Physiology of Respiration


Breathing exchanges oxygen and carbon dioxide between the body and the environment. Carbon Dioxide (C02) is essentially a waste product of the body but is important as a hameostatic feedback mechanism. The level of C02 in the blood is the most important influence on the regulation of ventilation. The blood level of C02 acts directly on the respiratory centres in the medulla and is a major influence on cerebro‑spinal fluid pH. An increase in C02 level leads to an increase in ventilation by stimulating phrenic and intercostal nerves that activate the respiratory muscles. In discussing the importance of carbon dioxide in the control of breathing this essay will first discuss the mechanics of breathing, the muscles involved and their control by the medulla and pons. It will also note that the influence of carbon dioxide during exercise is not consistent with that during rest.


Breathing consists of two phases: inspiration, when air flows into the lungs, and expiration, when gases leave the lungs. Air flows into the lungs when atmospheric pressure is higher than the air pressure within the thoracic cavity. This is because gases flow along a gradient from high pressure to lower pressure. Similarly, gases are expelled from the lungs when the pressure within the thoracic cavity is greater than that in the atmosphere.


The change in the air pressure within the thoracic cavity depends on the size of the thoracic cavity. The pressure of given amount of gas will be less when the thoracic cavity is enlarged and more when the volume of the thoracic cavity is reduced. The expansion and reduction in thoracic cavity volume is controlled by the muscles of respiration. The contraction of the diaphragm and external intercostal muscles expand the volume of the thoracic cavity in inspiration. In normal expiration they relax allowing the thoracic cavity to return to its size before inspiration. In forced expiration, the internal intercostal and abdominal muscles are contracted.


The basic pattern of breathing is set by the activity of neurons in the medulla and pons. The medulla oblangata, the inferior most part of the brain stem, sets the respiratory rhythm. The pons is the part of the brain stem connecting the medulla with the midbrain, providing linkage between the upper and lower levels of the central nervous system.


Within the medulla are two centres ‑ one for inspiration and one for expiration. The inspiratory centre contains a pace‑setting nucleus that fires neurones ‑ nerve impulses that travel along the phrenic and intercostal nerves to stimulate the diaphragm and external intercostal muscles respectively. This produces an expansion of the thoracic cavity resulting in air rushing into the lungs. Passive expiration follows as the inspiratory centre becomes dormant allowing the inspiratory muscles to relax and the lungs recoil. This on‑off activity cycle of the inspiratory neurons repeats continuously resulting in a normal breathing rate of between 12 and 18 breaths per minute. The inspiratory phase lasts for about two seconds and the expiratory phase about three seconds.


The second meduallary centre, the expiratory centre, contains both inspiratory and expiratory neurons. The expiratory centre does not actively promote expiration during normal quiet breathing where it serves to keep the respiratory muscles slightly contracted. When forceful breathing is necessary the expiratory centre sends activating impulses to the muscles of expiration ‑ the internal intercostal and abdominal muscles. This causes vigorous depression of the rib cage and more strenuous expiratory movements.


The medullary inspiratory centre generates the basic rhythm of inspiration but the pons respiratory centres are also involved in respiration. There role is thought to be one of smoothing the transition from inhalation to expiration and vice versa. There are two pons centres, each exerting opposing effects on the inspiratory centre of the medulla. The pneumotaxic centre fine tunes the breathing rhythm preventing over‑inflation of the lungs. It does this by sending continuous inhibitory impulses to the inspiratory centre of the medulla which, when particularly strong, shortens the duration of inspiration and quickens the breathing. The other pons centre, the apneustic centre, stimulates the medullary inspiratory centre serving to prolong inspiration or cause the breath to be held in the inspiratory phase so breathing becomes deep and slow.


The rate and depth of respiration vary in response to the demands of the body. The depth of inhalation depends on how fast the respiratory centre of the medulla stimulates the respiratory muscles. The rate of inhalation is deter‑mined by how long the inspiratory centre is active. The respiratory centres in the pons and medulla respond to excitary and inhibitory stimuli. Many factors can modify the baseline respiratory rate and depth set by the medullary inspiratory centre but the most important are the levels of carbon dioxide, oxygen and hydrogen ions in the arterial blood. Their fluctuations are sensed by chemoreceptors located in the medulla and the great vessels of the neck.


Carbon dioxide is the most potent influence over respiration. High levels of carbon dioxide correspond with high levels of acid (low pH) and signal the need for more oxygen. A rise in PC02 (a condition called hypercapnia) decreases the pH level of cerebrospinal fluid. This excites the central chemoreceptors resulting in an increase in the depth and rate of respiration, a condition called hyperventilation. The resulting increase in alveoli ventilation flushes carbon dioxide out of the blood which increases the blood pH. An increase of 5 mm Hg in arterial PC02 results in a 100% increase in alveolar ventilation. Hyperventilation continues until homestatic blood PC02 levels are restored.


This process needs to be viewed within the context of the dissociation of oxygen from hemoglobin in which carbon dioxide, along with pH levels, has a significant role. Oxygen is transported around the body on hemoglobin and needs to dissociate from the hemoglobin in order to be used in tissue cells. The greater the level of dissociation, the more oxygen is available for use. The rate of dissociation is increased when the partial pressure of carbon dioxide in the blood is increased and also when levels of acidity are increased. The partial pressure of carbon dioxide and pH are related because low blood pH (high acidity) results from a high partial pressure of carbon dioxide.


when carbon dioxide diffuses from the blood into the cerebrospinal fluid it hydrates and forms carbonic acid. The ensuing acid dissociation liberates hydrogen ions. Whilst carbon dioxide acts as the initial stimulus to hyperventilation, it is actually a rise in the level of hydrogen ions that stimulate the central chemoreceptors into action. The level of acidity increases as the concentration of hydrogen ions increases. Thus an increase in pC02 produces more acid which helps to release oxygen from hemoglobin. During exercise the lactic acid produced as a byproduct of anaerobic metabolism within muscles further decreases pH levels.


we can consciously alter our breathing pattern, for example when singing and speaking. in these instances signals are sent from cortical centres directly to motor neurons that control the respiratory muscles. Strong emotions and pain can also influence the rate of breathing by acting through the limbic system and activating sympathetic centres in the hypothalamus. The abrupt increase in ventilation at the beginning of exercise is likely to be a response to this.


working muscles during exercise consume much greater amounts of oxygen and produce large amounts of carbon dioxide resulting in a increase in ventilation up to thirty fold. However, the increased ventilation at the onset of exercise does not appear to be prompted by rising levels of carbon dioxide when arterial PC02 and P02 levels remain relatively constant. It is therefore likely to be the conscious anticipation of exercise stimulating the limbic system that increases the initial rate of ventilation.


Ventilation continues to increase during exercise when, after the initial onset stimulated by neural factors, chemical and physical changes in the bloodstream reassert their role as the major influences. When exercise stops there is an abrupt decrease in pulmonary ventilation once again due to neural factors. This is followed by a gradual decline in ventilation as the 'oxygen debt' is repaid. Ventilation is then stimulated by high C02 levels and the low arterial pH resulting from the build up of lactic acid during exercise.


In conclusion, many factors can modify the baseline respiratory rate and depth set by the medullary inspiratory centre but the most important factors are the levels of carbon dioxide, oxygen and hydrogen ions in the arterial blood. Breathing is normally involuntary and regulated by brain stem centres. We can by‑pass the medullary centres and consciously alter our breathing patterns. Emotions and anticipation can also act as an overriding influence. However, voluntary and emotional control of breathing is limited and respiratory centres will automatically take over when the partial pressure of carbon dioxide in the blood reaches a critical level.




3 April 1998



Elaine N Marieb: Human Anatomy and Physiology.

Tortora: Principles of Anatomy and Physiology

J A R Friend & J S Legge: Respiratory Medicine

M H Kryger: Introduction to Respiratory Medicine

P Howard: Respiratory Medicine in Clinical Practice

D C Flenley: Respiratory medicine




Miscellaneous notes re respiration:


The respiratory system delivers air containing oxygen to the blood and removes Carbon dioxide, the gaseous waste product of metabolism. The respiratory system includes lungs, several passage‑ways leading from outside the lungs, and the muscles that move air into and out of the lungs.


Pulmonary ventillation or breathing ‑ inspiration/expiration. External respiration (also called pulmonary respiration): occurs in lungs ‑involves exchange of gases between blood and lungs; oxygen from lungs diffuses into blood, the carbon dioxide diffuses from the blood into the lungs.


Internal respiration (also called tissue respiration): Exchange of gases in body tissues, Carbon dioxide from body cells is exchanged for oxygen from blood.


Movement of air into and out of lungs depends on pressure changes ‑Boyle's law ‑ vol of a gas varies inversely with pressure assuming constant temp.


Inspiration occurs when alveolar pressure falls below atmospheric pressure. Contraction of diaphragm & external intercostal muscles increase size of thorax thus decreasing intraplural pressure so that lungs expand. Expansion of lungs decreases alveolar pressure so air moves along pressure gradient from atmpsphere into lungs.


Expiration occurs when alveoler pressure is higher than atmospheric pressure ‑ relaxation of diaphragm & external intercostal musc. Elastic recoil of chest wall and lungs which increase intraplural preessure, lung vol decreases so air moves from lungs to atmosphere. .


Studies indicate that an individual will spontaneous balance the depth and frequency of respiration to obtain optimum efficiency in ventilation with minimal energy expenditure by the respiratory muscles (Milic‑Emili et al).