Animal respiration and low oxygen

Adaptation to low oxygen refers to several changes in metabolism or body function, or both, that animals use to survive low-oxygen conditions. Low-oxygen conditions mean a reduction in the amount of oxygen available in relation to the need or demand for oxygen by the cells, or tissues. Low oxygen, or hypoxia, therefore, can result from either a decrease in the supply at constant demand, or an increase in demand at a constant supply. The former, a reduction in oxygen supply, is the focus of the present discussion. Low oxygen resulting from increased oxygen demand usually is referred to as tissue hypoxia and is discussed only briefly here.

Oxygen is required by animal cells to produce energy used for growing, moving around, or simply maintaining normal body functions. At times when less oxygen is available, animals must either move to some place where there is sufficient oxygen or change some internal function or process. A change in internal function or process is an adaptation that allows the animal to live with less oxygen or that will be a means of keeping the supply of oxygen to the tissues great enough to meet the needs of the cell.

External or environmental hypoxia results from either a greater utilization of oxygen by plants and animals than can be renewed by natural processes, a lower density of air (at high elevations), or strong ocean upwelling and decreased oxygen solubility in warm, salty water. Animals must cope with a decrease in oxygen in some way, partly because of the consequences of a decrease in internal oxygen supply. If the oxygen supply to the tissues and cells falls, the functions requiring oxygen will fail or be reduced. The functions that fail include the maintenance functions of a cell, apart from growing or producing specialized chemicals. The low-oxygen conditions that have received the most attention from researchers are high altitude, diving by air breathers, and oxygen depletion in water. Some of these are temporary; others, such as high altitude, can last a lifetime for animals that do not migrate.

Increase in Ventilation

One common adaptation to hypoxia is an increase in ventilation—the amount of air or water that the animal breathes. This increase is referred to as hyperventilation, and it makes up for the reduced amount of oxygen in the air or water by breathing a greater volume. This response is especially common in mammals that move to high altitude, fish and crabs, and other water-breathing animals. A simple mathematical example will show how the response is effective. If an animal normally breathes one liter of air per minute and removes half the oxygen (air contains 209 milliliters of oxygen per liter), then it is taking in 104.5 milliliters of oxygen per minute. If the amount of oxygen in the air falls to only 104.5 milliliters per liter, and the animal still uses half of that (52.25 milliliters), then it must breathe two liters of air per minute to keep taking up 104.5 milliliters of oxygen per minute. Such an increase in ventilation can be accomplished by an increase in the frequency of the respiratory pump, or by increasing the volume of water or air that is moved with each “breath.” For this response to occur, the nervous system must sense the reduction in oxygen and provide a nerve impulse to the brain, which then stimulates the ventilatory pump(s) to increase activity.

It may seem that this adaptation is all that would be needed for animals to survive hypoxia, but there are some limitations to this adaptation. First, hyperventilation causes increased muscular activity and an increase in oxygen used to move the respiratory muscles. The greater ventilation volume is a benefit, but the cost is a greater demand for oxygen. For animals that breathe air, the increase is rather small, but for animals that breathe water, the increase in muscular activity causes a substantial increase in the oxygen used to pump the water, so that the “cost” may be greater than the “benefit” when the oxygen falls to low levels. Another problem exists for air breathers. Air breathers are in danger of losing water in the air that is exhaled (desert animals, such as camels, have elaborate mechanisms to conserve this respiratory water loss). Hyperventilation increases the water loss and requires the animal to drink more water. A final problem for both air and water breathers is that carbon dioxide is lost from the same respiratory surface where oxygen is taken up. Hyperventilation thus increases the loss of carbon dioxide, changing the chemical balance of the body as a whole.

Blood Flow and Oxygen Delivery

In response to internal hypoxia, many animals also exhibit an increase in the flow of blood to the tissues. This response is similar to that described for the ventilation system. An increased rate of flow compensates for a smaller amount of oxygen delivered for a given volume of blood (or respiratory medium in the case of ventilation). As with ventilation, blood flow can be elevated by increasing heart rate or by increasing the volume of blood pumped with each beat. There are numerous limitations to the effectiveness of this response, and it is only short-term. The limitations center on the critical role of blood flow and blood pressure in the function of other systemic body functions. An excellent example is how the kidney filtration rate increases with blood pressure.

Long-term adaptations to low oxygen often increase the ability of systemic respiratory functions to maintain oxygen delivery to the tissues. In the case of internal oxygen transport, this can be accomplished by increasing the amount of oxygen carried by the blood. A higher concentration of respiratory pigment accomplishes this, increasing either the number of red blood cells or the concentration of respiratory pigment in the blood. This adaptation requires the synthesis of new proteins and possibly new cells. Not surprisingly, many days or even weeks may be needed to increase respiratory pigment levels. Another way in which oxygen transport by the respiratory pigment may be improved is by increasing the concentration of a chemical that affects oxygen binding. This adaptation requires a change in metabolism, and is discussed below.

Metabolic Alteration

One final type of adaptation to low oxygen is an alteration in the basic metabolism of the animal. Metabolic changes can take one of several forms. First, a simple reduction in metabolism will lower the need and demand for oxygen by the cells. To be effective, this must occur before the oxygen has been exhausted, so as not to impair normal functions. A few animals show this type of adaptation, which is thought to result from the metabolic reactions being limited by the availability of oxygen. Second, the chemical reactions involved in metabolic pathways (a series of chemical reactions) may be altered in low-oxygen conditions so that different reactions take place to maintain energy production. The nature of these adaptations is that an alternative metabolic pathway requires different enzymes and perhaps different chemicals in the reactions. Last, metabolic adaptation may yield a product that enhances oxygen transport. An enhancement of oxygen transport occurs when certain chemicals increase the ability of the respiratory pigment to bind oxygen or cause the respiratory pigment to bind oxygen at lower oxygen levels; this is called an increase in oxygen affinity. The change in metabolism at low oxygen thus improves the oxygen supply to the tissues. This response is seen in both vertebrates and invertebrates.

An excellent example of an animal that exhibits a myriad of adaptations to low oxygen is the blue crab—the common commercial crab found throughout North America’s Gulf Coast and the East Coast from Florida to New York. To compensate for low oxygen, the blue crab increases the water flow over the gills, thereby keeping the amount of oxygen that passes over the gills nearly constant. Blue crabs also increase their heart rate, thereby increasing blood flow to the gills, muscles, and organs. This increase helps maintain the oxygen supply. If the period of hypoxia is brief, only a few hours, then these reactions may be all that is required for the animal to survive. If the hypoxia continues for days or weeks, other responses begin, including changes in metabolism and how oxygen is transported in the body. Metabolism decreases so that the animal needs less oxygen. When that happens, there must be some activity, such as swimming, that the animal gives up for lack of energy. The other change is an improvement in the way oxygen is transported to the tissues by the respiratory pigment, hemocyanin—a certain protein dissolved in the blood that binds to oxygen at the gills and can release the oxygen to the tissues where it is used by the cells. This improvement involves increasing a chemical level in the blood that changes the way oxygen binds with hemocyanin. In addition, the crab makes the hemocyanin in a new form that works better in hypoxic conditions.

Understanding the Respiratory and Circulatory Systems

Adaptation to low oxygen (either high demand or reduced supply) has been studied to understand the functional capabilities of the respiratory and circulatory systems that supply oxygen to the tissues. Many different experimental protocols and procedures are used to assess the balance between oxygen uptake and demand when the external supply of oxygen is limited, and demand remains constant. One approach to the study of low-oxygen conditions has been to compare animals that live at sea level in high-oxygen habitats with those living in habitats in which oxygen levels are low. A comparison of water breathers and air breathers is, strictly speaking, within the realm of consideration. Water holds much less oxygen than air and is, therefore, a low-oxygen condition. Freshwater at room temperature contains about 0.8 milliliters of oxygen per 100 milliliters of water; there are 20.9 milliliters of oxygen in the same volume of air. To obtain the same amount of oxygen, an animal must thus take all the oxygen from either 2,600 milliliters of water or 100 milliliters of air. Consequently, air breathers have much lower ventilation rates, at the same temperature, than do water breathers of the same size. The lower ventilation rate of air breathers is considered functional by reducing the loss of water from the respiratory surface.

Such adaptation is principally evolutionary and involves the transition from water breathing to air breathing in the evolutionary transition to land. There are a great many morphological as well as physiological consequences of this transition.

Adaptation to short-term hypoxia has been studied under controlled conditions in the laboratory in a variety of animals. Short-term conditions may mean anything from a few hours to weeks or even months. The length of the low-oxygen exposure generally depends on the animal used, its ability to withstand low oxygen, and the nature of the inquiry into the responses. Some clams, for example, can live in the absence of oxygen for several weeks. These experiments require careful monitoring of the animal and the conditions to ensure that oxygen neither rises nor falls too low and that the animals will survive.

A method that has been used to study adaptation to low oxygen in mammals is to conduct field studies in which the subjects are temporarily moved to high elevations. Mountain-climbing expeditions have been involved in some of these experiments in areas throughout the world. Additionally, experimental stations have been established at certain locations to conduct these research projects. In this way, medical researchers can bring in appropriate equipment and supplies necessary to make complex and precise measurements.

All approaches to the study of low-oxygen adaptation require measurements of respiratory function or metabolic processes, or both. These measurements assess the uptake and transport of oxygen and the transport and excretion of carbon dioxide. The specific measurements are of the rate of oxygen uptake, ventilation volume and rate, blood flow, heart rate, oxygen transport properties of the blood, and oxygen uptake. In long-term monitoring studies of free-ranging animals like turtles and rodents, the animals are frequently fitted with implanted electrodes and blood sampling tubes. In this way, measurements can be made routinely over long periods without disturbing the animals.

A common measure of respiratory function is the total amount of oxygen used by an animal in a given period. The rate of excretion of carbon dioxide is another measure of overall function. The ratio of carbon dioxide loss to oxygen uptake is used to determine the nature of the metabolic pathways at a given time. Different metabolic pathways have characteristic oxygen uptake and carbon dioxide excretion ratios, and these are used in a predictive or diagnostic fashion. Some of the methods do not impair normal activity and can be used in low-oxygen experiments. The technique of placing small animals in respiratory chambers is used in these types of experimentation. Measurement of single organ function is used more often with larger animals, such as humans.

Evolution, Metabolism, and Ecology

Adaptation to low oxygen has been studied to understand three concepts better: evolutionary changes associated with oxygen availability, cell metabolism, and ecology of hypoxic habitats. Literally every aspect of oxygen uptake, transport, and utilization has received some attention.

Some of the evolutionary changes during the transition from water to land and from low to high altitudes have been studied as problems related to low oxygen. Results indicate that air breathers have lower ventilation rates than water breathers of the same size. The lower ventilation rates are possible because of the higher oxygen levels, but they result in higher internal carbon dioxide levels. Animals such as insects, reptiles, and mammals have respiratory structures that are internalized and are inpocketings of the body wall. This arrangement aids in water conservation and helps keep the respiratory surfaces moist.

Just as important as research on the transition to land has been the information gained about the evolution of life in high-oxygen environments as compared to the low-oxygen conditions that are believed to have occurred in the ancient oceans. From this research, it is clear that the major advances in respiratory systems are present in invertebrates and probably evolved quite early in the history of life on Earth. Marine worms possess closed circulatory systems, respiratory pigments, red blood cells, special gas exchange structures, gills, and alternate metabolic pathways.

Modern oceans also offer further evidence of the adaptive evolution of animals' respiration systems. Some areas of low oxygen exist in places like the eastern Pacific Ocean. These low-oxygen areas are called oxygen minimum zones (OMZs). Rotaliids and nematode worms have adapted to low-oxygen habitats and thrive in the OMZ. Other marine animals that tolerate low oxygen include aplacophora mollusca and some midwater crustaceans. These crustaceans have high circulation rates, specialized genes, and an altered chitin metabolism, allowing them to experience long periods of low oxygen without harm.

Biologists interested in metabolism and the factors that cause metabolic rate to change have examined the relationship between metabolic rate and other physiological functions. Specifically, oxygen supply, carbon dioxide removal, and glucose supply have been examined because all three are directly involved in aerobic metabolism. Imposing a limitation on external oxygen supply has, therefore, been used as an experimental tool to probe the limits and capabilities of cellular metabolism.

Biologists have observed that animals can adapt to live in nearly uninhabitable places and can adapt to occupy new habitats. Understanding the physiological mechanisms required or used in adaptations to low-oxygen habitats, such as stagnant pools of water, has provided scientists with some explanations of evolutionary changes and adaptations that occurred in prehistoric animals.

Several habitat types routinely undergo hypoxia, and the utilization of the natural resources of those habitats, as well as the effective preservation of the habitats, generally dictates that attention be paid to the effects on the animals. One of the bodies of water that undergoes low-oxygen conditions is the Chesapeake Bay, and the effects on the animals there have been studied. Because this area’s low oxygen areas, called dead zones, result from nitrogen and phosphorus polluted runoff rather than a natural low-oxygen environment, the animals in the area struggle to adapt and survive. Other notable areas of natural low oxygen include plateaus and underground burrow systems, where animals, mainly small mammals like mole rats, have adapted to the environment. Scientists have noted changes in the VEGF (vascular endothelial growth factor) and EPO (erythropoietin) proteins in these animals, as well as other gene expression and phenotype changes.

Principal Terms

Hyperventilation: An increase in the flow of air or water past the site of gas exchange (lung, gill, or skin)

Hypoxia: From two Latin words, hypo and oxia, meaning “low oxygen”

Metabolism: The sum of all the reactions that take place in an animal allowing it to move, grow, and carry out body functions

Respiratory Pigment: A protein that “supercharges” the body fluid (blood) with oxygen; the oxygen can bind to the pigment and then be released

Respiratory Surface: The gill, lung, or skin site at which oxygen is taken up from the air or water into the animal, with the release of carbon dioxide at the same time and site

Systemic: Referring to a group of organs that function in a coordinated and controlled manner to accomplish some end, such as respiration

Ventilation: The movement, often by pumping, of air or water to the site of gas exchange; commonly thought of as breathing

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