(J.L. Bailey, J.Y. Grivetti, R.C. Adams, R. Bailey, D.E. Facey, R. Bailey)

(presented by Saint Michael's College, Colchester, VT, USA)


Do you like to breathe? Well, we do, and we learned a whole lot about how it works in mammals and in other groups of animals. If you’d like to know more, take a breather and enter our website. Just sit back, relax, take deep breaths, and inhale all of our information. Go for it!

What is respiration? Why do animals respire and why is it important?

Respiration is the process by which animals take in oxygen necessary for cellular metabolism and release the carbon dioxide that accumulates in their bodies as a result of the expenditure of energy. When an animal breathes, air or water is moved across such respiratory surfaces as the lung or gill in order to help with the process of respiration. Oxygen must be continuously supplied to the animal and carbon dioxide, the waste product, must be continuously removed for cellular metabolism to function properly. For example, if this does not happen and carbon dioxide levels increase in the body, pH levels decrease and the animals may eventually die (see Question: Why is the regulation of body pH important?).

Oxygen is valuable because it is important in many ATP-producing cycles occurring throughout the body such as, the Krebs cycle, and the electron transport chain. Glycolysis breaks down glucose, a six-carbon sugar, into the three-carbon molecule of pyruvic acid. The series of reactions associated with glycolysis are necessary for anaerobic and aerobic pathways to work, and are also the most fundamental in cellular metabolism. In the presence of 02, the pyruvic acid, which came about from the breakdown of glucose, is further oxidized. However, under anaerobic conditions the pyruvic acid is reduced to lactic acid. Glycolysis follows a specific pathway and ultimately, the oxidation of 1 mol of glucose to pyruvic acid ends in a net gain of only 2 mol of ATP and 2 NADH molecules.

The Krebs cycle is a series of eight major reactions following glycolysis. In these reactions, acetate residues are degraded to CO2 and H2O. With each turn of the Krebs cycle, 2 CO2 molecules and 8 H+ atoms are removed. These hydrogen atoms, which are removed two at a time, are transported by NADH and FADH2 and further go into the electron transport chain.

The electron transport chain, also known as the respiratory chain, oxidizes the NADH and FADH2 from the Krebs cycle to H2O by oxygen. This cycle involves electrons that move through about seven steps in order of their decreasing electron pressures, more specifically, from the high reducing potential of NADH to FADH2 to oxygen, the final electron acceptor. The electron transfer is the final pathway for all electrons during aerobic metabolism, and it uses the energy from the transfer for the phosphorylation of ADP to ATP. A total of 38 ATP molecules are collectively released from the three cycles of glycolysis, the Krebs cycle, and the electron transport chain working together. Without oxygen, the Kreb's cycle and electron transport chain would be disabled and only 2 ATPs would be produced by glycolysis.   To maintain an adequate supply of oxygen to cells, animals must have an efficient means of gas transfer and respiration.


What is oxygen debt?

In some animals, such as mammals, if the supply of oxygen to active muscle cells is not sufficient to produce enough ATP to maintain intense activity, the only source of additional ATP will be from glycolysis.  Without sufficient oxygen, some of the pyruvic acid produced is reduced to lactic acid, which accumulates in the tissues, resulting in fatigue.  Excess lactic acid may also enter the blood, decreasing blood pH and affecting other tissues in the body.  When muscle activity decreases, extra oxygen is needed to convert the lactic acid back to pyruvic acid, which is then utilized by the Kreb's cycle.   This extra oxygen represents the animal's oxygen debt.   Some animals, such as the goldfish and some intertidal invertebrates, can avoid oxygen debt through the use of biochemical pathways that convert lactic acid to alcohol, which can then be excreted.


What is the difference between air and water as respiratory environments? How does this affect the amount of energy spent obtaining oxygen in water and air and therefore the structures used in ventilation?

Water and air are radically different as respiratory environments in a number of ways. The most significant difference is that water contains only 1/13 as much O2 as air does, or 1% to 21% (water to air) by volume. Water also is over 800 times denser than air and 50 times more viscous, so aquatic breathers must use more energy to simply move water across their respiratory surfaces.   Fish, for example, use as much as 10% of the oxygen they take in to provide breathing muscles with enough oxygen to burn the energy needed to keep water passing over the gills in the right direction.  Humans use only 1-2 % of their oxygen intake to keep breathing.  Temperature also has an effect on the amount of oxygen each environment can hold. As water temperature increases the amount of dissolved oxygen decreases.  Air also shows a slight reduction in oxygen content with increasing temperature, but it isn't physiologically significant because there is so much oxygen in air to begin with.  Gas diffusion rates are also lower in water than in air.   Salt water contains less oxygen than fresh water because the higher salt concentration decreases gas solubility.  All of this produces a vast difference between aquatic and terrestrial organisms in the amount of energy expended to obtain oxygen.


How is oxygen carried through the blood and passed onto other cells? What role does hemoglobin play in oxygen transfer? What conditions affect hemoglobin/oxygen affinity?

Hemoglobin (Hb) is found in red blood cells, being the principle part of a red blood cell. Hemoglobin is a large protein with four polypeptide chains and four heme groups. Each heme group has an iron atom attached to it, which is where oxygen attaches to be carried to cells and tissues. It is important to note that the O2/Fe bond, that is initially made so the oxygen can be transported, can be readily broken in the right conditions. These conditions are altered depending on if oxygen needs to be picked up or released to tissue cells. The reason hemoglobin is found in red blood cells only is that the conditions needed for efficient oxygen transport by the Hb molecules can be quickly changed, and all of this can be done without changing the conditions throughout the body. Some of the conditions necessary for oxygen and carbon dioxide transport may be unsuitable for other reactions that need to take place throughout the body, so keeping Hb within the red blood cells allows oxygen transport to occur without interfering with other bodily functions. Conditions that control the ability of  hemoglobin (Hb) to bind to oxygen include the partial pressure of O2 in the surrounding respiratory medium (air or water), temperature, pH, CO2 levels.  A high partial pressure of O2 in the surrounding respiratory medium will increase the rate at which the O2 diffuses into the blood.  Hemoglobin's affinity for oxygen typically decreases if temperature increases, pH decreases, or CO2 levels increase.

There are a few different kinds of hemoglobin, all doing the same job, but each having its own affinity to O2. Normally hemoglobin will pick up an O2 when the partial pressure of the O2 in the blood (O2 dissolved in solution) is high, and there are fewer than 4 O2 molecules on the hemoglobin, 4 being the maximum number able to be carried. When an O2 molecule is attached to a hemoglobin molecule it is not affecting the partial pressure of the O2 in the blood, as there is a low concentration of O2 in the blood plasma, just not enough to supply the cells of the body. The best scenario for oxygen transfer from the lungs to body cells and tissues is hemoglobin to have high affinity at the respiratory surface (high amount of O2 diffusing across the lung surface) and low oxygen affinity (give the oxygen away) near body cells that need it (low O2 content).

Other factors that affect hemoglobin/oxygen affinity include a decrease in pH, which reduces hemoglobin/oxygen affinity (the Bohr effect). A decrease in pH reduces Hb/ O2 affinity because the shape of the oxygen-binding sites of the hemoglobin molecule changes, making it more difficult for them to bind to oxygen. (See "Why are red blood cells important to carbon dioxide transport?" for a complete explanation of the mechanisms involved). A rise in body temperature reduces Hb/O2 affinity as the increased energy (heat) will prevent bonds from forming or break bonds currently in place. Increased CO2 content can affect the affinity because CO2 can bind to sites where O2 would normally bind. Hemoglobin normally picks up CO2 at the tissues and releases it at the respiratory surface in exchange for oxygen to complete the chain. When the concentration of CO2 is too high it takes the place of oxygen on Hb at higher than normal rates.

Oxygen dissociation curves graphically represent the percent of hemoglobin's oxygen binding sites that are holding oxygen at different partial pressures of oxygen.  The sigmoid (S-shaped) curve is due to subunit cooperativity between the four oxygen binding sites on a hemoglobin molecule.  When no binding sites are occupied by oxygen, it is relatively difficult to get the first oxygen to bind.   After it does, however, the structure of the hemoglobin molecule is altered a bit, and the second binding site becomes more accessible.  This makes it a bit easier for the second molecule of oxygen to bind.  After this, additional oxygen molecules bind rather easily to the third and fourth binding sites.  Therefore, oxygen binds slowly at first, and then more quickly, giving the dissociation curve a sigmoid shape.


How is carbon dioxide transported in the blood?

The transportation of carbon dioxide is a very significant process of the gas-transfer systems within many animals. There are three main ways in which CO2 is transported in the blood. A small percentage of the CO2 that is in the blood is dissolved molecular CO2.  A larger amount of CO2 reacts with –NH2 groups of hemoglobin and other proteins to form carbamino compounds.   However, most of the CO2 that is transported in the blood is in the form of bicarbonate (HCO3-). In general, CO2 is diffused into the blood from the tissues. The blood transports CO2 to the respiratory surfaces of the lungs or gills, where it is released into the environment. The blood mainly consists of plasma and erythrocytes (red blood cells). Most of the CO2 entering and leaving the blood does so through erythrocytes.


Why are red blood cells important to carbon dioxide transport?

Most of the CO2 entering or leaving the blood go through red blood cells for two reasons. One reason is due to the enzyme carbonic anhydrase. This enzyme is present in red blood cells and not in the plasma. The enzyme is important in the transportation of CO2 because, within the red blood cells, it catalyzes the reaction of CO2 with OH- resulting in the formation of HCO3- ions. As the level of HCO3- ions increases within the erythrocytes, the HCO3- ions diffuse through the erythrocyte membranes into the plasma of the blood. In order to maintain electrical balance within the erythrocytes, an anion exchange occurs in a process called a chloride shift. In this process, HCO3- ions leave the red blood cells while a net influx of Cl- ions from the plasma enters the red blood cells. The membrane of red blood cells is very permeable to both ions because the membrane has a high concentration of a special anion carrier protein, the band III protein. This protein allows for a passive diffusion of the Cl- and HCO3- ions to and from the red blood cells and plasma. This keeps the bicarbonate from building up in the red blood cells, which would slow down or stop the reversible conversion of CO2 to HCO3-. Facilitated diffusion occurs in the movement of CO2 across the respiratory surfaces as bicarbonate (HCO3-) diffuses out of the red blood cells and into the epithelium where it is converted back to CO2. Excretion of CO2 is limited by the rate of bicarbonate-chloride exchange across the erythrocyte membrane.

The second reason why most of the CO2 is transported to and from the blood by passing through the erythrocytes is that O2 binds to Hemoglobin (Hb) at the respiratory surface, causing hydrogen ions (H+) to be released. The increase in H+ ions combines with HCO3- to form CO2 and OH-. Thus, more CO2 is formed and can leave the blood across the respiratory surface.  Excess H+ binds to OH-, forming water and allowing the pH to increase enough to promote the binding of oxygen to Hb.  The release of O2 from Hb in the tissues makes the Hb available to bind to H+, promoting the conversion of CO2 to HCO3-, which helps draw CO2 from the tissues. Therefore, CO2 that is being transported into and out of the red blood cells minimizes changes in pH in other parts of the body because of proton binding to and proton release from hemoglobin, as it is deoxygenated and oxygenated, respectively (Figure 1.).


Why is the regulation of body pH important?

The regulation of body pH is important because some organs, tissues, and various types of cells are more affected by changes in pH than others. Therefore, within an animal’s body are various mechanisms, including mechanisms at the cellular level, that regulate the body pH in order for the animal to maintain normal bodily functions. For example, the regulation of body pH is needed in animals in order to stabilize volume of hydrogen ions and to regulate enzyme activity. Within cells, pH is regulated in order for cellular functions to proceed. At the tissue level, the body has the ability to redistribute acid between body compartments because some tissues have the ability to tolerate much larger fluctuations in pH than others do. In general, animals have a body pH that is on the alkaline side of neutral, which means that there is less hydrogen than hydroxyl ions in the body. Human blood plasma, at 37 C (normal body temperature) has a pH of 7.4. Normal functioning can be maintained in mammals at 37 C over a blood plasma pH range of 7.0-7.8.


How does breathing regulate pH?

One of the main ways that a mammal regulates pH is through the control of respiration. For example, if the body pH in a mammal decreases, the respiration rate and depth of respiration increases in order to get rid of the excess CO2, which brings H+ levels back down and brings pH back up. Hence, when breathing is increased, CO2 levels in the blood decline and pH increases. If pH increases, respiration rate decreases, thereby increasing CO2 levels, which forms more carbonic acid and brings pH back down. 

In mammals, a stable body pH is achieved by adjusting the release of CO2 through the lungs and excretion of acid or bicarbonate through the kidneys, so that acid excretion and production are balanced. The collecting duct of the mammalian kidney has acid-excreting and base-excreting cells, which can be altered to increase or decrease acid or base excretion. In aquatic animals, the external surfaces have the capacity to extrude acid in similar ways to the collecting duct of the mammalian kidney. For example, a protein ATPase exists in the skin of frogs and gills of freshwater fish which excretes protons on the apical surface of the epithelium. Fish gills also have a HCO3-/Cl- exchange mechanism, which aids in the regulation of body pH.


What are alkalosis and acidosis, and what are the consequences?

When an animal’s body experiences changes in its body pH, many physiological changes occur within the body of the animal. When there is excessive alkalinity in the body and therefore an increase in body pH, this is referred to as alkalosis.   Conversely, when there is excessive acidity in the body and therefore a decrease in body pH, this is termed acidosis.

In terms of the effects of pH on the respiration of animals, when lung ventilation is decreased causing CO2 excretion to drop below CO2 production, body CO2 levels rise and pH falls. This is referred to as respiratory acidosis. When lung ventilation is increased causing CO2 excretion to rise above CO2 production, body CO2 levels fall and pH rises. This is referred to as respiratory alkalosis.

It is important to know that body fluids are electroneutral, which means that the sum of the anions equals the sum of the cations. Respiratory acidosis and alkalosis disturb the electroneutrality of the body fluids. However, at the cellular levels, the pH is regulated and electroneutrality is brought back to the body fluids. There are various mechanisms, which regulate cellular pH and thus maintain electroneutrality in the body fluids.

One cellular mechanism involves proteins and phosphates within the cell that act as physical buffers to regulate cellular pH. The most important buffers in the blood are proteins, especially hemoglobin, and bicarbonate because the CO2-to-bicarbonate ratio can be adjusted by excretion of CO2 in order to regulate pH.

A second mechanism that regulates cellular pH involves the important reaction of HCO3- with H+ ions. For example, when oxygen enters red blood cells within the blood, the molecules attach to the hemoglobin thus releasing H+ ions. The pH decreases, which increases cellular acidity and causes the reaction of HCO3- with H+ ions to form CO2. The CO2 then diffuses out of the red blood cells thus regulating the pH within the cells.

Also the proton-exchange and the anion-exchange mechanisms in the cell membrane play important roles in adjusting cellular pH. For example, if a cell is acidified, there is a H+ efflux, which is connected to a Na+ influx and there is a HCO3- influx, which is connected to Cl- efflux. This mechanism adjusts the pH of the cell to a less acidified state. Lastly, another mechanism for regulating cellular pH involves the simple passive diffusion or active transport of H+ ions from the cells.


What are the organs that facilitate gas exchange/respiration?

Gas transfer occurs by passive diffusion from the environment across the body surface. Air breathing, in most vertebrate animals, involves the movement of air into and out of the lungs. Insects have developed a very different method of gas transfer between the tissues and the environment and this includes a tracheal system. Water breathing, on the other hand, for most aquatic animals involves a unidirectional flow of water over the gills. Thus, the structure and design of the mammalian, insect, and fish respiratory systems are radically different. Each gas-transfer system is built according to the needs of the animal and to the medium in which it lives.

In air breathing animals, the related respiratory organ that facilitates gas transfer, is the lung. The lungs in air breathing vertebrates are large organs of respiration located in the chest cavity. In humans, the right lung is made up of three lobes and the left lung is composed of two lobes. They are suspended in the pleural cavity and opens to the outside by the trachea. The respiratory portion of the lung includes the terminal bronchioles (under glossary term as bronchus), the respiratory bronchioles, and the alveolar ducts and sacs.

In contrast, the associated respiratory organs of the fish include the gills. The gills consist of a feathery, branched tissue richly supplied with blood vessels. The gills facilitate the exchange of oxygen and carbon dioxide with the surrounding water.

Most insects respire by means of a tracheal system. In this system, gas is directly transported to the tissues by air-filled tubules that bypass blood. The pores to the outside, called spiracles, deliver the gases of respiration. The drawback of this system is that the gases diffuse slowly in the long narrow tubules; as a result, these tubes need to be limited in size for adequate gas transfer. The advantage is that O2 and CO2 diffuse much faster, 10,000 times faster, from the air than in water, blood, or tissues. This feature often uses less energy for ventilation and bypasses the need for a circulatory system.   Another advantage of the tracheal system is that oxygen can be delivered directly to tissues that need it, such as flight muscles.


What are the components of the mammalian lung?

The mammalian lung is more complex than that of the amphibian, reptile, or other non-mammal species, and consists of a complex network of tubes and sacs. To be more specific, the human respiratory system consists of the nasal cavity, pharynx, trachea, bronchi, and lungs. Although not considered a part of the respiratory system, the ribs, muscles, and diaphragm are important and help in the expansion and contraction of the lung. To begin with, the pharynx and larynx lead to the lungs; the larynx is connected to the trachea, which branch into the right and left bronchi. These bronchi further divide and lead to the terminal bronchioles. The terminal bronchioles continue and then lead air to the respiratory bronchioles. The respiratory bronchioles themselves connect to a fan of alveolar ducts and sacs. The function of the alveolar ducts and sacs is to moisten and cleanse the air taken in, and furthermore, transfer it to the gas-exchanging portion of the lung. These alveolar ducts and sacs are filled with many capillaries, the smallest of the blood vessels, and also consist of connective tissue fibers.

Alveoli, millions of interconnected sacs, also make up a large part of the lung. The human lung is made up of an average of 300 million alveoli. Through diffusion, gases from the air in the alveoli are exchanged with the gases in the pulmonary capillary blood. The transport of gases depends on this exchange and relationship between O2 pressure in the alveoli and the surrounding atmospheric pressure.

As seen, through a series of branches and smaller ducts, air is delivered to the respiratory portion of the lung (the terminal bronchioles, respiratory bronchioles, and the alveolar ducts and sacs); gas is transferred across the respiratory epithelium in these specific areas. Gas transfer also occurs across acini and the pores of Kohn, which allow for collateral (side-by-side) movement of air.


How do different animals ventilate their lungs/spiracles? (mammals, birds, reptiles, frogs, invertebrates)

The functional anatomy of the lungs and associated structures vary considerably among animals in the mechanism of lung/spiracle ventilation.


The lungs of mammals are elastic, multi-chambered bags, which open to the exterior through a single tube, called the trachea. The lungs are suspended within the pleural cavity. The ribs and the diaphragm form the walls of the pleural cavity, which are referred to as the thoracic cage. The thoracic cage mostly consists of the lungs, but between the lungs and the thoracic walls there is a low-volume of pleural space sealed and fluid filled.

During normal breathing, the thoracic cage expands and contracts by a series of skeletal muscles, the diaphragm, and the external and internal intercostal muscles. The respiratory center within the medulla oblongata controls the contractions of these muscles through the activity of motor neurons. During inhalation, the volume of the thorax increases due to the lowering of the diaphragm.  In addition, the ribs are raised and moved outward by the contraction of the external intercostal muscles. The increase in thoracic volume reduces alveolar pressure, and air is drawn into the lungs. During exhalation the diaphragm and external intercostal muscles relax, reducing the thoracic volume. Reducing the thoracic volume raises alveolar pressure and forces air out of the lungs.


In the lungs of birds, gas exchange occurs in air capillaries extending from parabronchi, a series of small tube-like structures, which are functionally equivalent to the alveoli in mammals. The parabronchi extend between large dorsobronchi and ventrobronchi, both of which are connected to an even larger tube, the mesobronchus. The parabronchi and connecting tubes form the lung, which is contained within a thoracic cavity. However, the volume of the thoracic cage and lung changes very little during breathing and therefore, are not directly involved in avian lung ventilation. In birds, the air-sac system connected to the lungs ventilates the avian lungs. During inspiration, air flows through the mesobronchus into the caudal air sacs. Air also moves through the dorsobronchus and the parabronchi into the cranial air sacs. Oxygen is then diffused into the air capillaries from the parabronchi and is taken up by the blood. During expiration, air leaving the caudal air sacs passes through the parabronchi and then through the mesobronchus to the trachea. The cranial air sacs, during expiration, move air through the ventrobronchi to the trachea and into the environment. The bird ventilation mechanism is special because birds are capable of flying at high altitudes while maintaining a sufficient supply of O2 in their bodies. Specifically, the unidirectional flow of air through the parabronchi aids in increasing the efficiency of gas exchange within the avian lungs thus giving birds the capability of flying at high altitudes.  This means of gas exchange is more efficient that thet tidal flow model seen in mammals.


The ribs of reptiles form a thoracic cage around the lungs. During inhalation, the ribs moving cranially and ventrally, enlarging the thoracic cage. This process reduces the pressure within the cage below atmospheric pressure. The nares and glottis open and air flows into the lungs. Exhalation occurs passively by the relaxation of the muscles that enlarge the thoracic cage, which release energy stored in stretching the elastic component of the lung and body wall.

In tortoises and turtles, the ribs are fused to a rigid shell. Outward movements of the limb flanks and/or the ventral part of the shell and by forward movements of the shoulders are what inflate the lungs. The reverse process results in lung deflation, involving the retraction of limbs and head into the shell leading to a decrease in pulmonary volume.  Therefore, when a turtle is withdrawn into its shell, its lungs are deflated and the turtle can't breathe.


In frogs, the nares open into a buccal cavity, which is connected through the glottis to a pair of lungs. During inhalation, air is drawn into the buccal cavity with the nares open and the glottis closed. Then the nares close and the glottis is opened. The buccal floor then rises, forcing air from the buccal cavity into the lungs. This lung-filling process may be repeated several times in sequence inhaling air in portions. This same process may also occur during expiration in which the lungs release air in portions. Inhaling and exhaling air in portions may produce a mixture of pulmonary air low in O2 and high in CO2. This complex method of lung ventilation may be to reduce fluctuations in CO2 levels in the lungs to stabilize and regulate blood PCO2 and control blood pH.   Frogs also exchange gasses across their skin, so the lungs are not the only repsiratory surface.


Invertebrates have a variety of gas-transfer mechanisms. In some invertebrates, ventilation does not occur. These invertebrates rely on diffusion of gases between the lung and the environment. Spiders have ventilated lungs called "book lungs". The lungs have respiratory surfaces consisting of thin, blood-filled plates that extend like the leaves of a book into a body cavity guarded by an opening (spiracle). The spiracles open and close to regulate the rate of water loss from these "book lungs". Snails and slugs also have ventilated lungs in which their lung volume changes enabling them to emerge from and withdraw into their rigid shells. In aquatic snails the lungs serve to reduce the animal’s density. Most insects have a gas-transfer mechanism called the tracheal system (to know more information on the insect tracheal system, link to the questions: How do insect tracheals work? How are they different from lungs and gills?)


How do gills work?

For most fish species gills work by a unidirectional flow of water over the epithelial surface of the gill, where the transfer of gases is made (O2 in, CO2 out). The reason for this unidirectional flow of water, and not an inhaling and exhaling of water, is due to the energetics of the system. The energy that would be required to move water into and out of a respiratory organ would be much more than that used to move air because water is more dense and viscous.

The blood flowing just under the epithelial gill tissue usually moves in a countercurrent flow to that of the water moving over it. This allows for the most O2 to be taken in by the blood because the diffusion gradient is kept high by the blood picking up oxygen as it moves along, but always coming in contact with water that has a higher O2 content. The blood receiving the O2 will continue to pick up O2 as it moves along because fresh water is being washed over the epithelial lining of the gills. An important aspect to remember here is that the water going over the gills needs to be moving unidirectional, either by the fish forcing the water to move in one direction or if the water is moving mostly in one direction.

There are two ways fish ventilate their lungs: buccal/opercular pumping (active ventilation) and ram ventilation (passive ventilation). The fish pulling in water through the mouth (buccal chamber) and pushing it over the gills and out of the opercular chamber (where the gills are housed) accomplishes buccal/opercular ventilation. The pressure in the buccal chamber is kept higher than the pressure in the opercular chamber so the fresh water is constantly being flushed over the gills. A fish swimming with its mouth open, allowing water to wash over the gills accomplishes ram ventilation. This method of ventilation requires fast water or a fast fish to keep enough oxygen going to the gill surface.


How do insect tracheoles work? How are they different from lungs and gills?

Insect tracheal systems are a series of air filled tubes that run from the edge of the exoskeleton to the cells/tissues far within the body. The tracheal system terminates at the tracheoles, that often go in between or right into cells to deliver O2 very close to the mitochondria. There is usually fluid between the terminal ends of the tracheols and the body cells, but as the insect becomes more active the fluid is replaced by air so gas exchange is heightened. The use of tracheal systems is superior to using water or blood as mediums of gas exchange because O2 and CO2 diffuse 10,000 times more rapidly in air so the necessary gases can be exchanged more quickly. However, there is a size limit for effective ventilation via a tracheal system, which is one reason that insects cannot grow to gargantuan sizes.

The inner wall surface of the tracheal system is made of the same material that composes the exoskeleton, which helps to prevent water loss. Spiracles, the openings to the outside air, can be opened and closed at will to in regulate air exchange, water loss, and to keep out debris.

Ventilation is usually accomplished through convection, the mass movement of gases. Some larger insects can compress and expand their body wall to coincide with the opening and closing of spiracles to pull air in and push air out. To reduce the amount of energy used in respiration some insects use the discontinuous ventilation cycle (DVC) which is composed of open, closed, and intermediate flutter phases. During the closed phase (spiracles closed) the O2 that is in the body is being used more rapidly than the CO2 being produced. Due to this, when the open phase begins there is a O2 gradient, the low end being within the body, forcing a rush of O2 from the surrounding air into the spiracles and releasing any CO2 that was produced. This process may be helped along by the expansion of respiratory sacs within the body to pull more air in or push more air out. During the flutter phase there is rapid inhalation and exhalation. This type of ventilation uses the most energy and it is not understood why it is done.


What is the role of pulmonary surfactants in respiration?

Pulmonary surfactants are lipoprotein complexes produced in the lungs that are used to reduce the effort in breathing and help prevent the collapse of alveoli. Pulmonary surfactants make expansion of the alveoli easier by lowering the surface tension that holds membranes of different alveoli together and minimizes expansion of individual alveoli. This makes it easier for alveoli membranes to slide against each other when they are expanded to take in air.

Surfactants also reduce the chances of alveolar collapse by stabilizing surface tension when an alveoli sac is expanded. When alveoli are expanded the surfactant is spread out more, which increases surface tension. Surface tension is a major contributor to wall tension, which determines if a small alveolar sac collapses into a larger alveolar sac. Collapse occurs when the pressure inside a small alveolar sac (wall tension in relation to the radius of the sac) is greater that the pressure in a larger alveolar sac, forcing the air in a small sac (high pressure) to force its way into the large sac (low pressure). The surfactant prevents this by minimizing the surface tension, which minimizes the difference in wall tension and thereby minimizing the pressure difference between alveoli.


How are breathing patterns controlled or regulated?

Breathing is an automatic and rhythmic behavior regulated by several nerve centers in the brain, more specifically, in the neurons of the pons and medulla oblongata. The central processing of many sensory inputs control breathing movements. The central processor is made up of a pattern generator and a rhythm generator. From these, the depth and amplitude of each breath is controlled and the frequency of breathing is controlled, respectively.

Ventilation helps maintain satisfactory rates of gas transfer and blood pH levels. Breathing movements with eating, talking, or other bodily functions are controlled by sensory inputs as well. The muscles and diaphragm help ventilate the lungs. This action is stimulated by the spinal motor neurons and the phrenic nerve that get information from the neurons that make up the medullary respiratory centers. The muscles of the respiratory system are finely controlled, and this allows humans to breathe, sing, and whistle. The medullary respiratory center also contains inspiratory and expiratory neurons. The activity of the inspiratory neurons correspond to inspiration.  The networks of neurons connect to higher brain centers, the chemoreceptors and mechanoreceptors.

Neuronal action has much to do with breathing and respiratory activity. From the phrenic nerve or from individual neurons in the medulla, scientists have been able to record inspiratory neuronal activity and learn more. Inspiration is characterized by a changing release of medullary neurons. The activity recorded shows a rapid onset, a gradual rise, and an abrupt termination with a sudden burst of activity related to inhalation. Following this activity, the inspiratory muscles contract and intrapulmonary pressure decreases. Inspiratory neuronal activity can be said to depend on the cycle of various neurons- inspiratory, early inspiratory, off-switch, post inspiratory, and expiratory neurons. The "off-switch" neurons come about at the sharp cutoff point in the activity of inhalation, and also when neuronal activity has reached a threshold level. Pulmonary stretch receptors that are stimulated by lung expansion decrease the threshold level. Without these receptors working on the inspiratory neurons, there would be over-expansion of the lung. At the beginning of expiration, the amount of work by the inspiratory muscles begins to decrease, which is caused by the post-inspiratory neurons. The post-inspiratory neurons are responsible for slowing the rates of expiration. At the end of the post-inspiratory activity, the expiratory neurons are then released.

The time between each breath is determined by the interval between the bursts of activity of the inspiratory neurons. The interval between a burst of activity is related to the amount of activity in the burst that came before it, as well as with nerves in the pulmonary stretch receptors. If the activity of inspiration is great, as is when taking a deep breath, there is a longer interval between inspirations. This allows the ratio of duration on inspiratory and expiratory activity to stay constant no matter how long the breath taken is. The pulmonary stretch receptors can influence this ration, however, depending on their activity. If these receptors are very active, the duration of expiration may be extended, leaving a longer time for exhalation. This can occur during expiration when the lung empties out slowly and when the pulmonary stretch receptors are still active while the lung stays inflated.

Expiratory neuronal activity appears not to influence normal exhalation. Exhalation most often occurs passively, as the thoracic cavity relaxes after inhalation. Expiratory neurons are used for forced exhalation, however, and are only active when the inspiratory neurons are still.

The human respiratory system has the ability to adjust its breathing patterns to different environments and to disturbances in breathing, such as asthma (a narrowing of the airway which causes breathing difficulties). This flexibility is due to a number of sensors found throughout the body, which send signals to the respiratory networks in the brain. The chemoreceptors detect any changes of acidity that may occur in the cerebral spinal fluid (CSF) in the brain, or in blood. For example, when PCO2 levels increase in the body, the levels of pH in the CSF decrease. The chemoreceptors act to drive ventilation, and the amount of breathing is increased. The mechanoreceptors of the body help maintain any expansions of the lung and also help maintain the size of the airway.


How does an animal respond to extreme conditions?

Animals have the ability to respond to extreme conditions, such as reduced oxygen levels (hypoxia), increased carbon dioxide levels (hypercapnia), diving, and exercise. As we will see, each of the extremes mentioned will induce a respiratory response specific to its demands.

Decreased O2 levels (hypoxia)

In aquatic environments, gas mixing and diffusion occur less rapidly than in air. Because of this, aquatic animals experience frequent changes in O2 levels and face regions of hypoxia. CO2 levels may or may not come about with different O2 levels.

Some animals can survive periods of hypoxia. To do so, the animals either use anaerobic pathways, or will adjust their respiratory and cardiovascular systems in order to deliver oxygen throughout their bodies while experiencing reduced O2 availability.

In air, the levels of O2 and CO2 can remain relatively stable. There is, however, a decrease in O2 levels with higher altitudes. With increasing altitude, there is a gradual reduction in PO2, and each animal has a different way of fighting these conditions.  For example, and increase in blood levels of  2,3 DPG will decrease the affinity of Hb for O2, thereby releasing more O2 for the tissues to use. 

A decrease in PO2 of the air will cause a decrease in blood PO2. The carotid and aortic bodies are stimulated when this happens, causing an increase in lung ventilation. When there is an increase in lung ventilation there is more CO2 eliminated and a reduction in blood PCO2 as well. As a result, the pH of the CSF rises and tends to reduce ventilation. When an animal is in an area of hypoxia for a longer period of time, blood and CSF pH levels are brought back down to normal by the release of bicarbonate in the body. For instance, for a human who has moved to a higher altitude, this process takes about one week. The carotid bodies and the aortic body chemoreceptors may be reset to the lower CO2 levels. Hypoxic conditions cause a vasoconstriction in the pulmonary capillaries and a rise in pulmonary blood pressure. This circulates the blood away from the poorly ventilated areas of the lung.

There are other effects to living in such an extreme condition. Humans, for example, tend to be smaller in size, barrel chested, and have an increased lung volume. There is a reduction in limb development and often excessive growth or development of the right ventricle, due to increased pulmonary blood pressures. Also, over long periods of time, most animals will increase the number of red blood cells and the amount of hemoglobin in the blood. This feature increases the oxygen capacity of the blood. If there is a decrease in O2 levels in the blood, erythropoietin, a hormone of the kidney and liver, is produced. This hormone stimultes red blood cells are production in bone marrow. Hypoxia may also result in systemic vasodilation, as well as an increased cardiac output. When O2 supplies are restored from increased hemoglobin levels in the blood and through ventilation, cardiac output is brought back to normal.

Increased CO2 levels (hypercapnia)

PCO2 represents the amount of CO2 in solution. When there is an increase in blood PCO2, there is an increase in ventilation. The aortic and carotid body chemoreceptors, the mechanoreceptors in the lungs, and most especially, the central H+ receptors, regulate this activity. They do so by sending messages to the respiratory center of the brain. The pH of the CSF is brought back to normal levels in order to bring ventilation levels back to normal as well. When there is an increase in CO2 levels, there is a distinct increase in ventilation. After the stress of increased CO2 levels is relieved, ventilation gradually returns to a level slightly above the ventilation level that occurred before hypercapnia. The reason it returns to a level only slightly above the initial ventilation volume relates to a rise in plasma and CSF bicarbonate levels. As a result of the increased plasma and CSF bicarbonate, pH levels are brought back to normal, even though there may still be a high level of CO2.

Diving by air-breathing animals

During a dive, animals are subjected to periods of hypoxia. Anoxia, severe hypoxic conditions that can result in permanent damage, is a large problem for a mammal’s central nervous system (CNS) and because of this, oxygen must be continuously supplied to the animal. Throughout a dive, animals combat anoxia by making use of oxygen stores in the lungs, blood, and tissues. Animals that dive have higher hemoglobin levels, which increase the oxygen capacity of the blood, and also have larger oxygen stores in muscle ( myoglobin ) to efficiently supply the body with O2. In order to utilize the stores efficiently during a dive, blood is delivered to the brain and heart first. The tissues and organs to where blood did not go to resort to an anaerobic pathway. As a result, the heart rate slows and cardiac output decreases. The O2 stores need to be large enough to sustain aerobic metabolism because diving animals cannot tolerate the large buildup of lactic acid from anaerobic metabolism.

During a dive, inspiration is prevented and water is detected from receptors found near the glottis, mouth, or nose. Although there is an increase in CO2 levels and a decrease in blood pH, ventilation is prevented. This is because the carotid and aortic body chemoreceptors are not acted upon by the respiratory neurons to cause ventilation.

One potential danger of a prolonged dive is that gases in solution in the blood under the higher pressure of greater depth may come out of solution too quickly and form air bubbles in the blood vessels when the pressure diminishes.  In humans, this can cause a condition known as "the bends", in which gas bubbles accumulate in the joints, and can even obstruct blood flow in small vessels in the brain and other parts of the body.  Many diving mammals prevent this condition by exhaling when they dive, thereby emptying most of the air out of their lungs.  In addition, under the pressure of diving, the alveoli collapse, thereby forcing air into the bronchioles, where it cannot go into solution in the blood.


During exercise, more oxygen is needed, and more CO2 and metabolic acid are produced. In addition, there is an increased cardiac output because the tissues need more oxygen supplied to them. This is also caused due to an increase of lung ventilation to support gas tensions in arterial blood, which experiences faster blood flow. When an individual is exercising, the venous blood shows signs of decreased O2 levels, increased CO2 levels, and an increase in H+ levels. In the arterial blood, however, the average PO2 and PCO2 do not differ much as they do in the venous blood, except when under extreme exercise. When exercise has stopped, there is a decrease in the amount of breathing and eventually, a decline in ventilation volume as well once the balance between O2 consumption and CO2 production is restored and the O2 needs are met.  This may take a while, if a significant oxygen debt has been built up by a prolonged period of anaerobic muscle activity.



What are some of the physiological problems associated with high altitude?

Altitude Sickness, and the related disorders and symptoms, pose an immediate threat to athletes who spend their time exercising at high altitudes. The most commonly affected athletes are high altitude mountain climbers. It is not uncommon to find them above 20,000 feet using skill, strength and concentration to scale some of the most dangerous mountains our Earth has to offer. Unfortunately, the challenge of high altitude mountaineering also brings with it the risk of serious illness and possibly death. Why is this? Why does our body respond so negatively to high altitude environments?

Increased altitude is coupled with decrease atmospheric pressure meaning that for every breath inhaled; there is less O2 available. Think of breathing inside a bedroom filled with 1000 liters of O2. There is plenty of air around you and the pressure is high, like it is at sea level. Now imagine you are breathing in a warehouse that is filled with an equal amount of air. The decreased in pressure would make it harder to breathe. The atmospheric pressure on top of Mt. Everest (29,028 ft) is 33% less than it is at sea level. This means that 66% less oxygen is available. This is what climbers face when performing at high altitudes.

Due to the oxygen constraint, our bodies are forced to work harder to continue to metabolize. Respiration must increase to get sufficient oxygen across the lungs. Increasing our respiration can be taxing to our systems. If the body overdoes it, Acute Mountain Sickness (AMS) can occur. This is the result of increased respiration and circulation. The body overcompensates for the decreased oxygen by sending too much to the brain. Leakage into the brain occurs and causes swelling. Decreased oxygen also starves nerve cells, triggering the release of adenosine. This chemical decreases the body’s metabolism, decreasing our need for oxygen. It also dilates blood vessels into the head and neck, which allows more oxygen to go to the brain. This is the same dilation that is correlated with migraine headaches. A common treatment for the migraine symptoms is the use of caffeine. Caffeine blocks the adenosine receptors, thus preventing vasodilatation. If AMS goes unnoticed, a more serious sickness can occur. High Altitude Cerebral Edema (HACE) has occurred from 10,000 ft. and above. It occurs when AMS is overlooked and thus brain swelling increases. In extreme cases, death can result. The symptoms of HACE are imbalance, severe headache, vomiting, nausea, and hallucinations. Known treatments include rapid descent, supplemental oxygen, water, and a diuretic called Diamox. Victims of HACE often experience comas and death. The increased blood flow, as a result of high altitude that was mentioned before, can also lead to High Altitude Pulmonary Edema (HAPE). This occurs when excessive blood pressure causes fluid to leak from the blood vessels into the alveoli sacs of the lungs. Cases have been seen at 8,000 ft. and above and were characterized by difficulty breathing, gurgling sound in lungs, fever, coughing, and exhaustion. The fluid in the lungs blocks the oxygen-blood interface. The body compensates by increasing heart rate and blood pressure, thereby forcing more fluid into the lungs. Eventually, if altitude is not decreased, the victim drowns. No oxygen reaches the lung/capillary interface.

Other problems associated with high altitude include Periodic Breathing and Khumbu Cough. In Periodic Breathing, during sleep above 14,000 ft., climbers will repeatedly stop breathing, gasp, hyperventilate, and then stop again. The medulla of the brain is affected causing breathing to become irregular. CO2 builds up, the sleeper hyperventilates, CO2 decrease, respiration stops, and the cycle continues. The body actually responds to a state of alkalosis, which causes the shut off of breathing. Khumbu Cough is commonly seen with high altitude climbing. It is characterized by a dry cough that results from too high a breathing rate. The mucosa of the bronchi dries out due to the increased breathing rate and contact with dry, cold air. Besides irritation, the Khumbu Cough can result in broken ribs as a result of severe coughing episodes. The only prevention is to keep the breathing rate down. This reduces the drying out of the mucosa.