Fourth part
ERYTHROPOIETIN (EPO), FACTOR INDUCED BY HYPOSIA (HIF) AND HYPERTENTILATION
EPO has long been recognized as the physiological regulator of red blood cell production. It is produced mainly in the kidney in response to hypoxia and cobalt chloride.
Most cells, exposed to hypoxia, are in a quiescent state, reducing mRNA synthesis by about 50-70%. Some genes, like the factor induced by hypoxia, are stimulated instead.
HIF is a protein contained in the cell nucleus that plays a fundamental role in gene transcription in response to hypoxia. It is in fact a transcription factor that codes for the proteins involved in the hypoxic response and is fundamental for the synthesis of erythropoietin.
Under hypoxic conditions the oxygen sensor pathway (for many cells is represented by cytochrome aa3) is blocked, therefore HIF increases. The events that take place downstream of the sensor to activate the expression of the EPO gene require a new protein synthesis and the production of specific transcription factors. Transcription of the EPO gene on the chromosome begins in the nucleus.
Hyperventilation occurs at rest already at about 3400 m (in proportion to the height reached). Acute hypoxia stimulates chemoreceptors (in particular carotid glomas), sensitive to the lowering of PO2 in arterial blood, which can increase ventilation up to around 65%.
After a few days at high altitude, the so-called "ventilatory acclimatization" is established, characterized by an evident increase in pulmonary ventilation at rest.
Physical exercise, both in acute and chronic hypoxia, determines hyperventilation much higher than at sea level; the cause would be found in an increase in the activity of the chemoreceptors and respiratory centers caused by the reduced partial pressure of O2.
Finally it should be noted that the energy cost of pulmonary ventilation increases in altitude due to hyperventilation. In fact, as reported in studies conducted by Mognoni and La Fortuna in 1985, at altitudes varying between 2300 and 3500 m, an energy cost for pulmonary ventilation was found to be 2.4 to 4.5 times higher than at sea level (with the same effort ).
The average value of blood pH in normoxic conditions is 7.4. The hyperventilation that appears in ascension at high altitude, in addition to having the effect of increasing the amount of oxygen available to the tissues, causes an increase in the elimination of carbon dioxide with expiration. The consequent drop in the CO2 blood concentration leads to a shift in blood pH towards alkalinity, increasing to values of 7.6 (respiratory alkalosis).
The blood pH is influenced by the blood concentration of bicarbonate ions [HCO3-], which represent the body's alkaline reserve. To compensate for respiratory alkalosis, during acclimatization the body increases the excretion of bicarbonate ion with the urine, bringing the blood pH values back to normal. This mechanism of compensation of the respiratory alkalosis that occurs in the subject perfectly acclimatized has as a consequence the reduction of the alkaline reserve, therefore of the buffering power of the blood towards for example the lactic acid produced during exercise. It is in fact known that in the acclimatized there is a considerable reduction in the "lactic capacity".
After about 15 days at high altitude there is a progressive increase in the concentration of red blood cells in the circulating blood (poliglobulia), the more marked the higher the altitude, reaching the maximum values after about 6 weeks. This phenomenon represents a further attempt by the body to compensate for the negative effects of hypoxia. In fact, the reduced partial pressure of oxygen in arterial blood causes an increased secretion of the hormone erythropoietin that stimulates the bone marrow to increase the number of red blood cells, so as to allow the hemoglobin contained in them, to carry a greater quantity of O2 to fabrics. In addition, together with the red blood cells the concentration of hemoglobin [Hb] and the value of the hematocrit (Hct) also increase, ie the percentage volume of blood cells in relation to its liquid part (plasma). The increase in hemoglobin concentrations [Hb] is opposed to the reduction of PO2 and, during long stays at high altitudes, can increase by 30-40%.
Even the O2 saturation of hemoglobin undergoes changes with altitude, ranging from a saturation of about 95% at sea level to 85% between 5000 and 5500 m of altitude. This situation creates serious problems in transporting oxygen to the tissues, particularly during muscular work.
Under the stimulus of acute hypoxia the heart rate increases, to compensate with a greater number of beats per minute, the lower availability of oxygen, while the systolic range decreases (ie the amount of blood that the heart pumps at each beat decreases). In chronic hypoxia the heart rate returns to normal values.
The maximum effort heart rate undergoes due to acute hypoxia a limited reduction and scarcely influenced by altitude. In the acclimatized subject, on the other hand, the maximum effort heart rate is very reduced in proportion to the height reached.
Ex .: MAX effort level at sea level: 180 beats per minute
MAX FC effort at 5000 m: 130-160 beats per minute
Systemic blood pressure shows a transient increase in acute hypoxia, while in the acclimatized subject the values are similar to those recorded at sea level.
Hypoxia seems to exert a direct action on the pulmonary artery muscles, causing vasoconstriction and causing a significant increase in arterial pressure in the pulmonary district.
The consequences of altitude on metabolism and performance capabilities cannot be easily schematized, in fact there are several variables to consider, related to individual characteristics (eg age, health conditions, residence time, training conditions and altitude habit, type of sporting activity) and environmental (eg altitude of the region where the service is performed, climatic conditions).
As for the effects on energy metabolism, it can be said that hypoxia causes a limitation both at the level of aerobic and anaerobic processes. In fact, it is known that, both in acute and chronic hypoxia, the maximum aerobic power (VO2max) decreases proportionally with increasing altitude. However up to about 2500 m of altitude, the athletic performance in some sports performances, such as the 100 m run and the 200 m run, or launch or jump competitions (in which aerobic processes are not affected) improves slightly. This phenomenon is linked to the reduction in air density which allows a slight energy saving.
The lactic acid capacity after a maximal effort in acute hypoxia does not change with respect to sea level. After acclimatization instead it undergoes an evident reduction, probably due to the decrease in the buffer power of the organism in chronic hypoxia. In these conditions, in fact, the accumulation of lactic acid caused by maximal physical exercise would lead to an excessive acidification of the organism, which could not be buffered by the reduced alkaline reserve due to acclimatization.
Generally, excursions up to 2000 m above sea level do not require special precautions for people in good health and training. In the case of particularly demanding excursions, it is worthwhile to reach the altitude the day before, in order to allow the body to have a minimum adaptation to the altitude (which can cause tachycardia and moderate tachypnea), so as to allow physical activity without excessive fatigue.
When one intends to reach altitudes between 2000 and 2700 m, the precautions to be followed do not differ much from the previous ones, it is advisable only a period of adaptation to the altitude a little longer (2 days) before starting an excursion, or in alternatively reach the site gradually, possibly with your own physical resources, by starting the hike from a height that is close to those in which you normally stay.
If you make challenging excursions of several days at altitudes ranging from 2700 to 3200 m asl, ascents must be divided into several days, programming a climb to the maximum altitude followed by re-entry at lower altitudes.
The pace of walking during excursions must be constant and of low intensity to avoid phenomena of early onset of fatigue due to the accumulation of lactic acid.
We must also always keep in mind that even at heights above 2300 m, supporting training sessions at the same intensity as those at sea level is practically impossible, and with increasing altitude the intensity of the exercises is proportionally reduced. At altitudes around 4000 m, for example, cross-country skiers can withstand training loads around 40% of VO2 max compared to those at sea level that are around 78% of VO2 max. Over 3200 m, challenging hikes lasting several days recommend staying at altitudes of less than 3000 m for a period of time ranging from a few days to 1 week, time for acclimatization to avoid or at least reduce the physical problems produced by hypoxia.
It is necessary to prepare for the excursion with a training appropriate to the intensity and difficulty of the excursion, in order not to risk endangering one's own safety and that of those who accompany us, as well as that of any rescuers.
The mountain is an extraordinary environment of which it is possible to experience many aspects, abandoning oneself to unique and personal experiences, such as the intimate satisfaction of having with one's own means crossed and reached magical places, enjoying splendid natural environments, far from chaos and pollution. Some cities.
At the end of a demanding excursion, the feelings of well-being and serenity that accompany us make us forget the hardships, the inconveniences and the dangers that we have sometimes faced.
It must always be borne in mind that the risks in the mountains can be multiplied by the particular and extreme characteristics of the environment itself (altitude, climate, geomorphological characteristics), so simple walks in the woods or demanding hikes must always be planned accordingly and in proportion to the physical conditions and the technical preparation of each participant, organizing themselves responsibly and leaving aside unnecessary competitions.
Overall, the studies therefore indicate that, after acclimatization, there is a significant increase in hemoglobin (Hb) and hematocrit (Hct), the two simplest and most studied parameters. Going into the details, however, we realize that the results are far from univocal, both because of the different protocols used and because of the presence of "confounding" factors. It is known, for example, that the acclimatization to hypoxia causes a reduction in plasma volume (VP) and consequently a relative increase in Hct values. This process could be due to a loss of proteins from the plasma, an increase in capillary permeability, dehydration or an increase in diuresidiuresi. Furthermore, during physical exercise, there is a redistribution of the VP that passes from the vascular bed to the muscular interstitium, due to an increase in tissue osmotic pressure and a greater capillary hydrostatic pressure. These two mechanisms suggest that, in athletes already acclimatized to high altitude, the plasma volume may be significantly reduced during strenuous exercises conducted in hypoxia.
The hypoxic stimulus (natural or artificial) of adequate duration therefore produces a real increase in the red cell mass, albeit with a certain individual variability. In order to improve performance, however, it is likely that other peripheral adaptations will occur, such as a greater ability on the part of the muscle tissue to extract and use oxygen. This statement is true both in sedentary subjects and in athletes, as long as they manage to train with workloads of adequate intensity to remain competitive.
In conclusion, it can be stated that exposure to climatic conditions different from the usual ones represents a stressful event for the organism; high altitude is a challenge not only for the mountaineer but also for the physiologist and the doctor.
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Edited by: Lorenzo Boscariol
