Respiratory Physiology

An understanding of the physiology of respiration will enable an increased understanding of some of the disease processes encountered.

It is worth spending some time trying to understand some of the concepts involved.

The main purpose behind respiration is to supply the cells with oxygen and to remove carbon dioxide, the waste product. There are three key elements to this process: pulmonary ventilation, external (pulmonary) respiration, and internal (tissue) respiration.

Pulmonary ventilation

Inspiration is the process by which we breathe in. The pressure inside the lungs before each breath equals about 760 mm Hg or 1 atmosphere at sea level.

The pressure inside the lungs needs to be lower than this for air to enter and this is achieved by increasing the volume of the thoracic cavity.


Boyles law states that the pressure of a gas in a closed container is inversely proportional to the volume of the container.

So the difference in pressure created when we breathe in forces air into our lungs.

In order to increase the volume the principal muscles must contract. These muscles are the diaphragm and the intercostals or those muscles between the ribs.

The diaphragm is a dome shaped skeletal muscle which is innervated by the phrenic nerve, which emerges from spinal cord at cervical levels 3, 4, and 5.


Contraction of the diaphragm causes it to flatten which increases the vertical dimension of the thoracic cavity and therefore its volume.

The diaphragm moves from 1cm to 10cm depending on whether there is normal or heavy breathing. Obesity and pregnancy can both obstruct this process leading to breathlessness.

As the diaphragm is being pulled down the external intercostals also contract pulling the ribs upwards.

The pressure between the two pleural membranes is also important to consider. During normal breathing this intrapleural pressure is always below atmospheric pressure.

As the diaphragm contracts the intrapleural pressure falls from 756 mm Hg to 754 mm Hg and this pressure change pulls the walls of the lungs outwards.

The two pleura adhere strongly to each other because of the below atmospheric pressure and the surface tension between them.

So the combination of the diaphragm and the external intercostals help to increase the volume of the thoracic cavity, which then drops the pressure within the cavity.

The alveolar pressure drops from 760 mm Hg to 758 mm Hg, and the pressure gradient created between the inside of the lungs and the atmosphere draws air in.

During deep breathing, caused by exertion or lung disease other muscles become involved in inspiration and these are known as the accessory muscles. These include the sternomastoid, scalenes and pectoralis major.

Expiration is the reversal of the pressure gradient. This is normally a passive process depending on relaxation of the muscles involved in inspiration. It does however depend upon the elastic recoil of the lung and the inward pull of the surface tension due to the alveolar fluid.

As the external intercostals and the diaphragm relax, the ribs move downwards and the dome of the diaphragm moves back up. This reduces the volume of the thoracic cavity and hence the pressure increases to around 762 mm Hg.

The surface tension in the alveoli also creates a pull which causes the bronchioles and the alveolar ducts to recoil.

Air then flows out of the lung.

During active expiration, when breathing becomes laboured, the abdominal and internal intercostal muscles become involved in further flattening the dome of the diaphragm to help expel the air.

Atelectasis, Compliance and Airway Resistance

The alveoli are inclined to collapse in on themselves at the end of expiration due to the surface tensions involved. A collapsed lung or portion of lung is know as atelectasis.. This collapse is normally prevented by the presence of surfactant within the lung which acts to decrease the surface tension.

Compliance depends upon elasticity and surface tension. A lung with high compliance will expand more easily and one with lower compliance will resist expansion.

Compliance decreases with any condition which destroys lung tissue or causes it to become filled with fluid, and a reduction in surfactant will have the same effect.

The walls of the bronchi and bronchioles offer some resistance to air flow. As the lungs expand the airway diameter is increased which lowers the resistance, allowing the flow of air. Conditions which increase the resistance make the effort of breathing greater. COPD or asthma are two of these conditions.

Lung Volumes and Capacities

Lung volumes can be measured by an instrument known as a spirometer producing a graph called a spirogram as can be seen above. Inspiration is recorded as an upward deflection and inspiration as a downward one.

The volume of air that is inspired in normal, quiet breathing in the healthy lung is approximately 500mls. This will vary depending on the size of the person. This normal volume is called the tidal volume and approximately only 350mls of this actually reaches the alveoli.

The rest is in that part of the lung which does not take part in gas exchange, otherwise known as the dead space of the lung. The total amount of air taken in during one minute can be found by multiplying this number by the number of normal breaths per minute, which is about 12. This will give a normal minute volume of about 6 litres.

By taking a very deep breath another 3.5 litres can be taken into the lungs. This is known as inspiratory reserve volume.

Inspiratory reserve volume is the air you can exhale if you do so forcibly and this volume is approximately 1.2 L.

Even after forced exhalation of air there is still a good volume of our remaining in the lungs which cannot be exhaled.

This is known as the residual volume, and usually amounts to about 1.2 L.

The various capacities of the lungs are made up of specific lung volumes. The total inspiratory ability of the lungs is the sum of tidal volume plus inspiratory reserve volume, approximately 3.6 L. This is otherwise known as the inspiratory capacity.

The sum of the residual volume plus the experience true reserve volume is otherwise known as the functional residual capacity. It is this capacity that the anaesthetist tries to wash out using oxygen prior to intubation. This ensures that the anaesthetist increases the period of time to intubate the patient before they start to become hypoxic.

Vital capacity is the inspiratory reserve volume, the tidal volume, and the experience true reserve volume combined. This normally amounts to approximately 4.8 L.

Total lung capacity is the sum of all the volumes and amounts to approximately 6 L.

Exchange of Gases

Remember Boyle’s Law, where the volume of gas varies inversely with the pressure. So as the pressure increases for example the volume of the gas decreases as it becomes squeezed within whichever container it is in. In order to fully understand the exchange of gases within the lungs it is necessary to have a brief understanding of three more gas laws.

Charles’s Law

In this law the volume of gas and the temperature of that gas are directly proportional assuming that the pressure remains constant.

So let’s assume that the gas is in a cylinder with a piston above it which is halfway down. The piston can move freely allowing the pressure to remain the same.

So when we heat the gas this causes the gas molecules to move faster and therefore the number of collisions within the cylinder increases. The force of the molecules will cause the piston to move upwards thereby increasing the volume of the gas.

As the cylinder has moved the pressure remains unchanged and therefore the volume increases in direct proportion to the temperature increase

Daltons Law

Dalton’s Law relates to the partial pressures of a gas. According to this law each gas in a mixture of gases exerts its own pressure as if all the other gases were not present. The pressure of a specific gas in a mixture is called its partial pressure and is denoted as p. Adding all the partial pressures of the gases within a mixture gives you the total pressure of the mixture.


Atmospheric air is a mixture of several gases the main ones being oxygen, nitrogen, carbon dioxide and water vapour. So atmospheric pressure is the son of the pressure of all of these gases.

The partial pressure of oxygen for example is approximately 160 mmHg and the partial pressure of carbon dioxide in atmospheric air is 0.3 mmHg.

Gases in the lungs have to defuse across a permeable membrane, the alveoli. Each gas will diffuse from an area of high pressure to an area of low pressure.


Because of this cellular respiration there is a lower concentration of oxygen within the pulmonary venous supply than in the alveoli, which creates a pressure difference.


This then ensures that oxygen will diffuse from the alveoli across the membrane and into the blood supply. Conversely there will be a higher concentration of carbon dioxide in the blood supply so this gas will move from the blood to the alveoli across its concentration gradient.

Henry's Law

This law states that the quantity of gas that will dissolve in a liquid is proportional to the partial pressure of the gas and its solubility coefficient, when the temperature remains constant.

The solubility coefficient relates to gases physical or chemical attraction for water. The higher the solubility coefficient the more readily the gas will stay in the solution.

Physiology of external respiration

Deoxygenated blood enters the lungs from the right side of the heart. Oxygenated blood then leave the lungs to enter the left side of the heart. Atmospheric air enters the lungs and moves into the alveoli.

The partial pressure of oxygen in deoxygenated blood is only 40 mmHg, whilst the partial pressure of oxygen in atmospheric air in the alveoli is 105 mmHg. Because of the pressure gradient created between these different partial pressures of oxygen will move from an area of high concentration to an area of low concentration. In this case moving from the alveoli across the membrane and into the pulmonary capillaries.

The partial pressure of carbon dioxide in alveoli air is 40 mmHg whilst in the deoxygenated blood the partial pressure of carbon dioxide is 45 mmHg. Again, because of the pressure gradient created, carbon dioxide will therefore move from an area of high concentration to an area of low concentration. So the carbon dioxide moves from the pulmonary capillary into the alveoli.

The rate of respiration will depend on several factors:


1.  The rate of diffusion across any membrane is directly proportional to the size of that membrane, or its surface area. The surface area of the lung is approximately 70 m², which provides a large area over which the gas can exchange. This is surface area is reduced then gas exchange becomes more difficult. An example of a condition which may cause this would be emphysema where the alveoli walls disintegrate and the surface area of the lung is therefore reduced.

2. The thickness of the membrane is also crucial. The thick of the membrane the harder it is for the gas to diffuse across. This is why the total thickness of the alveoli are-capillaries membranes is only about 0.5 micro metres. Anything which increases this distance will also make gas exchange more difficult. So for example a buildup of fluid or lung secretions as in a severe pneumonia will worsen the gas exchange.

3. The partial pressure difference of the gases will also affect how well respiration can take place. If the partial pressure is reduced, when for example one goes to a higher altitude, then the rate of gas exchange will slow down giving the typical symptoms of high altitude sickness caused by the low partial pressure of oxygen in the blood.

Physiology of internal respiration

The process of gas exchange between the tissue blood capillaries and tissue cells is called internal respiration. This also occurs because of the partial pressure differences between the gases on either side of the membrane.

Oxygenated blood in the tissue capillaries has a partial pressure of 105 mmHg where is that in the tissue as a partial pressure of oxygen of only 40 mmHg.

So once again the gas moves from an area of high pressure to an area of low pressure. The same occurs with carbon dioxide at the tissue level, with this obviously moving in opposition to the oxygen.

Transport of gases

Because oxygen does not dissolve easily in water very little of it can actually be carried directly in the plasma, only about 1.5%. The rest of it has to be combined with the haemoglobin in the blood in order to be transported.

The oxygen and the haemoglobin have to bind together, and there are four heme groups which can each combine with one molecule of oxygen. When combined it is then known as oxyhaemoglobin.

When the oxygen binds from the haemoglobin this is known dissociation and there are several factors to take into consideration when considering binding and dissociation.

The partial pressure of oxygen is the most important factor when considering how much oxygen combines with haemoglobin. When deoxyhaemoglobin is completely converted to oxyhaemoglobin it is said to be fully saturated, and when it contains a mixture of the two it is said to be only partially saturated.

The relationship between the percentage saturation of haemoglobin and partial pressure of oxygen is illustrated in the figure above, this is usually known as the oxygen-haemoglobin dissociation curve.

You can see from the above that when the partial pressure of oxygen is high haemoglobin binds with large amounts of oxygen and is almost fully saturated. So the greater the partial pressure of oxygen the more oxygen will combine with haemoglobin.

You can also see from the above figure that the haemoglobin is still 90% or more saturated with oxygen even at partial pressures of between 60 to 100 mmHg. So the blood can still pick up nearly a full load of oxygen even when the alveoli partial pressure of oxygen is low.

As the partial pressure of oxygen becomes even lower, at 40 mmHg you can see that the percentage of haemoglobin saturated with oxygen drops off quite quickly. So large amounts of oxygen are released from haemoglobin at these partial pressures.

This is important in some of the more active tissues where the partial pressure of oxygen can decrease well below 40 mmHg. The large amount of oxygen released as a consequence means that the tissues can continue to work.

Whilst the partial pressure of oxygen is the most important factor when considering the binding and dissociation to haemoglobin there are also a number of other factors to take into account;

1. The pH of an environment is directly related to the number of hydrogen ions. Hydrogen ions alter the structure of haemoglobin decreasing its oxygen carrying capacity. The lowered pH therefore means that more oxygen is available for tissue cells as the pH will be lower here.

2. Carbon dioxide can also bind to haemoglobin and therefore as the partial pressure of carbon dioxide rises the haemoglobin releases oxygen more readily. Thus an increased partial pressure of carbon dioxide producer a more acid environment that helps to split oxygen from haemoglobin.

3. A raised temperature also tends to result in an increased amount of oxygen released from haemoglobin. As heat is a by product of cellular activity, and more active cells will generate more heat this will further promote the release of oxygen from the oxyhaemoglobin.

4. 2,3-biphosphoglycerate is formed in red blood cells when they break down glucose. When this combines with haemoglobin the haemoglobin binds oxygen less tightly. So the greater the level, the more oxygen is released from haemoglobin. Some hormones such as epinephrine, and norepinephrine increase the formation of 2,3-biphosphoglycerate.

Carbon dioxide is carried by the blood in three main ways. A small amount is dissolved in plasma. This diffuses into the alveoli upon reaching the lungs.

More of it combines with the globin in haemoglobin.

But the greatest percentage of carbon dioxide is transported in plasma is bicarbonate ions. The carbon dioxide in the tissue capillaries reacts with water to form carbonic acid. This carbonic acid then dissociates into hydrogen ions and bicarbonate ions

Control of respiration

There is an area in the brain stem called the respiratory centre. This consists of the medullary rhythmicity area which controls the basic rhythm of respiration, the pneumotaxic area which helps coordinate the transition between inspiration and expiration and the apneustic area which also coordinates the transition between inspiration and expiration.

The respiratory centre establishes the basic rhythm of respiration however sometimes this rhythm needs to be modified in response to demands made by nerve impulses to the brain.

We can voluntarily alter our pattern of breathing and this can be controlled via the cerebral cortex. We may need to hold our breath for example when putting our head under water. However due to rising carbon dioxide levels are ability to do this is limited. When the partial pressure of carbon dioxide and the concentration of hydrogen ions increase the inspiratory area is stimulated which causes inspiration.

There are also stretch receptors in the walls of the bronchitis and bronchioles. When these become overstretched nerve impulses sent along the vagus nerves which causes expiration.

Chemical regulation of respiration is also very important. Within the medulla neurons that are highly sensitive to pH form the central chemo sensitive area. In the peripheral nervous system are peripheral chemo receptors which are sensitive to changes in hydrogen ions carbon dioxide and oxygen in the blood. These are located within the carotid bodies near the branching of the common carotid arteries and in the aortic bodies.

With a slight rise in the partial pressure of carbon dioxide the central chemo sensitive areas are stimulated. The peripheral chemo receptors in the carotid and aortic bodies are also stimulated by both the high partial pressure of carbon dioxide and the rise in hydrogen iron concentration.

The input from both these areas causes the inspiratory area to become highly active and the rate and depth of breathing will therefore increase

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