STANLEY G. SCHULTZ

• Physiologic processes have evolved to maintain the constancy or stability of the internal environment. This tendency toward maintenance of physiologic stability is homeostasis.

• Living things are open systems.

• The total body water is contained within two major compartments—the intracellular compartment and the extracellular compartment. The intracellular compartment is further subdivided into the plasma and the interstitial fluid compartments.

• The intracellular compartment is characterized by low intracellular Na+ and Cl− concentrations and a high K+ concentration. The intracellular compartment comprises approximately 25 L, which is approximately 35% of total body weight.

• The extracellular compartment is divided into the plasma and interstitial compartments; the former comprises approximately 3 L and the latter approximately 12 L. These compartments are characterized by high Na+ and Cl− concentrations and a low K+ concentration.

• Four organs provide the interfaces between the extracellular fluid compartment and the outside world: the skin, alimentary canal, lung, and kidney. The proper interactions among these organs and the external environment is essential for homeostasis.

HOMEOSTASIS: THE SUBJECT OF PHYSIOLOGY

If one had to describe, with a single word, what physiology is all about, that word would be homeostasis. This word was coined by the great American physiologist, Walter B. Cannon, in his book entitled The Wisdom of the Body (1939) and refers to regulatory mechanisms by which biologic systems tend to maintain the internal stability necessary for survival while adjusting to internal or external threats to that stability. If homeostasis is successful, life continues; if it is unsuccessful, disease and perhaps death ensue.

Cannon’s notion of homeostasis was an extension of the concept first introduced by one of the founders of modern physiology, Claude Bernard, a physician by training who made many seminal contributions to our early understanding of digestion, metabolism, vasomotor activity of nerves, neuromuscular transmission, and other areas of physiology. But perhaps his greatest lasting contribution was the notion that all physiologic processes are designed to maintain the internal environment, the milieu interieur, that bathes our cells, tissues, and organs. The following is from his opening lecture in a course in general physiology given at the College de France in 1887:

In short, he suggested that we exist within our own “hot houses” and that our existence depends on our abilities to maintain that “hot house.”

Although this notion may seem trivial now, at the time when it was introduced it was revolutionary. It proved to be prophetic and has influenced all physiologic thinking to this day.

ORIGIN OF OUR MILIEU INTERIEUR

There is good evidence that our predecessors, the protovertebrates or prochordates, migrated from the seas into brackish or fresh water during the Cambrian period, almost 500 million years ago. During that migration, which lasted some 200 million years, they “locked” within themselves a fluid similar in composition to that of the seas from which they emerged. Some of these early vertebrates returned to the oceans, which had become saltier; others stayed in brackish or fresh water; and still others chose to live on land. But, regardless of their final habitats, the “sea” within all vertebrates is remarkably similar in ionic composition to the salinity of the Cambrian seas from which they emerged. This sea that bathes all cells is rich in Na+ and Cl−, in contrast with the intracellular fluid, which, in all living forms including microorganisms, is rich in K+ and poor in Na+ and Cl−.

LIVING THINGS ARE OPEN SYSTEMS

Maintaining a constant internal environment would pose no problem if living things were closed systems, like a solution in a sealed bottle. Instead, however, all freely living forms are open systems constantly exchanging matter and energy with the environment. The remarkable thing is that despite this constant exchange, essential for life, the compositions of our intracellular and extracellular fluids are maintained remarkably constant; this is what homeostasis is all about. How is this accomplished?

BODY FLUID COMPARTMENTS AND THEIR CONTACTS WITH THE OUTSIDE WORLD

The total body water (TBW) in higher animals is distributed among three major compartments: the blood plasma, the interstitial fluid (ISF), and the intracellular fluid (ICF). The plasma is separated from the ISF compartment by highly permeable capillaries; together, plasma and ISF constitute the extracellular fluid (ECF) compartment. This compartment is separated from the ICF compartment by cell membranes, which in most instances, as discussed in Chapter 3, are highly permeable to water but very selective with respect to the passage of solutes. A fourth, small compartment, called the transcellular fluid compartment, consists primarily of fluid in transit in the lumina of epithelial organs (e.g., the gall bladder, stomach, intestines, and urinary bladder), as well as the cerebrospinal fluid and the intraocular fluid.

In an average human adult weighing approximately 70 kg, the TBW makes up approximately 60% of body weight or about 40 L. The distribution of this water among the plasma ISF and ICF compartments is shown in Fig. 1, and the way in which the sizes of these compartments are determined is discussed below. The transcellular fluid compartment in such an individual comprises approximately 2 to 4% of the TBW and contains approximately 1 to 2 L of water.

The ECF of all vertebrates is in intimate contact with four organs that interface with the external environment. One is a tube that runs from mouth to anus—the alimentary canal. It is responsible for absorbing water, essential elements, and the metabolites that form our building blocks and fuel our activities; for the most part, however, it is indiscriminant with respect to what it will permit to enter the body. The second organ is the lungs, which are responsible for exchanging oxygen and carbon dioxide with the environment and, as discussed below, are a source of water loss. The third organ is the kidneys, which turn over the sea within us many times each day and correct for the indiscretions of our gastrointestinal tracts. In short, the composition of our body fluids is determined not by what the mouth takes in but by what our kidneys keep (Smith, 1961). The final organ in contact with the external environment is, of course, the skin, which plays a primary role in temperature regulation, but is also a source of water loss.

It is the precise interplay of these interfaces (particularly the alimentary canal, lungs, and kidneys) and the external environment that maintains the constancy of our milieu interieur and permits us to live a relatively free and independent life. A large portion of this text is devoted to...