The functional unit of the body, the cell, must have oxygen to carry out its varied activities.  In utilizing oxygen, the body cells produce carbon dioxide which must be removed from the body.  Few of the body cells have access to the atmospheric air to directly acquire oxygen and dispose of carbon dioxide.  It is the respiratory system which provides the mechanisms for obtaining oxygen and disposing of carbon dioxide.

The respiratory system can be divided into the upper and lower respiratory passages.  The upper respiratory passages are comprised of the nasal chambers, nasopharynx and pharynx.  These passages humidify, warn and filter the air as it is conducted through them.  When the air leaves the upper respiratory passages it is completely humidified, warmed to body temperature and all particles greater than six micrometers in diameter have been removed.

The lower respiratory passages are comprised of the trachea, bronchial system, and the alveoli.  The progression of these passages would be as follows:

1) Alveolar epithelial cells (type I cell) - These cells are squamous shaped cells and are the  principle alveolar epithelial cell.
2) Septal cell (type II cell) - These are large epithelial cells and are responsible for the production of surfactant.
 
There are reticular fibers and elastic fibers in the walls of the alveoli.  Alveoli are highly vascularized with the alveolar capillaries.  Within the lumen of the alveoli there are Alveolar Phagocyte (dust) cells which remove particles from the alveoli by phagocytosis.   The alveoli phagocytes are derived from the blood monocytes. 

 1) Ventilation
 2) Diffusion
 3) Transport 

Ventilation is the movement of air in and out of the lings.  This movement of air is dependent on pressure differences between the atmosphere and the spaces in the lung ( alveolar lumen).  As you are aware, at sea level the atmosphere creates a pressure of 760 mmHg.  The factors causing the flow of air in and out of the lungs can be expressed by the same formula used in the flow of blood through vessels:

   Flow =   (P1 - P2)/R
P1 = atmospheric pressure (Patm)
P2 = intra-alveolar pressure (Palv)
R = Resistance

When the air pressure inside the lungs (Palv) is less than the atmospheric pressure (Patm) air will flow into the lungs.

    Inhalation = Patm > Palv

When the alveolar pressure exceeds the atmospheric pressure, the air will flow out of the lungs.

    Exhalation = Patm < Palv

Resistance (R) in the respiratory system is primarily a factor of the radius of the bronchial passages.    Similar to the circulatory system,  as the radius decreases the resistance increases and flow goes decreases.   The radius of the bronchial system can be modified by the smooth muscle surrounding the passages or by mucous collecting inside the bronchioles.

What are the factors which cause the changes in pressure and drive the ventilation process?  One
A major factor is dependent on one of the gas laws - Boyle’s law.  Boyle’s law states  when the temperature is constant and a chambers volume is increased, the pressure in the chamber decreases and vice versa.

  Increased volume = decreased pressure

  Decreased volume = increased pressure

This is the major way ventilation is driven.  When the lungs are expanded during inhalation, Palv decreases below Patm and air flow into the lungs.  When the lungs are compressed during exhalation, Palv is increased to greater than Patm and air flows out of the lungs.
 

 The lungs do not contain any skeletal muscle and the smooth muscle present in the lung is associated with the bronchial system.  Thus, the lung is incapable of expanding and contracting by itself due to a lack of proper muscularization.  Lung expansion is dependent on the skeletal muscle associated with the chest wall and the diaphragm.  The lungs are only physically attached at their hilus, there is no physical attachment to the chest wall or diaphragm.  Instead, the lungs are held to the chest wall and diaphragm by the pleural membranes.  The surface of the lungs is covered by a thin epithelial membrane termed the visceral pleural membrane.  At the hilus, the visceral membrane is reflected back and covers the chest wall and diaphragm.  The pleural membrane covering the chest wall and diaphragm is termed the parietal pleural membrane.
 
 
 
 

The space between the visceral and parietal pleura constitutes the pleural cavity and the presure within the pleural cavity is the Intrapleural Pressure (Pip).

The lungs have a tendency to collapse due to two factors:

 1) elastic fibers
 2) surface tension

Elastic fibers are found in the walls of the alveoli.  When the lungs are at rest the lungs and the elastic fiber in the walls of the alveoli are stretched.  The stretched elastic fibers attempt to contract to a relaxed situation and in doing so generate a force to collapse the lungs.

In order for gas to diffuse across a membrane the surface of the membrane must be moist.  The inner surface of the alveolar lumen is coated with a layer of water which facilitates diffusion.  When the alveoli decrease their size during exhalation, the water molecules are attracted to each one another and attempt to collapse the alveoli.  This attraction between the water molecules which acts to collapse the alveoli is termed surface tension.  The lung septal cells produce surfactant, a phospholipoprotein, which forms an interface between the water molecules and the air decreasing the surface tension and allows the alveoli to expand during inhalation.  Due to these collapse tendencies,  the lungs attempt to pull away from the chest wall and diaphragm.  This pulls the visceral pleura away from the parietal pleura and increases the volume of the pleural cavity. Increasing the volume of the pleural cavity results in a decrease in the pressure inside the pleural cavity.  Now the Palv is greater than the Pip and the lower pressure in the pleural cavity holds the lungs to the chest walls and diaphragm.
 
 
 If atmospheric air can enter the pleural cavity, the negative pressure would be lost and the lungs would collapse.  Air in the pleural cavity is called pneumothorax and may be caused by a knife wound or a broken rib.

Actual expansion and contraction of the lungs is carried out by muscles of the chest wall and diaphragm which change the volume of the thoracic cavity.  Because the lungs are held to the chest wall and diaphragm, changes in thoracic cavity volume result in volume changes in the lung.   The major muscles involved in thoracic cavity volume changes are:

   Chest wall
    Inspiration = external intercostal muscles
    Expiration =  internal intercostal muscles
   Diaphragm

At rest the ribs are collapsed and hanging down.  The diaphragm muscles are relaxed resulting in the diaphragm being dome shaped.

 
 During inhalation, the external intercostal muscles contract raising the ribs and increasing the depth of the thoracic cavity.  In addition, the diaphragm contracts which results in its flattening and increasing the length of the thoracic cavity.
 
 
 
 
 

 
Increased volume in the thoracic cavity results in an increased volume in the lungs.  This increased volume decreases the pressure resulting in the Palv dropping below the Patm and air flows into the lungs. Exhalation occurs by muscle relaxation resulting in the ribs and diaphragm returning to their original position resulting in a decreased volume.  The decreased volume increases the Palv above the Patm and air flows out of the lungs.  During forced expiration, the abdominal muscles (rectus abdominus) are contracted which forces the viscera up against the diaphragm increasing the Palv far above normal. 

Ventilation moves the air in and out of the alveoli but the air is still in the alveoli and is inaccessible to the body cells.  In order for the gases to be accessible,  the oxygen must move from the alveolar lumen into the blood and carbon dioxide must move from the blood into the alveoli.  The movement of the gases across the respiratory membrane is due to the process of diffusion.   Recall that diffusion is the net movement of a substance from an area of high concentration to an area of low concentration.  When discussing gases the concentration of the gas is expressed as the partial pressure of the gas - PCO2, PO2.

Air is not made up of a single gas, but a mixture of gases as follows:

                  Atmospheric Air     Humidified Air        Alveolar Air
Gas              %       mmHg           %     mmHg          %     mmHg

N2             78.6     597.0           74.0    563.4         74.9    569.0

O2             20.8     159.0           19.0    149.3         13.6    104.0

CO2             0.04       0.3             0.04     0.3            5.3      40.0

H2O             0.50      3.7              6.2     47.0            6.2      47.0

The total pressure exerted by all the gases together is the atmospheric pressure - 760 mmHg.  Each gas exerts a pressure proportional to its concentration - a percent of the total pressure.  Oxygen constitutes 20.8 % of the atmospheric gases,  therefore it would exert a partial pressure of 20.8 % of 760 mmHg or a P02 of 159.0 mmHg.  Carbon dioxide constitutes .04 % of the atmospheric gases, therefore .04 % of 760 mmHg or a partial pressure (Pc02) of 0.3 mmHg. CO2 and O2 then diffuse from an area of high partial pressure to an area of low partial pressure.  P02 in the alveoli is 104 mmHg and the blood entering the alveolar capillaries is 40 mmHg.  Therefore the oxygen will diffuse from the alveoli into the blood.  When the blood leaves the alveoli it has a P02 of 95 mmHg.  The interstitial fluid surrounding the cell has a P02 of 40 mmHg.  The cells are using oxygen for cellular metabolism so the lowest P02 in the body is in the intracellular fluid (P02 - 23 mmHg).  In the lungs the oxygen diffuses from the alveoli into the blood and when the blood reaches the tissue the oxygen diffuses from the plasma into the interstitial fluid.   The oxygen then diffuses from the interstitial fluid into the cell.  The diffusion of oxygen would be as follows:

ALVEOLIi (P02 = 104 mmHg)  - oxygen diffuses to  BLOOD entering alveoli  ( P02 = 40 mmHg ) ?BLOOD Leaving alveoli  ( P02 = 95 mmHg) - oxygen diffuses to INTERSTITIAL Fluid (P02 = 40 mmHg) - oxygen diffuses to INTRACELLULAR FLUID ( P02 = 23 mmHg ).

As the cell uses oxygen it produces carbon dioxide.  Thus, the highest concentration of carbon dioxide (PCO2 = 47 mmHg) is in the cell.  The CO2 produced in the cell diffuses into the interstitial fluid ( PCO2 = 46 mmHg).  Blood entering the tissue capillaries has a PCO2 of 40 mmHg and when it leaves the capillaries it has a PCO2 of 46 mmHg.   When the blood enters the alveolar capillaries it diffuses into the alveolar lumen which has a PCO2 of 40 mmHg.

Both oxygen and carbon dioxide are relatively insoluble in the plasma so there must be other mechanisms for transporting these gases in the blood.  When oxygen diffuses into the plasma it becomes associated with hemoglobin.  Essentially all the oxygen is transported by hemoglobin.  The oxygen associates with the iron in the heme component of the hemoglobin.  The degree to which the hemoglobin is saturated by oxygen is dependent on the partial pressure of the oxygen.  This relationship is expressed in the oxygen-hemoglobin dissociation curve.   In addition to oxygen partial pressure other factors such as carbon dioxide concentration, temperature, 2-3 DPG and H+ can influence the oxygen-hemoglobin dissociation curve.

When carbon dioxide enters the blood very little of it, about 7%, can be dissolved in the plasma.  A limited amount of carbon dioxide can react with water as expressed in the following equation:

   CO2 + H2O <-------> H2CO3 <-------> HCO3- + H+

Because the enzyme necessary to catalyze this reaction (carbonic anhydrase) is not present in the plasma, less than 1% can be transported by this reaction.  The remainder of the Carbon dioxide enters the erythrocyte (red blood cell - RBC).   In the RBC, the carbon dioxide has two alternative pathways:

1) Carbonic anhydrase is present in the RBC so about 73% of the carbon dioxide is converted to the bicarbonate ion (HCO3-) and H+.   The H+ produced combines with hemoglobin, which acts as a buffer.  The HCO3- diffuses out of the cell and is transported to the lungs in the plasma in this form.  In the lungs,  the reaction is reversed and the carbon dioxide diffuses out of the blood into the alveoli.

2) When entering the RBC about 20-25% of the carbon dioxide combines with hemoglobin to form carbaminohemoglobin.   When the blood reaches the lungs the carbon dioxide dissociates from the hemoglobin and diffuses into the alveoli.