Respiration, which means "breathe again", is very critical for life because it is necessary to supply all parts of de body with oxygen and to get rid of the produced carbon dioxide. When oxygen supply is too low, cells are unable to produce enough energy for normal functions. Also, when carbon dioxide is carried away inefficiently, its accumulation leads to acidosis.

The process of respiration can be divided into five stages:

The upper respiratory tract

Air enters the respiratory tract through the nose and the nasal cavity. The walls of the latter are formed by conchae and grooved passageways called meatures in order to increase the surface. This surface is composed of a highly vascularized mucous membrane which function is to warm and humidify the incoming air. Then the air passes through the pharynx (throat) into the larynx.

The lower respiratory tract

The larynx (voicebox) is the part of the tract were sounds can be produced. It includes the epiglottis, which covers the glottis (entrance of the larynx) during swallowing to prevent food or drink from entering the lower respiratory tract, the thyroid cartilage (Adam's apple), and the vocal folds. The trachea (windpipe) joins the larynx to the two primary bronchi. It is covered with a mucous membrane containing ciliated cells (cilia) moving mucus trapped foreign substances away from the lungs. The primary bronchi (one to left and the other to the right) divide into smaller secondary bronchi which lead into the different lobes of the lungs. There they branch into tertiary bronchi which in turn branch into bronchioles. The latter are completely surrounded by smooth muscle tissue in order to regulate airway resistance. The terminal bronchioles divide into alveolar ducts at which numerous alveoli are situated. The alveolar wall is only a single-cell layer thick and contacts with the single-cell thick wall of the capillaries. At this level the actual gas exchange takes place (external respiration).



The respiratory muscles

Inhalation is initiated by the contraction of both the diaphragm and the external intercostal (between the ribs) muscles, which cause expansion of the vertical and horizontal dimension of the thorax (including the lungs) respectively. Whereas inspiration is an active process, expiration is passive. As the respiratory muscles relax, the elastic recoil of the lungs, chest wall and the abdominal viscera combined with gravity cause the thoracic volume to decrease and air moves out from the lungs. Forced expiration on the other hand is active, involving contractions of the abdominal and internal intercostal muscles.

Work performed by the respiratory muscles

The stretchability of the thorax and lungs (elastic work), viscosity (tissue resistance work) and the amount of resistance the air encounters within de respiratory tract (airway resistance work) are the main parameters affecting the amount of work performed by the respiratory muscles. The airway resistance largely depends on the diameter of the passageways. In normal situations the energy expenditure of the respiratory muscles is only a few percent of the total energy expenditure.

External respiration

As stated above, in the alveoli the gas exchange between the lungs and the blood takes place. Oxygen will move from the lungs into the blood and carbon dioxide from the blood into the lungs. This diffusion of gasses mainly depends on their solubility in water and their partial pressures (Henry's law). Upon entering the pulmonary capillaries the blood is oxygenated, since its partial pressure (PO2) is lower than the PO2 in the lungs and for carbon dioxide it's just the other way around. The solubility of oxygen in water is very low. Therefore, 98% of the oxygen is transported by hemoglobin.

Internal respiration

Internal respiration is the process of gas exchange at the level of target tissues. Once the oxygen enriched blood (or plasma) encounters tissue with a lower PO2, oxygen will move from the blood into that tissue. Also, when the partial pressure of carbon dioxide (PCO2) in the tissue exceeds that of the blood, carbon dioxide will move from the tissue into the blood and is transported to the lungs.

Cellular respiration

Energy needed by cells is liberated (in the form of ATP) from fuel molecules by a complex series of catabolic reactions referred to as cellular respiration. These reactions include the glycolysis (conversion of glucose to pyruvate), citric acid cycle or Krebs cycle (oxidation of acetate to carbon dioxide), -oxidation of fatty acids and the electron transport system (transport of electrons to oxygen yielding water).

Transport of oxygen en carbon dioxide

As mentioned earlier, nearly all oxygen transported through blood is bound to hemoglobin of red blood cells and only a few percent is dissolved in the plasma. Hemoglobin consists of four subunits (blue, purple, green and yellow in the 3D-model below), each containing a heme group (red). Each heme in turn contains an iron atom which can combine with oxygen. Hemoglobin is an allosteric protein in that oxygen binds cooperatively (binding of O2 enhances the binding of additional O2) and metabolic factors (for example pH, PCO2 and temperature) influence the affinity for oxygen.

3D-model of hemoglobin

Carbon dioxide is transported through the blood in its dissolved form (7%), bound to hemoglobin (23%) and in the form of bicarbonate (70%). Bicarbonate is produced when CO2 reacts with water:

CO2 reacts with water

Note that in this reaction H+ ions are released leading to a lower pH.

Control of respiration

The control of respiration is mainly affected by the efficiency of gas exchange and ventilation. Gas exchange in the lungs is regulated by carbon dioxide and oxygen. High CO2 causes bronchodilation (relaxation of the smooth muscle of bronchioles), whereas low CO2 causes bronchoconstriction (contraction of the smooth muscle of bronchioles). This mechanism regulates the diameter of the bronchioles and thus airflow. When O2 is low in some local regions of the lung, the smooth muscle of pulmonary arterioles in that area contract, causing vasoconstriction. High amounts of oxygen cause vasodilation of the arterioles. This mechanism ensures that blood is led to regions of the lungs with more oxygen. The smooth muscle of the arterioles are also sensitive to H+ ions, which mainly reflect the PCO2 (see reaction above). Thus, carbon dioxide indirectly affects blood flow as well, although this effect is opposite to the effect of oxygen.

Pulmonary volumes and capacities

To identify many pulmonary disorders the amount of air a person inspires and expires and the rate of ventilation are measured by a method called spirometry. The movement of air in and out of the lungs is recorded resulting in a spirogram (see figure below).

spirogram or spirograph

The tidal volume is the volume of air inspired or expired with each normal breath. The inspiratory reserve volume is the extra volume of air that can be inspired above the tidal volume. The expiratory reserve volume is the extra volume of air that can be expired by forceful expiration after the end of a normal tidal expiration. The residual volume is the volume of air remaining in the lungs after the most powerful expiration.

The inspiratory capacity is the sum of the tidal volume and the inspiratory reserve volume. It resembles the amount of air a person can breathe beginning at the normal expiratory level and distending the lungs to the maximal amount. The functional residual capacity equals the expiratory reserve volume plus the residual volume. This is the amount of air that remains in the lungs at the end of normal expiration. The vital capacity equals the inspiratory reserve volume plus the tidal volume plus the expiratory reserve volume. This is the amount of air a person can expel from the lungs after first filling the lungs to their maximum extent and then expiring to the maximum extent. The total lung capacity is the maximum volume to which the lungs can be expanded with the greatest possible inspiratory effort. It is the sum of the vital capacity and the residual volume.

In pulmonary function studies a number of abbreviations and symbols have become standardized. Some frequently used ones are listed in the table below:

VT tidal volume PO2 partial pressure of O2
FRC functional residual capacity PaO2 PO2 in arterial blood
ERV expiratory reserve volume PAO2 PO2 in alveolar gas
RV residual volume PCO2 partial pressure of CO2
IC inspiratory volume PaCO2 PCO2 in arterial blood
IRV inspiratory reserve volume PACO2 PCO2 in alveolar gas
TLC total lung capacity RQ respiratory exchange ratio
FEV1 forced expiratory volume in 1s SO2 % saturation of blood with O2
V'O2 amount of consumed O2 SaO2 SO2 in arterial blood
V'CO2 amount of produced CO2 DLO2 diffusing capacity of the lung for O2
Raw airway resistance DLCO diffusing capacity of the lung for CO

Respiratory disorders


Asthma is a respiratory condition in which air flow becomes obstructed due to bronchoconstriction, increased mucus secretion and inflammation. Most asthma attacks are (frequently allergic) reactions to substances in the air or sometimes in food. The smooth muscle of bronchi and bronchioles spasm, causing increased Raw resulting in extremely difficult breathing. Also the FRC and the RV are increased.

Bronchogenic carcinoma (lung cancer)

Lung cancer is often initiated by irritants to the bronchi. Excessive mucus production and inactivity of the cilia allow these irritants to enter the lungs resulting in alveolar tissue damage (emphysema). Subsequently, the lower respiratory tract is invaded by squamous cancer cells which spread, causing more and more damage.

Chronic obstructive pulmonary disease (COPD)

COPD is a functional category of pulmonary disorders that are indicative of persistent obstruction of airflow through the bronchi. Bronchitis and emphysema are often referred to as COPD. The first is characterized by chronic or recurrent excessive mucus production and the latter is a condition of the lung characterized by permanent, abnormal enlargement of airspaces. Both disorders are indicated by tests of abnormal expiratory flow (reduced maximal expiratory flow and low FEV1).


Emphysema is a disorder that is characterized by obstruction and destruction of the lungs, which can be determined by making a CT-scan (see picure below). Due to bronchiolar obstruction the Raw greatly increases and due to loss of alveolar walls the DLCO and DLO2 decrease. The loss of alveolar walls also decreases the number of pulmonary capillaries through which the blood can pass, causing an increase in pulmonary vascular resistance and subsequent pulmonary hypertension. This in turn overloads the right side of the heart and frequently causes right-sided heart failure.


CT-scanning (CT stands for computed tomography) is a way of producing images of cross sections through the body. An x-ray source rotates around the patient, as does the detector on the other side. Differences in the detected absorbtion are visualized by a computer. The CT-scan above shows the lungs (the black areas) of which the right one shows coloured spots. These spots indicate that emphysema is present.


Tuberculosis is a lung infection caused by the bacterium Myobacterium tuberculosis. The disease is contagious and can be deadly. The lung tissue is destroyed and replaced by scar tissue, resulting in a diminished gas exchange (low DLO2 and DLCO).

The effect of smoking

The solution...The susceptibility to most respiratory diseases is greatly increased by cigarette smoking and the most striking consequences of smoking are lung cancer and COPD. The ciliary epithelium cells in the bronchioles become damaged, leading to accumulation of mucus. This, in combination with hypertrophy of bronchiolar smooth muscle tissue, eventually causes alveoli to collaps. Nicotine enhances this process in that it paralyzes the cilia. Another effect of nicotine is that it inhibits the alveolar macrophages, so they become less effective in combating the infection. Besides the probably most dangerous "tar" fraction, cigarette smoke contains cyanide and often even radioactivity, derived from the fertilizer which is used to grow the tobacco plant.

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