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Functions of the Respiratory System

I.  Ventilation - Movement of air into (inspiration) and out of (expiration) the respiratory tract.

    A.  Contractions of respiratory muscles change the volume of the thoracic cavity.

        1.  Pail Handle Effect increases the thoracic cavity laterally.
                 a.  Contraction of external intercostal muscles is due to stimulation by the intercostal
                 nerves.
                 b.  Ribs lift up and swing out on the sides of the thorax.

        2.  Pump Handle Effect increases the volume of the thoracic cavity in the anterior to
        posterior dimension.  As the ribs move up,  the sternum moves out.

        3.  Diaphragm increases the thoracic cavity in the superior to inferior dimension.
                a.  Contraction of the diaphragm is due to stimulation by the phrenic nerves.
                b.  Diaphragm pushes down and flattens, enlarging the thoracic cavity.

    B.  Adhesion between pleural membranes

    1.  The water lining the insides of the parietal and visceral pleural causes the two membranes 
     to bond to each other.  This is due to the polarity of the water molecules.

    2.  The outer parietal membrane is fused to the inner chest wall.

    3.  The visceral pleura is fused to the lung's exterior.

    4.  As the chest wall moves out due to the actions of the external intercostals and diaphragm,
    the lung is stretched out.

    5.  The ability of the lung to stretch depends on the elasticity of the lung which is decreased by
    disease and aging.

    C.  Boyle's Law -  As the volume occupied by a gas increases, the pressure of that  gas
     decreases.  Mathematically speaking, the pressure on a contained gas and the volume it
     occupies are inversely proportional.
                                                        P  =  1/V
     1.  As the lung stretches out the pressure of air in the intrapulmonic space decreases.

         2.  When intrapulmonic pressure decreases below atmospheric pressure (760 mm Hg), air
        moves into the respiratory tract from the outside producing inspiration.

         3.  When the respiratory muscles relax, the thorax becomes smaller.  This causes the
        pressure of the air in the intrapulmonic space to exceed the air pressure outside.  This results
        in air moving out of the respiratory tract producing passive expiration.

Tidal Breathing - When we are at rest we use the external intercostals and the diaphragm to inspire.  Expiration is passive.   The muscles of inspiration simply relax. 

Forceful Breathing - With exertion or exercise we use additional muscles for inspiration and expiration.  

II.  Gas Exchange

External Respiration - Consists of movement of oxygen from the alveolar space into the blood and movement of carbon dioxide from the blood into the alveolar space.

Factors Influencing the Diffusion of Gases During External Respiration

1.  Pressures of the gases - Gases will show a net movement of molecules along a pressure gradient from high to low.  In this regard, each gas will follow Dalton's Law which states that each gas in a gas mixture will behave independently of the other gases in the mixture.  At the same time, the total pressure of a gas mixture is equal to the sum of the pressures that each gas would exert independently.  For example,

P(total) = P(nitrogen) + P(oxygen) + P(CO₂) + P(water vapor)

    The greater pressure of oxygen in the alveolar space will drive this gas into the blood.  The higher pressure of CO₂ will cause a net movement of this gas into the alveolus.

2.  Solubility of the gases in water (Henry's Law) - The amount of gas in the liquid depends on the solubility of each gas in that liquid.  There are a number of factors that influence the solubility of a gas in a liquid:
   
    a.  The chemical reactivity of the gas with water - CO₂ dissolves readily in water because it reacts rapidly forming carbonic acid.  Carbonic acid, in turn, dissociates into hydrogen and bicarbonate ions.

                     CO₂  +  H₂O produces  H₂CO₃  ionizes to form  H⁺   +  H₂CO₃

    The solubility of CO₂ in plasma, interstitial and alveolar fluid compensates for the lack of a steep pressure gradient in permitting the rapid diffusion of this gas from the blood.  Oxygen is much less soluble in water than CO₂.  However, the very high affinity of hemoglobin for oxygen continues to remove the small amount of dissolved O₂ from these fluids.  This insures a continually high gradient and rapid diffusion of this gas.

b.  Temperature - As the temperature of water increases, the solubility of gases decreases.  When you open a warm bottle of soda much more gas bubbles out of solution than from a cold soda.  Since the fluids of our bodies are generally kept at 98.6 degrees F, the influence of temperature on the solubility of blood gases is insignificant.

c.  Partial pressure - The partial pressure of the gas in the liquid and in the immediate environment will determine how much gas remains in solution.

3.  Thickness of the alveolar-capillary membrane - The alveolar-capillary membrane consists of the alveolar wall together with the capillary wall.  It measures only 0.5 micrometers in thickness.  That would be 1/2 of 1/1000 of the thickness of a dime.  As a result, diffusion of O2 and CO2 occurs very rapidly, in about 0.25 seconds.  Pulmonary edema will thicken the membrane and impede the diffusion of these gases.

4.  Surface Area - The total surface area of the alveolar membranes is enormous, between 70 and 80 square meters.  This greatly facilitates diffusion.  Respiratory diseases such as emphysema, tuberculosis, lung cancer and pneumonia reduce gas exchange by decreasing functional surface area.

Internal Respiration

    Internal respiration is the movement of oxygen from the blood to the tissues by diffusion and the movement of CO₂ from the tissues to the blood by diffusion.  All of the factors influencing external respiration at the alveoli are at work at the blood tissue interface.  The dominant factor would be the partial pressures of the gases.  Higher O₂ partial pressure in the blood drives oxygen into the tissues.  Higher CO₂ partial pressure in the tissues drives this gas into the blood.

III.  Transport of Respiratory Gases in the Circulation

Transport of O₂ - Most of the O₂ is carried in the blood combined with hemoglobin as oxyhemoglobin.  As a result, the factors which affect hemoglobin's ability to bind to O₂ will have the greatest impact on O₂ transport in the blood.

Factors Influencing the Transport of Oxygen
(Refer to the  Oxyhemoglobin Dissociation Curve Interactive Tool )

1.  Partial pressure of O₂ - directly affects the binding of oxygen and hemoglobin.  The oxygen dissociation curve is a convenient method of visualizing this relationship.  After examining the dissociation curve, a number of observations can be made.

    a.  Blood returning to the heart from the tissues has an oxygen partial pressure of 40mmHg.
    However, at this pressure, the hemoglobin (Hb) is still 75% saturated with oxygen.

    b.  At an O₂ partial pressure of 70mmHg, Hb is 95% saturated.  The significance of this is that at
    high altitudes or in cases of cardiopulmonary disease adequate oxygen transport can still occur.

    c.  During prolonged vigorous exercise, the blood has the capacity to increase oxygen unloading
    to the muscles and increase O₂ pick up at the alveoli without putting an undue strain on the
    heart.

2.  Partial pressure of CO₂ - As the pCO₂ in the blood increases, the affinity of oxygen for Hb is reduced.  This can be seen in the shift of the O₂ - Hb dissociation curve to the right (Bohr shift).  The chief consequence of the shift is that the pO₂ needed to produce any given saturation of Hb must be greater in the presence of increased CO_2.  In addition:

    a.  In rapidly metabolizing tissues, there will be an increased unloading of oxygen.

    b.  Anything that slows down the movement of CO₂ from the blood to the alveolus will decrease
    oxygen loading.  This will result in lower levels of oxygen in the blood leaving the lungs.

3.  pH - When the hydrogen ion concentration in the blood increases and lovers the pH of the blood below 7.35, the affinity of Hb for oxygen is reduced.  Blood pH levels below 7.35 are mostly associated with increases in pCO2 in the plasma and RBC.

                         CO₂  +  H₂O produces  H₂CO₃  ionizes to form   H⁺   +   H₂CO₃

4.  Temperature - Higher than normal body temperature lowers the affinity of Hb for O₂.  Actively metabolizing tissues are warmer than tissues at rest.  As a result, an increase in O₂ unloading occurs in these more active tissues. 

Transport of CO₂

    CO₂ is carried by the blood in three forms:

        1.  As bicarbonate - 70% of CO2 in the blood .  In the plasma, bicarbonate is formed by the
         familiar reaction:
                            CO₂  +  H₂O produces  H₂CO₃ ionizes to form   H⁺   +   H₂CO₃

            Inside the RBC, this reaction is speeded up due to the enzyme carbonic anhydrase which
        catalyzes the production of carbonic acid.  As a result, the level of bicarbonate inside the RBC
        is always higher than in the plasma.

        2.  As carbaminohemoglobin - 20% of the CO2 in the blood combines with the amino acids of
        the globin portion of the Hb molecule.  CO2 does not compete the O2 for binding to iron.

        3.  As a dissolved gas - 10% of CO2 in the blood is found in a dissolved state as a gas.

Factors Influencing the Transport of CO2

1.  pCO2 - The loading and unloading of CO2 from and to the blood is primarily affected by the pCO2.  The movement of CO2 along a concentration gradient is facilitated by the high solubility of CO2 in water which is the chief constituent of plasma, interstitial fluid and intracellular fluid.

2.  Bicarbonate formation - The largest amount of CO2 in the blood is carried in the form of bicarbonate.  As CO2 enters the blood bicarbonate ions form.  This formation occurs rapidly in the RBC due to the presence of the enzyme carbonic anhydrase.  In the plasma this formation occurs relatively slowly.

    a.  At the tissues, as bicarbonate ions form in the RBC, hydrogen ions are generated.   The H⁺ ions combine with Hb in the RBC.  The binding of H⁺ with Hb weakens the bond between O2 and hemoglobin.  This leads to the unloading of O2 to the tissues (figure A).

    b.  Due to the overabundance of bicarbonate in the RBC, bicarbonate diffuses to the plasma.  In order to balance the loss of negative charges from the RBC, chloride (Cl^-) diffuses into the RBC.  This is called the chloride shift (figure A).

    c.  The unloading of oxygen to the tissues supplies more hemoglobin that can bind to hydrogen ions.  This additional formation of reduced hemoglobin
(Hb + H⁺) leads to the uptake of more CO₂ from the tissues.  This phenomenon of  O₂ unloading leading to CO₂ loading in the blood near the tissues is called the Haldane effect.   

   d.  At the alveolus (figure B), the diffusion of CO₂ from the blood leads to a reduction of H⁺ inside the RBC.  This frees up hemoglobin to bind with incoming O₂.  In effect, the unloading of CO₂ into the alveolus, favors the loading of O₂ into the blood.  In addition, the binding of oxygen with Hb releases H⁺ inside the RBC.  This will favor the unloading of CO₂ into the alveoli (Haldane)
 

Fetal hemoglobin or HbF is the main oxygen transport protein  in the fetus during the last seven months of development in the womb. Functionally, fetal hemoglobin differs most from adult hemoglobin in that it is able to bind oxygen with greater affinity than the adult form, giving the developing fetus better access to oxygen from the mother's bloodstream.

In newborns, fetal hemoglobin is nearly completely replaced by adult hemoglobin by approximately the twelfth week of postnatal life. In adults, fetal hemoglobin production can be reactivated pharmacologically, which is useful in the treatment of such diseases as sickle cell anemia.

After the first 10 to 12 weeks of development, the fetus' primary form of hemoglobin switches from embryonic hemoglobin to fetal hemoglobin. At birth, fetal hemoglobin comprises 50-95% of the child's hemoglobin. These levels decline after six months as adult hemoglobin synthesis is activated while fetal hemoglobin synthesis is deactivated. Soon after, adult hemoglobin  takes over as the predominant form of hemoglobin in normal children.

IV.  Role of the Respiratory System in Regulation of the pH of the Extracellular Fluids

    Body cells release CO₂ to the extracellular fluids (ECF) such as the blood, interstitial fluid and the cerebrospinal fluid.  As CO₂ enters the ECF, 70% of it reacts with water as seen in the formula below:

                                     CO₂ + H₂O     >       H₂CO₃        >      H⁺  +  HCO₃

    As the CO₂ enters the blood, this reaction is driven to the right causing the accumulation of H⁺ and bicarbonate ions.  If this accumulation of CO₂ becomes excessive (hypercapnia) the resulting condition of acidosis would prevent the blood from carrying sufficient oxygen to keep ;the brain functioning.    The solution to this problem is a readjustment in pulmonary ventilation to eliminate the excess CO₂ more rapidly.  This adjustment is called hyperventilation.
    CO₂ passes into the cerebrospinal fluid from the blood,  In the CSF, the CO₂ reacts with water producing an elevation in the concentration of H⁺.  Special receptors in the medulla oblongata are stimulated by the rise in H⁺.  These receptors stimulate the neurons of the Dorsal Respiratory Group to depolarize more rapidly increasing the breathing rate.  As extra CO₂ is blown off, the reaction seen above is driven to the left.  This ultimately reduces the H⁺ concentration in the blood and in the CSF. 

If too much CO₂ is released during hyperventilation, the pH of the blood and CSF may rise as high as 7.45 a condition called alkalosis.  At this pH, hemoglobin will not release sufficient O₂ to the brain.  The corrective response to alkalosis is hypoventilation.  The scarcity of H⁺ in the CSF will lead to a decrease in the respiratory rate allowing the CO₂ to accumulate bringing up the H⁺ concentration and lowering the pH to the optimal level (7.35)