книги студ / color atlas of physiology 5th ed[1]. (a. despopoulos et al, thieme 2003)

Surface Tension, Surfactant

Surface tension is the main factor that determines the compliance of the lung-chest system (!p. 116) and develops at gas-liquid interfaces or, in the case of the lungs, on the gas exchange surface of the alveoli (ca. 100 m2).

The effectiveness of these forces can be demonstrated by filling an isolated and completely collapsed lung with (a) air or (b) liquid. In example (a), the lung exerts a much higher resistance, especially at the beginning of the filling phase. This represents the opening pressure, which raises the alveolar pressure (PA) to about 2 kPa or 15 mmHg when the total lung capacity is reached (!p. 113 A). In example (b), the resistance and therefore PA is only one-fourth as large. Accordingly, the larger pressure requirement in example (a) is required to overcome surface tension.

If a gas bubble with radius r is surrounded by liquid, the surface tension γ (N ! m– 1) of the liquid raises the pressure inside the bubble relative to the outside pressure (transmural pressure P !0). According to Laplace’s law

Since γ normally remains constant for the respective liquid (e.g., plasma: 10– 3 N ! m– 1), P becomes larger and larger as r decreases.

Soap bubble model. If a flat soap bubble is positioned on the opening of a cylinder, r will be relatively large (!A1) and P small. (Since two air-liquid interfaces have to be considered in this case, Eq. 5.3 yields P = 4γ/r). For the bubble volume to expand, r must initially decrease and P must increase (!A2). Hence, a relatively high “opening pressure” is required. As the bubble further expands, r increases again (!A3) and the pressure requirement/volume expansion ratio decreases. The alveoli work in a similar fashion. This model demonstrates that, in the case of two alveoli connected with each other (!A4), the smaller one ( P2 high) would normally become even smaller while the larger one ( P1 low) becomes larger due to pressure equalization.

Surfactant (surface-active agent) lining the inner alveolar surface prevents this problem by lowering γ in smaller alveoli more potently than in larger alveoli. Surfactant is a mixture of

proteins and phospholipids (chiefly dipalmitoyl lecithin) secreted by alveolar type II cells.

Respiratory distress syndrome of the newborn, a serious pulmonary gas exchange disorder, is caused by failure of the immature lung to produce sufficient quantities of surfactant. Lung damage related to O2 toxicity (!p. 136) is also partly due to oxidative destruction of surfactant, leading to reduced compliance. This can ultimately result in alveolar collapse (atelectasis) and pulmonary edema.

Dynamic Lung Function Tests

The maximum breathing capacity (MBC) is the greatest volume of gas that can be breathed (for 10 s) by voluntarily increasing the tidal volume and respiratory rate (!B). The MBC normally ranges from 120 to 170 L/min. This capacity can be useful for monitoring diseases affecting the respiratory muscles, e.g., myasthenia gravis.

The forced expiratory volume (FEV or Tiffeneau test) is the maximum volume of gas that can be expelled from the lungs. In clinical medicine, FEV in the first second (FEV1) is routinely measured. When its absolute value is related to the forced vital capacity (FVC), the relative FEV1 (normally !0.7) is obtained. (FVC is the maximum volume of gas that can be expelled from the lungs as quickly and as forcefully as possible from a position of full inspiration; !C). It is often slightly lower than the vital capacity VC (!p. 112). Maximum expiratory flow, which is measured using a pneumotachygraph during FVC measurement, is around 10 L/s.

Dynamic lung function tests are useful for distinguishing restrictive lung disease (RLD) from obstructive lung disease (OLD). RLD is characterized by a functional reduction of lung volume, as in pulmonary edema, pneumonia and impaired lung inflation due to spinal curvature, whereas OLD is characterized by physical narrowing of the airways, as in asthma, bronchitis, emphysema, and vocal cord paralysis (!C2).

As with VC (!p. 112), empirical formulas are also used to standardize FVC for age, height and sex.

Pulmonary Gas Exchange

Alveolar ventilation. Only the alveolar part (VA) of the tidal volume (VT) reaches the alveoli. The rest goes to dead space (VD). It follows that VA = VT – VD (L) (!p. 114). Multiplying these volumes by the respiratory rate (f in min. –.1) results. in the respective. ventilation,. . . i.e.,

VA, VE (or VT), and VD. Thus, VA = VE–VD (L ! min. – 1). Since VD is anatomically determined,

VD (= VD.! f) rises with f. If, at a given total ventilation (VE = VT ! f), the breathing becomes. more frequent (f ") yet more. shallow (VT #), VA will decrease because VD increases.

.

Example: At a VE of 8 L ! min– 1, a VD.of 0.15 L and a normal respiratory. rate f of 16 min-1 VA = 5.6 L ! min– 1 or 70%. of VE. When f is doubled and VT drops to onehalf,. VA drops to 3.2 L ! min– 1 or 40% of VT, although VE (8 L ! min– 1) remains unchanged.

Alveolar gas exchange can therefore decrease due to flat breathing and panting (e.g., due to a painful rib fracture) or artificial enlargement

during. strenuous. physical work (!p. 74). The VCO2 to VO2 ratio is called the respiratory quotient (RQ), which depends on a person’s nutritional state. RQ ranges from 0.7 to 1.0 (!p. 228).

The exchange of gases between the alveoli and the blood occurs by diffusion, as described by Fick’s law of diffusion (!Eq. 1.7, p. 22,). The driving “force” for this diffusion is provided by the partial pressure differences between alveolar space and erythrocytes in pulmonary capillary blood (!A). The mean alveolar partial pressure of O2 (PAO2) is about 13.3 kPa

(100 mmHg) and that of CO2 (PACO2) is about 5.3 kPa (40 mmHg). The mean partial pres-

sures in the “venous” blood of the pulmonary artery are approx. 5.3 kPa (40 mmHg) for O2 (PVO2) and approx. 6.1 kPa (46 mmHg) for CO2 (PVCO2). Hence, the mean partial pressure difference between alveolus and capillary is

about 8 kPa (60 mmHg) for O2 and about 0.8 kPa (6 mmHg) for CO2, although regional variation occurs (!p. 122). PAO2 will rise when PACO2 falls (e.g., due to hyperventilation) and vice versa (!alveolar gas equation, p. 136).

O2 diffuses about 1–2 µm from alveolus to bloodstream (diffusion distance). Under normal resting conditions, the blood in the pulmonary capillary is in contact with the alveolus for about 0.75 s. This contact time (!A) is long enough for the blood to equilibrate with the partial pressure of alveolar gases. The capillary blood is then arterialized. PO2 and PCO2 in arterialized blood (PaO2 and PaCO2) are about the same as the corresponding mean alveolar pressures (PAO2 and PACO2). However, venous blood enters the arterialized blood through arteriovenous shunts in the lung and from bronchial and thebesian veins (!B). This extra-alveolar shunt as well as ventilation–per- fusion inequality (!p. 122) make the PaO2 decrease from 13.3 kPa (after alveolar passage) to about 12.0 kPa (90 mmHg) in the aorta (PaCO2 increases slightly; !A and p. 107).

The small pressure difference of about 0.8 kPa is large enough for alveolar CO2 exchange, since Krogh’s diffusion coefficient K for CO2 (KCO2 !2.5 ! 10–16 m2 ! s– 1 ! Pa– 1 in tissue) is 23 times larger than that for O2 (!p. 22). Thus, CO2 diffuses much more rapidly than O2. During physical work (high cardiac output), the contact time falls to a third of the resting value. If diffusion is impaired (see below), alveolar equilibration of O2 partial pressure is less likely to occur during physical exercise than at rest.

Impairment of alveolar gas exchange can occur for several reasons: (a) when the blood flow rate along the alveolar capillaries decreases (e.g., due to pulmonary infarction;

!B2), (b) if a diffusion barrier exists (e.g., due to a thickened alveolar wall, as in pulmonary edema; !B3), and (c) if alveolar ventilation is reduced (e.g., due to bronchial obstruction;

!B4 ). Cases B2 and B3 lead to an increase in functional dead space (!p. 114); cases B3 and

B4 lead to inadequate arterialization of the blood (alveolar shunt, i.e. non-arterialized blood mixing towards arterial blood). Gradual impairments of type B2 and B4 can occur even in healthy individuals (!p. 122).

CO2 Binding in Blood, CO2 in CSF

The total carbon dioxide concentration (= chemically bound “CO2” + dissolved CO2) of mixed venous blood is about 24–25 mmol/L; that of arterial blood is roughly 22–23 mmol/L. Nearly 90% of this is present as HCO3– (!A, right panel, and table on p. 124). The partial pressure of CO2 (PCO2) is the chief factor that determines the CO2 content of blood. The CO2 dissociation curve illustrates how the total CO2 concentration depends on PCO2 (!A).

The concentration of dissolved CO2, [CO2], in plasma is directly proportional to the PCO2 in plasma and can be calculated as follows:

where αCO2 is the (Bunsen) solubility coefficient for CO2. At 37 !C,

αCO2 = 0.225 mmol ! L–1 ! kPa–1,

After converting the amount of CO2 into volume CO2 (mL = mmol ! 22.26), this yields

αCO2 = 5 mL ! L–1 ! kPa–1.

The curve for dissolved CO2 is therefore linear (!A, green line).

Since the buffering and carbamate formation capacities of hemoglobin are limited, the relation between bound “CO2” and PCO2 is curvilinear. The dissociation curve for total CO2 is calculated from the sum of dissolved and bound CO2 (!A, red and violet lines).

CO2 binding with hemoglobin depends on the degree of oxygen saturation (SO2) of hemoglobin. Blood completely saturated with O2 is not able to bind as much CO2 as O2-free blood at equal PCO2 levels (!A, red and violet lines). When venous blood in the lungs is loaded with O2, the buffer capacity of hemoglobin and, consequently, the levels of chemical CO2 binding decrease due to the Haldane effect (!p. 124). Venous blood is never completely void of O2, but is always O2-satu- rated to a certain degree, depending on the degree of O2 extraction (!p. 130) of the organ in question. The SO2 of mixed venous blood is about 0.75. The CO2 dissociation curve for SO2 = 0.75 therefore lies between those for SO2 = 0.00 and 1.00 (!A, dotted line). In arterial blood,

PCO2 !5.33 kPa and SO2 !0.97 (!A, point a). In mixed venous blood, PCO2 !6.27 kPa and SO2

!0.75 (!A, point V). The normal range of CO2

dissociation is determined by connecting these two points by a line called “physiologic CO2 dissociation curve.”

The concentration ratio of HCO3– to dissolved CO2 in plasma and red blood cells differs (about 20 : 1 and 12 : 1, respectively). This reflects the difference in the pH of plasma (7.4) and erythrocytes (ca. 7.2) (!p. 138ff.).

CO2 in Cerebrospinal Fluid

Unlike HCO3– and H+, CO2 can cross the bloodcerebrospinal fluid (CSF) barrier with relative

ease (!B1 and p. 310). The PCO2 in CSF therefore adapts quickly to acute changes in the PCO2

in blood. CO2-related (respiratory) pH changes in the body can be buffered by non-bicarbonate buffers (NBBs) only (!p. 144). Since the concentration of non-bicarbonate buffers in CSF is very low, an acute rise in PCO2 (respiratory acidosis; !p. 144) leads to a relatively sharp decrease in the pH of CSF (!B1, pH""). This decrease is registered by central chemosensors (or chemoreceptors) that adjust respiratory activity accordingly (!p. 132). (In this book, sensory receptors are called sensors in order to distinguish them from hormone and transmitter receptors.)

The concentration of non-bicarbonate buffers in blood (hemoglobin, plasma proteins) is high. When the CO2 concentration increases, the liberated H+ ions are therefore effectively buffered in the blood. The actual HCO3– concentration in blood then rises relatively slowly, to ultimately become higher than in the CSF. As a result, HCO3– diffuses (relatively slowly) into the CSF (!B2), resulting in a renewed increase in the pH of the CSF because the HCO3–/CO2 ratio increases (!p. 140). This, in turn, leads to a reduction in respiratory activity (via central chemosensors), a process enhanced by renal compensation, i.e., a pH increase through HCO3– retention (!p. 144). By this mechanism, the body ultimately adapts to chronic elevation in PCO2— i.e., a chronically elevated PCO2 will no longer represent a respiratory drive (cf. p. 132).