PHYSIOLOGY OF RESPIRATION

Respiration is the exchange of gases between the atmosphere, blood and the cells. There are three phases:

     1. Pulmonary ventilation—flow of air into and out of the lungs      

           Breathing in: Inhalation or inspiration

           Breathing out: Exhalation or expiration

 

     2. External (pulmonary) respiration--exchange of gases between lungs and the blood in pulmonary capillaries

 

     3. Internal (tissue) respiration--exchange of gases between the blood and tissue  cells in systemic capillaries

 

I. PULMONARY VENTILATION—exchange of air between atmosphere & lungs.    

      A. Inhalation—this is the active phase of breathing that brings air into the lungs.

Original Boyle’s law: the volume of a gas varies inversely with the pressure. Boyle's Law restated: as the volume of a container increases pressure of the gas in the container decreases and vice versa. Inhalation occurs when air pressure in the alveoli is made to fall below atmospheric pressure. Steps to accomplish this:

          1. Contraction of the diaphragm and external intercostal muscles increases the size of the thoracic cavity

          2. Lungs expand to fill the increased space, partly due to a drop in intrapleural pressure and partly due to a pull on the visceral pleura by the parietal pleura

          3. As the volume of the lungs increases, alveolar pressure drops below that of the atmosphere, creating a pressure gradient, and air rushes in

 

The diaphragm and external intercostals muscles are responsible for normal quiet inhalations. For deeper inhalations, accessory muscles of inhalation become active. These are the sternocleidomastoid, scalenes, and pectoralis minor muscles.

 

   B. Exhalation—movement of air out of the lungs. Under normal conditions it is passive and results from relaxation of the inspiratory muscles along with elastic recoil of the chest wall and lungs. It occurs when alveolar pressure is higher than atmospheric pressure. As inspiratory muscles relax, the size of the thoracic cavity decreases. The elastic fibers of the lungs that were stretched during inspiration recoil and alveolar pressure rises, so air rushes out of the lungs. Exhalation can become active during labored breathing. Abdominal muscles contract, pushing abdominal contents and the diaphragm upwards. Also the internal intercostals pull the ribs downward.

 

 

A detergent-like substance called surfactant is produced within the lungs. It acts to prevent the walls of the alveoli from sticking together during elastic recoil. Many premature babies suffer from respiratory distress syndrome of the newborn due to a lack of surfactant.

 

Atelectasis (collapsed lung) can occur when intrapleural pressure rises due to a puncture of the chest wall or lung wall. Lack of surfactant can also contribute to this.

 

Compliance--ease with which the lungs and thoracic wall can be expanded.

   High compliance--expand easily (this is normal)

   Low compliance--resist expansion

The 2 main factors that influence compliance are elasticity and surfactant. Compliance can be decreased by:

     1. Formation of scar tissue in the lungs

     2. Accumulation of fluid in lung tissue (pulmonary edema)

     3. Deficiency of surfactant

     4. Anything that impedes expansion of the chest wall

     5. Loss of elastic fibers in alveolar walls

 

Eupnea--normal quiet breathing consisting of one or (usually) both:

   Costal breathing (shallow)--external intercostal muscles

   Abdominal breathing (deep)--diaphragm

Apnea---cessation of breathing

Dyspnea---difficult or labored breathing

 

MODIFIED RESPIRATORY MOVEMENTS TABLE  23-1 P. 868

 

 

PULMONARY AIR VOLUMES AND CAPACITIES

The normal respiratory rate is 12-15 per minute. A spirometer is used to measure air moving in and out during breathing.

 

1. Tidal volume--500 ml--amount of air moving in and out during normal quiet inhalation and exhalation. Minute ventilation is tidal volume X respiratory rate

 

2. Alveolar ventilation rate—volume of air per minute that actually reaches the respiratory zone—normally about 70% of tidal volume

 

3. Inspiratory reserve volume--3100 ml--amount above normal tidal volume that can be inhaled in a very deep breath

 

4. Expiratory reserve volume--1200 ml--amount that can be pushed out after a normal exhalation

 

5. Residual volume--1200 ml--always some air remains in the lungs

 

6. Inspiratory capacity--3600 ml--tidal volume + inspiratory reserve

 

7. Functional residual capacity--2400 ml--residual volume + expiratory reserve

 

8. Vital capacity--4800 ml--sum of inspiratory reserve volume, tidal volume, expiratory reserve volume

 

9. Total lung capacity--6000 ml--sum of all volumes

 

All of the figures above are given for an average size male. An average size female would be smaller and the values would be somewhat less.

 

 

COPD—chronic obstructive pulmonary disease—anything that causes obstruction of air flow, most common causes are emphysema and chronic bronchitis

 

 

GASEOUS EXCHANGE

 

   Dalton's Law--each gas in a mixture of gases exerts its own pressure as if all other gases were not present. When a mixture of gases diffuses across a membrane, each gas diffuses from an area where its pressure (concentration) is higher to an area where its pressure (concentration) is lower. This is why O2 and CO2 can diffuse in opposite directions at the same time.

 

PARTIAL PRESSURES—the partial pressure of a gas is the percentage of that gas found in a mixture of gases. Total pressure of the mixture of gases equals the sum of all of the partial pressures. Partial pressures have the same effect on diffusion as concentration—gases move from an area of higher partial pressure (higher concentration) to an area of lower partial pressure (lower concentration).

 

Total atmospheric pressure of air = 760 mm Hg

 

Oxygen makes up 21% of this air, so the partial pressure (PO2) of oxygen is 20.9% X 760 mm Hg = 158.8 mm Hg

 

Carbon dioxide makes up .04%, so the partial pressure of CO2 (PCO2) is .04% X 760 mm Hg = 0.3 mm Hg

 

 

 

 

 

 

 

 

 

 

Partial pressures of gases in various areas (in mm Hg):

 

 

ATMOSPHERIC

AIR

 

ALVEOLAR AIR

OXYGENATED BLOOD IN PULMONATY VEINS

TISSUES

DEOXYGENATED BLOOD

 

PO2

 

 

    160

 

 

   105

 

   *100

 

     40

   

 

 40 AT REST

(LOWER WITH               EXERCISE)

 

PCO2

 

 

 

    .3

 

    40

 

     4O

 

      45

 

     45

 

II. EXTERNAL RESPIRATION--exchange of gases between the lungs and the blood that occurs in the lungs because of pressure differentials.

     Oxygen diffuses from alveoli into the blood until partial pressures (concentrations) are equal in both areas

     Carbon dioxide diffuses out of the blood into the alveoli until partial pressures (concentrations) are equal in both areas

 

This depends on several factors:

   1. Partial pressure (concentration) difference--we need the air we inhale to contain a fairly high PO2 so the pressure gradient will favor movement of O2 from alveoli into the blood. At higher altitudes the PO2 drops, so a shortage of oxygen may occur since the PO2 in oxygenated blood can only be equal to the PO2 in alveolar air.

   2. Surface area for gas exchange—pulmonary disorders can cause the surface area for diffusion to become smaller and therefore slows gaseous exchange. This lowers the PO2 in oxygenated blood. Emphysema is an example.

   3. Diffusion distance--pulmonary edema or any thickening of alveolar walls increases the diffusion distance and slows gaseous exchange.

   4. Solubility of gases---CO2 diffuses faster than O2 because it is more soluble in membranes. If diffusion is slowed, O2 shortage (hypoxia) occurs before excess CO2 builds up.

 

 

 

III. INTERNAL RESPIRATION--exchange between blood and tissue cells. At rest about 1/4 of the oxygen in oxygenated blood diffuses into tissue cells, so deoxygenated blood still contains considerable oxygen. In times of strenuous exercise more of this oxygen can diffuse out of the blood into active cells.

 

 

 

TRANSPORT OF GASES :  OXYGEN TRANSPORT

 

Oxygen does not dissolve readily in water, so only about 1.5% of the oxygen the blood carries is dissolved in plasma. The remaining 98.5% is carried in chemical combination with hemoglobin inside RBC. Each hemoglobin (Hb) molecule consists of a protein (globin) and 4 iron-containing heme groups. Each heme can carry 1 oxygen molecule. Oxygen and hemoglobin combine in an easily reversible reaction to form oxyhemoglobin:

          Hb + O2     ↔  Hb-O2                       

The most important factor that determines how much oxygen combines with hemoglobin is the PO2. The more oxygen in the immediate surroundings, the more oxygen hemoglobin can hold. The less oxygen present, the less oxygen hemoglobin can hold. In areas where the PO2 is high (pulmonary capillaries), hemoglobin binds with large amounts of oxygen and is said to be fully saturated (carrying a maximum amount of oxygen). This saturated hemoglobin leaves the lungs and travels to the tissues, where PO2 is lower, so the reaction reverses and oxygen is released. The more active a cell is, the lower the PO2 drops, so more oxygen is released.

 

Factors that determine how much oxygen is released from hemoglobin as the blood flows through a tissue:

 

     1. PO2  in the tissues is always lower than it was in the lungs, so a good bit of the oxygen is always released.

 

     2. Acidity (pH)—In an acid pH the affinity (attraction) of hemoglobin for oxygen is lower, so more oxygen is released (the Bohr effect).  H+ ions (present in areas of acidity) bind to hemoglobin and decrease its ability to carry oxygen. Lowered pH results from increased CO2 levels or production of lactic acid in muscle during exercise.

 

     3. PCO2—CO2 can also combine with hemoglobin, and as it does so it causes the hemoglobin to release oxygen. The more CO2 present, the more oxygen is released by hemoglobin. Another effect of increased CO2 levels is due to the fact that CO2 in the blood undergoes the following reaction:

     CO2  +  H2O  ↔  H2CO3   ↔   H+  + HCO3‾                                  

These H+ ions increase the acidity and act as in #2 above.

 

     4. Temperature—the warmer the tissue,  the more oxygen will be released from hemoglobin. Active cells produce heat and this results in increased oxygen availability.

 

     5. BPG (also known as DPG)--this is 2,3 bisphosphoglycerate formed in RBC. RBC have no mitochondria and release energy for their needs only by glycolysis. BPG is produced in this process and combines with hemoglobin, encouraging the release of oxygen.

 

Fetal hemoglobin is different in structure from adult hemoglobin and has a stronger affinity for oxygen. Fetal hemoglobin can attract and carry about 30% more oxygen than maternal hemoglobin, so in the placenta oxygen is readily transferred to fetal blood. This prevents hypoxia in the fetus.

 

Carbon monoxide poisoning occurs because if this gas is inhaled it also combines with heme, and the bonds are much stronger bonds than those formed with oxygen. Small amounts of CO can make hemoglobin unavailable for transporting oxygen.

 

 

 

CARBON DIOXIDE TRANSPORT

 

Carbon dioxide is carried in 3 forms:

   1. Dissolved in plasma--7%              

 

   2. Carbaminohemoglobin (Hb-CO2)--23%--some CO2 combines with the globin portion of hemoglobin (not the part that carries oxygen). Hb-CO2 forms readily in areas with a high PCO2 and breaks down in areas of low PCO2.  It tends to form in the tissues and break down in the lungs.

 

   3. Bicarbonate ions--70%--the reaction that produces these ions occurs in the RBC:

        CO2  +  H2O  ↔    H2CO3   ↔   H+  +  HCO3-

                                        

Many of the H+ ions combine with hemoglobin as noted earlier. As HCO3- ions accumulate inside RBC, some diffuse out into plasma because of the concentration gradient. These negative ions are replaced with Cl- ions to maintain the ionic balance and this is known as the chloride shift.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Deoxygenated blood entering the lungs contains the following substances related to CO2:

     CO2 dissolved in plasma         H+ ions

     Hb-CO2                                    H-Hb

     HCO3-

   

In pulmonary capillaries:

   Dissolved CO2 diffuses into alveoli and is exhaled

   Hb-CO2 splits and releases the CO2

   HCO3-  and H+ ions undergo the following reaction (starting with those inside RBC):

       H+  + HCO3 -  ↔    H2CO3  ↔  CO2  +  H2O

 

As the concentration of HCO3- inside the RBC drops, more HCO3- ions diffuse in from plasma (Cl- diffuses out). These  HCO3- ions enter the above reaction. CO2 produced diffuses out of the RBC into alveoli and is exhaled.

 

Just as an increase in CO2 in the blood causes O2 to split from hemoglobin, the binding of O2 to hemoglobin causes the release of CO2 from blood (Haldane effect).

 

 

 

 

 

The carbonic acid reaction can go 2 ways. In areas of high PCO2 (tissues):

    H2CO3   →  H+  +  HCO3-

 

In areas of low PCO2 (lungs):

    H2CO3  →  CO2  +  H2O

    

CONTROL OF RESPIRATION

 

RESPIRATORY CENTER

The size of the chest cavity is controlled by the action of the respiratory muscles. These muscles are directly controlled by groups of neurons in the brain stem collectively known as the respiratory center, which contains these areas:

   1. Medullary rhythmicity area--controls the basic rhythm of respiration. In eupnea inspiration lasts 2 seconds and expiration 3 seconds.

      a. Inspiratory area—this group of neurons sends impulses to the diaphragm (by phrenic nerves) and external intercostals (by intercostal nerves). This continues for 2 seconds and then stops for 3 seconds, allowing the muscles to relax and expiration to occur.

      b. Expiratory area—does NOT send impulses during quiet breathing, but during labored breathing and forced exhalation it sends impulses to the internal intercostal muscles while the inspiratory area is inactive.

   2. Pneumotaxic area—in upper pons—transmits inhibitory impulses to the inspiratory area so that it is turned off before the lungs become too filled with air.

   3. Apneustic area—in lower pons—sends stimulatory impulses to inspiratory area and prolongs inspiration.

The pneumotaxic area can override the apneustic area so the length (and depth) of inhalation cannot be increased to the point of lung damage.

 

A number of factors influence the type of output sent by the respiratory center. The basic rhythm of respiration can be modified by:

   1. Cortical impulses—conscious direction of breathing

   2. Chemical regulation—concerned with maintaining proper levels of CO2 and O2. When CO2 level rises a rise in H+ ions (acidity) follows, so pH is monitored also.

      a. Central chemoreceptors—in or near the medulla, these are neurons that are highly sensitive to levels of CO2 and pH in cerebrospinal fluid. If the PCO2 rises even a little (hypercapnia) this area is stimulated because both PCO2 and H+ ions increase. Impulses are sent to the inspiratory area which cause it to become highly active and the rate and depth of breathing increase (hyperventilation). Excess CO2 is exhaled and the level returns to normal.

Central chemoreceptors do not monitor O2 levels.

      b. Peripheral chemoreceptors detect levels of H+ ions, CO2 and O2 in the blood.

          1) Carotid bodies—in wall of common carotids where they split

          2) Aortic bodies—in wall of arch of the aorta

These also respond to cause an increase in respiration through the inspiratory area.        

 

Oxygen chemoreceptors are sensitive only to large decreases in O2. Arterial PO2 must drop from 100 mm Hg to about 50 mm Hg for these chemoreceptors to become active. At this level impulses to the inspiratory area will attempt to cause respiration to increase, but if the response does not quickly correct the problem, the lowered oxygen will cause brain damage and efforts will cease.

 

HYPOXIA--deficiency of oxygen at the tissue level

   a. Hypoxic hypoxia--low PO2 in arterial blood--high altitude, obstructed air passages, fluid in lungs

   b. Anemic hypoxia--too little functioning hemoglobin--hemorrhage, anemia, CO poisoning

   c. Stagnant hypoxia--insufficient circulation of blood reduces oxygen available to tissues--heart failure

   d. Histotoxic hypoxia--blood delivers oxygen to tissues but tissues cannot use it--cyanide poisoning

 

 

 

 

 

   3. Proprioceptors--these detect movement of joints and muscles and stimulate the inspiratory area when activity increases, even before gas levels change.

 

   4. Inflation reflex--stretch receptors in the walls of bronchi and bronchioles detect overinflation of the lungs. Impulses travel up the vagus nerves to the brain stem, where the inspiratory area and apneustic area are inhibited, causing expiration to occur. This is the Hering-Breuer reflex. This is a protective mechanism.

 

OTHER FACTORS

  

1. Limbic system---anxiety or anticipation of activity increases rate and depth of respiration

 

2. Temperature--increased body temp increases respiratory rate, decreased temp decreases. A sudden cold stimulus causes apnea, a temporary cessation of breathing.

 

3. Pain increases respiratory rate.  

 

4. Stretching anal sphincter--increases respiratory rate.

 

5. Irritation of air passages--cessation of breathing followed by coughing or sneezing.

 

6. Blood pressure—baroreceptors of the aortic and carotid bodies are primarily concerned with BP but also affect respiration:

           Sudden increase in BP decreases rate of respiration

           Sudden decrease in BP increases rate of respiration