High Altitude Pulmonary Edema

HAPE, or high altitude pulmonary edema, is a disease that occurs from unsuccessful acclimatization that can occur in humans over elevations of 8,200 ft. In HAPE, a build-up of fluid in the air pockets or alveoli of the lungs prevents oxygen from entering the lungs, resulting in a further decrease in the body's oxygen levels and quickly leading to death.

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Mt. Everest
The Mechanics of Breathing

Breathing is the activity of pumping air into and out of the lungs. There are two stage of breathing: inhalation, which brings air into the lungs, and exhalation, where pumps the air back into the atmosphere. During inhalation, muscle contraction causes the chest cavity to expand and the rib cage to move outward and upward resulting in air flowing into the lungs. In exhalation, the ribs and diaphragm relax, decreasing the volume of the chest cavity and exerting pressure on the lungs which forces the air back out into the atmosphere.
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Mechanics of Breathing
Air enters the lungs by creation of negative pressure in the lungs (a lower pressure than the outside atmosphere), which causes air to be drawn into the lungs. Prior to inhalation, the air pressure in the lungs is the same as the pressure in the atmosphere. During inhalation, the thoracic cavity expands decreasing the pressure in the lungs and forcing outside air to rush in. In exhalation, the lungs decrease in volume causing an increase in pressure in the lungs (a greater lung pressure than atmospheric pressure), and causing the air in the lungs to go out.

Oxygen and Carbon Dioxide Transportation in the Bloodstream

Oxygen enters the bloodstream by passing through the alveoli, tiny sacs incased in an extensive capillary network, and into the capillaries. Oxygen then moves throughout the body attached to hemoglobin proteins in red blood cells. Oxygen binds to the iron atoms on hemoglobin, which can then offload the oxygen when it reaches the body’s tissues. Hemoglobin is found within red blood cells and oxygen binds to the hemoglobin as the red blood cells pass through the capillaries next to the alveoli. Because the levels of oxygen in the lungs are greater than the oxygen levels in the blood, oxygen molecules flood into the red blood cells until each hemoglobin carries its capacity. The oxygen-rich red blood cells then flow to the heart and out into the body. As the red blood cells travel to tissues in the body, oxygen levels are much lower causing the oxygen to diffuse out into the tissues. As carbon dioxide flows into the red blood cells, the hemoglobin molecule alters its shape to one more conducive to giving up oxygen molecules, speeding up the release of oxygen to the body’s cells. The role of carbon dioxide is important because it ensures that more oxygen will reach the cells undergoing metabolism, generating CO2 and requiring oxygen. The oxygen-poor blood is then carried back to the heart where it returns to the lungs and can acquire more oxygen.

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Oxygen and Carbon Dioxide Exhange during Respiration

Carbon dioxide enters the blood while oxygen is being released from the hemoglobin. There is a smaller percentage of carbon dioxide in the blood than in the tissues in the body, causing the carbon dioxide to flow into the blood. A small percentage of carbon dioxide simply dissolves into the blood plasma, another portion binds to hemoglobin (causing the protein to alter its shape) and the majority of carbon dioxide diffused into the red blood cells. To ensure that the maximum amount of carbon dioxide diffuses into the bloodstream, it is necessary to keep carbon dioxide levels in the plasma low. Because carbon dioxide molecules would prefer to diffuse back into the blood plasma, an enzyme combines carbon dioxide molecules with water molecules in the red blood cells to form carbon acid, a molecule which then dissociates into bicarbonate and hydrogen ions. The ions bind to hemoglobin while the bicarbonate is transported out of the red blood cells and into the plasma in a process called the chloride shift. This process is critical in ensuring that carbon dioxide will diffuse from the cells and into the blood and also maintaining the acid-base balance of blood. The oxygen-deficient blood along with the bicarbonate is then carried back to the heart and the lungs. Because there is a lower concentration of carbon dioxide in the outer atmosphere than in the lungs, the bicarbonate then performs the reverse reaction it did before and transforms back into carbon dioxide. This releases gaseous carbon dioxide back into the alveoli, through the lungs and out into the atmosphere. The small percentage of carbon dioxide that had bound to hemoglobin also leaves the body because the hemoglobin gathers new oxygen and releases the carbon dioxide.

Physiological problems Encountered at High Altitudes

Humans encounter many physiological problems at high altitudes. As humans increase their elevation, the amount of oxygen in the atmosphere decreases while the amount of carbon dioxide around them increases. The decrease in oxygen in the atmosphere causes the human body’s system to function differently, leading to the problems attributed to acclimatization such as Acute Mountain Sickness and eventually HAPE. AMS is a sickness that can range in severity but the symptoms include shortness of breath, lack of sleep, headache, lack of appetite, sea sickness, balance, trouble with coordination and diarrhea. A mild case of AMS shows that fluid is beginning to accumulate in either the brain or the lungs, a situation that develops into HAPE. With a decrease in the density of oxygen in the atmosphere, it becomes difficult for the body to inhale enough oxygen into the lungs. This causes a lack of oxygen in the blood stream, which in turn causes a lack of oxygen in the brain and in the muscles. A lack of oxygen in the brain causes a loss of brain cells and many other problems such as decreased cognitive ability, decreased reaction time and speech impediment. A deficient amount of oxygen flowing to the muscles results in muscle decline and extreme weakness and fatigue. As the heart pumps faster to try to get enough oxygen to the different organs, the pulse rate speeds up and breathing increases. With too little oxygen the body becomes hypoxic, a condition where the body is deprived of adequate oxygen, and without enough oxygen or energy the body begins to use itself for food.
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HAPE


HACE and HAPE are both severe forms of AMS and are both extremely dangerous. HACE (high altitude cerebral edema) is a sickness that results from build-up of fluids within the brain. This results in loss of coordination and balance, decrease in reaction time and slurred speech. HACE can be deadly as the fluid results in a fatal swelling of brain tissues. HAPE (high altitude pulmonary edema) is a sickness that results from the build-up of fluids in the lungs and results in a hacking cough, frothy spit, difficulty in breathing and general weakness. As the density of oxygen in the atmosphere decreases, the pressures in the pulmonary artery and associated capillaries greatly increase leading to pulmonary hypertension. This is followed by a constriction of the pulmonary arteries due to hypoxia. These conditions are also coupled with an increase in the permeability of the endothelium, the thin layer of cells that line blood vessels. This two afflictions cause the fluid in the blood to be pushed into the small air pockets, the alveoli, of the lungs, preventing the air pockets from letting oxygen into the blood stream. When the blood lacks enough oxygen other dangerous and reactive substances are formed in the blood, leading to more problems.


Mountain Sickness and HAPE Symptoms


At high altitudes climbers are subject to many harmful physiological symptoms. The most prominent of which are fatigue, dizziness, shortness of breath upon exertion and drowsiness. These are all related to a lack of oxygen when in high altitudes. As the air has fewer and fewer oxygen particles in it, humans have a harder and harder time receiving the necessary oxygen that is so vital to the body. Without the oxygen it needs, many of the bodies common functions do not work properly. A severe form of this is HAPE, where ones lungs are filled with fluid due to high altitude. Symptoms of this are a persistent dry cough, fever and shortness of breath even when resting. Though these symptoms seem to be similar to those one may have during a common cold, they are much more severe and threatening because of an increasing amount of water in the lungs.

Deadly Mountain Atmosphere
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Gamow Bag Rescue

As one climbs higher and higher the atmospheric pressure drops steadily. The saturation level for hemoglobin in the blood begins to plummet at 8,000 ft. This is very important because hemoglobin determines the content of oxygen in our blood. Thus, when our level of a hemoglobin saturation falls so does does our oxygen level and all oxygen related actions (e.g. use of muscles) begin to weaken. This also occurs with nitrogen at high altitudes. The percentage of oxegyn in the air is approximately 20% (nitrogen- 75%, carbon dioxide- under 1%) from sea level up to around 70,000 ft. This means that while the percentage remains the same, though the amount of particles is spread so thin at higher altitudes that when a climber breathes air that is still 20% oxygen they are receiving a significantly smaller amount than they would be at sea level. These changes are not hugely important to a climber because a lack of sufficient oxygen or other vital gases can cause the serious symptoms discusses previously. A Gamow bag, like the one in this picture, has a reduced atmospheric pressure inside the bag and can be used as a capsule to put people suffering from acute mountain sickness or HAPE. When the person is inside there are surrounded by air with a higher concentration of oxygen, making it seem as though they are breathing at 8,000 ft rather than over 18,000 ft.

Pulmonary Response to High Elevation

High Altitude Pulmonary Edema can occur when people are above 10,000 feet. The specific pulmonary response to high altitudes is the heart pumps blood at a faster rate (this is why as climbers rise in elevation their pulse quickens). There are very low levels of oxygen in the air at altitude and so the heart quickens the rate it pumps blood so that a larger volume of blood will pass through the pulmonary system per minute. Since the heart is pumping blood more frequently at high altitudes, pressure begins to build up in the pulmonary artery. The pulmonary arterioles are also very sensitive to the lack of oxygen at high altitudes and so these arteries constrict and this also causes blood pressure to increase. As altitude increases the heart pumps blood into the pulmonary artery with increasing frequency and so pressure increases. At some point this pressure reaches a critical level and causes liquid to leak from the capillaries surrounding the lungs. This is how High Altitude Pulmonary Edema occurs. Pressure in the blood vessels surrounding the alveoli builds up and as a result some of the liquid from the blood vessels seeps in the alveoli. The alveoli are tiny air sacs in the lungs. All of the gas exchange between the lungs and the bloodstream occurs across the membrane of the alveoli. When the blood flows through the capillaries surrounding the alveoli, oxygen diffuses from the alveoli into the capillaries. This oxygen is then carried back to the heart by the pulmonary vein. It is then transported to the rest of the body by the systemic part of the circulatory system.
The alveoli are only ever supposed to contain gases and so the liquid in the alveoli causes problems with the gas exchange. The liquid makes it harder for the oxygen to diffuse out of the alveoli into the blood. This liquid build-up in the alveoli is why people with HAPE have very low levels of blood oxygenation, shortness of breath and trouble breathing. It is usual to hear crackles when HAPE patients breathe and this is a bubbling noise that corresponds to the splashing of the fluid in the alveo
li.

Effects of High Altitude on Blood Gases

People with pulmonary edema have an extra layer of fluid in the alveoli and this interferes with the lungs' ability to get rid of CO2. This leads to a rise in the amount of CO2 dissolved in the blood. Oxygen Saturation measures the percent of hemoglobin which is fully combined with oxygen. Oxygen saturation is very low in people with HAPE because blood pressure is higher and so blood is pumped through the capillaries with more pressure and so there is less time for oxygen to diffuse into the blood. Oxygen does not have as much time to load onto the hemoglobin and so this causes a lower oxygen saturation level because not as much oxygen diffuses into the blood.

How Does the Body Adapt to High Altitude?

One way the body adapts to high altitude is an increase in the production of the compound 2,-DPG after several days at high elevation. 2,3-DPG or 2,3-bisphosphoglycerate is a carbon isomer that is present in all red blood cells. 2,3-DPG has a high affinity for de-oxygenated hemoglobin, and therefore binds to the hemoglobin molecule when it contains a smaller amount of oxygen. As elevation increases, the amount of oxygen in the atmosphere decreases as well as the amount of oxygen that can bind onto hemoglobin. This produces a greater amount of hemoglobin without the adequate amount of oxygen, creating room for other compounds such as 2,3-DPG to bind onto. This increases the amount of 2,3-DPG the body produces. The amount of increase of 2.3-DPG relates directly to the loss of oxygen in the atmosphere, and therefore can be used to detect oxygen levels or vice versa. When 2,3-DPG binds to hemoglobin, it increases the hemoglobin molecules release of oxygen, thus enhancing the release of much-needed oxygen into body tissues. So a large amount 2,3-DPG can actually benefit a suffering respiration process at high altitudes because it forces hemoglobin to release all of the oxygen it can get into the tissues of the body. Scientists have found a relationship between HAPE and low levels of 2,3-DPG, a dangerous combination that not only results in a severe inability to access oxygen, but also a decrease in the release of oxygen by hemoglobin.
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Happy Hikers!


Bibliography:
http://www.itfnz.org.nz/ref/essays/physiological_effects_of_high_al.htm
http://www.altitude.org/altitude_sickness.php#HAPE

http://www.weasel.com/hape.html
http://www.princeton.edu/~oa/safety/altitude.html

http://www.brooksidepress.org/Products/OperationalMedicine/DATA/operationalmed/Lab/ABG_ArterialBloodGas.htm