The respiratory system comprises the lungs, the airways leading to them, and the chest structures responsible for movement of air into and out of them.
The conducting zone of the airways consists of the trachea, bronchi, and terminal bronchioles.
The respiratory zone of the airways consists of the alveoli, which are the sites of gas exchange, and those airways to which alveoli are attached.
The alveoli are lined by type I cells with some type II cells, which produce surfactant.
The lungs and interior of the thorax are covered by pleura between the surfaces of which is an extremely thin layer of intrapleural fluid.
The lungs are elastic structures whose volume depends upon the pressure difference across the lungs (the transpulmonary pressure) and how stretchable the lungs are.
SUMMARY OF STEPS INVOLVED IN RESPIRATION
The steps involved in respiration are (1) ventilation, (2) gas exchange between alveolar air and lung capillaries, (3) bulk flow the circulation, (4) gas exchange between capillaries and tissue cells, and (5) cellular utilization and production of gases. In the steady state, the net volumes of oxygen and carbon dioxide exchanged in the lungs per unit time are equal to the net volumes exchanged in the tissues. Typical volumes per minute are 250 ml for oxygen consumption and 200 ml for carbon dioxide production.
VENTILATION AND LUNG MECHANICS
Bulk flow of air between the atmosphere and alveoli is proportional to the difference between the atmospheric and alveolar pressures and inversely proportional to the airway resistance:
F = (P- P)/R
Between breaths at the end of an unforced expiration P= P, no air is flowing, and the dimensions of the lungs and thoracic cage are stable as the result of opposing elastic forces. The lungs are stretched and are attempting to recoil, whereas the chest wall is compressed and attempting to move outward. This creates a subatmospheric intrapleural pressure and hence a transpulmonary pressure that opposes the forces of elastic recoil.
During inspiration, the contractions of the diaphragm and inspiratory intercostal muscles increase the volume of the thoracic cage.
This makes intrapleural pressure more subatmospheric, increases transpulmonary pressure, and causes the lungs to expand to a greater degree than between breaths.
This expansion initially makes alveolar pressure subatmospheric, which creates the pressure difference between atmosphere and alveoli to drive air flow into the lungs.
During expiration, the inspiratory muscles cease contracting, allowing the elastic recoil of the chest wall and lungs to return them to their original between-breath size.
This initially compresses the alveolar air, raising alveolar pressure above atmospheric pressure and driving air out of the lungs.
In forced expirations, the contraction of expiratory intercostal muscles and abdominal muscles actively decreases thoracic dimensions.
Lung compliance is determined by the elastic connective tissues of the lungs
and the surface tension of the fluid lining the alveoli. The latter is
greatly reduced, and compliance increased, by surfactant produced by the
type II cells of the alveoli.
Airway resistance determines how much air flows into the lungs at any given pressure difference between atmosphere and alveoli. The major determinant of airway resistance is the radii of the airways.
The vital capacity is the sum of resting tidal volume, inspiratory reserve volume, and expiratory reserve volume. The volume expired during the first second of a forced vital capacity (FVC) measurement is the FEV and normally averages 80 percent of FVC.
Minute ventilation is the product of tidal volume and respiratory rate;
alveolar ventilation = (tidal volume − anatomic dead space) × (respiratory
EXCHANGE OF GASES IN ALVEOLI AND TISSUES
Exchange of gases in lungs and tissues is by diffusion, as a result of differences in partial pressures. Gases diffuse from a region of higher partial pressure to one of lower partial pressure.
Normal alveolar gas pressure for oxygen is 105 mm Hg and for carbon dioxide 40 mm Hg.
At any given inspired P, the ratio of oxygen consumption to alveolar ventilation determines alveolar P -- the higher the ratio, the lower the alveolar P.
The higher the ratio of carbon dioxide production to alveolar ventilation, the higher the alveolar P.
The average value at rest for systemic venous Pis 40 mm Hg and for Pis 46 mm Hg.
As systemic venous blood flows through the pulmonary capillaries, there is net diffusion of oxygen from alveoli to blood and of carbon dioxide from blood to alveoli. By the end of the pulmonary capillaries, the blood gas pressures have become equal to those in the alveoli.
Inadequate gas exchange between alveoli and pulmonary capillaries may occur when the alveolus-capillary surface area is decreased, when the alveolar walls thicken or when there are ventilation-perfusion inequalities.
Significant ventilation-perfusion inequalities cause the systemic arterial Pto be reduced. An important mechanism for opposing mismatching is that a low local Pcauses local vasoconstriction, thereby shunting blood away from poorly ventilated areas.
In the tissues, net diffusion of oxygen occurs from blood to cells, and net diffusion of carbon dioxide from cells to blood.
TRANSPORT OF OXYGEN IN THE BLOOD
Each liter of systemic arterial blood normally contains 200 ml of oxygen, more than 98 percent bound to hemoglobin and the rest dissolved.
The major determinant of the degree to which hemoglobin is saturated with oxygen is blood
Hemoglobin is almost 100 percent saturated at the normal systemic arterial Pof 100 mm Hg. The fact that saturation is already more than 90 percent at a Pof 60 mm Hg permits relatively normal uptake of oxygen by the blood even when alveolar P is moderately reduced.
Hemoglobin is 75 percent saturated at the normal systemic venous Pof 40 mm Hg. Thus, only 25 percent of the oxygen has dissociated from hemoglobin and entered the tissues.
The affinity of hemoglobin for oxygen is decreased by an increase in P, hydrogen-ion concentration, and temperature. All these conditions exist in the tissues and facilitate the dissociation of oxygen from hemoglobin.
The affinity of hemoglobin for oxygen is also decreased by binding DPG synthesized by the erythrocytes. DPG increases in situations associated with inadequate oxygen supply and helps maintain oxygen release in the tissues.
TRANSPORT OF CARBON DIOXIDE BY THE BLOOD
When carbon dioxide molecules diffuse from the tissues into the blood, 10 percent remains dissolved in plasma and erythrocytes, 30 percent combines in the erythrocytes with deoxyhemoglobin to form carbamino compounds, and 60 percent combines in the erythrocytes with water to form carbonic acid, which then dissociates to yield bicarbonate and hydrogen ions. Most of the bicarbonate then moves out of the erythrocytes into the plasma in exchange for chloride ions.
As venous blood flows through lung capillaries, Pdecreases because of diffusion of carbon dioxide out of the blood into the alveoli, and the above reactions are reversed.
TRANSPORT OF HYDROGEN IONS BETWEEN TISSUES AND LUNGS
Most of the hydrogen ions generated in the erythrocytes from carbonic acid during blood passage through tissue capillaries bind to deoxyhemoglobin because deoxyhemoglobin, formed as oxygen unloads from oxyhemoglobin, has a high affinity for hydrogen ions.
As the blood flows through the lung capillaries, hydrogen ions bound to deoxyhemoglobin are released and combine with bicarbonate to yield carbon dioxide and water.
CONTROL OF RESPIRATION
Breathing depends upon cyclical inspiratory muscle excitation by the nerves to the diaphragm and intercostal muscles. This neural activity is triggered by the medullary inspiratory neurons.
The most important inputs to the medullary inspiratory neurons for the involuntary control of minute ventilation are from the peripheral chemoreceptors (the carotid and aortic bodies) and the central chemoreceptors.
Ventilation is reflexly stimulated, via the peripheral chemoreceptors, by a decrease in arterial
P, but only when the decrease is large.
Ventilation is reflexly stimulated, via both the peripheral and central chemoreceptors, when the arterial Pgoes up even a slight amount. The stimulus for this reflex is not the increased Pitself, but the concomitant increased hydrogen-ion concentration in arterial blood and brain extracellular fluid.
Ventilation is also stimulated, mainly via the peripheral chemoreceptors, by an increase in arterial hydrogen-ion concentration resulting from causes other than an increase in P. The result of this reflex is to restore hydrogen ion concentration toward normal by lowering P.
Ventilation is reflexly inhibited by an increase in arterial Pand by a decrease in arterial P or hydrogen-ion concentration.
During moderate exercise, ventilation increases in exact proportion to metabolism, but the signals causing this are not known. During very strenuous exercise, ventilation increases more than metabolism.
The proportional increases in ventilation and metabolism during moderate exercise cause the arterial PP and hydrogen-ion concentration to remain unchanged.
Arterial hydrogen-ion concentration increases during very strenuous exercise because of increased lactic acid production. This accounts for some of the hyperventilation seen in that situation.
Ventilation is also controlled by reflexes originating in airway receptors and by conscious intent.
The causes of hypoxic hypoxia are (1) hypoventilation, (2) diffusion impairment, (3) a shunt, and (4) ventilation-perfusion inequality.
During exposure to hypoxia, as at high altitude, oxygen supply to the tissues is maintained by (1) increased ventilation, (2) erythropoietin secretion, (3) increase in DPG, (4) increases in capillary density, mitochondria, and muscle myoglobin, and (5) increased loss of sodium and water in the urine.
NONRESPIRATORY FUNCTIONS OF THE LUNGS
The lungs influence arterial blood concentrations of biologically active substances by removing some from systemic venous blood and adding others to systemic arterial blood.
The lungs also act as sieves that dissolve small clots formed in the systemic tissues.