility causing ultimately increase in the cardiac output. So, when cardiac output increases more blood goes to the lungs as well more is obviously going to the systemic vessels that is why the left ventricle but more will go to the lungs as well. So, these pulmonary vessels show a phenomena known as capillary recruitment capillary recruitment because in you see normal conditions some of the capillaries are in closed state. So, to accommodate this extra blood they open up and whatever capillaries are open there is some dilation also. So, there is opening of the capillary and distension of the capillaries as well and because of this there is increase in the surface area across which the diffusion can take place. So, hence causing increase in the diffusion capacity. So, that is the third change in the pulmonary system and with this we shift to the cardiovascular system where we have already seen that there is increase in the cardiac output. So, that more blood is available to the lungs for diffusion and more goes to the peripheral tissues as well. Then secondly there is change in the vascular system. See what is the effect of hypoxia on vessels it causes local vasodilation. So, the vessels become dilated. So, this accommodates more blood also and more delivery of blood to the tissues also occurs. So, these are the cardiovascular changes which are occurring in acclimatization. Then one very important factor for delivery of oxygen to the tissues is RBCs and there are mechanisms where hypoxia leads to increase in production of the RBCs. That is why erythropoietin whenever there is hypoxia in the kidneys in the interstitial cells that is the fibroblast which are there there is increased production of erythropoietin and that is because of a factor which increases in the cells that is the hypoxia inducible factor. Very important see a noble price has also been given for the discovery of this mechanism that how hypoxia leads to certain changes and that is via hypoxia inducible factor. So, erythropoietin causes increase in the production of the RBCs and even though oxygen binds less to the hemoglobin because of increase in RBCs the total oxygen content is going to increase and then finally there is effect at the tissue level as well. So, whatever oxygen is going to the tissues they are able to utilize it better though these changes take much more time. The changes for increase in RBC it takes around a one week okay. So, this is also because the increased production of RBC it will take some time so little longer time is required for this chain and then at tissue level also the changes which occur they require some time and these are increase in the blood vessels right. So, that is one change and that occurs again via angiogenesis and the factor involved is hypoxia inducible factor which causes increase in production of vascular endothelial growth factor and this is the factor which is responsible for angiogenesis. Then there is increase in the mitochondrial enzymes also for better oxygen utilization. So, you see how the various changes are occurring at various tissues in the lungs in the cardiovascular system in the production of the RBCs at the tissue level and all are directed to increase the supply of the oxygen to the tissues and better utilization of oxygen as well by the tissues. So, that was about acclimatization but what will happen if acclimatization changes are not proper for example, when the ascent is very fast to high altitude or in case say suppose the person is susceptible like in case of a person having frequent respiratory tract infections. So, in that case these changes may not be enough for adaptation to high altitude and in that case there is maladaptation to high altitude leading to altitude syndrome. So, what are these altitude syndromes? These are certain changes which occur in the brain and in the pulmonary system. So, the changes which occur in the brain they range from what is known as acute mountain sickness or AMS and in extreme cases it causes high altitude cerebral edema. So, why this high altitude cerebral edema may occur? What is the mechanism or acute mountain sickness? If it is very mild then what is the cause? See this acute mountain sickness is basically a benign condition and high altitude cerebral edema is a life-threatening condition. So, they are like the opposite ends of the same spectrum and why they occur is because of development of cerebral edema. How the cerebral edema develops? See again and again we are telling that hypoxia causes vasodilation in the tissues in the systemic vessels. So, this hypoxia also causes cerebral vasodilation and when there is cerebral vasodilation it causes increase in the hydrostatic pressure in the cerebral vessels and if you remember the starlings forces even if you don't remember I have another video you can go watch that very concept-based video on starlings forces. So, increase in hydrostatic pressure in cerebral vessels will cause leakage of the fluid leading to cerebral edema because more fluid will be leaving the vessels right and this cerebral edema affects the functioning of the neurons. So, what will be the features of this? Well, acute mountain sickness is a benign condition and the symptoms which are there are non-specific symptoms like nausea, vomiting, headache and there is fatigue then anorexia because that is the person doesn't want to take food. So, that means the cerebral edema is mild cerebral edema and this acute mountain sickness appears around 6 to 12 hours after SN2 high altitude. On the other hand this haze I told you it is light threatening condition and one of the very important component of haze is ataxia. Hallmark is ataxia and decrease in consciousness very important features of high altitude cerebral edema. So, what to do if these features start developing? Since these features are caused by a decrease in the partial pressure of oxygen in the blood. So, our main goal is to cause increase in the partial pressure of oxygen and how to do that? Very important is descent to a lower altitude. So, that is the main important thing which should occur and if descent is not possible in that case there should be availability of oxygen cylinders as I told you that there are certain occupations in which it is needed that the person goes to the high altitude instantly and remains there to rescue other people but for that we have to rescue the person himself if he develops these features. So, oxygen cylinders should be made available to them so as to increase the partial pressure of oxygen. So, when the person breathes from these oxygen cylinders which are basically having increase in the percentage of oxygen in them. So, what we are doing is that we are increasing FiO2 because we said that in high altitude basically total atmospheric pressure which is declining but if we breathe from a mixture of gases which is having increased percentage of oxygen in that case we will be increasing the partial pressure of oxygen in blood. Second important drug is dexamethasone. Dexamethasone has shown to decrease the cerebral edema. So, that is also very important and how to prevent this AMSN he has developed one obviously ascent should be slow right that again I am repeating again and again so ascent should be slow and it is said that at a high altitude of greater than 3000 meters ascent should not be more than 300 meters per day and after three days of continuous ascent we should have one extra day of rest also. So, that is the guidelines which have come for prevention of development of AMSN he has. Then second we can also give a preventive drug that is acetazolamide. What does this acetazolamide do? This is basically a diuretic and this diuretic works by inhibiting the enzyme carbonic anhydrase but one main side effect of acetazolamide when used as diuretic is metabolic acidosis. So, the side effect which develops when we use it as a diuretic here we are using it for its beneficial purpose. So, metabolic acidosis will counter the respiratory alkalosis and thus it will help in faster reclimatization to high altitude. So, basically it is a started one day before the start of the ascent and is continued for two to three days while the person is at high altitude. So, that was about AMSN he has. Let's come to another important maladaptation to high altitude that is HAPE, high altitude pulmonary edema. Why this high altitude pulmonary edema develops because these pulmonary vessels respond differently than that of the systemic vessels. When there is hypoxia that is decreased in partial pressure of oxygen, pulmonary vessels undergo vasoconstriction unlike that of systemic vessels very important. Now, you see there are various alveoli right various alveoli are there in lungs and there will be vessels. So, whenever in a particular alveoli there is decrease in partial pressure of oxygen that particular blood vessel will undergo vasoconstriction. So, the diameter is going to decrease and hence the blood will be diverted to other blood vessels where the partial pressure of oxygen is much better. So, that is why these pulmonary vessels respond to hypoxia differently than that of systemic vessels because it causes better VQ match wherever ventilation is more there perfusion should be there. If ventilation is not good then perfusion should not go to that particular alveoli. But in case of high altitude it works negatively for us because partial pressure of oxygen is like decreased in almost all the alveoli and they undergo this vasoconstriction. So, what happens that overall there is increase in the pulmonary hydrostatic pressure ok. And as we have seen in the case that how increase in the hydrostatic pressure causes increase in filtration of the fluid. So, here also increase in hydrostatic pressure will cause increase in the filtration of fluid in the pulmonary vessels causing development of edema. So, pulmonary edema develops and you see if pulmonary edema develops that means there is fluid collection here in the interstitial space what will happen? You see the diffusion of oxygen will be decreased further because of thickness through which now the oxygen has to diffuses increasing. So, more and more development of pulmonary edema more and more it causes hypoxia. So, what are the symptoms which occur in hip is there is a development of cuff ok. Then because of more and more hypoxia there occurs tachycardia, there occurs increase in the rate of ventilation again. So, that is known as tachypnea and these tachycardia and tachypnea are important markers that disease is progressing. So, how to prevent the development of hip? Again, ascent should be very slow as given by the guideline. So, slow ascent should be there and then there is a drug that is nifedipine. Nifedipine is a calcium channel blocker which can be given and this calcium channel blocker basically causes vasodilation and hence causes decrease in pulmonary vascular resistance. Then there is phosphodiesterase inhibitors, phosphodiesterase 5 inhibitors actually their use is not that proven, but still it is used clinically. This phosphodiesterase 5 inhibitors cause increase in CGMP and because of this increase in nitric oxide occurs. So, endothelial cells release nitric oxide and this nitric oxide increase release is responsible for pulmonary vasodilation. So, this is for prevention and what could be the treatment? Yes, give oxygen immediately because main cause is decrease in the partial pressure of oxygen and second, descent to low altitude as fast as possible. So, that was about high altitude pulmonary edema. Then there is another disease which occurs in people who reside at high altitude for too long basically the residence of high altitude that is chronic mountain sickness also known as mongaze disease. And what happens that we have seen that in adaptation to high altitude there is increase in the production of the RBCs, but when there is too much increase in RBC production it leads to increase in viscosity and viscosity when increases there is increase in resistance to blood flow. If you remember that what are the factors which affect resistance to blood flow then the formula is somewhat like this and that R is the radius of the blood vessels that is a vasodilation vasoconstriction which we discussed too often, but this eta that is the viscosity. So, increase in viscosity causes increase in the resistance to blood flow and hence it also increases resistance in the pulmonary vessels. So, there is pulmonary hypertension which develops. Now, with pulmonary hypertension right heart has to pump against a greater resistance to push blood to the lungs, isn't it? And when this occurs for a very long time it leads to development of right ventricular hypertrophy and ultimately it leads to heart failure. So, that is chronic mountain sickness and how to treat that? Well, we have to ask the person obviously to move to low altitude and for immediate effect when a section may work that is the loss of blood we have to ensure that some loss of blood occurs so as to remove excess RBCs. So, as the person to move to low altitude the venous section can help and again acetazolamide can help because it will ensure a better ventilatory response so that the partial pressure of oxygen is not too low and the stimulus for RBC production decreases. So, that was all about the physiology of high altitude why there is development of the hypoxic hypoxia what are the changes which occur in body for acclimatization and what are the mal-adaptation syndromes which can occur. Thanks for watching the video if you liked it do press the like button share the video with others and don't forget to subscribe to the channel Physiology Open. Thank you.