FLUID REGULATIION Fluid regulation is essential to homeostasis.

If water or electrolyte levels rise or fall beyond normal limits, many bodily functions fail to proceed at their normal rates. Maintaining normal pH levels is also important for normal body functioning because small changes in pH can produce major changes in metabolism. Water is a constituent of all living things. It is often referred to as the universal biological solvent. Only liquid ammonia is able to dissolve more substances than water. The importance of water as a biological solvent is due to its polar asymmetry (H+- OH-) and its high affinity for other water molecules. As a polar molecule, water is highly interactive with other polar molecules and acts to compete with them for hydrogen bonding, thus weakening their electrostatic forces. This allows a greater number of polar molecules to coexist and undergo reactions; in a non-polar solvent, these polar molecules would form strong bonds with one another and thus be unavailable for further reaction. The affinity of water molecules for each other is very high. When non-polar molecules are placed in water, the polar water molecules are attracted to other water molecules. This action tends to leave the non-polar molecules clustered together. This clustering property is important in structuring macromolecules, binding enzymes to their substrates, and in membrane formation. Water acts to minimize temperature changes throughout the body because of its high specific heat. A considerable amount of energy is needed to break the hydrogen bonds between water molecules in order to make the water molecules move faster (that is, increase the temperature of water). Therefore, water can absorb much heat without rapidly changing it's own temperature. The adult human body consists of about 60% water by weight, depending upon age and the amount of body fat. The water content of the tissues of the body varies. Adipose tissue (fat) has the lowest percent of water; the skeleton has the second lowest water content. Skeletal muscle, skin, and the blood are among the tissues that have the highest content of water in the body. Infants have a higher percent of water than adults do as much as 77%. The total water content of the body decreases most dramatically during the first 10 years and continues to decline through old age, at which time it may be only 45% of the total body weight. Men tend to have higher percentages of water (about 65%) than women (about 55%) mainly because of their increased muscle mass and lower amount of subcutaneous fat. Fat has less water content than any other body tissue. This also accounts for a lower than normal water percentage in obese people. Functions of water within the body: All chemical reactions occur in the medium. Crucial in regulating chemical and bioelectrical distributions within cells. Transports substances such as hormones and nutrients. O2 transport from lungs to body cells. CO2 transport in the opposite direction. Dilutes toxic substances and waste products and transports them to the kidneys and the liver. Distributes heat around the body Water in the body is in a constant state of motion. Shifting between the three major fluid compartments of the body and in addition is continuously lost from and taken into the person. In a normal, healthy human being WATER INPUT = WATER OUTPUT. Maintaining this ratio is of prime importance in maintaining health. Approximately 90% of the body's water intake comes via the gastro-intestinal tract. The remaining 10% is called metabolic water and is produced as the result of various chemical reactions in the cells of the body's tissues. The normal healthy adult loses water via: Gastro-intestinal tract (feces) 6% Lungs (water vapor) 13% Skin (diffusion & sweat) 19% Kidneys (urine) 62%

THE FLUID REGULATION SYSTEM

Introduction

Have you ever wondered why you sometimes excrete great volumes of urine and sometimes almost none at all? Have you ever wondered why sometimes you feel so thirsty that you can hardly get enough to drink and other times you want no liquids at all? Have you ever wondered why every time you go to the movie theater and drink a large soda at the beginning of the movie, you almost always have to go to the bathroom during the middle of the movie (the worst time possible)? Did you know that if you were eating salty popcorn along with your large soda, you would not have to interrupt your movie to go to the bathroom? These conditions, and many more, relate to one of the body's most important functions -- that of maintaining its fluid and electrolyte balance. If you are a healthy young person weighing 120 pounds, one substance alone, out of the hundreds of compounds present in your body, weighs about 72 pounds, or 60% of your total weight. This, the body's most abundant compound, is water. It occupies three main locations in the body known as fluid compartments.

Figure 1 illustrates the relative sizes of these fluid compartments. Note that the largest volume of water by far lies inside cells and is called, appropriately, intracellular fluid (ICF). Note, too, that the water outside of cells -- extracellular fluid (ECF) -- is located in two compartments: in the microscopic spaces between cells, where it is called interstitial fluid (IF); and in the blood vessels, where it is the principal constituent of plasma, the liquid part of blood. A normal body maintains fluid balance. The term fluid balance means that the volumes of ICF, IF, plasma and the total volume of water in the body all remain relatively constant. Under normal conditions,homeostasis (relative uniformity of the body's internal environment) of the total volume of water in the body is maintained or restored primarily by devices that adjust urine output to fluid intake, and secondarily by mechanisms that adjust fluid intake. There is no question about which of the two mechanisms is more important. The body's chief mechanism, by far, for maintaining fluid balance is to adjust its fluid output so that fluid output equals fluid intake. Everyone knows this by experience. The more liquid one drinks, the more urine one excretes. Conversely, the less the fluid intake, the less the urine volume output. This balance is maintained mainly through the kidney acting together with certain hormones in the body. We will discuss the formation of urine in a moment; however, let us understand what electrolytes are. Electrolytes are chemical compounds that dissociate (or break up) in solution into separate positively or negatively charged particles. For example, table salt is an electrolyte that dissociates in water to form the particles sodium (Na+) and chloride (Cl-). The dissociated particles of an electrolyte are called ions; positively charged particles, such as Na+, are called cations; and negatively charged particles, such as Cl-, are called anions. A variety of anions and cations serve important nutrient or regulatory roles in the body. Important cations include sodium (Na+), calcium (Ca++), potassium (K+), and magnesium (Mg++). Important anions include chloride (Cl-), bicarbonate (HCO3), phosphate (HPO4--), and many proteins. Although blood plasma contains a number of important electrolytes, by far the most abundant one is sodium chloride (ordinary table salt, Na+Cl-). The production of urine is vital to the health of the body. Urine is composed of water and wastes that are filtered out of the blood system. Remember, as the blood flows through the body, wastes resulting from the metabolism of foodstuffs in the body cells are deposited into the blood stream, and this waste must be disposed of in some way. This "cleaning" of the blood takes place in the kidney, where the blood is filtered to produce the urine. (Select here to learn more about some space-related problems in this filtration process.) There are two kidneys in the body to carry out this essential blood cleansing function. Normally, about 20% of the total blood pumped by the heart each minute will enter the kidneys. The rest of the blood (about 80%) does not go

through the filtering portion of the kidney, but flows through the rest of the body to service the various nutritional, respiratory, and other needs that are always present.

The Kidney's Internal Structure

If you were to slice through a kidney from side to side and open it like the pages of a book, you would see the structures shown in Figure 2. Identify each of the following:
1. Cortex -- the outer part of the kidney;

2. 3. 4. 5.

Medulla -- the inner portion of the kidney; Pyramids -- the triangular-shaped divisions of the medulla of the kidney; Papilla -- narrow, innermost tip of the pyramid; Pelvis -- the kidney or renal pelvis is an extension of the upper end of the ureter (the tube that drains urine into the bladder); 6. Calyx -- each calyx is a division of the renal pelvis; opening into each calyx is the papilla of a pyramid.

Figure 2. Cross section through the right kidney. (Courtesy of Mosby-Year Book, Inc., St. Louis, MO)

More than a million microscopic-sized units named nephrons make up each kidney's interior. The shape of the nephron is unique, unmistakable, and admirably suited to its function of producing urine. It looks like a tiny funnel with a very long stem. The stem is unusual in that it is highly convoluted, that is, it has many bends in it. Locate each of the following parts of a nephron in Figure 3.

Figure 3. Magnified wedge cut from a renal pyramid. (Courtesy of Mosby-Year Book, Inc., St. Louis, MO) 1. RENAL CORPUSCLE -- the glomeruli surrounded by Bowman's capsules. 1. Bowman's capsule -- the cup-shaped top of a nephron. It is the sack-like Bowmans's capsule that surrounds the glomerulus. 2. Glomerulus -- a network of blood capillaries tucked into Bowman's capsule. 2. RENAL TUBULE 1. Proximal convoluted tubule -- the first segment of a renal tubule, called proximal because it lies nearest the tubule's origin from Bowman's capsule, and convoluted because it has several bends in it. 2. Loop of Henle -- the extension of the proximal tubule; observe that the loop of Henle consists of a straight descending (directed downward) limb, a loop, and a straight ascending limb (directed upwards). 3. Distal convoluted tubule -- the part of the tubule distal to the ascending limb of Henle. It is the extension of the ascending limb of Henle. 4. Collecting tubule -- a straight (not convoluted) part of a renal tubule; distal tubules of several nephrons join to form a single collecting tubule. In summary, nephrons, the microscopic units of a kidney, have two main parts, a renal corpuscle (Bowman's capsule with glomerulus) and a renal tubule. How Kidneys Form Urine The kidneys' two million or more nephrons form urine by three processes: filtration, reabsorption, and secretion. Urine formation begins with the process of filtration, which goes on continually in the renal corpuscles (glomeruli plus Bowman's capsule encasing them). (see Figure 3.) Blood flowing through the glomeruli exerts pressure, and this glomerular blood pressure is sufficiently high to push water and dissolved substances from the blood out of the glomeruli into the Bowman's capsules. Briefly, glomerular blood pressure causes filtration through the glomerular-capsular membrane. If glomerular blood pressure drops below a certain level, filtration of the blood and urine formation drops to a minimal obligatory level which, if continued for some time, could develop into a life-threatening condition. The total rate of glomerular filtration (Glomerular Filtration Rate or GFR) for the whole body (i.e., for all of the nephrons in both kidneys) is normally about 125 ml. per minute. The following calculations may help you visualize how enormous this volume is. The GFR per hour is: 125 ml/min x 60 min/hr = 7500 ml/hr.

The volume of fluid filtered through the glomeruli per day is: 7500 ml/hr x 24 hr/day = 180,000 ml/day or 180 liters/day. Obviously, no one ever excretes anywhere near 180 liters (or about 190 quarts) of urine per day! Why? Because most of the fluid that leaves the blood by glomerular filtration, the first process in urine formation, returns to the blood by the second process -- reabsorption. Reabsorption, by definition, is the movement of substances out of the renal tubules into the blood capillaries located around the tubules (called the peritubular capillaries). Substances reabsorbed are water, glucose and other nutrients, and sodium (Na+) and other ions. Reabsorption begins in the proximal convoluted tubules and continues in the loop of Henle, distal convoluted tubules, and collecting tubules. (See Figure 4.)

Figure 4. Diagram showing the steps in urine formation in successive parts of a nephron: filtration, reabsorption, and secretion (dissection view for illustrative purposes). In this figure, the term "resorption" is equivalent to "reabsorption" used here. Large amounts of water -- approximately 178 liters per day -- are reabsorbed by osmosis from the proximal tubules. In other words, nearly 99% of the 180 liters of water that leave the blood each day by glomerular filtration returns to the blood from the proximal tubule through the process of reabsorption. The nutrient glucose is entirely reabsorbed from the proximal tubules. it is actively transported out of them into the peritubular capillary blood. None of this valuable nutrient is wasted by being lost in the urine. (An exception to this occurs in a person who suffers from diabetes mellitus, where the urine contains more glucose than the kidneys are able to reabsorb.) Sodium ions (Na+) and other ions are only partially reabsorbed from the renal tubules back into the blood. For the most part, sodium ions are actively transported back into blood from the tubular fluid. The amount of sodium reabsorbed varies from time to time; it depends largely on salt intake. As stated earlier, sodium is a major component of table salt (known chemically as sodium chloride). As a person increases the amount of salt intake, that person's kidneys decrease the amount of sodium reabsorption back into the blood. Therefore, the amount of salt excreted in the urine increases. The process works the other way as well. The less the salt intake, the greater the amount of sodium reabsorption back into the blood, and the amount of salt excreted in the urine decreases. Secretion is the process by which substances move into the distal and collecting tubules from blood in the capillaries around these tubules. (See Figure 4.) in this respect, secretion is reabsorption in reverse. Whereas reabsorption moves substances out of the tubules into the blood, secretion moves substances out of the blood into the tubules. Substances secreted are hydrogen ions (H+), potassium ions (K+), ammonia (NH3), and certain drugs. Kidney tubule secretion plays a crucial role in maintaining the body's acid/base balance. In summary, three processes occurring in successive portions of the nephron accomplish the function of urine formation (Figure 4): 1. Filtration of water and dissolved substances out of the blood in the glomeruli into Bowman's capsule.

2. Reabsorption of water and dissolved substances out of the kidney tubules back into the blood. (Note that this process prevents substances needed by the body from being lost in the urine.) 3. Secretion of hydrogen ions (H+), potassium ions (K+), ammonia (NH3), and certain drugs out of the blood into the kidney tubules. Control of Urine Volume The body has ways to control both the amount and the composition of the urine it excretes. It does this mainly by controlling the amount of water and dissolved substances reabsorbed out of the tubules and into the blood. One of the mechanisms that the body uses to control such things is through the action of hormones, chemical messengers that travel through the blood system acting as regulators of many of the body's internal activities. (Hormones are secreted by specialized glands that form the endocrine system.) For example, the hormone ADH (antidiuretic hormone), which is secreted by the pituitary gland, tends to decrease the amount of urine by making distal and collecting tubules permeable to water. If no ADH is present, both distal and collecting tubules are practically impermeable to water, and little or no water is reabsorbed from them. When ADH is present in the blood, distal and collecting tubules are permeable to water and water is reabsorbed from them. As a result, water moves from the tubules back into the blood, and, therefore, more water is retained. For this reason, ADH is accurately described as the "water-retaining hormone." You might also think of it as the "urine-decreasing hormone." The hormone aldosterone, secreted by the adrenal cortex gland located at the top of each kidney, plays an important part in controlling the kidney tubules' reabsorption of salt, the most abundant electrolyte in the blood. (Aldosterone is also responsible for the regulation of other electrolytes as well, particularly potassium.) Primarily, aldosterone stimulates the tubules to reabsorb sodium salts at a faster rate. This means that in the presence of aldosterone, the salt moves more rapidly out of the kidney tubules back into the blood. Secondarily, aldosterone tends also to increase tubular water reabsorption (that is, water tends to flow out of the kidney tubules back into the blood). The term "salt- and water-retaining hormone" therefore is a descriptive nickname for aldosterone. The kidney tubule regulation of salt and water is the most important factor in determining urine volume. Urine volume control is influenced by many factors and the precise regulation of urine volume is important and essential for many different reasons. Ultimately, the body's main requirement is to maintain a balance of fluids and a balance of body chemistry. From earlier in this document, you know that fluid volumes are affected by space flight. Overall fluid volume is decreased in microgravity. It is important to find out how microgravity affects the regulatory systems that control the fluid volumes and

Normal Fluid Regulation in the Body

Your body has a complex system for balancing the volume and composition of body fluids. Your kidneys remove extra body fluids from your bloodstream. This fluid waste is stored in the bladder as urine. If your fluid regulation system is working properly, your kidneys make less urine to conserve fluid when the body is losing water. Your kidneys also make less urine at night when the body's metabolicprocesses are slower.

The hypothalamus makes antidiuretic hormone (ADH), which directs the kidneys to make less urine. In order to keep the volume and composition of body fluids balanced, the rate of fluid intake is governed by thirst, and the rate of excretion is governed by the production of antidiuretic hormone (ADH), also called vasopressin. This hormone is made in the hypothalamus, a small gland located in the base of the brain. ADH is stored in the nearby pituitary gland and released from it into the bloodstream when necessary. When ADH reaches the kidneys, it directs the kidneys to concentrate the urine by returning excess water to the bloodstream and therefore make less urine. Diabetes insipidus occurs when this precise system for regulating the kidneys' handling of fluids is disrupted. The most common form of clinically serious diabetes insipidus, central diabetes insipidus, results from damage to the pituitary gland, which disrupts the normal storage and release of ADH. Another form, nephrogenic diabetes insipidus, results when the kidneys are unable to respond to ADH. Rarer forms occur because of a defect in the thirst mechanism (dipsogenic diabetes insipidus) or during pregnancy (gestational diabetes insipidus ). A specialist should determine which form of diabetes insipidus is present before starting any treatment.