Control of Breathing

Transcription

1 Physio # 11 Dr. Yanal Shafaqoj Done By: Lejan Al - Dof'at 13/12/13 Control of Breathing We talked previously about Oxygen extraction and CO 2 production, and how these are transfused through blood (in different forms) In this lecture we will talk about how O 2, CO 2 and H + affect respiration. CO 2 stimulates peripherally through the H + ion, in CSF the H + ion is important, it comes from CO 2 high/low CO 2 with normal levels of H + ion (that is ph) is not expected to affect the resp. centre. So CO 2 doesn't have any direct effect on the dorsal or ventral resp. groups. Low O 2 levels and high CO 2 levels are able to suppress the dorsal and ventral resp. groups through direct effect but of course this occurs at severely low or severely high (like PaCO 2 of 100) levels of O 2 and CO 2 respectively. Previously before the modern anaesthesia methods were introduced, doctors used to use hazardous ways to anaesthetise their patients; one of which is by giving CO 2 gas since it has deleterious effects on the brain; one of which is analgesia, but the problem that they were facing is their inability to control the dose of what they are giving sometimes they might suppress ventilation and might kill their patient. You can increase your CO 2 level to 50, but in order to accomplish anaesthesia, you need to reach a level of 75 or so, but if it reaches 100 you'll kill your patient and his ventilation is completely suppressed no matter how strong the stimulus from the chemoreceptor area. Now we will discuss an example that will help you understand the physiology of control of breathing which is respiration control while ascending high altitudes Before we discuss such an example, there is a bunch of information we need to know: 1- In our example we will take the Andes as an example and we have to know that the highest village there reaches a level of 5500 m and people live there! 2- The atm. pressure there is around one half of the normal sea level atm. pressure around 380 mmhg 3- The partial pressure of H 2 O vapour in the anatomic dead space is not affected by differences in atm. pressure.

2 So if we take somebody there, what will happen? And what are the physiologic changes that will occur? And how his body will respond to these changes? First of all there is no enough O 2 in the outside area which means that there will be no enough O 2 in blood (hypoxia): O 2 partial pressure in the atmosphere = 21% x 380 = 80 O 2 partial pressure in the anatomic dead space = 21% (380-47) = 70 And this corresponds to PaO 2 of almost 45 this value is low and enough to stimulate peripheral chemoreceptors present in carotid and aortic bodies. In the carotid and aortic bodies, the signal is transferred to the medulla oblongata through the glossopharyngeal nerve (CN 9), while in carotid it is transferred through the vagus nerve (CN 10), so this person now starts hyperventilating where the stimulus here is hypoxia. Now, what does the term hyperventilation exactly means? Hyperventilation means when ventilation leads to decreased PaCO 2 below 40. During exercise for example, there is increased ventilation (not hyperventilation), and increased CO 2 production but PaCO 2 remains normal so this person is not hyperventilating and in this case there is no hyperventilation. On the other hand hypoventilation means when ventilation leads to increased PaCO 2. To understand this we need to remember that: PaCO 2 α CO 2 production/alveolar ventilation So if both CO 2 production and alveolar ventilation increase/decrease proportionally PaCO 2 remains the same hence no hyper/hypoventilation occurs. But if one of these is increased in a larger proportion than the other, hyper/hypoventilation occurs. For example the mother during pregnancy (esp. lately) is hyperventilating slightly therefore she has a slightly low PaCO 2. Now back to our example, as we said it was hypoxia which drove hyperventilation, the purpose of driving ventilation here is to add more O 2 (trying to increase PaO 2 to a level near the atm. level).

3 But when this person hyperventilates, he will wash out CO 2 and end up with a lower PaCO 2 hyperventilation leads to increased PaO 2 and decreased PaCO 2 Of course you remember this equation: CO 2 +H 2 O H + + HCO3 - (1) ph = log ([HCO3 - ]/[CO 2 ]) (Henderson - Hasselbach equation) And since HCO3 - = 24 mmolar in blood and PaCO 2 = 40mmHg (and to convert this to mmloar, our conversion factor is 0.3 [CO 2 ] = 40x0.3 = 1.2 mmolar), then: ph = log20 = = 7.4 which is the normal ph of blood in which there is no hyper/hypoventilation In our example the person is hyperventilating and CO 2 is being washed out, and PaCO 2 is decreased i.e. if it is decreased to 20 [CO 2 ]=0.6 increased ph so we will end up with alkalosis. Let us take few seconds to discuss blood ph: Normal blood ph = 7.40 ± 0.05 any deviation from these levels is considered abnormal < 7.35 is acidosis and >7.45 is alkalosis. Now if the origin of this defect was higher/lower [CO 2 ] then it is considered resp. in origin and if it was higher/lower [HCO3 - ] then it is considered metabolic in origin, to sum up: Decreased [CO 2 ] causing ph > 7.45 is said to be resp. alkalosis. Increased [CO 2 ] causing ph < 7.35 is said to be resp. acidosis. Increased [HCO3 - ] causing ph > 7.45 is said to be metabolic alkalosis. Decreased [HCO3 - ] causing ph < 7.35 is said to be metabolic alkalosis. So alkalosis might be caused by either increased [HCO3 - ] or decreased [CO 2 ], and in our case it is resp. alkalosis. [H + ] in blood normally = 40 nanomolar = 4 x 10-8 when ph = 7.4 According to the equation (1), decreased [CO 2 ] means higher ph and so decreased [H + ] and as we mentioned before H + is an important stimulator for the resp. centre. So in our example we have two opposing stimuli; the first is hypoxia which drives ventilation and the second is alkalosis which suppresses ventilation, this means that hypoxia was not able to completely express itself because of the opposing alkalosis, but in order to allow hypoxia to express itself well we need to maintain ph at normal level. Again in our example, this person was expected to increase his RMV (Resp. Minute Ventilation) to a value near 25 litre instead of the normal 6 litre, but this did not

4 occur, what happened actually that his RMV increased only slightly to a value near 10 litre that is less than double, again due to the opposing effect of low [H + ] (alkalosis) since it stimulates centrally to stop hyperventilation. Now as we said before, in order for hypoxia to express its effect well on RMV, the body has to maintain its ph, so what happens here is that on the next day the RMV increases to 12 then to 14, 16, 18, 20 and so on to reach the expected level (25 litre) on the next 4-5 days. This is accomplished by decreasing the level of HCO3 - to 12 (its half) so that blood ph normalises to 7.4 thus [H + ] is normal and does not cause an opposing effect on respiration meaning that hypoxia now is able to express itself well. HCO3 - (bicarbonate) ion can be symbolized as the diamonds of the body, we can't tolerate its loss; our urine is almost bicarbonate free, in our case the kidneys start excreting bicarbonate in order to keep ph at normal levels. To sum up, after 4-5 days we will end up with: Low PaCO 2 caused by hyperventilation Low bicarbonate (in order for ph to return back to normal) Low PaO 2 (compared to normal sea levels) even with hyperventilation Blood ph (arterial [H + ]) is normal At this level what drives ventilation is hypoxia alone and there is no other opposing factor. As we have seen, kidneys compensated for the low PaCO 2 by excreting bicarbonate in urine, so now if we do urinalysis to this patient we shall notice that he will have a high level of bicarbonate in his urine. Now we need to emphasize on these points: In our example, this person when he was ascending, there was peripheral stimulation associated with central suppression Also this person after 6 weeks of ascending, his [Hb] will increase to 20 g/dl from the normal 15 g/dl, his Hct will increase to 60% and blood volume will increase by 16% in order to compensate for hypoxia O 2 carrying capacity depends on [Hb] and saturation of Hb, so increasing [Hb] will compensate for the low saturation in people who live there People who live there at the Andes have big chests and small bodies (small muscles), and this is not genetic at all, it is adaptive to the environment and occurs at the first years of life (if a baby from the Andes is taken to live at an area of normal altitude he will develop normal chest and body and then if he is taken back he will keep the same size of his chest and body)

5 People who live there have learned that during late pregnancy women should descend down because the two effects (pregnancy and high altitude) combine together to cause more hyperventilation Also people at the Andes have increased vascularisation in their muscles, but on the other hand the changes mentioned in this point and the second point will cause the people living there to have increased risk of thrombosis and thrombotic attacks; polycythemia causes increased viscosity of blood and increased risk of clot formation In addition to the pre-mentioned adaptations, people living there have more sensitive carotid bodies (sensitive to lower levels of PaCO 2 ) An important point to mention here is that the carotid bodies are more important than aortic bodies due to the following: 1. Carotid bodies are more sensitive than aortic bodies which is also true for BP 2. Aortic but not the carotid bodies are more sensitive to H +, O 2 and CO 2, but only with a power of 1/7 th of central stimulation. On the other hand it occurs faster i.e. if CO 2 is increased they will be sensitised early while central stimulation takes time since it needs CO 2 to reach CSF and to be converted to H + to stimulate the chemoreceptors. 3. Although they respond faster to increasing levels of CO 2, in terms of quantity aortic bodies have less effect on stimulation of respiration (that is 1/7 th of central stimulation). This response is important since it gives the body a chance to face increasing levels of CO 2 earlier An important thing to know now is the altitude at which we start facing hypoxia, actually we can reach altitudes of m above sea level without affecting our respiration, and that we shall reach higher altitudes in order to face hypoxia that is likely to affect our respiration Now we can imagine what would happen during descending, ventilation would decrease because the hypoxic event stopped and there is no stimulus to increase ventilation but we will see that the person still has increased ventilation for several days because as he ascends PaCO 2 increases which will cause resp. acidosis which will drive ventilation, and again in the coming few days the kidneys will compensate by retaining more bicarbonate in order to reach its normal levels (around 24) so that blood ph normalises. We have seen that the body needs to reach the acclimatised level (التأقلم) during ascending and descending so that it keeps ph at normal levels. During Exercise: before the onset of exercise, ventilation starts increasing so the person starts washing out CO 2 but he is not producing CO 2 (did not start exercising yet) thus his ventilation might return back to normal. Now during exercise his

6 ventilation increases and keeps on increasing but at this level CO 2 production is proportional to ventilation so PaCO 2 remains normal and PaO 2 remains normal as well. This indicates that the lungs are very good ventilators; it can provide enough O 2 and wash out CO 2 even during severe exercise. By the way, at very severe exercise, ventilation becomes increased more than CO 2 production because severe exercise might become anaerobic producing lactic acid stimulating respiratory centre through peripheral receptors, so we have more washing out of CO 2 than its production thus CO 2 levels decrease during late stages of severe exercise although through all this the person was breathing faster he was never hyperventilating since PaCO 2 did not decrease except at late stages of severe exercise. On the other hand we shall note that O 2 (as a whole) did not increase, although PaO 2 might increase and even reach like 110, this is unlikely to affect the total content of O 2 in blood, since it is not expected to change the percent saturation of Hb (recall O 2 Hb dissociation curve). Now when the person stops exercise all of sudden, you see that his ventilation is still increased although there is no hypoxia, no CO 2 production, and no lactic acid production! So what drives ventilation is not hypoxia, CO 2, and not H +, it is definitely something in the muscles; actually the proprioreceptors in the muscles carry impulses to medulla oblongata and in addition to this the burst of impulses going to muscles to contract also go to resp. centre in order to prepare it for the coming event. To sum up PaCO 2 and PaO 2 (blood gases as a whole) remain normal during exercise and they don't drive ventilation as we said. Important notes we need to emphasise: Increased ventilation means increased RMV Tachypnea means increased rate of breathing CO 2 is a suppressor at very high levels (100 or so) but at high-near normal levels it is a stimulator No one can kill himself by holding his breath, but if a person takes an overdose of morphine which will suppress resp. centre and cause diminished breathing, his PaCO 2 might reach 100 which kills him I think this is the end of the sheet, hope it was well clarified, and nothing was missed, and please forgive me for any mistake.