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THE EFFECTS OF ALTITUDE ON HUMAN PHYSIOLOGY Changes in altitude have a profound effect on the human body. The body attempts to maintain a state of homeostasis or balance to ensure the optimal operating environment for its complex chemical systems. Any change from this homeostasis is a change away from the optimal operating environment. The body attempts to correct this imbalance. One such imbalance is the effect of increasing altitude on the body's ability to provide adequate oxygen to be utilized in cellular respiration. With an increase in elevation, a typical occurrence when climbing mountains, the body is forced to respond in various ways to the changes in external environment. Foremost of these changes is the diminished ability to obtain oxygen from the atmosphere. If the adaptive responses to this stressor are inadequate the performance of body systems may decline dramatically. If prolonged the results can be serious or even fatal. In looking at the effect of altitude on body functioning we first must understand what occurs in the external environment at higher elevations and then observe the important changes that occur in the internal environment of the body in response. HIGH ALTITUDE In discussing altitude change and its effect on the body mountaineers generally define altitude according to the scale of high (8,000 - 12,000 feet), very high (12,000 - 18,000 feet), and extremely high (18,000+ feet), (Hubble, 1995). A common misperception of the change in external environment with increased altitude is that there is decreased oxygen. This is not correct as the concentration of oxygen at sea level is about 21% and stays relatively unchanged until over 50,000 feet (Johnson, 1988). What is really happening is that the atmospheric pressure is decreasing and subsequently the amount of oxygen available in a single breath of air is significantly less. At sea level the barometric pressure averages 760 mmHg while at 12,000 feet it is only 483 mmHg. This decrease in total atmospheric pressure means that there are 40% fewer oxygen molecules per breath at this altitude compared to sea level (Princeton, 1995). HUMAN RESPIRATORY SYSTEM The human respiratory system is responsible for bringing oxygen into the body and transferring it to the cells where it can be utilized for cellular activities. It also removes carbon dioxide from the body. The respiratory system draws air initially either through the mouth or nasal passages. Both of these passages join behind the hard palate to form the pharynx. At the base of the pharynx are two openings. One, the esophagus, leads to the digestive system while the other, the glottis, leads to the lungs. The epiglottis covers the glottis when swallowing so that food does not enter the lungs. When the epiglottis is not covering the opening to the lungs air may pass freely into and out of the trachea. The trachea sometimes called the "windpipe" branches into two bronchi which in turn lead to a lung. Once in the lung the bronchi branch many times into smaller bronchioles which eventually terminate in small sacs called alveoli. It is in the alveoli that the actual transfer of oxygen to the blood takes place. The alveoli are shaped like inflated sacs and exchange gas through a membrane. The passage of oxygen into the blood and carbon dioxide out of the blood is dependent on three major factors: 1) the partial pressure of the gases, 2) the area of the pulmonary surface, and 3) the thickness of the membrane (Gerking, 1969). The membranes in the alveoli provide a large surface area for the free exchange of gases. The typical thickness of the pulmonary membrane is less than the thickness of a red blood cell. The pulmonary surface and the thickness of the alveolar membranes are not directly affected by a change in altitude. The partial pressure of oxygen, however, is directly related to altitude and affects gas transfer in the alveoli. GAS TRANSFER To understand gas transfer it is important to first understand something about the behavior of gases. Each gas in our atmosphere exerts its own pressure and acts independently of the others. Hence the term partial pressure refers to the contribution of each gas to the entire pressure of the atmosphere. The average pressure of the atmosphere at sea level is approximately 760 mmHg. This means that the pressure is great enough to support a column of mercury (Hg) 760 mm high. To figure the partial pressure of oxygen you start with the percentage of oxygen present in the atmosphere which is about 20%. Thus oxygen will constitute 20% of the total atmospheric pressure at any given level. At sea level the total atmospheric pressure is 760 mmHg so the partial pressure of O2 would be approximately 152 mmHg. 760 mmHg x 0.20 = 152 mmHg A similar computation can be made for CO2 if we know that the concentration is approximately 4%. The partial pressure of CO2 would then be about 0.304 mmHg at sea level. Gas transfer at the alveoli follows the rule of simple diffusion. Diffusion is movement of molecules along a concentration gradient from an area of high concentration to an area of lower concentration. Diffusion is the result of collisions between molecules. In areas of higher concentration there are more collisions. The net effect of this greater number of collisions is a movement toward an area of lower concentration. In Table 1 it is apparent that the concentration gradient favors the diffusion of oxygen into and carbon dioxide out of the blood (Gerking, 1969). Table 2 shows the decrease in partial pressure of oxygen at increasing altitudes (Guyton, 1979). Table 1 ATMOSPHERIC AIR ALVEOLUS VENOUS BLOOD OXYGEN 152 mmHg (20%) 104 mmHg (13.6%) 40 mmHg CARBON DIOXIDE 0.304 mmHg (0.04%) 40 mmHg (5.3%) 45 mmHg Table 2 ALTITUDE (ft.) BAROMETRIC PRESSURE (mmHg) Po2 IN AIR (mmHg) Po2 IN ALVEOLI (mmHg) ARTERIAL OXYGEN SATURATION (%) 0 760 159* 104 97 10,000 523 110 67 90 20,000 349 73 40 70 30,000 226 47 21 20 40,000 141 29 8 5 50,000 87 18 1 1 *this value differs from table 1 because the author used the value for the concentration of O2 as 21%. The author of table 1 choose to use the value as 20%. CELLULAR RESPIRATION In a normal, non-stressed state, the respiratory system transports oxygen from the lungs to the cells of the body where it is used in the process of cellular respiration. Under normal conditions this transport of oxygen is sufficient for the needs of cellular respiration. Cellular respiration converts the energy in chemical bonds into energy that can be used to power body processes. Glucose is the molecule most often used to fuel this process although the body is capable of using other organic molecules for energy. The transfer of oxygen to the body tissues is often called internal respiration (Grollman, 1978). The process of cellular respiration is a complex series of chemical steps that ultimately allow for the breakdown of glucose into usable energy in the form of ATP (adenosine triphosphate). The three main steps in the process are: 1) glycolysis, 2) Krebs cycle, and 3) electron transport system. Oxygen is required for these processes to function at an efficient level. Without the presence of oxygen the pathway for energy production must proceed anaerobically. Anaerobic respiration sometimes called lactic acid fermentation produces significantly less ATP (2 instead of 36/38) and due to this great inefficiency will quickly exhaust the available supply of glucose. Thus the anaerobic pathway is not a permanent solution for the provision of energy to the body in the absence of sufficient oxygen. The supply of oxygen to the tissues is dependent on: 1) the efficiency with which blood is oxygenated in the lungs, 2) the efficiency of the blood in delivering oxygen to the tissues, 3) the efficiency of the respiratory enzymes within the cells to transfer hydrogen to molecular oxygen (Grollman, 1978). A deficiency in any of these areas can result in the body cells not having an adequate supply of oxygen. It is this inadequate supply of oxygen that results in difficulties for the body at higher elevations. ANOXIA A lack of sufficient oxygen in the cells is called anoxia. Sometimes the term hypoxia, meaning less oxygen, is used to indicate an oxygen debt. While anoxia literally means "no oxygen" it is often used interchangeably with hypoxia. There are different types of anoxia based on the cause of the oxygen deficiency. Anoxic anoxia refers to defective oxygenation of the blood in the lungs. This is the type of oxygen deficiency that is of concern when ascending to greater altitudes with a subsequent decreased partial pressure of O2. Other types of oxygen deficiencies include: anemic anoxia (failure of the blood to transport adequate quantities of oxygen), stagnant anoxia (the slowing of the circulatory system), and histotoxic anoxia (the failure of respiratory enzymes to adequately function). Anoxia can occur temporarily during normal respiratory system regulation of changing cellular needs. An example of this would be climbing a flight of stairs. The increased oxygendemand of the cells in providing the mechanical energy required to climb ultimately produces a local hypoxia in the muscle cell. The first noticeable response to this external stress is usually an increase in breathing rate. This is called increased alveolar ventilation. The rate of our breathing is determined by the need for O2 in the cells and is the first response to hypoxic conditions. BODY RESPONSE TO ANOXIA If increases in the rate of alveolar respiration are insufficient to supply the oxygen needs of the cells the respiratory system responds by general vasodilation. This allows a greater flow of blood in the circulatory system. The sympathetic nervous system also acts to stimulate vasodilation within the skeletal muscle. At the level of the capillaries the normally closed precapillary sphincters open allowing a large flow of blood through the muscles. In turn the cardiac output increases both in terms of heart rate and stroke volume. The stroke volume, however, does not substantially increase in the non-athlete (Langley, et.al., 1980). This demonstrates an obvious benefit of regular exercise and physical conditioning particularly for an individual who will be exposed to high altitudes. The heart rate is increased by the action of the adrenal medulla which releases catecholamines. These catecholamines work directly on the myocardium to strengthen contraction. Another compensation mechanism is the release of renin by the kidneys. Renin leads to the production of angiotensin which serves to increase blood pressure (Langley, Telford, and Christensen, 1980). This helps to force more blood into capillaries. All of these changes are a regular and normal response of the body to external stressors. The question involved with altitude changes becomes what happens when the normal responses can no longer meet the oxygen demand from the cells? ACUTE MOUNTAIN SICKNESS One possibility is that Acute Mountain Sickness (AMS) may occur. AMS is common at high altitudes. At elevations over 10,000 feet, 75% of people will have mild symptoms (Princeton, 1995). The occurrence of AMS is dependent upon the elevation, the rate of ascent to that elevation, and individual susceptibility. Acute Mountain Sickness is labeled as mild, moderate, or severe dependent on the presenting symptoms. Many people will experience mild AMS during the process of acclimatization to a higher altitude. In this case symptoms of AMS would usually start 12-24 hours after arrival at a higher altitude and begin to decrease in severity about the third day. The symptoms of mild AMS are headache, dizziness, fatigue, shortness of breath, loss of appetite, nausea, disturbed sleep, and a general feeling of malaise (Princeton, 1995). These symptoms tend to increase at night when respiration is slowed during sleep. Mild AMS does not interfere with normal activity and symptoms generally subside spontaneously as the body acclimatizes to the higher elevation. Moderate AMS includes a severe headache that is not relieved by medication, nausea and vomiting, increasing weakness and fatigue, shortness of breath, and decreased coordination called ataxia (Princeton, 1995). Normal activity becomes difficult at this stage of AMS, although the person may still be able to walk on their own. A test for moderate AMS is to have the individual attempt to walk a straight line heel to toe. The person with ataxia will be unable to walk a straight line. If ataxia is indicated it is a clear sign that immediate descent is required. In the case of hiking or climbing it is important to get the affected individual to descend before the ataxia reaches the point where they can no longer walk on their own. Severe AMS presents all of the symptoms of mild and moderate AMS at an increased level of severity. In addition there is a marked shortness of breath at rest, the inability to walk, a decreasing mental clarity, and a potentially dangerous fluid buildup in the lungs. ACCLIMATIZATION There is really no cure for Acute Mountain Sickness other than acclimatization or descent to a lower altitude. Acclimatization is the process, over time, where the body adapts to the decrease in partial pressure of oxygen molecules at a higher altitude. The major cause of altitude illnesses is a rapid increase in elevation without an appropriate acclimatization period. The process of acclimatization generally takes 1-3 days at the new altitude. Acclimatization involves several changes in the structure and function of the body. Some of these changes happen immediately in response to reduced levels of oxygen while others are a slower adaptation. Some of the most significant changes are: Chemoreceptor mechanism increases the depth of alveolar ventilation. This allows for an increase in ventilation of about 60% (Guyton, 1969). This is an immediate response to oxygen debt. Over a period of several weeks the capacity to increase alveolar ventilation may increase 600-700%. Pressure in pulmonary arteries is increased, forcing blood into portions of the lung which are normally not used during sea level breathing. The body produces more red blood cells in the bone marrow to carry oxygen. This process may take several weeks. Persons who live at high altitude often have red blood cell counts 50% greater than normal. The body produces more of the enzyme 2,3-biphosphoglycerate that facilitates the release of oxygen from hemoglobin to the body tissues (Tortora, 1993). The acclimatization process is slowed by dehydration, over-exertion, alcohol and other depressant drug consumption. Longer term changes may include an increase in the size of the alveoli, and decrease in the thickness of the alveoli membranes. Both of these changes allow for more gas transfer. TREATMENT FOR AMS The symptoms of mild AMS can be treated with pain medications for headache. Some physicians recommend the medication Diamox (Acetazolamide). Both Diamox and headache medication appear to reduce the severity of symptoms, but do not cure the underlying problem of oxygen debt. Diamox, however, may allow the individual to metabolize more oxygen by breathing faster. This is especially helpful at night when respiratory drive is decreased. Since it takes a while for Diamox to have an effect, it is advisable to start taking it 24 hours before going to altitude. The recommendation of the Himalayan Rescue Association Medical Clinic is 125 mg. twice a day. The standard dose has been 250 mg., but their research shows no difference with the lower dose (Princeton, 1995). Possible side effects include tingling of the lips and finger tips, blurring of vision, and alteration of taste. These side effects may be reduced with the 125 mg. dose. Side effects subside when the drug is stopped. Diamox is a sulfonamide drug, so people who are allergic to sulfa drugs such as penicillin should not take Diamox. Diamox has also been known to cause severe allergic reactions to people with no previous history of Diamox or sulfa allergies. A trial course of the drug is usually conducted before going to a remote location where a severe allergic reaction could prove difficult to treat. Some recent data suggests that the medication Dexamethasone may have some effect in reducing the risk of mountain sickness when used in combination with Diamox (University of Iowa, 1995). Moderate AMS requires advanced medications or immediate descent to reverse the problem. Descending even a few hundred feet may help and definite improvement will be seen in descents of 1,000-2,000 feet. Twenty-four hours at the lower altitude will result in significant improvements. The person should remain at lower altitude until symptoms have subsided (up to 3 days). At this point, the person has become acclimatized to that altitude and can begin ascending again. Severe AMS requires immediate descent to lower altitudes (2,000 - 4,000 feet). Supplemental oxygen may be helpful in reducing the effects of altitude sicknesses but does not overcome all the difficulties that may result from the lowered barometric pressure. GAMOW BAG This invention has revolutionized field treatment of high altitude illnesses. The Gamow bag is basically a portable sealed chamber with a pump. The principle of operation is identical to the hyperbaric chambers used in deep sea diving. The person is placed inside the bag and it is inflated. Pumping the bag full of air effectively increases the concentration of oxygen molecules and therefore simulates a descent to lower altitude. In as little as 10 minutes the bag creates an atmosphere that corresponds to that at 3,000 - 5,000 feet lower. After 1-2 hours in the bag, the person's body chemistry will have reset to the lower altitude. This lasts for up to 12 hours outside of the bag which should be enough time to travel to a lower altitude and allow for further acclimatization. The bag and pump weigh about 14 pounds and are now carried on most major high altitude expeditions. The gamow bag is particularly important where the possibility of immediate descent is not feasible. OTHER ALTITUDE-INDUCED ILLNESS There are two other severe forms of altitude illness. Both of these happen less frequently, especially to those who are properly acclimatized. When they do occur, it is usually the result of an increase in elevation that is too rapid for the body to adjust properly. For reasons not entirely understood, the lack of oxygen and reduced pressure often results in leakage of fluid through the capillary walls into either the lungs or the brain. Continuing to higher altitudes without proper acclimatization can lead to potentially serious, even life-threatening illnesses. HIGH ALTITUDE PULMONARY EDEMA (HAPE) High altitude pulmonary edema results from fluid buildup in the lungs. The fluid in the lungs interferes with effective oxygen exchange. As the condition becomes more severe, the level of oxygen in the bloodstream decreases, and this can lead to cyanosis, impaired cerebral function, and death. Symptoms include shortness of breath even at rest, tightness in the chest, marked fatigue, a feeling of impending suffocation at night, weakness, and a persistent productive cough bringing up white, watery, or frothy fluid (University of Iowa, 1995.). Confusion, and irrational behavior are signs that insufficient oxygen is reaching the brain. One of the methods for testing for HAPE is to check recovery time after exertion. Recovery time refers to the time after exertion that it takes for heart rate and respiration to return to near normal. An increase in this time may mean fluid is building up in the lungs. If a case of HAPE is suspected an immediate descent is a necessary life-saving measure (2,000 - 4,000 feet). Anyone suffering from HAPE must be evacuated to a medical facility for proper follow-up treatment. Early data suggests that nifedipine may have a protective effect against high altitude pulmonary edema (University of Iowa, 1995). HIGH ALTITUDE CEREBRAL EDEMA (HACE) High altitude cerebral edema results from the swelling of brain tissue from fluid leakage. Symptoms can include headache, loss of coordination (ataxia), weakness, and decreasing levels of consciousness including, disorientation, loss of memory, hallucinations, psychotic behavior, and coma. It generally occurs after a week or more at high altitude. Severe instances can lead to death if not treated quickly. Immediate descent is a necessary life-saving measure (2,000 - 4,000 feet). Anyone suffering from HACE must be evacuated to a medical facility for proper follow-up treatment. CONCLUSION The importance of oxygen to the functioning of the human body is critical. Thus the effect of decreased partial pressure of oxygen at higher altitudes can be pronounced. Each individual adapts at a different speed to exposure to altitude and it is hard to know who may be affected by altitude sickness. There are no specific factors such as age, sex, or physical condition that correlate with susceptibility to altitude sickness. Most people can go up to 8,000 feet with minimal effect. Acclimatization is often accompanied by fluid loss, so the ingestion of large amounts of fluid to remain properly hydrated is important (at least 3-4 quarts per day). Urine output should be copious and clear. From the available studies on the effect of altitude on the human body it would appear apparent that it is important to recognize symptoms early and take corrective measures. Light activity during the day is better than sleeping because respiration decreases during sleep, exacerbating the symptoms. The avoidance of tobacco, alcohol, and other depressant drugs including, barbiturates, tranquilizers, and sleeping pills is important. These depressants further decrease the respiratory drive during sleep resulting in a worsening of the symptoms. A high carbohydrate diet (more than 70% of your calories from carbohydrates) while at altitude also appears to facilitate recovery. A little planning and awareness can greatly decrease the chances of altitude sickness. Recognizing early symptoms can result in the avoidance of more serious consequences of altitude sickness. The human body is a complex biochemical organism that requires an adequate supply of oxygen to function. The ability of this organism to adjust to a wide range of conditions is a testament to its survivability. The decreased partial pressure of oxygen with increasing altitude is one of these adaptations. Sources: Electric Differential Multimedia Lab, Travel Precautions and Advice, University of Iowa Medical College, 1995. Gerking, Shelby D., Biological Systems, W.B. Saunders Company, 1969. Grolier Electronic Publishing, The New Grolier Multimedia Encyclopedia, 1993. Grollman, Sigmund, The Human Body: Its Structure and Physiology, Macmillian Publishing Company, 1978. Guyton, Arthur C., Physiology of the Human Body, 5th Edition, Saunders College Publishing, 1979. Hackett, P., Mountain Sickness, The Mountaineers, Seattle, 1980. Hubble, Frank, High Altitude Illness, Wilderness Medicine Newsletter, March/April 1995. Hubble, Frank, The Use of Diamox in the Prevention of Acute Mountain Sickness, Wilderness Medicine Newsletter, March/April 1995. Isaac, J. and Goth, P., The Outward Bound Wilderness First Aid Handbook, Lyons & Burford, New 1991. Johnson, T., and Rock, P., Acute Mountain Sickness, New England Journal of Medicine, 1988:319:841-5 Langley, Telford, and Christensen, Dynamic Anatomy and Physiology, McGraw-Hill, 1980. Princeton University, Outdoor Action Program, 1995. Starr, Cecie, and Taggart, Ralph, Biology: The Unity and Diversity of Life, Wadsworth Publishing Company, 1992. Tortora, Gerard J., and Grabowski, Sandra, Principles of Anatomy and Physiology, Seventh Edition, Harper Collins College Publishers, 1993. Wilkerson., J., Editor, Medicine for Mountaineering, Fourth Edition, The Mountaineers, Seattle, 1992.