The Respiratory System
- Alveoli are microscopic thin-walled air sacs that provide an enormous surface
area for gas diffusion.
- The region of the lungs where gas exchange with the blood occurs is known
as the respiratory zone.
- The trachea, bronchi, and bronchioles that deliver air to the respiratory
zone comprise the conducting zone.
- The thoracic cavity is limited by the chest wall and diaphragm.
- The structures of the thoracic cavity are covered by thin, wet pleural
- The lungs are covered by a visceral pleura that is normally flush against
the parietal pleura that lines the chest wall.
- The potential space between the visceral and parietal pleurae is called
the intrapleural space.
Physical Aspects of Ventilation
- The intrapleural and intrapulmonary pressures vary during ventilation.
- The intrapleural pressure is always less than the intrapulmonary pressure.
- The intrapulmonary pressure is subatmospheric during inspiration and greater
than the atmospheric pressure during expiration.
- Pressure changes in the lungs are produced by variations in lung volume,
in accordance with the inverse relationship between the volume and pressure
of a gas described by Boyle's law.
- The mechanics of ventilation are influenced by the physical properties of
- The compliance of the lungs, or the ease with which they expand, refers
specifically to the change in lung volume per change in transpulmonary pressure
(the difference between intrapulmonary pressure and intrapleural pressure).
- The elasticity of the lungs refers to their tendency to recoil after distension.
- The surface tension of the fluid in the alveoli exerts a force directed
inward, which acts to resist distension.
- On first consideration, it would seem that the surface tension in the alveoli
would create a pressure that would cause small alveoli to collapse and empty
their air into larger alveoli.
- This would occur because the pressure caused by a given amount of surface
tension would be greater in smaller alveoli than in large alveoli, as described
by the law of La Place.
- Surface tension does not normally cause the collapse of alveoli, however,
because pulmonary surfactant (a combination of phospholipid and protein)
lowers the surface tension sufficiently.
- In hyaline membrane disease, the lungs of premature infants collapse because
of a lack of surfactant.
Mechanics of Breathing
- Inspiration and expiration are accomplished by the contraction and relaxation
of striated muscles.
- During quiet inspiration, the diaphragm and external intercostal muscles
contract and thus increase the volume of the thorax.
- During quiet expiration, these muscles relax, and the elastic recoil of
the lungs and thorax causes a decrease in thoracic volume.
- Forced inspiration and expiration are aided by contraction of the accessory
- Spirometry aids the diagnosis of a number of pulmonary disorders.
- In restrictive disease, such as pulmonary fibrosis, the vital capacity
measurement is decreased to below normal.
- In obstructive disease, such as asthma and bronchitis, the forced expiratory
volume is reduced to below normal because of increased airway resistance
to air flow.
- Asthma results from bronchoconstriction; emphysema and chronic bronchitis
are frequently referred to collectively as chronic obstructive pulmonary disease.
Gas Exchange in the Lungs
- According to Dalton's law, the total pressure of a gas mixture is
equal to the sum of the pressures that each gas in the mixture would exert
- The partial pressure of a gas in a dry gas mixture is thus equal to the
total pressure times the percent composition of that gas in the mixture.
- Since the total pressure of a gas mixture decreases with altitude above
sea level, the partial pressures of the constituent gases likewise decrease
- When the partial pressure of a gas in a wet gas mixture is calculated,
the water vapor pressure must be taken into account.
- According to Henry's law, the amount of gas that can be dissolved
in a fluid is directly proportional to the partial pressure of that gas in
contact with the fluid.
- The concentrations of oxygen and carbon dioxide that are dissolved in
plasma are proportional to an electric current generated by special electrodes
that react with these gases.
- Normal arterial blood has a PO2 of 100 mm Hg, indicating a
concentration of dissolved oxygen of 0.3 ml per 100 ml of blood; the oxygen
contained in red blood cells (about 19.7 mil per 100 ml of blood) does not
affect the PO2 measurement.
- The PO2 and PCO2 measurements of arterial blood provide
information about lung function.
- In addition to proper ventilation of the lungs, blood flow (perfusion) in
the lungs must adequate and matched to air flow (ventilation) in order for
adequate gas exchange to occur.
- Abnormally high partial pressures of gases in blood can cause a variety
of disorders, including oxygen toxicity, nitrogen narcosis, and decompression
Regulation of Breathing
- The rhythmicity center in the medulla oblongata directly controls the muscles
- Activity of the inspiratory and expiratory neurons varies in a reciprocal
way to produce an automatic breathing cycle.
- Activity in the medulla is influenced by the apneustic and pneumotaxic
centers in the pons, as well as by sensory feedback information.
- Conscious breathing involves direct control by the cerebral cortex via
- Breathing is affected by chemoreceptors sensitive to the PO2,
pH, and PCO2 of the blood.
- The PCO2 of the blood and consequent changes in pH are usually
of greater importance than the blood PO2 in the regulation of
- Central chemoreceptors in the medulla oblongata are sensitive to changes
in blood PCO2 because the resultant changes in the pH of the
- The peripheral chemoreceptors in the aortic and carotid bodies are sensitive
to changes in blood PCO2 indirectly, because of consequent changes
in blood pH.
- Decreases in blood PO2 directly stimulate breathing only when
the blood PO2 is lower than 50 mm Hg. A drop in PO2
also stimulates breathing indirectly, by making the chemoreceptors more sensitive
to changes in PCO2 and pH.
- At tidal volumes of 1 L or more, inspiration is inhibited by stretch receptors
in the lungs (the Hering, Breuer reflex). A similar reflex may act to inhibit
Hemoglobin and Oxygen Transport
- Hemoglobin is composed of two alpha and two beta polypeptide chains and
four heme groups, each containing a central atom of iron.
- When the iron is in the reduced form and not attached to oxygen, the hemoglobin
is called deoxyhemoglobin, or reduced hemoglobin; when it is attached to
oxygen, it is called oxyhemoglobin.
- If the iron is attached to carbon monoxide, the hemoglobin is called carboxyhemoglobin.
When the iron is in an oxidized state and unable to transport any gas, the
hemoglobin is called methemoglobin.
- Deoxyhemoglobin combines with oxygen in the lungs (the loading reaction)
and breaks its bonds with oxygen in the tissue capillaries (the unloading
reaction). The extent of each reaction is determined by the PO2
and the affinity of hemoglobin for oxygen.
- A graph of percent oxyhemoglobin is saturation at different values of PO2
is called an oxyhemoglobin dissociation curve.
- At rest, the difference between arterial and venous oxyhemoglobin saturations
indicates that about 22% of the oxyhemoglobin unloads its oxygen to the
- During exercise, the venous PO2 and percent oxyhemoglobin saturation
are decreased, indicating a higher percent of the oxyhemoglobin unloaded
its oxygen to the tissues.
- The pH and temperature of the blood influence the affinity of hemoglobin
for oxygen and thus the extent of loading and unloading.
- A fall in pH decreases the affinity of hemoglobin for oxygen, and a rise
in pH increases the affinity. This is called the Bohr effect.
- A rise in temperature decreases the affinity of hemoglobin for oxygen.
- When the affinity is decreased, the oxyhemoglobin dissociation curve is
shifted to the right. This indicates a greater percentage unloading of oxygen
to the tissues.
- The affinity of hemoglobin for oxygen is also decreased by an organic molecule
in the red blood cells called 2,3-diphosphoglyceric acid (2,3-DPG).
- Since oxyhemoglobin inhibits 2,3-DPG production, 2,3-DPG concentrations
will be higher when anemia or low PO2 (as in high altitude) causes
a decrease in oxyhemoglobin.
- If a person is anemic, the lowered hemoglobin concentration is partially
compensated for because a higher percent of the oxyhemoglobin will unload
its oxygen as a result of the effect of 2,3-DPG.
- Fetal hemoglobin cannot bind to 2,3-DPG, and thus it has a higher affinity
for oxygen than the mother's hemoglobin. This facilitates the transfer
of oxygen to the fetus.
- Inherited defects in the amino acid composition of hemoglobin are responsible
for such diseases as sickle-cell anemia and thalassemia.
- Striated muscles have myoglobin, a pigment related to hemoglobin, which
can combine with oxygen and deliver it to the muscle cell mitochondria at
Carbon Dioxide Transport and Acid-Base Balance
- Red blood cells contain an enzyme called carbonic anhydrase, which catalyzes
the reversible reaction whereby carbon dioxide and water are used to form
- This reaction is favored by the high PCO2 in the tissue capillaries,
and as a result, carbon dioxide produced by the tissues is converted into
carbonic acid in the red blood cells.
- Carbonic acid then ionizes to form H+ and HCO3-
- Since much of the H+ is buffered by hemoglobin, but more bicarbonate
is free to diffuse outward, an electrical gradient is established that draws
Cl- into the red blood cells. This is called the chloride shift.
- A reverse chloride shift occurs in the lungs. In this process, the low
PCO2 favors the conversion of carbonic acid to carbon dioxide,
which can be exhaled.
- By adjusting the blood concentration of carbon dioxide and thus of carbonic
acid, the process of ventilation helps to maintain proper acid-base balance
of the blood.
- Normal arterial blood pH is 7.40; a pH less than 7.35 is termed acidosis,
and a pH greater than 7.45 is termed alkalosis.
- Hyperventilation causes respiratory alkalosis, and hypoventilation causes
- Metabolic acidosis stimulates hyperventilation, which can cause a respiratory
alkalosis as a partial compensation.
Effect of Exercise and High Altitude on Respiratory Function
- During exercise there is increased ventilation, or hyperpnea, which is matched
to the increased metabolic rate so that the arterial blood PCO2
- This hyperpnea may be caused by proprioceptor information, cerebral input,
and/or changes in arterial PCO2 and pH.
- During heavy exercise the anaerobic threshold may be reached at about
55% of the maximal oxygen uptake. At this point, lactic acid is released
into the blood by the muscles.
- Endurance training enables muscles to utilize oxygen more effectively,
so that greater levels of exercise can be performed before the anaerobic
threshold is reached.
- Acclimatization to a high altitude involves changes that help to deliver
oxygen more effectively to the tissues, despite reduced arterial PO2.
- Hyperventilation occurs in response to the low PO2.
- The red blood cells produce more 2,3-DPG, which lowers the affinity of
hemoglobin for oxygen and improves the unloading reaction.
- The kidneys produce the hormone erythropoietin, which stimulates the bone
marrow to increase its production of red blood cells, so that more oxygen
can be carried by the blood at given values of PO2.
After studying this chapter, students should be able to . . .
- describe the functions of the respiratory system, distinguish between the
conducting and respiratory zone structures, and discuss the significance of
the thoracic membranes.
- explain how the intrapulmonary and intrapleural pressures vary during ventilation
and relate these pressure changes to Boyle?s law.
- define the terms compliance and elasticity and explain how
these lung properties affect ventilation.
- discuss the significance of surface tension in lung mechanics, explain how
the law of La Place applies to lung function, and describe the role of pulmonary
- explain how inspiration and expiration are accomplished in unforced breathing
and describe the accessory respiratory muscles used in forced breathing.
- define the various lung volumes and capacities that can be measured by spirometry
and explain how obstructive diseases may be detected by the FEV test.
- describe the nature of asthma, bronchitis, emphysema, and pulmonary fibrosis.
- explain Dalton?s law and illustrate how the partial pressure of a gas in
a mixture of gases is calculated.
- explain Henry?s law, describe how blood PO2and PCO2are
measured, and discuss the clinical significance of these measurements.
- describe the roles of the medulla oblongata, pons, and cerebral cortex in
the regulation of breathing.
- explain why the PCO2 and pH of blood, rather than its oxygen
content serve as the primary stimuli in the control of breathing.
- explain how the chemoreceptors in the medulla oblongata and the peripheral
chemoreceptors in the aortic and carotid bodies respond to changes in PCO2,
pH, and PO2.
- describe the Hering, Breuer reflex and discuss its significance.
- describe the different forms of hemoglobin and discuss the significance
of these different forms.
- describe the loading and unloading reactions and explain how the extent
of these reactions is influenced by the PO2 and affinity of hemoglobin
- describe the oxyhemoglobin dissociation curve, discuss the significance
of its shape, and demonstrate how this curve is used to derive the unloading
percentage for oxygen.
- explain how oxygen transport is influenced by changes in blood pH and temperature,
and explain the effect and physiological significance of 2,3-DPG on oxygen
- list the different forms in which carbon dioxide is carried by the blood
and explain the chloride shift in the tissues and the reverse chloride shift
in the lungs.
- explain how carbon dioxide affects blood pH and how hypoventilation and
hyperventilation affect acid-base balance.
- describe the hyperpnea of exercise and explain how the anaerobic threshold
is affected by endurance training.
- explain the respiratory adjustments to life at a high altitude.