October 10, 2017 Page 1 Respiration 2

NROSCI/BIOSC 1070 and MSNBIO 2070October 10, 2017

Respiration 2

Note in the graph that alveolar pressure reaches its most negative value about halfway into inspiration. Pleural pressure decreases as long as the thoracic cavity continues to expand, but air flow into the alveoli offsets the negative pressure that is being generated.

Air flow into the lungs continues until alveolar pressure equals atmospheric pressure, which occurs at the end of the inspiratory cycle.

When discussing ventilation, it is important to differentiate pleural pressure, alveolar pressure, and transpulmonary pressure. Pleural pressure is the pressure of the fluid in the narrow space between the lung pleura and the chest wall pleura. Pleural pressure is normally slightly negative, due to the mechanical interaction between the lung and the chest wall. The lung tends to decrease its volume because of its inward elastic recoil. The lung would collapse unless it was stuck to the chest wall by the pleural fluid. The actions of the recoil forces of the lung on the pleural fluid cause the pleural fluid to have a negative pressure.

Alveolar pressure is the pressure in the alveoli. Alveolar pressure is negative at the onset of inspiration as a reflection of Boyle’s Law (the alveolar space is expanded when the lungs are stretched, such that pressure in the alveoli drops). During expiration, alveolar pressure is positive when the alveolar space collapses such that more gas molecules are located in a smaller space.

Transpulmonary pressure (also called transmural pressure) is the difference between the two values: PTRANSPULMONARY = PALVELOLAR—PINTRAPLEURAL

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The graph above provides another perspective about the relationships between pleural pressure, alveo-lar pressure, and transpulmonary pressure. Note that pleural pressure becomes more negative during inspiration, as the recoil tendency for the lungs is higher (the elastic elements are stretched), which tends to cause transpulmonary to increase as well.

Passive recoil is mainly responsible for forcing air out of the lungs during expiration, which occurs when alveolar pressure exceeds atmospheric pressure. This passive recoil is generated by the elastic forces in the lungs, and also by the chest wall (muscle and bone). If ventilation exceeds 30 breaths per minute (the average in resting is 12-20 breaths per minute), the contraction of the expiratory muscles also contributes to expiration. Contraction of the abdominal muscles during active expiration pulls the lower ribcage inward and decreases abdominal volume. This causes the visceral contents to be pushed up into the diaphragm, thereby decreasing chest volume and forcing air out of the lungs. The internal intercostal muscles also contribute to active expiration, in that they act to compress the ribcage.

It is interesting that respiration depends on such a fragile thing as the lung and thoracic cavity pleural membranes sticking together. This “bond” assures that the lung expands with the ribcage, so that air will be inspired, and that recoil after the inspiration can produce expiration. Thus, it is tragic when air gets into the thoracic cavity, as it breaks the bond between the pleural membranes. This is what happens when a penetrating wound makes a hole in the thoracic cavity. This condition, called pneumothorax, results in a collapsed lung that is unable to work properly. A pneumothorax can also be created if the lung ruptures, allowing air into the thoracic cavity.

The process of respiration also depends on the lungs being able to stretch properly. In fact, most of the “work” of breathing goes into overcoming the resistance of the elastic lungs and the respiratory muscles. Thus, if the compliance of the lungs changes, breathing can be impaired. Too much compliance is just as bad as too little, as there is no elastic recoil to help force air out of the lungs during expiration. Emphysema is a disease in which the elastin fibers in the lungs break down; people with this disease find it very difficult to achieve gas exchange. In addition, many alveoli are lost in emphysema patients, as we will see later.

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Restrictive lung diseases occur when lung compliance drops markedly. One example of such as disease is fibrotic lung disease, which results when prolonged exposure to irritants such as asbestos leads to an accumulation of scar tissue in the lungs.

Another condition that leads to a reduction of lung compliance is a loss of surfactant. The fluid that moisturizes the alveolar wall tends to produce surface tension, which increases the resistance of the lung to stretch. This is due to a natural tendency of water molecules to aggregate, and to form a sphere. If surface tension went unchecked, it would be very difficult to expand the lung. Fortunately, the lung secretes surfactants that disrupt cohesive forces between water molecules. Surfactants are typically lipoproteins.

If surfactant production does not occur, many alveoli would collapse. This is explained by the Law of LaPlace, which describes the physics of a fluid sphere or bubble. LaPlace’s law states that the pres-sure inside a fluid-filled alveolus is dependent on surface tension of the fluid and radius of the alveolus:

The pressure-volume curves to the left show how alterations in lung compliance in different pulmo-nary diseases affects filling of the lungs during breathing. In emphysema, the compliance of the lungs is high, so it is easy to distend the lungs. In re-strictive lung diseases, the compliance of the lungs is low, so expanding the lungs is very difficult.

P=2 * T/rP=pressure of alveolus; T=surface tension; r=radius of alveolus

Thus, if surface tension is high, then pressure inside small alveoli would be great, and they would collapse as air flowed to lower-pressure larger alveoli. Surfactants are not produced until about 8 weeks before birth, which explains why premature infants have a hard time in breathing.

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Another factor that should be considered is the resistance of the airways. Normally, the respiratory effort required to overcome this resistance is trivial compared to that required to overcome elastic forces of the lungs and thoracic cavity.

However, during pathological states this situation can change. Poiseuille’s Law states:

R = 8ηl / πr4 or Q = π∆Pr4/ 8ηl

Q = flow π/8 is a constant∆P = the pressure driving forcer = radius of the vesselη = viscosity of the fluidl = length of the vessel

Thus, if the radius of the airway diminishes, there can be a huge change in resistance and flow. Overcoming mucus accumulation in the airway passages during infection can require tremendous respiratory effort. Another factor that can affect airway resistance is constriction of smooth muscle of the bronchioles. This constriction can be induced neurally, by activation of the parasympathetic nervous system. This response helps to protect the alveoli from inhaled irritants. The smooth muscle of bronchioles receives practically no sympathetic innervation. However, this smooth muscle possesses β2 receptors, and dilates when exposed to circulating epinephrine. It is for this reason that epinephrine is sometimes injected to reduce respiratory resistance.

A number of paracrine factors also affect the constriction of smooth muscles of bronchioles. Carbon dioxide is the most potent agent, and acts to induce vasodilation. Histamine, released during allergic reactions, acts to produce bronchoconstriction. Asthma occurs in persons who are subject to bron-choconstriction during exposure to particular conditions that lead to release of appropriate paracrine factors. As you might expect, β2 adrenergic agonists have been used to treat asthma.

Lung VolumesClinically, measures of lung volumes can be useful. A spirometer measures the volume of air moving during each breath. It is useful to know the terms that refer to lung volumes, and their values.

The amount of air that moves in a single normal inspiration or expiration is called tidal volume (VT). In an average-sized male, this volume is approximately 500 ml. The amount of additional air that you can inspire following a normal tidal inspiration is called inspiratory reserve volume (IRV). In a typi-cal male, this volume is about 3 L. The term expiratory reserve volume (ERV) refers to the amount of additional air that can be exhaled after a normal expiration, and is about 1 L. Even after a maximal expiration, some air is left in the lungs. This volume is called residual volume (RV), and is about 1.2 L. Residual volume exists because the lungs are normally stuck to the pleura of the thoracic wall.

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Other terms refer to summation of the volumes discussed above. The maximal amount of air that can normally be moved is called vital capacity, and is the summation of tidal volume, inspiratory reserve volume and expiratory reserve volume. As you can calculate, the vital capacity is about 4.5 L. Total lung capacity is the total amount of air in the lungs, and is about 5.7L (summation of vital capacity and residual volume).

Effectiveness of Pulmonary Ventilation

The term “total pulmonary ventilation” refers to the amount of air moved into and out of the lungs per minute. As you might imagine, total pulmonary ventilation is calculated by the following formula: VT * Ventilation Rate = Total Pulmonary ventilation.

In an “average” male, tidal volume is 500 ml and Ventilation Rate is 12 breaths/min. Thus, total pul-monary ventilation = 500 ml/breath * 12 breaths/min = 6000 ml/min.

Total pulmonary ventilation is a misleading quantity, as not all of this volume reaches the exchange surface. Part of the air remains in the conducting passageways, which are referred to as dead space (because they are not involved in gas exchange). Thus, to determine total alveolar ventilation, dead space volume should be subtracted from tidal volume. In other words:

Alveolar Ventilation = Ventilation rate * (Tidal Volume - Dead Space Volume)

In an “average” man, dead space volume = 150 ml, so:

Alveolar Ventilation = 12 breaths/min * (500 ml/breath - 150 ml/breath) = 4200 ml/min.

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Alveolar gas exchange

During increases and decreases in alveolar ventilation, the partial pressure of oxygen and carbon dioxide in the alveoli can change mark-edly. However, during normal tidal breathing, the partial pressures of these gases remains stable in the alveoli. This may seem contradictory, as you might expect the levels to change markedly between inspiration and expiration.

Two factors contribute to the maintenance of constant levels of oxygen and carbon dioxide in the alveoli. First, the amount of oxygen that enters an alveolus during each breath is approxi-mately equal to the amount that enters the blood. Second, as discussed above, the amount of fresh air brought into the alveoli during each breath is only a fraction of the total air in the lungs.

Matching of ventilation and alveolar blood flowBringing oxygen into the alveoli does little good unless the circulatory system can pick-up the inspired gas. There is a precise matching between air and blood flow to the alveoli for this purpose.

In the lungs, local factors are mainly responsible for this matching. Arterioles in the lungs, unlike those in most other vascular beds, are not extensively regulated by the autonomic nervous system.

Furthermore, capillaries in the lungs are collapsible. Near the apex (top) of the lung, the capillaries are normally collapsed, and blood flow is diverted to the base of the lung where gravity causes hydrostatic pressure to be higher. During exercise, when mean arterial pressure increases, the apex capillaries open, and gas exchange takes place in a larger area of the lung. This process is part of the reserve capacity of the lung.

Pulmonary arterioles are mainly sensitive to local levels of oxygen. When oxygen levels rise, the capil-laries dilate to permit more gas exchange. In contrast, the bronchiole smooth muscle is most affected by carbon dioxide levels. When carbon dioxide levels rise, then the smooth muscle relaxes to permit more ventilation of the alveoli.

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Gas Exchange in the LungsSimple diffusion explains the movement of gases between the alveolus and the blood, and between the blood and the body tissues. As you may recall, diffusion is limited by the following conditions:

1) The rate of diffusion across membranes is directly proportional to the partial pressure (concen-tration) gradient.

2) The rate of diffusion across membranes is directly proportional to the available surface area.3) The rate of diffusion across membranes is inversely proportional to the thickness of the mem-

brane.4) Diffusion is most rapid over short distances.

The gas laws state that gases move from regions of higher partial pressure to regions of lower partial pressure. Also recall that the PO2 in the alveoli is near 100 mm Hg. The PO2 in the blood returning to the lungs is near 40 mm Hg. Thus, diffusion will cause oxygen to move from the alveolus to the blood.

Normally, diffusion between the alveolus and blood occurs rapidly and efficiently, because both oxy-gen and carbon dioxide are small molecules that are both lipid and water soluble. Furthermore, the specializations that we discussed in the last class (much of the surface area of the alveolus is covered with capillaries; the interstitial space is small) will serve to maximize the diffusion process.

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If the partial pressure of oxygen in an alveolus drops, then oxygenation of the blood will be impaired. This will occur if ventilation is impaired by diseases (e.g., asthma, which increases resistance in the bronchioles), or if atmospheric pressure drops (as occurs at high altitudes). For example, on the top of Mount Everest, atmospheric pressure is 253 mm Hg, and so the partial pressure of oxygen in the air is (0.21 * 253 = 53 mm Hg). Because air inspired during each breath is only a fraction of air in lungs, the partial pressure of air in the alveolus would only be 35 mm Hg (a value less than that normally in venous blood). Obviously, then, it would be impossible for a person to achieve proper blood oxygenation if living on Mount Everest.

The principles of diffusion also indicate that gas exchange between the alveoli and lungs will be impaired if there is a decrease in the surface area available for gas exchange, or if there is an increase in the diffusion distance between air and the blood. Emphysema is associated with both the loss of alveoli and connective tissue from the lungs. As a result, surface area available for diffusion of oxygen into the blood is low, and PO2 in blood will be low.

Diseases such as fibrosis can lead to a thickening of the alveoli, which will affect diffusion of gases into the blood, and PO2 will be low. Pulmonary edema, which results from left ventricular failure, will result in an expansion of fluid volume in the interstitial space of the lung and have the same effect (YOU SHOULD BE ABLE TO EXPLAIN WHY THIS OCCURS). Diseases such as asthma, in which alveolar ventilation decreases, will result in low PO2 in the alveoli, which translates to low PO2 in the blood.

If too little oxygen is in the blood, then the cells will be deprived. This condition is referred to as hypoxia. Often, hypoxia goes hand-in-hand with hypercapnia, or elevated concentrations of carbon dioxide.