Understanding the Human Machine - A Primer for Bioengineering - Max E. Valentinuzzi

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returns to the initial resting situation. During maximal normal inspiration, intrapleural pressure can be 6 to 7 mmHg below atmospheric.

The records of Figure 2.46 were obtained from an experimental dog. Intrapleural pressure (third channel) was recorded with a cannula inserted through the ribs into the pleural cavity and connected to a sensitive transducer. Its base line lies below the zero pressure level (which coincides with the atmospheric pressure). The dog has only one pleural space because it has no mediastinum, as man has. The decrease during inspiration is clearly associated with the increase in impedance (inspiration) shown by the fourth channel, recorded with two lateral electrodes and an impedance meter. Besides, there is also a good respiratory heart rate response manifested by the varying rate in the ECG and in the blood pressure channels, respectively. The anesthesia given to this animal favored

Figure 2.46. INTRAPLEURAL PRESSURE. These records were obtained from an experimental dog. Intrapleural pressure (third channel) was recorded with a cannula inserted through the ribs in the pleural cavity and connected to a sensitive transducer. Its base line lies below the zero pressure level (which coincides with the atmospheric pressure). Records obtained by the author in the Department of Physiolgy, Baylor College of Medicine, Houston, TX, 1970.

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such response: inspiration associated with higher RR.

If air gets into the pleural cavity, as the case is in chest stabbing or in some car accidents, it is called a pneumothorax (pneumo = air). Due to the intrinsic elastic properties of the lung walls, they recoil and collapse while the thoracic wall pulls in the opposite direction. The person is unable to breathe, it is painful and, obviously, it means an emergency. If it is a dog, since it has a single pleural cavity (no mediastinum dividing the thorax in two), artificial respiration must be instituted and the air accumulated in the cavity has to be removed using well-known and not too difficult techniques. In man, instead, with a mediastinum and two pleural cavities (left and right), the situation is somewhat easier because frequently only one side gets air in it (it depends on the accident), and the person, although painfully, can continue breathing with one lung. However, it is also an emergency that requires immediate attention.

Question: Artificial respiration can be instituted in two ways, with positive pressure and with negative pressure. How would you basically implement them? Hint: In the old days of poliomyelitis (before the vaccine was developed in the early 50’s), many patients (especially children) suffered respiratory paralysis. Sad but true, the negative pressure respirator used to become their enclosure. It was commonly termed the “lung machine”. The positive pressure type is easier to implement.

Practice to demonstrate the negative pressure effect: Select a short (15 to 20 cm) plastic or glass bottle, about 8 to 12 cm in diameter, with a wide neck (3 to 5 cm). Remove the bottom and replace it with a piece of soft rubber, as a diaphragm. You can hold it with an elastic band if the piece of rubber is bigger than the bottle diameter. Drill a hole in a cork to be inserted later on in the bottleneck. Pass through the hole a glass or plastic tube about 3 to 5 mm in diameter and fasten a little rubber balloon on one end (lower end) so that when you blow in the tubing the balloon is inflated. Deflated balloon and tube inserted in the cork are to be placed within the bottle, the cork closing its upper mouth and showing the tubing sticking out while the balloon is in the central region inside the bottle. Thus, you can see through the transparent bottle wall the deflated balloon. There should be no leaks. When the diaphragm is pulled down with the fingertips (say, thumb and index), the balloon should inflate. Why?

2.3.2.4. Compliance

The elastic properties of the lungs and thorax play a significant role in respiratory mechanics. The concept is similar to that already introduced in the cardiovascular system, i.e., a relationship between volume change and pressure change. Since one structure (thorax) embraces the other

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(lungs), they behave as a series coupling so that the resulting compliance is always smaller than the smaller of the two. In other words, the hardest bag to inflate will offer the limiting value no matter how soft or compliant the second one may be. Mathematically, such behavior is described by,

	1	=	1	+	1	(2.84)
	CTOT		CTH		CL

where CTOT, CTH, and CL stand, respectively, for the total resulting compliance (thorax and lungs), thoracic compliance and lung compliance. The lung compliance and the thoracic compliance are each in the order of 200 mL/cmH2O, leading to about 100 mL/cmH2O for the total or overall compliance.

Pulmonary compliance is relatively high (that means easier to inflate) because of a substance, called surfactant (a lipoprotein), covering the alveolar surface and secreted by specific small glands. If the amount of surfactant is low, the lungs become less compliant and difficult to inflate and the inspiratory muscular effort increases (respiratory distress syndrome). This is precisely the situation in cases of hyaline membrane, mostly found in premature newborn babies. Although reduced, the incidence and severity of complications of this syndrome continue to present significant morbidities.

An excess of oxygen may also lead to the condition, but it is reversible. An interesting fact is that saline solution further reduces pulmonary surface tension to nearly zero. John A. Clements (1957), a famous respiratory physiologist, demonstrated that surface tension in the lung fluid is high when the lungs are inflated and very low when they are deflated. It may be thought of as an intrinsic passive protective mechanism.

2.3.2.5. Work of respiration

The pulmonary system is essentially an expansible chamber holding at any instant of the respiratory cycle a given variable volume under a definite variable pressure, thus, as in the cardiac chambers, a pressurevolume curve can be obtained experimentally by recording simultaneously, as an x-y plot, pulmonary volume and intrapulmonary pressure (both with suitable detectors, respectively). In such case, the data will refer to the combined double bag system as outlined in the inset of Figure

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	THORAX
	LUNGS
V	PLEURAL SPACE
D	B

C

E

A

O

P

Figure 2.47. RESPIRATORY PRESSURE-VOLUME DIAGRAM. Experimentally, it can be obtained by recording simultaneously as an x-y plot pulmonary volume and intrapulmonary pressure. In such case, the data will refer to the combined double bag system as outlined in the inset. If intrapleural pressure is used instead, then the data will yield information regarding the lungs alone. The two types of data collection must be used when one wants to get pulmonary compliance and overall compliance (see text).

2.47. If intrapleural pressure is used instead, then the data will yield information regarding the lungs alone. The two types of data collection must be used when one wants to get pulmonary compliance and overall compliance. Chest compliance is, thereafter, calculated from eq. (2.84).

In the diagram there are several areas with different physiological meanings: The area contained within the boundaries marked by OABDO represents the work during inspiration. A smaller area within the former is OEBDO, which considers the work performed to stretch the lungs. The area below the straight line E and limited by the curve A, that is, OABEO, is work to overcome airway and tissue resistances. The area on the upper left side, BCODB, is work returned mostly passively during expiration. Finally, the area encompassed by the respiratory loop, or OABCO, represents the work expended during the respiratory cycle.

Exercise: Work out the units of the pressure-volume diagram of Figure 2.47, where volume is usually given in mL of air and pressure is in cmH2O. Their product must produce units of work. If the cycle length is considered, then the power consumed in one breath can be cal-

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culated. A normal value should be between 0.3 and 0.8 kgm/min. Search in the literature for the appropriate numerical values.

The work of respiration is negligible in the normal animal or person, however, in conditions like asthma, emphysema or congestive heart failure, say, in respiratory distress generally speaking, it may reach significant clinical levels that call for assist procedures.

2.3.3. Pulmonary Circulation

In many respects, this minor or lesser circulation is similar to the systemic or major or greater circulation, however, there are some important differences: it is a distensible low pressure and low vascular resistance system. Systolic pressure is about 25 mmHg and diastolic just about 10 or 12 mmHg with a mean of 15-16 mmHg. Inserting a special catheter carrying a very small pressure transducer through the subclavian vein, the pressure records shown in Figure 2.48 can be recorded as the catheter tip crosses the right atrium, right ventricle, pulmonary artery and, beyond the latter and as far as it can go, the so called pulmonary artery wedge pressure. The pulmonary pressure gradient is given by the difference

Figure 2.48. PULMONARY WEDGE PRESSURE. A special catheter was inserted via one of the subclavian veins. It held at its tip a very small pressure transducer. As the catheter was pushed in, it traversed the right atrium, right ventricle, pulmonary artery and, beyond the latter and as far as it could go, acting as a wedge in that artery. Thus, the respective blood pressure records correspond to the right atrium (low pressure of about 4–5 mmHg), right ventricle (26/1 mmHg), pulmonary artery pressure (25/10 mmHg), and wedge pressure (about 13/8 mmHg). Taken from www.mtsinai.org/pulmonary/books/physiology/chap8_2.htm. Proper recognition is acknowledged to the authors at Mount Sinai Hospital who generously make this material freely available without even giving their names. Students are invited to visit the site.

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between the mean pulmonary arterial pressure (15 or 16 mmHg) and the venous pressure (about 7 mmHg) looking towards the left heart, i.e., about 8 to 9 mmHg. This gradient is responsible for the indispensable capillary blood flow through the lungs. It takes approximately 750 ms for a red cell to fully traverse the capillary network.

Its principal function is taking venous blood returning from all the peripheral system to the alveolar capillaries (pulmonary perfusion) to permit the gaseous exchange. As a consequence, a salient physiological parameter is represented by the alveolar ventilation-perfusion ratio, or

Q´A	= ratio ≈ 0.8	(2.85)
Ft

where the numerator stands for the alveolar ventilation (about 4.5 L of air/min) and the denominator represents cardiac output or total blood flow (about 5.5 L of blood/min). Thus, a typical numerical normal ratio is as indicated above. In other words, for each liter of blood getting through the lungs, only 0.8 liters of air actually interact with the former. Non the less, do not be fooled by an apparent normal ratio. Let us imagine a hypothetical situation in which one lung gets normal blood flow and no air at all (obstruction of the bronchus) while the other is well ventilated but there is full obstruction of its blood inflow. The ratio (2.85) would give a normal value but the subject will doubtless die.

Pulmonary vessels contain almost one liter of blood and, out of that amount, more than one half is held within the venous side. This blood volume is about 1/5 to 1/4 of the total blood volume in a normal adult, in fact much more than the lung blood requirement for only about 100 mL can be captured within the capillaries at any instant. This is why the lungs behave as a dynamic blood reservoir from which the left heart takes blood when, for a few beats, the right heart ejects less than the normal stroke volume.

Body position affects significantly the pulmonary blood content. Lying down increases it by as much as 300 or even 400 mL more than normal, while standing up brings that amount back to the general circulation. Under conditions of cardiac failure, the individual may be led to orthopnea, that is, the patient can breath normally only when in the vertical position

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(orthos = vertical) because, when in bed, his/her lungs are congested making more difficult the respiratory act.

The discovery of the pulmonary circulation is an interesting and debated subject. It is commonly believed that the discovery of the pulmonary circulation had its inception in Europe, in the sixteenth century, by Servetus, Vesalius, Colombo, and Harvey. However, in view of the discovery of ancient manuscripts, the real credit for the discovery of the pulmonary circulation seems to belong to an eminent physician of the thirteenth century: Ibn Nafis. Ibn Nafis, or Abu-Alhassan Alauldin Ali Bin Abi-Hazem Al-Quarashi, was born about 1210 in Damascus. On December 17, 1288 he died at the age of 78 after an unknown illness. Downloaded from INTERNET, after The Discovery of the Pulmonary Circulation Revisited

(1994), by Ayman O. Soubani and Faroque A. Khan, from New England Medical Center, Tufts University School of Medicine (Dr. Soubani), Boston, and the Department of Medicine (Dr. Khan), Nassau County Medical Center, SUNY at Stony Brook, East Meadow, New York. Address reprint requests and correspondence to Dr. Soubani, 208 Gerry Road, Brookline, MA 02146.

2.3.4. Gas Exchange

We reach now the core function of the system, the gas exchange process, during which the diffusion capacity, D, plays a fundamental role. It is defined, either for oxygen or for carbon dioxide, as the amount of gas G (in mL) crossing from the alveolar space to the capillary blood compartment, or viceversa, per unit of area A (in square cm), per unit time t (in min or s) and per unit of differential partial pressure ∆P (in mmHg), that is,

	D =	G	(2.86)
		At ∆P

For all the alveolar exchange surface area, in the order of 70 m2, the total oxygen diffusion capacity is 20 mL/min×mmHg. Under exercise, it increases up to 65 or even more. For carbon dioxide, instead, the diffusion capacity is much larger and extremely difficult to measure.

In other words and from the latter equation, the flow of gas per unit time is proportional to the partial pressure difference. This is usually referred to as Fick’s Law and describes an entirely passive process. Under normal resting conditions, blood is in contact with the alveoli for about 0.75s and O2 reaches equilibrium between capillary blood and alveolar air in about 0.25 s. If the O2 pressure gradient decreases or the diffusion resistance increases, the movement of O2 from alveoli to blood will slow. From

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Table 2.1. Common numerical blood values
Parameter	Arterial Blood	Venous Blood
P02 (mmHg)	95	45
O2 (mL/100 mLblood = V%)	19.5	15
PCO2 (mmHg)	40	46
CO2 (V%)	47	52
Hb (% saturation)	97	75

Fick’s law: decreasing the pressure gradient (hypoxia) will reduce the rate of oxygen transfer into blood, and increasing resistance (low diffusing capacity) will decrease the rate of oxygen uptake by the blood.

Oxygen and carbon dioxide dissolve in blood, however, hemoglobin increases by about 70 fold the transport capacity of the former and the different processes involved in the latter produce a 17 times increment in its transport capacity. Each gram of saturated hemoglobin can carry 1.3 mL of oxygen and 100 mL of blood contain about 15 g of hemoglobin. Table 2.1 below summarizes some common numerical blood values. Note for the first and third rows: Partial pressure of a gas in a liquid is that pressure in the gaseous phase which, in equilibrium with a liquid, would produce the concentration of gas molecules found in the liquid. Note for the second and fourth rows: Frequently, the number of mL of a substance found in 100 mL of blood is called volume percent (V%).

Let us explain the concept of “saturated hemoglobin” by comparing the molecule of this substance to a bus that is to transport passengers. The bus has, say, 40 seats, and if all seats are occupied, it is said to be full or, in our terms, “100% saturated with passengers”. However, at times, the bus could carry only 10 or 20 passengers, in which case it would only be saturated to 25% or to 50% or simply not fully saturated. The hemoglobin molecule, in a complex biochemical dynamics, can bind to more or less oxygen and, as already stated, at maximum capacity it is said to be saturated (see Table 2.1). In fact, it never reaches full saturation although it gets pretty close (97%).

Any perturbation that affects the passage of gases affects also the individual’s life. The abovementioned parameters indicate the normal expected values that are used as reference in daily practice. Factors such as air pollution, anesthetic agents and general metabolic conditions of the

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subject tend to deeply influence them. Thus, detectors to implement monitoring systems are of the utmost importance.

Study subject: Search in the literature or in INTERNET for information about the oxygenhemoglobin dissociation curve (which relates percent of O2 in hemoglobin with partial pressure of O2 in blood) and factors that influence the curve (such as temperature and blood pH).

2.3.5. Respiratory Control

It is a major subject not fully explained yet and, thus, opened to research. Figure 2.49 is a schematic of the neural control of the respiratory act. The circuit formed by the pneumotaxic center (located in the pons, a structure within the brain stem) and the inspiratory center (at the level of the me-

From higher centers

PONS

E

I

Inspiratory

Muscles

Expiratory muscles

Figure 2.49. NEURAL CONTROL OF THE RESPIRATORY ACT. The circuit formed by the pneumotaxic center (located in the pons) and the inspiratory center (at the level of the medulla) constitutes an oscillator that determines the respiratory frequency. Neurons in white are excitatory and in black are inhibitory.

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dulla) constitutes an oscillator that determines the respiratory frequency. The inspiratory center tends to permanently send activating signals to inspiratory muscles. Signals from the pons activate facilitatory neurons (in white) and, thereafter, inhibitory neurons (in black) to stop the inspiratory signal from I. The latter center sends signals to the motor neurons of the inspiratory muscles (such as the diaphragm and the external muscles) while inhibit the action of the expiratory agonist ones. The expiratory center E, only stimulated by voluntary action, distributes its signals (action potentials) to the expiratory muscles motor neurons inhibiting simultaneously the inspiratory agonist ones. In the lungs L, there are stretch receptors which, according to it stretching state and via afferent vagal fibers, send action potentials to the inspiratory center I. The tighter they become due to inflation, the larger the number of action potentials so that they signal the inflation level to the inspiratory center which, in turn, reduces its activity in order to decrease and even stop the inspiratory muscular action. This is called the Hering–Breuer reflex that can be thought of as a protective negative feedback mechanism.

Besides, there are central and peripheral chemoreceptors to detect oxygen, carbon dioxide and acidity levels in the blood stream from which information is sent back to the central nervous system where, after processing (called integration in the physiology jargon), a quick decision is reached to compensate for the initial deviation by changing rate and depth of respiration. For example, a carbon dioxide increase in blood is a powerful drive to triggering a deeper and more rapid respiration so that this gas is washed out faster. However, other controlling sensors are distributed in different regions of the respiratory system. Everybody is familiar with the effect of tickling inside the nose with a very fine brush (leads to sneezing) or of getting a small crumb of bread in the throat (leads to coughing or, if the stimulus is strong and deep enough, even to vomiting). Obviously, these are some kind of mechanical sensors. In this respect, all the respiratory system is extremely sensitive. Small foreign particles in the bronchi or in the bronchioles can cause major noxious effects. Temperature and emotions are also strong stimuli to respiration.

Josef Breuer (1842–1925), Austrian physiologist and pioneer of psychoanalysis. After successfully treating hysteria in one of his patients, Breuer collaborated with Sigmund Freud in writing Studies in Hysteria, in 1895. Earlier, working with Ewald Hering (1834–1918), Breuer