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Carbon Reflex

Respiration - an introduction


 In this essay we will consider Respiration. We shall first consider the interesting history of the study of respiration before moving on to our modern understanding of respiration. We will look at the structure and function of the respiratory system including the upper and lower respiratory tracts with a note on the control system for respiration. Secondly we will consider the physiology of respiration. Thirdly we will discuss some of the major common disorders and diseases which affect the system with a special focus on asthma.

A Brief History of the Study of Respiration

 Hippocrates "counted air as an instrument of the body" just as food was eaten. Galen (129-200)  felt that respiration served a triple purpose 1) breathing cooled the heart, 2) air needed for production of vital spirits 3) respiration got rid of the friiligimous or products of the innate fire burning in the heart. Basically Galen's ideas were followed for many centuries until the era of the 17th century.  Robert Boyle ( 1627-1691) who was primarily a physicist was interested in the weight and pressure of the air and in 1660 he showed that air was essential to both life and combustion by placing a candle and a small animal in a vessel. Robert Hooke ( 1635-1703 ) showed that after the thorax of a dog had been opened life could be prolonged by artificial respiration  - this proved that the whole of the essential business of respiration takes place in the lungs. Richard Lower ( 1631-1691) upset the old ideas that the change in blood colour took place in the heart rather than in the lungs. He also demonstrated the necessity of fresh air in life rather than air generally and that in fact where a fire burns readily there we can easily breathe. He was close to conceptualizing oxygen here but this had to wait until Lavoisier ( 1743-1794 ).

However, John Mayow ( 1641-1679 ) an English chemist had come very close to this in his experiments. He said that air entered the lungs during inspiration simply because the pressure or elastic force of the atmosphere drove it in to fill in the increased space afforded by the enlarged and dilated thorax. Mayow had in reality come near to discovering oxygen but did not isolate it or realise that carbon Dioxide passed in the reverse direction. However, he has achieved a good deal. The next developments came with Joseph Priestly ( 1733-1804 ) but perhaps Lavoisier had the clearest expressions of oxygen and respiration. Finally it was Gaston Magnus , by use of the mercuric air pump that showed that both arterial and venous blood contain both CO2 and O2, though in different proportions.

The Structure and Function of the Respiratory System

The respiratory system is concerned with the exchange of oxygen and carbon dioxide between the blood and the lungs. This is essential for the provision of energy for cellular metabolic function. Most energy extractions can only take place in the presence of oxygen and the route of oxygen intake into the body is via the respiratory system. Basically inspiration brings in oxygen and expiration excretes carbon dioxide. This is known as the exchange of gases. Before we consider this in more detail lets look at the main organs of the respiratory system. Firstly we should consider the nasal cavity. As air is breathed in it is warmed and moistened and dust and debris are filtered out by cilia or hairs and mucus producing goblet cells. Air which passes through the nasal cavity joins air which is brought in through the mouth. The nasal cavity itself is divided by the septum. There are openings to the nostrils at the front and to the pharynx at the back. In addition there are small openings to the maxillary, frontal and ethmoidal sinuses.

Now we can move on to the pharynx. At the base of the pharynx there are two openings - one leading to the larynx and the rest of the respiratory system and the other to the oesophagus and the digestive system. The epiglottis prevents both openings being open simultaneously. The larynx is located between the pharynx and the trachea. This is commonly known as the voice box. The trachea is a tube which extends from the larynx and divides to form the bronchi. It is lined with cilia and air is further warmed, and filtered. The bronchi lead to the lungs.The lungs are a pair of organs located on either side of the thoracic cavity and enclosed in double membranes or pleura. The bronchi enter the lungs at a point known as the helium. They divide into smaller and smaller branches known as bronchioles and finally alveolar ducts and alveoli. These are sack like structures and this is the site of gas exchange. Their total surface area is approximately 70 square meters.

Let us consider the actual mechanism of breathing for a moment.  Inspiration involves movement of the diaphragm and the internal and external intercostal muscles. On inspiration the diaphragm contracts pulling downwards on the lung and drawing air into the lungs. The ribs move upwards and outwards at the same time. Expiration is said to be a passive event which arises from the relaxation of the diaphragm and intercostals. The volume of air breathed in and out is known as the tidal volume and is normally about half a litre. However total lung capacity includes inspiratory reserve volume, expiratory reserve volume and residual volumes so brining the overall lung  capacity to about 6 litres for men and 4.2 for women.

The Control System for Respiration

The control unit of ventilation consists of a processor or breathing centre in the brain which integrates emotional, chemical and physical stimuli inputs and controls an effector - in this case the lungs via motor nerves from the spinal cord. Ventilation is normally autonomic with a limited voluntary override. Ondine's curse is the exception to this where the autonomic control is lost. The mechanism of generation is not completely understood but involves the integration of neural signals by respiratory control centres in the medulla and pons. In the medulla we have the ventral respiratory group i.e. nucleus retroambigualis, nucleus ambiguus, nucleus parambigualis and the pre-Botzinger complex.

This group controls voluntary forced exhalation and also works to increase the force of inspiration. The medulla also contains the dorsal respiratory group consisting mainly of the nucleus tractus solitarius and this controls mostly inspiratory movements and their timing. The pons contains the pneumotaxic centre which is involved with the fine tuning of the respiration rate and the apneustic centre. In addition there is further integration in the anterior horn cells of the spinal cord. The actual breathing rate of a human is controlled in the following way. Chemoreceptors detect the levels of carbon dioxide in the blood by monitoring the number of hydrogen ions in the blood, which decreases the pH of the blood. This is as a direct consequence of increase in carbon dioxide concentration because carbon dioxide becomes carbonic acid in an aqueous environment. The response is that the inspiratory centre in the medulla sends nervous impulses to the external intercostal muscles and diaphragm via the phrenic nerve to increase breathing rate and volume of lung inhalation.

There are two main kinds of chemoreceptors with affect breathing rates. Firstly the central chemoreceptors located on the medulla oblongata detect changes in the pH of the cerebrospinal fluid and secondly the peripheral chemoreceptors in the Aortic body detects changes in blood oxygen and carbon dioxide, but not blood pH., but those in the carotid body detect all levels. In addition there are pulmonary stretch receptors which are mechanoreceptors found in the lungs. When the lung expands the receptors imitate the Hering-Breuer reflex which reduces respiratory rate and increases production of pulmonary surfactant We have now considered the structure and functions of the respiratory system and its mechanics and its control systems. We should now consider the physiology of the system starting with the exchange of gases.

The Exchange of Gases and physiology of respiration

In basic terms the exchange of the gases oxygen and carbon dioxide occurs in the alveoli. These are surrounded by a network of small blood vessels with extremely thin walls. Blood which enters these vessels has a high level of carbon dioxide picked up from the body tissues. The carbon dioxide leaves the blood, passes through the walls of the blood vessels into the alveoli and into the lungs. Oxygen then passes the other way into the blood and the blood, now rich in oxygen leaves the lungs and travels to the heart. On a slightly more detailed level it can be said that the diffusion of oxygen and carbon dioxide is a continuous process but dependent on atmospheric pressure compared to that of blood and tissues.

Normal atmospheric pressure at sea level is 101.3 kilopascals (KPa). Air that is inspired contains nitrogen, oxygen, carbon dioxide, water vapour and inert gases. Exchange of gases occurs when there is a difference in the partial pressures across the semi-permeable membrane (in this case alveolar membrane). The movement by diffusion is from the higher concentration to the lower until equilibrium is achieved. For example the pressure of alveolar content oxygen is 13.3 KPa and in deoxygenated blood it is 5.3 KPa.

In contrast the pressure of alveolar content carbon dioxide is 5.3 KPa and deoxygenated blood is 5.8KPa. The pressure of nitrogen and other inert gases remains unchanged as they are not used by the body.In addition trace gases present in breath at extremely low levels are ammonia, acetone and isoprene. The  primary force in the respiratory tract is atmospheric pressure - this explains why it is harder to breath at higher altitudes for example. The above process is known as external respiration. Internal respiration is the process by which diffused oxygen reaches the cells and this is achieved by a lower partial pressure concentration in body tissue than in capillary fluid. Furthermore oxygen is released from oxyhaemoglobin because of low tissue or cellular oxygen levels, low pH, and rise in temperatures. Cell metabolism also increases the release of carbon dioxide into blood encouraging the disassociation of the oxygen molecules from red blood cells.

 In fact is it is difficult to discuss respiration without some reference to red blood cells and the cardiac cycle. Let us take each in turn briefly: In fact one of the main functions of blood is the transportation of oxygen from the lungs to the tissues and the removal of carbon dioxide from the blood to the lungs for excretion ( in addition to transportation of hormones to organs and tissues, carrying of protective substances such as antibodies and blood also contains clotting factors to minimize blood loss in case of injury). As we stated above the oxygen is associated with the red blood cells or RBC. Red blood cells ( erythrocytes) have the following structure . They are bi-concave, have no nucleus, produced in bone marrow, live about 7 months, responsible for exchange of gases and are flexible to help transportation. They contain haemoglobin which is rich in iron and responsible for gas transportation and are broken down in the spleen, bone marrow and liver. Blood grouping is determined by different antigens and the main groups are A, B, O, AB. and some contain either a positive or negative Rhesus factor. Red blood cells are involved in oxygen transportation and oxyhaemoglobin is formed when the blood is saturated with oxygen and the iron atoms or binding sites are full.

We also need to look briefly at the cardiac cycle as this drives the transportation of oxygenated blood. The cardiac cycle is otherwise known as the heart beat and in general this lasts about 0.8 seconds in duration. The contraction of the heart (systole) occurs in the left and right atria and blood is forced through the valves into the ventricles and from there into the aorta and distributed throughout the body. Following the ventricular contraction the heart relaxes (diastole) and the heart is prepared for the next cycle. A healthy heart beats 60-80 times per minute on average with variations for sex, age and fitness levels.

In more detail it should be noted that the vena cava transports deoxygenated blood into the right atrium as the four pulmonary veins bring oxygenated blood into the left atrium. The valves and vessels of the heart open and close in response to changing pressures in the heart chambers and this ensures that blood flows only in one direction. The sinoatrial node (SA node) and the atrioventricular node (AV node) are very important in the cycle. Electrical changes within the heart can be recorded by electrocardiogram or ECG. Finally another related aspect of the physiology of respiration are the differences in inhaled and exhaled air. The major differences in composition between inhaled and exhaled air are as follows. Nitrogen content. In inhaled air this is about 70% and in exhaled 79%. Oxygen content is approximately 20% in inhaled air and 16% in exhaled. Carbon Dioxide content is about 0.03% in inhaled air and 4% in exhaled. Water vapour varies in inhaled air but in exhaled air there is saturation. Finally the temperature of inhaled air varies with atmospheric conditions but exhaled air is close to body temperature. We have now discussed the structure and function of the respiratory systems, some of the mechanics involved and the basic physiology.

We should now turn to the third topic adumbrated in our introduction - namely a review of some of the main disorders and diseases of the respiratory system. Here there will be a focus on asthma as this is currently on the increase worldwide. Disorders and Diseases of the Respiratory System Respiratory disease is really an umbrella term for diseases of the lung, bronchial tubes, trachea and pharynx and they range from mild like the common cold to life threatening diseases such as bacterial pneumonia and pulmonary embolism.

Respiratory diseases can be classified as either obstructive - conditions that impeded the rate of flow into and out of the lungs e.g. asthma or restrictive - conditions that cause a reduction in the functional volume of the lungs e.g. pulmonary fibrosis. A further example of a restrictive disease would be emphysema. Emphysema results in the permanent destruction of the alveoli because of over distension.. Predisposing factors can include smoking and also exposure to toxic chemicals in addition to inflammation of the bronchi and alveoli, increases in pressures due to coughing and enzymatic deficiency. The damage can not be reversed, only slowed down. and can lead to shortage of breath and low levels of circulating oxygen and high levels of circulating carbon dioxide. Emphysema can develop alongside chronic bronchitis and be known as a form of chronic obstructive pulmonary disease or COPD.

The sufferer can have cyanosis or lack of oxygen. Diagnoses can be by spirometry and diffusion testing, X rays, high resolution spiral chest CT scan, bronchoscopy, blood tests and pulse. Treatments currently can only really slow the disease down unless there is a lung transplant although the most important measure is to slow down the progression by stopping the patient smoking and avoid all exposure to smoke and lung irritants. Also pulmonary rehabilitation can be helpful in optimizing quality of life. Basically asthma is an inflammatory disease of the air passages which is associated with the intermittent overactivity of the smooth muscles associated with the respiratory tract. The mucous membrane and muscle layers of the bronchi thicken , mucous glands enlarge and airflow is restricted. During an attack the bronchi contract and excessive mucous is produced. Due to the narrowing of the air passages the lungs can not empty properly and this may lead to hyperinflation. Severe attacks can lead to respiratory failure.

Much more research needs to be done in the area of asthma. It may be caused by a complex interaction of genetic and environmental factors and these can also influence how severe a persons asthma is and how they respond to medication. We could divide the causes into environmental, genetic or a combination of both.. Lets look at some environmental causes first. It is thought that some of the contributory factors towards asthma attacks are low air temperatures, air pollution and cigarette smoke, respiratory tract infections , stress and exercise. In children viral illnesses such as the common cold may trigger asthma too. Asthma is actually on the increase in the developing world - especially among children.

In fact there are a plethora of possible causes of asthma ranging from allergens such as house dust mites, cockroaches, pollen, mold and pets. Perfumes, hairsprays and volatile organic compounds can trigger asthma. Aspirin, beta blockers and penicillin can start an attack. Food allergies can contribute. Use of fossils fuels, smog, sulfur dioxide cause asthma is urban areas perhaps. Industrial compounds such as sulfites, chlorinated swimming pools may induce. Hormonal triggers in adolescent girls can trigger asthma as can emotional stress. In one genetic study of asthma over 100 genes were found to associate with asthma in some way, however some of these are only influential in combination with environmental factors and as stated previously much more research needs to be done in this area.

However, one thing is apparent. Asthma is on the increase worldwide. According to one study there has been a 75% increase in asthma in children in the USA in recent decades. More than 6% of children in the USA have asthma and this increases dramatically to 40% in the urban areas. According to the Centres for Disease Control some 9% of children in the US had asthma in 2001 compared with just 3.6% in 1980. A study by the WHO reports that some 8% of the Swiss population suffer from asthma compared to only 2% some 25-30 years ago. Asthma is more common in affluent countries but it is not restricted to them. WHO estimate that there are up to 20 million asthmatics in India alone. Also there is a socio-economic pattern to asthma. The incidence of asthma is highest among lower income populations and these also tend to be disproportionately ethnic minorities in some Western countries and are also more likely to live nearer industrial areas.

The good news is that asthma is preventable in many cases. Inhaled glucucorticoids are the most common preventative medication and usually come in inhaler devices. However, long term use of these devices can have side effects including redistribution of fat, blood glucose problems, , weight gain and even osteoporosis. Leukotriene modifiers can be used and Mast cell stabilizers. Antimuscarinics can be used as a mixed reliever and preventer. Antihistamines can be used to treat allergic symptoms that may underlie the chronic inflammation or allergy shots can be used. Methotrexate can be used in some difficult to treat patients. The most effective treatment for asthma is simply to identify the triggers such as smoke, pets, cockroaches, chemicals, exercise, aspirin and limit to exposure to them.


In the discussion above we have explored the early history of the study of respiration. This leads to modern studies and explanations of the respiration with a look at the structure, function, mechanics and control systems of the respiratory system. This was followed by a more detailed discussion of the physiology of respiration with a final note on respiratory system diseases and disorders. This is of the utmost importance in today's environment. As we seek to come too terms with greenhouse gas emissions and pollution we can see the effects they have on humanity - asthma is just one clear illustration of this.

Dr Simon Harding

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