Medical Physiology, 3rd Edition

The Environment

Voluntary feedback control mechanisms can modulate the many layers of our external environment

Claude Bernard introduced the concept of the milieu intérieur (basically the extracellular fluid in which cells of the organism live; see pp. 3–4) and the notion that fixité du milieu intérieur (the constancy of this extracellular fluid) is the condition of “free, independent life.” Most of this book focuses mainly on the interaction between cells and their extracellular fluid. In this chapter, we consider how the milieu extérieur, which physically surrounds the whole organism, affects our body functions and how we, in turn, modify our surroundings when it is necessary to improve our comfort or to extend the range of habitable environments.

The milieu extérieur, in fact, has several layers: the skin surface, the air that surrounds the skin, clothing that may surround that air, additional air that may surround the clothing, a structure (e.g., a house) that may surround that air, and finally a natural environment that surrounds that structure. As we interact with our multilayered environment, sensors monitor multiple aspects of the milieu extérieur and involuntary physiological feedback control mechanisms—operating at a subconscious level—make appropriate adjustments to systems that control a panoply of parameters, including blood pressure (see pp. 533–545), ventilation (see pp. 675–683), effective circulating volume (see pp. 554–555), gastric secretions (see pp. 865–872), blood glucose levels (see p. 1038), and temperature (see p. 1193).

The sensory input can also rise to a conscious level and, if perceived as discomfort, can motivate us to take voluntary actions that make the surroundings more comfortable. For example, if we sense that we are uncomfortably hot, we may move out of the sun or, if indoors, turn on the air conditioning. If we then sense that we are too cool, we may move into the sun or turn off the air conditioning. Such conscious actions are part of the effector limb in a complex negative-feedback system that includes sensors, afferent pathways, integration and conscious decision making in the brain, efferent pathways to our muscles, and perhaps inanimate objects such as air conditioners.

For a voluntary feedback system to operate properly, the person must be aware of a signal from the surroundings and must be able to determine the error by which this signal deviates from a desirable set-point condition. Moreover, the person must respond to this error signal by taking actions that reduce the error signal and thereby restore the milieu intérieur to within a normal range. Humans respond to discomfort with a wide variety of activities that may involve any layer of the environment. Thus, we may adjust our clothing, build housing, and eventually even make equipment that allows us to explore the ocean depths, mountain heights, and outer space.

Physiological control mechanisms—involuntary or voluntary—do not always work well. Physicians are acutely aware that factors such as medication, disease, or the extremes of age can interfere with involuntary feedback systems. These same factors can also interfere with voluntary feedback systems. For example, turning on the air conditioning is a difficult or even impossible task for an unconscious person, a bedridden patient, or a perfectly healthy baby. In these situations, a caregiver substitutes for the voluntary physiological control mechanisms. However, to perform this role effectively, the caregiver must understand how the environment would normally affect the care recipient and must anticipate how the involuntary and voluntary physiological control mechanisms would respond. imageN61-1


Role of a Caregiver

Contributed by Arthur DuBois

In the text, we pointed out that a person's involuntary or voluntary physiological control mechanisms sometimes may not function properly. Under these conditions, a caregiver must take control. In a systematic approach, the caregiver would (1) assess the environmental stresses to which the care recipient may be subjected, including their range of intensity; (2) predict the body's ideal involuntary and voluntary reactions to the stresses; (3) consider how the limitations of the care recipient interfere with the natural reactions; (4) determine how to supplement or replace control mechanisms that are not functioning adequately; and (5) express the essential empathy between the caregiver and the patient (i.e., the important words, “I care”).

Environmental temperature provides conscious clues for triggering voluntary feedback mechanisms

Involuntary control mechanisms (see pp. 1198–1201) can only go so far in stabilizing body core temperature in the face of extreme environmental temperatures. Thus, voluntary control mechanisms can become extremely important.

The usual range of body core temperature is 36°C to 38°C (see Table 59-1). At an environmental temperature of 26°C to 27°C and a relative humidity of 50%, a naked person is in a neutral thermal environment (see p. 1196)—feeling comfortable and being within the zone of vasomotor regulation of body temperature. At 28°C to 29°C, the person feels warm, and ~25% of the skin surface becomes wetted with perspiration. At 30°C to 32°C, the person becomes slightly uncomfortable. At 35°C to 37°C, the person becomes hot and uncomfortable, ~50% of the skin area is wet, and heat stroke (see Box 59-1) may become a hazard. The environmental temperature range of 39°C to 43°C is very hot and uncomfortable, and the body may fail to regulate core temperature. At 46°C, the heat is unbearable and heat stroke is imminent—the body heats rapidly, and the loss of extracellular fluid to sweat (see pp. 1215–1219) may lead to circulatory collapse and death (see p. 1215).

At the other extreme, we regard environmental temperatures of 24°C to 25°C as cool, and 21°C to 22°C as slightly uncomfortable. imageN61-2 At temperatures of 19°C to 20°C, we feel cold, vasoconstriction occurs in the hands and feet, and muscles may be painful. imageN61-3


Temperature Sensations and Computer Models

Contributed by Arthur DuBois

Thermal sensations reported by sedentary people wearing a summer shirt and trousers correspond closely to those predicted by computer models that simulate the changes in circulation between the core and surface of the body at either warm or cool environmental temperatures. Skin and clothing temperatures can be measured at a distance using an inexpensive infrared detector available at auto supply stores and used for measuring engine temperatures.


Physical Work and the Conscious Control of Body Core Temperature

Contributed by Arthur DuBois

Performance of physically demanding labor in the heat or cold requires assessment of environmental temperature, wind speed, humidity, the clothing worn, and whether the work is light (standing at a bench), moderate (walking with a 3-kg load), or heavy (e.g., working with a pick and shovel). From these considerations one may predict the permissible duty cycle—for instance, 75% work and 25% recovery, where recovery is a rest period with warming up from a cold environment or cooling off from a hot environment. For a period of up to 3 weeks, acclimatization to heat improves tolerance for working in a hot environment.

Room ventilation should maintain imageimage, and levels of toxic substances within acceptable limits

Ventilation of a room (image) must be sufficient to supply enough O2 and to remove enough CO2 to keep the partial pressures of these gases within acceptable limits. In addition, it may be necessary to increase image even more to lower relative humidity and to reduce odors. Dry air in the natural environment at sea level (see Table 26-1) has a image of ~159 mm Hg (20.95%) and a image of ~0.2 mm Hg (0.03%).

Acceptable Limits for image and image

In the United States, the Occupational Safety and Health Administration (OSHA) has adopted an acceptable lower limit for O2 of 19.5% of dry air at sea level (i.e., 148 mm Hg).

According to OSHA, the acceptable upper limit for image in working environments at sea level is 3.8 mm Hg, or 0.5% of dry air. This image would increase total ventilation (image) by ~7% (see p. 716), a hardly noticeable rise. Exposures to 3% CO2 in the ambient air—which initially would cause more substantial respiratory acidosis (see p. 633)—could be tolerated for at least 15 minutes, by the end of which time image would be nearly double. With longer exposures to 3% CO2, the metabolic compensation to respiratory acidosis (see p. 641) would have already begun to increase plasma [image] noticeably. imageN61-4


Effect of Disease on the Acute Response to Hypercapnia

Contributed by Arthur DuBois

How do subjects respond to increasing levels of CO2 in the surrounding air? An example follows. A normal person who breathed 3% CO2 for 5 or 6 minutes had a total ventilation (image or minute volume of ventilation) of 8 L/min; then after a rest, the person breathed 5% CO2, which produced a image of 27 L/min, and after another rest breathed 7.5% CO2, which produced a image of 48 L/min.

We then repeated the experiment with a person with chronic obstructive pulmonary disease (COPD). For the same three CO2 levels, this COPD patient had image values of 12, 19, and 27 L/min instead of 8, 27, and 48 L/min. The reason why—at 3% CO2—the COPD patient had a higher image (12 L/min) than the normal person (8 L/min) was that the COPD patient had a pathologically broad distribution of image ratios and thus arterial hypoxemia. But the incremental values in response to 5% and 7.5% CO2 were clearly depressed in the COPD patient, compared to the control, owing to a combination of mechanical obstruction and diminished responsiveness to CO2 (due to metabolic compensation for respiratory acidosis).

Finally, we repeated the experiment with a person having a depressed respiratory center. For the same three CO2 levels, this patient had image values of 11, 11, and 12 L/min. In other words, this patient exhibited virtually no increase in image in response to inhaling CO2.

In some cases, particularly if the person is anesthetized, it becomes necessary to take over the mechanical work of breathing by using a ventilation pump that is set to provide sufficient ventilation in liters per minute to keep the arterial CO2 level at ~40 mm Hg (equal to an end-tidal alveolar CO2 level of ~5.6% of dry gas in healthy lungs). A spring-loaded safety valve is used to prevent the pump from delivering too much pressure, which could burst the lungs, and an alarm system alerts an attendant in case the pump fails to deliver the necessary amount of ventilation.

Measuring Room Ventilation

Two approaches are available for determining image. The first is a steady-state method that requires knowing (1) the rate of CO2 production (image) by the occupants of the room and (2) the fraction of the room air that is CO2. The equation is analogous to the one we introduced for determining alveolar ventilation, beginning with Equation 31-9:



We could use a similar equation based on the O2 mole fraction and the rate of O2 extraction (image) by the occupants. imageN61-5


Steady-State Method for Computing Room Ventilation

Contributed by Arthur DuBois

Suppose the occupant of a room has a resting metabolic rate that produces 200 mL/min (standard temperature and pressure/dry [STPD]) of CO2 and removes 250 mL/min (STPD) of O2. STPD means mL at 760 mm Hg (or torr), 0°C, dry gas. However, if the ambient temperature is 24°C and the relative humidity is 50%, then the resting metabolic rate would have to increase by ~10%, so that the image would be ~220 mL/min (0.220 L/min) and the image would be ~275 mL/min (0.275 L/min).

In addition, suppose that air (ambient temperature 24°C and relative humidity 50%) enters and leaves this room at a rate of 100 L/min—the room ventilation (image). Fresh air has almost zero CO2 and 20.9% O2. The pulmonary ventilation of the occupant would raise the CO2 of the air inside and leaving the room by (0.220 L/min)/(100 L/min) = 0.22%, and would lower the O2 by (0.275 L/min)/(100 L/min) = 0.275%. Thus, the inspired O2 would be reduced from 20.9% to (20.9% − 0.27%) = 20.63%, and this concentration of O2 (and also the correspondingly elevated concentration of CO2) would be easily tolerated by the occupant. Suppose, however, that the person were exercising, with 10 times the metabolic rate, or that 10 people were in the room in a resting condition. The CO2 level would increase to 10 persons × 0.22%/person = 2.2%, and the O2 would fall to 20.9% − (10 persons × 0.275%/person) = 20.9 − 2.75 = 18.15%. Given a minimal standard for O2 of 19.5%, we would clearly need to increase room ventilation.

In the exponential decay method, the second approach for determining image, the washout of a gas from the room is monitored. The approach is to add a test gas (e.g., CO2) to the room and then measure the concentrations of the gas at time zero (Cinitial) and—as image washes out the gas over some time interval (Δt)—at some later time (Cfinal). The equation for exponential decay is as follows: imageN61-6




Exponential-Decay Method for Determining Room Ventilation

Contributed by Arthur DuBois

The Principle

The equation that describes the washout of a volume (V) by a flow (image) is:


(NE 61-1)

Here τ is the time constant. For example, imagine that we have stirred a 1-L beaker filled with water containing some dye. If we flow clear water into this beaker at a rate of 1 L/min and simultaneously remove 1 L/min of the newly mixed solution, the dye concentration will decrease exponentially with a time constant of (image) = (1 L)/(1 L/min) = 1 min. One minute after the start of the flow (i.e., after 1 time constant), the dye concentration will have fallen to 1/e of its initial value. We could compute the time constant by comparing dye concentrations obtained at any two convenient times. For example, if Cinitial is the initial dye concentration and Cfinal is the dye concentration after some time Δt, then


(NE 61-2)

Substituting Equation NE 61-2 into Equation NE 61-1, we have


(NE 61-3)

The above is analogous to Equation 61-2 in the text.

The Implications

In Equation 61-3, we saw that the ventilation of the hypothetical room (image) is 1871 L/min. This amount of ventilation would be adequate for a person exercising at 10 met (i.e., a metabolic rate that is 10-fold higher than resting metabolism) because the CO2 production of 2.20 L/min imageN61-5 would be diluted by 1871 L/min of ventilation to raise the room CO2 concentration to 0.12%. Similarly, the O2 uptake of 2.75 L/min imageN61-5—diluted by 1871 L/min—would lower the incoming level from 20.9% to (20.9% − 0.15%) = 20.75%. Both the computed CO2 level and the computed O2 level are easily tolerated. Note that the room ventilation of 1871 L/min in this example is 18 times as much as the room ventilation in the example in imageN61-5, where the occupant had to work with a room ventilation of only 100 L/min.

For example, imagine that we wish to measure the ventilation of a room that is 3 × 3 × 3 m—a volume of 27 m3 or 27,000 L. Into this room, we place a tank of 100% CO2 and a fan to mix the air. We then open the valve on the tank until an infrared CO2 meter reads 3% CO2 (Cinitial = 3%), at which point we shut off the valve on the tank. Ten minutes later (Δt = 10 minutes), the meter reads 1.5% (Cfinal = 1.5%). Substituting these measured values into Equation 61-2 yields imageN61-6



This approach requires that the incoming air contain virtually no CO2 and that the room contain no CO2 sources (e.g., people). Diffusion, thermal convection, and turbulence produce proper mixing of the gases.

Carbon Monoxide

More insidious than hypoxia, and less noticeable, is the symptomless encroachment of carbon monoxide (CO) gas on the oxyhemoglobin dissociation curve (see pp. 649–652). CO—which can come from incomplete combustion of fuel in furnaces, in charcoal burners, or during house fires—suffocates people without their being aware of its presence. Detectors for this gas are thus essential for providing an early warning. CO can be lethal when it occupies approximately half of the binding sites on hemoglobin (Hb), which occurs at a PCO of ~0.13 mm Hg or 0.13/760 ≅ 170 parts per million (ppm). imageN61-7 However, the half-time for washing CO into or out of the body is ~4 hours. Thus, if the ambient CO level were high enough to achieve a 50% saturation of Hb at equilibrium, then after a 2-hour exposure (i.e., one half of the half-time) the CO saturation would be image × image × 50% = 12.5%. The symptoms imageN29-5 at this point would be mild and nonspecific and would include headache, nausea, vomiting, drowsiness, and interference with night vision. Victims with limited coronary blood flow could experience angina. imageN61-8 After a 4-hour exposure (i.e., one half-time), the CO saturation would be image × 50% = 25%. The symptoms would be more severe and would include impaired mental function and perhaps unconsciousness.


Calculating the Lethal Partial Pressure of CO

Contributed by Arthur DuBois

To calculate the carboxyhemoglobin (HbCO) concentration, remember that when the Hb is exposed to CO the HbCO concentration will equal the HbO2 concentration when the Hb is exposed to oxygen at 210 times the CO concentration. For example, at equilibrium, Hb is 50% saturated with O2 when the image is 28 mm Hg. Similarly, the Hb is 50% saturated with CO at a PCO of 28/210 mm Hg, which would be 0.13 mm Hg of CO. Because an atmosphere of pressure is 760 mm Hg, 0.13 mm Hg of CO is 0.13/760 of an atmosphere of CO, that is, 0.000,170 of an atmosphere or 170 ppm of CO.


Effects of CO Poisoning in Patients with Reduced Coronary Blood Flow

Contributed by Arthur DuBois

The heart muscle extracts most of the oxygen from the blood supplied to it in the coronary circulation. With exercise, autoregulation of coronary blood flow normally supplies more oxygen to the myocardium by increasing coronary blood flow. However, in stable angina, the fixed rate of coronary blood flow prevents autoregulation. Thus, when carboxyhemoglobin (HbCO) reduces the ability of arterial blood to release O2 due to the leftward shift of the Hb-O2 dissociation curve (see pp. 654–655), the heart muscle is deprived of oxygen and anginal pain develops even upon mild exercise.

Threshold Limit Values and Biological Exposure Indices

Threshold limit values (TLVs) are reasonable environmental levels of toxic substances or physical agents (e.g., heat or noise) to which industrial workers can be exposed—over a lifetime of working days—without causing predictable harm. Rather than depending on concentrations measured in air or food, we can use biological exposure indices (BEIs) to limit exposure to toxic substances by detecting changes in the body—biomarkers of exposure (e.g., carboxyhemoglobin levels in blood)—that correlate with the intensity and duration of exposure to toxic substances (e.g., CO). imageN61-9


Threshold Limit Values and Biological Exposure Indices

Contributed by Arthur DuBois

A list of threshold limit values and biological exposure indices applicable to industrial exposure can be obtained from the American Conference of Governmental Industrial Hygienists (ACGIH) in Cincinnati, Ohio (, accessed February 2015).

Tissues must resist the G force produced by gravity and other mechanisms of acceleration

Standing motionless on the earth's surface at sea level, we experience a gravitational force (ℱ) imageN61-10—our weight—that is the product of our mass (m) and the acceleration due to gravity (g = 9.8 m · s–2):




The Laws of Motion

Contributed by Arthur DuBois

Newton's first law of motion establishes the concept of inertia: an object at rest remains at rest, and a body in motion remains in motion—at the same velocity—unless acted upon by an external force.

The second law of motion deals with changes in momentum, which is the product of mass and velocity. Because velocity has both magnitude and direction, so does momentum. When an external force (which also has magnitude and direction) acts on a body, the change in the body's momentum is in the direction of the force. Furthermore, momentum changes at a rate that is proportional to the magnitude of the force. Thus, the change in the momentum (i.e., velocity) of a spacecraft depends on the magnitude, direction, and duration of the force (i.e., thrust) exerted by the engine.

The third law of motion states that application of an external force generates an equivalent, but opposing, inertial force (“for every action, there is an equal and opposite reaction”).

Under a particular condition, we may experience a different acceleration (a) from that due to gravity. The G force is a dimensionless number that describes force (m · a) that we experience under a particular condition relative to the gravitational force (m · g):



Thus, we normally experience a force of +1G that would cause us to fall with an acceleration of 9.8 m · s–2 if we were not supported in some way.

Accelerations besides that due to gravity also affect physiology. An accelerometer, placed on a belt, would show that we can jump upward with an acceleration of ~3G. It would also show that, on landing, we would strike the ground with a force of +3G—a force that our bones and other tissues can tolerate if we flex the joints. We discuss G forces from the perspective of air and space flight on pages 1232–1233.

At +1G, each square centimeter of the cross section of a vertebral body, for example, can withstand the compressive force generated by a mass of ~20 kg before the trabeculae begin to be crushed. imageN61-11 Thus, at +1G a vertebral body with a surface area of 10 cm2 could support the compressive force generated by a mass of ~200 kg, far more than enough to support 35 kg, the mass of the upper half of the body of a 70-kg person. In fact, this strength would be adequate to withstand a G force of a (200 kg)/(35 kg) = +5.7G—provided the backbone is straight. However, if the backbone is not straight, the tolerance could be +3G, or approximately the acceleration achieved by jumping upward and landing on the feet with the back curved. When a pilot ejects from an aircraft, the thrust of the explosive cartridges accelerates the seat upward, and this can crush a vertebral body unless the pilot keeps the back straight.


Forces Supported by a Vertebral Body

Contributed by Arthur DuBois

In the text, we analyzed the body mass that a vertebral body could withstand at +1G. Another way to approach the problem is to determine the maximal pressure that a vertebral body can withstand.

At +1G, each square centimeter of a vertebral body, for example, can withstand the compressive force generated by a mass of ~20 kg before the trabeculae begin to be crushed. In other words, a vertebral body can withstand a compressive pressure of


(NE 61-4)

Thus, a vertebral body with a cross-sectional area of 10 cm2 could support a maximal force (ℱMax) of


(NE 61-5)

This ℱMax is more than enough to support the upper half of the body of a 70-kg person (i.e., 35 kg). Because a vertebral body with a cross-sectional area of 10 cm2 could support a mass of 20 kg/cm2 × 10 cm2 = 200 kg at 1 × G, it could withstand a headward acceleration of (200 kg/35 kg) = +5.7G—provided the backbone were straight.

With increasing age, bones tend to demineralize (see p. 1243), which weakens them. Stepping off a curb, an elderly person with demineralized bones may fracture the neck of the femur or crush a vertebra. Demineralization of the vertebrae also reduces stature. Other causes of demineralization are immobilization and space flight. In one study a 6- to 7-week period of immobilization from bed rest led to losses of 14 g of calcium from bones, 1.7 kg of muscle, 21% in the strength of the gastrocnemius muscle, and 6% in average blood volume. The subjects became faint when suddenly tilted on a board, head above feet. After resuming ambulation, the subjects required 4 weeks for muscle strength to return to normal.

The partial pressures of gases—other than water—inside the body depend on PB

As discussed in the next two subchapters, extremely high or extremely low values of PB create special challenges for the physiology of the body, particularly the physiology of gases.  imageN26-8 Dalton's law (see Box 26-2) states that PB is the sum of the partial pressures of the individual gases in the air mixture. Thus, in the case of ordinary dry air (see Table 26-1), most of the sea-level PB of 760 mm Hg is due to N2(~593 mm Hg) and O2 (~159 mm Hg), with smaller contributions from trace gases such as argon (~7 mm Hg) and CO2 (~0.2 mm Hg). As PB increases during diving beneath the water, or as PB decreases during ascent to high altitude, the partial pressure of each constituent gas in dry ambient air changes in proportion to the change in PB. At high values of PB, this relationship is especially important for ambient image and image, which can rise to toxic levels. At low values of PB, this relationship is important for ambient image, which can fall to levels low enough to compromise the O2 saturation of Hb (see pp. 649–652) and thus the delivery of O2 to the tissues.

The proportionality between PB and the partial pressure of constituent gases breaks down in the presence of liquid water. When a gas is in equilibrium with liquid water—as it is for inspired air by the time it reaches the trachea (see p. 600)—the partial pressure of water vapor (image) depends not on PB but on temperature. Thus, image becomes a negligible fraction of PB at the very high pressures associated with deep-sea diving, whereas image becomes an increasingly dominant factor as we ascend to altitude.