Image summary: This is a photograph. The image depicts a woman outdoors in a natural setting, drinking water from a clear plastic bottle. She is wearing a sleeveless top and is captured in profile while tilting her head back to drink. The scene suggests a moment of hydration and refreshment during an outdoor activity, implying a focus on health and wellness.

Fluid, Electrolyte, and Acid-Base Homeostasis

Fluid, Electrolyte, and Acid-Base Homeostasis

Regulating the volume and composition of body fluids, controlling their distribution throughout the body, and balancing the pH of body fluids are crucial to maintaining overall homeostasis and health.

In Chapter 26 you learned how the kidneys form urine. One important function of the kidneys is to help maintain fluid balance in the body. Regulatory mechanisms involving the kidneys and other organs normally maintain homeostasis of the body fluids. Malfunction in any or all of them may seriously endanger the functioning of organs throughout the body. In this chapter, we will explore the mechanisms that regulate the volume and distribution of body fluids and examine the factors that determine the concentrations of solutes and the pH of body fluids.

27.1 Fluid Compartments and Fluid Homeostasis

• Compare the locations of intracellular fluid (I.C.F) and extracellular fluid (E.C.F).

• Describe the various fluid compartments of the body.

• Discuss the sources and regulation of water and solute gain and loss.

• Explain how fluids move between compartments.

A body fluid is a substance, usually a liquid, that is produced by the body and consists of water and dissolved solutes. In lean adults, body fluids constitute between 55% and 60% of total body mass in females and males, respectively (Figure 27.1). Body fluids are present in two main “compartments”—inside cells and outside cells. About two-thirds of body fluid is intracellular fluid (I.C.F) (intra-= within) or cytosol, the fluid within cells. The other third, called extracellular fluid (E.C.F) (extra-= outside), is outside cells and includes all other body fluids. About 80% of the E.C.F is interstitial fluid (inter-= between), which occupies the microscopic spaces between tissue cells, and 20% of the E.C.F is blood plasma, the liquid portion of the blood. Other extracellular fluids that are grouped with interstitial fluid include lymph plasma in lymphatic vessels; cerebrospinal fluid in the nervous system; synovial fluid in joints; aqueous humor and vitreous body in the eyes; endolymph and perilymph in the ears; and pleural, pericardial, and peritoneal fluids between serous membranes.

Figure 27.1 summary: This figure consists of stacked bar charts and a detailed anatomical diagram. The bar charts illustrate the proportional distribution of solids and fluids within the total body mass of average lean adult females and males, while the diagram depicts the sub-compartments of body fluid and the movement of water between them. It can be inferred that males possess a higher proportion of total body fluid compared to females, who have a higher proportion of solids. Within the total body fluid, the majority is contained as intracellular fluid, with the remaining portion consisting of extracellular fluid. This extracellular fluid is further divided into interstitial fluid and blood plasma, with interstitial fluid making up the bulk of this category. The diagram concludes that water continuously exchanges between these various compartments to maintain osmotic balance.

Two general “barriers” separate intracellular fluid, interstitial fluid, and blood plasma.

1. The plasma membrane of individual cells separates intracellular fluid from the surrounding interstitial fluid. You learned in Chapter 3 that the plasma membrane is a selectively permeable barrier: It allows some substances to cross but blocks the movement of other substances. In addition, active transport pumps work continuously to maintain different concentrations of certain ions in the cytosol and interstitial fluid.

2. Blood vessel walls divide the interstitial fluid from blood plasma. Only in capillaries, the smallest blood vessels, are the walls thin enough and leaky enough to permit the exchange of water and solutes between blood plasma and interstitial fluid.

The body is in fluid balance when the required amounts of water and solutes are present and are correctly proportioned among the various compartments. Water is by far the largest single component of the body, making up 45 to 75% of total body mass, depending on age, gender, and the amount of adipose tissue (fat) present in the body. Obese people have proportionally less water than leaner people because water comprises less than 20% of the mass of adipose tissue.

Skeletal muscle tissue, by contrast, is about 65% water. Infants have the highest percentage of water, up to 75% of body mass. The percentage of body mass that is water decreases until about 2 years of age. Until puberty, water accounts for about 60% of body mass in boys and girls. In lean adult males, water still accounts for about 60% of body mass.

However, lean adult females have more subcutaneous fat than do lean adult males. Thus, their percentage of total body water is lower, accounting for about 55% of body mass.

The processes of filtration, reabsorption, diffusion, and osmosis allow continual exchange of water and solutes among body fluid compartments (Figure 27.1b). Yet the volume of fluid in each compartment remains remarkably stable. The pressures that promote filtration of fluid from blood capillaries and reabsorption of fluid back into capillaries can be reviewed in Figure 21.7. Because osmosis is the primary means of water movement between intracellular fluid and interstitial fluid, the concentration of solutes in these fluids determines the direction of water movement. Because most solutes in body fluids are electrolytes, inorganic compounds that dissociate into ions, fluid balance is closely related to electrolyte balance. Because intake of water and electrolytes rarely occurs in exactly the same proportions as their presence in body fluids, the ability of the kidneys to excrete excess water by producing dilute urine, or to excrete excess electrolytes by producing concentrated urine, is of utmost importance in the maintenance of homeostasis.

Sources of Body Water Gain and Loss

The body can gain water by ingestion and by metabolic synthesis (Figure 27.2). The main sources of body water are ingested liquids (about 1600 mL) and moist foods (about 700 mL) absorbed from the digestive canal, which total about 2300 mL/day. The other source of water is metabolic water that is produced in the body mainly when electrons are accepted by oxygen during aerobic respiration (see Figure 25.2) and to a smaller extent during dehydration synthesis reactions (see Figure 2.15). Metabolic water gain accounts for only 200 mL/day. Daily water gain from these two sources totals about 2500 mL.

Figure 27.2 summary: This figure is a stacked bar chart. It illustrates the daily balance of water gain and water loss in the human body, detailing the various sources of intake and the different pathways of excretion. The data shows that the largest contribution to water gain comes from ingested liquids, followed by ingested foods and metabolic water. Conversely, the primary route of water loss is through the kidneys, with additional losses occurring through the skin, lungs, and gastrointestinal tract. It can be inferred that under normal physiological conditions, the total volume of water entering the body is equivalent to the total volume of water leaving the body, maintaining a steady state of fluid balance.

Normally, body fluid volume remains constant because water loss equals water gain. Water loss occurs in four ways Figure 27.2 Sources of daily water gain and loss under normal conditions. Numbers are average volumes for adults.

(Figure 27.2). Each day the kidneys excrete about 1500 mL in urine, the skin evaporates about 600 mL (400 mL through insensible perspiration—sweat that evaporates before it is perceived as moisture—and 200 mL as sweat), the lungs exhale about 300 mL as water vapor, and the digestive canal eliminates about 100 mL in feces. In women of reproductive age, additional water is lost in menstrual flow. On average, daily water loss totals about 2500 mL. The amount of water lost by a given route can vary considerably over time. For example, water may literally pour from the skin in the form of sweat during strenuous exertion. In other cases, water may be lost in diarrhea during a digestive canal infection.

Regulation of Body Water Gain

The volume of metabolic water formed in the body depends entirely on the level of aerobic respiration, which reflects the demand for A.T.P in body cells. When more A.T.P is produced, more water is formed. Body water gain is regulated mainly by the volume of water intake, or how much fluid you drink. An area in the hypothalamus known as the thirst center governs the urge to drink.

When water loss is greater than water gain, dehydration—a decrease in volume and an increase in osmolarity (concentration of solutes) of body fluids—occurs. A decrease in blood volume causes blood pressure to fall. Increased activity from osmoreceptors in the hypothalamus, triggered by increased blood osmolarity, stimulates the thirst center in the hypothalamus (Figure 27.3). Other signals that stimulate the thirst center come from (1) volume receptors in the atria that detect the decrease in blood volume, (2) baroreceptors in blood vessels that detect the decrease in blood pressure, (3) angiotensin two that is formed due to activation of the renin-angiotensin-aldosterone pathway by the decrease in blood pressure, and neurons in the mouth that detect dryness due to a decreased flow of saliva. As a result of these stimuli, the sensation of thirst increases, which usually leads to increased fluid intake (as long as fluids are available) and restoration of normal fluid volume. Overall, fluid gain balances fluid loss. Sometimes, however, the sensation of thirst does not occur quickly enough or access to fluids is restricted, and significant dehydration ensues.

Figure 27.3 summary: This figure is a flow chart. It illustrates the physiological pathways that lead to the sensation of thirst and the subsequent behavioral response. The process begins with several triggers, including elevated blood osmolarity, reduced blood volume, lowered blood pressure, and a dry mouth. These stimuli activate various mechanisms, such as osmoreceptors in the hypothalamus, atrial volume receptors, baroreceptors in blood vessels, and the renin-angiotensin system in the kidneys. All these pathways converge to stimulate the thirst center in the hypothalamus, which increases the feeling of thirst and prompts higher water intake. The conclusion of the process is a negative feedback loop where increased water intake restores balance by lowering blood osmolarity and increasing both blood volume and pressure, while also relieving mouth dryness.

This happens most often in elderly people, in infants, and in those who are in a confused mental state. When heavy sweating or fluid loss from diarrhea or vomiting occurs, it is wise to start replacing

Figure 27.3 Pathways Involved in the Thirst Response.

body fluids by drinking fluids even before the sensation of thirst occurs.

Regulation of Water and Solute Loss

Even though the loss of water and solutes through sweating and exhalation increases during exercise, elimination of excess body water or solutes occurs mainly by control of their loss in urine. The extent of urinary salt (N-A-C-L) loss is the main factor that determines body fluid volume. The reason for this is that “water follows solutes” in osmosis, and the two main solutes in extracellular fluid (and in urine) are sodium ions (Na⁺) and chloride ions (Cl⁻). In a similar way, the main factor that determines body fluid osmolarity is the extent of urinary water loss.

The major hormone that regulates water loss is antidiuretic hormone (A.D.H). This hormone, also known as vasopressin, is produced by neurosecretory cells in the hypothalamus. and stored in the posterior pituitary gland. When the osmolarity of body fluids increases, osmoreceptors in the hypothalamus not only stimulate thirst; they also increase the synthesis and release of A.D.H (Figure 27.4). A.D.H promotes the insertion of water-channel proteins (aquaporin-2) into the apical membranes of principal cells in the late distal tubules and collecting ducts of the kidneys. As a result, the permeability of these cells to water increases.

Figure 27.4 summary: This figure is a flow chart. It illustrates the physiological pathway that leads to the production and release of antidiuretic hormone (ADH) and its subsequent effect on the kidneys. The process begins with triggers such as elevated blood osmolarity, reduced blood volume, lowered blood pressure, or external stressors like pain and nausea. These triggers activate specific receptors in the hypothalamus and blood vessels, which stimulate the synthesis of ADH in the hypothalamus and its release from the posterior pituitary gland. The hormone then increases the permeability of the distal tubules and collecting ducts in the kidneys to water. Consequently, this mechanism enhances water reabsorption, which serves to lower blood osmolarity and restore blood volume and pressure.

Water molecules move by osmosis from the renal tubular fluid into the cells and then from the cells into the bloodstream. This results in a decrease in blood osmolarity, an increase in blood volume and blood pressure, and the production of a small volume of concentrated urine. Once the body has adequate water, the A.D.H level in the bloodstream decreases.

As the amount of A.D.H in the blood declines, some of the aquaporin-2 channels are removed from the apical membrane via endocytosis. Consequently, the water permeability of the principal cells decreases and more water is lost in the urine.

Factors other than blood osmolarity influence A.D.H secretion (Figure 27.4). A decrease in blood volume or blood pressure also stimulates A.D.H release. Atrial volume receptors detect the decrease in blood volume, and baroreceptors in blood vessels detect the decrease in blood pressure. A.D.H release is also stimulated by factors that are unrelated to water balance, such as pain, nausea, and stress. Secretion of A.D.H is inhibited by alcohol, which is why consumption of alcoholic beverages promotes diuresis (voiding large amounts of urine).

Because our daily diet contains a highly variable amount of sodium chloride, urinary excretion of sodium ions and chloride ions must also vary to maintain homeostasis. Hormones regulate the urinary loss of sodium ions. Chloride ions usually follow sodium ions because of electrical attraction or because they are transported along with sodium ions via symporters. The two most important hormones that regulate the extent of renal sodium reabsorption (and thus how much is lost in the urine) are aldosterone and atrial natriuretic peptide.

1. Aldosterone. When there is a decrease in blood pressure, which occurs in response to a decrease in blood volume, or when there is a deficiency of Na superscript plus in the plasma, the kidneys release renin, which activates the renin-angiotensin-aldosterone pathway (Figure 27.5). Once aldosterone is formed, it increases Na ^{+} reabsorption in the late distal tubules and collecting ducts of the kidneys, which relieves the Na ^{+} deficiency in the plasma. Because antidiuretic hormone (A.D.H) is also released when blood pressure is low, water reabsorption accompanies Na ^{+} reabsorption via osmosis. This conserves the volume of body fluids by reducing urinary loss of water.

Figure 27.5 summary: This figure is a flow chart. It illustrates the physiological pathway through which aldosterone regulates sodium balance in the body, starting from triggers such as reduced blood pressure or low sodium levels in the plasma. These conditions prompt the kidneys to release renin, which leads to the production of aldosterone. This hormone then stimulates the reabsorption of sodium in the distal tubules and collecting ducts of the kidneys, a process accompanied by water reabsorption via osmosis, aided by antidiuretic hormone. The final outcome is an increase in plasma sodium levels, blood volume, and blood pressure, thereby restoring homeostasis.

2. Atrial natriuretic peptide. An increase in blood volume, as might occur after you finish one or more supersized drinks, stretches the atria of the heart and promotes release of atrial natriuretic peptide (A.N.P) (Figure 27.6). A.N.P promotes natriuresis, elevated excretion of Na⁺ into the urine. The osmotic consequence of excreting more Na⁺ is loss of more water in urine, which decreases blood volume and blood pressure.

Figure 27.6 summary: This figure is a flowchart. It illustrates the physiological sequence of events involving atrial natriuretic peptide to regulate sodium balance. The process begins with an increase in blood volume, which leads to the stretching of the atria, triggering the release of atrial natriuretic peptide. This peptide promotes the excretion of sodium ions into the urine, which subsequently drives increased water excretion through osmosis. The final outcome of this pathway is a reduction in both blood volume and blood pressure. It can be inferred that atrial natriuretic peptide acts as a corrective mechanism to lower blood pressure and volume by increasing the elimination of salt and water from the body.

In addition to stimulating the release of A.N.P, an increase in blood volume also slows the release of renin from the kidneys. When the renin level declines, less aldosterone is formed, which causes reabsorption of filtered Na⁺ to slow in the late distal tubules and collecting ducts of the kidneys. More filtered Na⁺ and water (due to osmosis) thus remain in the tubular fluid to be excreted in the urine.

Table 27.1 summarizes the factors that maintain body water balance.

Table 27.1 summary: This table outlines the various physiological factors that regulate body water balance. It contrasts mechanisms that increase water retention, such as the thirst center's drive for fluid intake and the actions of antidiuretic hormone and aldosterone to decrease urinary water loss, with the role of atrial natriuretic peptide, which promotes the excretion of water and sodium.

Movement of Water Between Body Fluid Compartments

Normally, the cells of the body neither shrink nor swell because the extracellular fluid that surrounds them is isotonic. This means that intracellular fluid and extracellular fluid have the same osmolarity. Changes in the osmolarity of extracellular fluid, however, cause fluid imbalances. If extracellular fluid becomes hypertonic (i.e., it has a greater concentration of solutes than intracellular fluid because its osmolarity has increased), water moves from cells into extracellular fluid by osmosis, causing the cells to shrink. If extracellular fluid becomes hypotonic (i.e., it has a lower concentration of solutes than intracellular fluid because its osmolarity has decreased) water moves from extracellular fluid into cells by osmosis, causing the cells to swell. Changes in osmolarity most often result from changes in the concentrations of Na superscript plus and Cl superscript minus (the major contributors to osmolarity of extracellular fluid).

An increase in the osmolarity of extracellular fluid can occur, for example, after you eat a salty meal. The increased intake of N-A-C-L produces an increase in the levels of Na superscript plus and Cl superscript minus in extracellular fluid. As a result, the osmolarity of extracellular fluid increases, which causes net movement of water from cells into extracellular fluid. Such water movement shrinks the cells of the body.

If neurons of the brain remain in this state for a significant period of time, mental confusion, convulsions, coma, and even death can occur. Body cells usually shrink only slightly and only for a short duration in response to an increase in the osmolarity of extracellular fluid because corrective measures such as the thirst mechanism and secretion of antidiuretic hormone increase the amount of body water, thereby reducing the concentration of solutes in extracellular fluid back to normal levels.

A decrease in the osmolarity of extracellular fluid can occur, for example, after drinking a large volume of water. This dilution causes the levels of Na superscript plus and Cl superscript minus in extracellular fluid to fall below the normal range. When the extracellular concentrations of Na superscript plus and Cl superscript minus decrease, the osmolarity of extracellular fluid also decreases. The net result is movement of water from extracellular fluid into cells, which causes the cells to swell. Usually when the osmolarity of extracellular fluid decreases, secretion of A.D.H is inhibited and the kidneys excrete a large volume of dilute urine, which restores the osmolarity of body fluids back to normal. As a result, body cells swell only slightly and only for a brief period. But when a person steadily

Clinical Connection

Enemas and Fluid Balance

An enema (enema) is the introduction of a solution into the rectum to draw water (and electrolytes) into the colon osmotically. The increased volume increases peristalsis, which evacuates feces. Enemas are used to treat constipation. Repeated enemas, especially in young children, increase the risk of fluid and electrolyte imbalances. consumes water faster than the kidneys can excrete it (the maximum urine flow rate is about 15 milliliters per minute) or when renal function is poor, the result may be water intoxication, a state in which excessive body water causes cells to swell dangerously (Figure 27.7). As is the case when neurons of the brain shrink, swelling of the brain's neurons can result in mental confusion, seizures, coma, and possibly death. To prevent this dire sequence of events in cases of severe electrolyte and water loss, solutions given for intravenous or oral rehydration therapy (O.R.T) include a small amount of table salt (N-A-C-L).

Figure 27.7 summary: This figure is a flowchart. It outlines the physiological sequence of events leading to water intoxication, starting with triggers such as excessive fluid loss through sweating, vomiting, diarrhea, or blood loss combined with the consumption of plain water. This process leads to a reduction in sodium concentration in the extracellular fluid, which subsequently lowers the osmolarity of that fluid. This imbalance causes water to move via osmosis from the extracellular space into the intracellular space. The resulting water intoxication causes cells to swell, which can lead to severe neurological symptoms including mental confusion, seizures, coma, and potentially death.

Checkpoint

27.2 Electrolytes in Body Fluids

Objectives

- Compare the electrolyte composition of the three major fluid compartments: blood plasma, interstitial fluid, and intracellular fluid.

• Discuss the functions and regulation of sodium, chloride, potassium, bicarbonate, calcium, phosphate, and magnesium ions.

The ions formed when electrolytes dissolve and dissociate serve four general functions in the body. Because they are largely confined to particular fluid compartments and are more numerous than nonelectrolytes, certain ions control the osmosis of water between fluid compartments. Ions help maintain the acid-base balance required for normal cellular activities. Ions carry electrical current, which allows production of action potentials and graded potentials. Several ions serve as cofactors needed for optimal activity of enzymes.

Concentrations of Electrolytes in Body Fluids

To compare the charge carried by ions in different solutions, the concentration of ions is typically expressed in units of milli-equivalents per liter (mEq/liter) (millimolar equivalents). These units give the concentration of cations or anions in a given volume of solution. One equivalent is the positive or negative charge equal to the amount of charge in one mole of H⁺; a milli-equivalent is one one-thousandth of an equivalent. Recall that a mole of a substance is its molecular weight expressed in grams. For ions such as sodium (Na⁺), potassium (K⁺), and bicarbonate (H.C.O₃⁻), which have a single positive or negative charge, the number of mEq/liter is equal to the number of millimoles/liter. For ions such as calcium (Ca²⁺) or phosphate (H.P.O₄²⁻), which have two positive or negative charges, the number of mEq/liter is twice the number of millimoles/liter.

Figure 27.8 compares the concentrations of the main electrolytes and protein anions in blood plasma, interstitial fluid, and intracellular fluid. The chief difference between the two extracellular fluids—blood plasma and interstitial fluid—is that blood plasma contains many protein anions, in contrast to interstitial fluid, which has very few. Because normal capillary membranes are virtually impermeable to proteins, only a few The electrolytes present in extracellular fluids are different from those present in intracellular fluid. plasma proteins leak out of blood vessels into the interstitial fluid. This difference in protein concentration is largely responsible for the blood colloid osmotic pressure exerted by blood plasma. In other respects, the two fluids are similar.

Figure 27.8 summary: This figure is a bar chart. It displays the concentrations of various electrolytes and protein anions across three different body fluid compartments: blood plasma, interstitial fluid, and intracellular fluid. The measured substances include sodium, potassium, calcium, magnesium, chloride, bicarbonate, organic phosphate, sulfate, and protein anions. Comparing the fluid compartments reveals distinct distribution patterns for different ions. Sodium and chloride are found in much higher concentrations in the extracellular fluids, specifically blood plasma and interstitial fluid, than in the intracellular fluid. Conversely, potassium and organic phosphate are significantly more concentrated within the intracellular fluid. Magnesium also shows a higher concentration inside the cell. Bicarbonate levels are relatively similar across compartments but are slightly higher in the extracellular fluids. Protein anions are notably more prevalent in the intracellular fluid and blood plasma compared to the interstitial fluid. Overall, the data demonstrates a clear chemical differentiation between the internal environment of the cell and the surrounding extracellular spaces.

The electrolyte content of intracellular fluid differs considerably from that of extracellular fluid. In extracellular fluid, the most abundant cation is Na⁺, and the most abundant anion is Cl⁻. In intracellular fluid, the most abundant cation is K⁺, and the most abundant anions are proteins and phosphates (H.P.O₄²⁻). By actively transporting Na⁺ out of cells and K⁺ into cells, sodium-potassium pumps (Na⁺–K⁺ A.T.P-ases) play a major role in maintaining the high intracellular concentration of K⁺ and high extracellular concentration of Na⁺.

Sodium

Sodium ions (Na⁺) are the most abundant ions in extracellular fluid, accounting for 90% of the extracellular cations. The normal blood plasma Na⁺ concentration is 136 to 148 mEq/liter. As we have already learned, Na⁺ plays a pivotal role in fluid and electrolyte balance because it accounts for almost half of the osmolarity of extracellular fluid. The flow of Na⁺ through voltage-gated channels in the plasma membrane also is necessary for the generation and conduction of action potentials in neurons and muscle fibers.

The typical daily intake of Na⁺ in North America often far exceeds the body's normal daily requirements, due largely to excess dietary salt. The kidneys excrete excess Na⁺, but they also can conserve it during periods of shortage.

The Na⁺ level in the blood is controlled by aldosterone, antidiuretic hormone (A.D.H), and atrial natriuretic peptide (A.N.P). Aldosterone increases renal reabsorption of Na⁺. When the blood plasma concentration of Na⁺ drops below 135 mEq/liter, a condition called hyponatremia, A.D.H release ceases. The lack of A.D.H in turn permits greater excretion of water in urine and restoration of the normal Na⁺ level in E.C.F. Atrial natriuretic peptide increases Na⁺ excretion by the kidneys when the Na⁺ level is above normal, a condition called hypernatremia.

Clinical Connection

Indicators of Na ^{+} Imbalance

If excess sodium ions remain in the body because the kidneys fail to excrete enough of them, water is also osmotically retained. The result is increased blood volume, increased blood pressure, and edema, an abnormal accumulation of interstitial fluid. Renal failure and hyperaldosteronism (excessive aldosterone secretion) are two causes of Na⁺ retention. Excessive urinary loss of Na⁺, by contrast, causes excessive water loss, which results in hypovolemia (hi⁻-po-vo-Le-me-a), an abnormally low blood volume. Hypovolemia related to Na⁺ loss is most frequently due to the inadequate secretion of aldosterone associated with suprarenal insufficiency or overly vigorous therapy with diuretic drugs.

Chloride

Chloride ions (Cl⁻) are the most prevalent anions in extracellular fluid. The normal blood plasma Cl⁻ concentration is 95 to 105 mEq/ liter. Cl⁻ moves relatively easily between the extracellular and intracellular compartments because most plasma membranes contain many Cl⁻ leakage channels and antiporters. For this reason, Cl⁻ can help balance the level of anions in different fluid compartments.

One example is the chloride shift that occurs between red blood cells and blood plasma as the blood level of carbon dioxide either increases or decreases (see Figure 23.23b). In this case, the antiporter exchange of Cl⁻ for H.C.O₃⁻ maintains the correct balance of anions between E.C.F and I.C.F. Chloride ions also are part of the hydrochloric acid secreted into gastric juice. A.D.H helps regulate Cl⁻ balance in body fluids because it governs the extent of water loss in urine. Processes that increase or decrease renal reabsorption of sodium ions also affect reabsorption of chloride ions. (Recall that reabsorption of Na⁺ and Cl⁻ occurs by means of Na⁺–Cl⁻ symporters.)

Potassium

Potassium ions (K⁺) are the most abundant cations in intracellular fluid (140 mEq/liter). K⁺ plays a key role in establishing the resting membrane potential and in the repolarization phase of action potentials in neurons and muscle fibers; K⁺ also helps maintain normal intracellular fluid volume. When K⁺ moves into or out of cells, it often is exchanged for H⁺ and thereby helps regulate the pH of body fluids.

The normal blood plasma K⁺ concentration is 3.5 to 5.0 mEq/liter and is controlled mainly by aldosterone. When blood plasma K⁺ concentration is high, more aldosterone is secreted into the blood. Aldosterone then stimulates principal cells of the renal collecting ducts to secrete more K⁺ so excess K⁺ is lost in the urine. Conversely, when blood plasma K⁺ concentration is low, aldosterone secretion decreases and less K⁺ is excreted in urine. Because K⁺ is needed during the repolarization phase of nerve impulses, abnormal K⁺ levels can be lethal. For instance, hyperkalemia (above-normal concentration of K⁺ in blood) can cause death due to ventricular fibrillation.

Bicarbonate

Bicarbonate ions (H.C.O₃⁻) are the second most prevalent extracellular anions. Normal blood plasma H.C.O₃⁻ concentration is 22 to 26 mEq/liter in systemic arterial blood and 23 to 27 mEq/liter in systemic venous blood. H.C.O₃⁻ concentration increases as blood flows through systemic capillaries because the carbon dioxide released by metabolically active cells combines with water to form carbonic acid; the carbonic acid then dissociates into H⁺ and H.C.O₃⁻. As blood flows through pulmonary capillaries, however, the concentration of H.C.O₃⁻ decreases again as carbon dioxide is exhaled. (Figure 23.23 shows these reactions.) Intracellular fluid also contains a small amount of H.C.O₃⁻. As previously noted, the exchange of Cl⁻ for H.C.O₃⁻ helps maintain the correct balance of anions in extracellular fluid and intracellular fluid.

Figure 23.23 summary: This figure is a series of chemical equations. It depicts the biochemical process of carbon dioxide transport and oxygen release in the blood. The sequence shows water reacting with carbon dioxide to form carbonic acid, which then dissociates into hydrogen ions and bicarbonate ions. Finally, the hydrogen ions react with oxyhemoglobin to produce reduced hemoglobin and release oxygen. The figure demonstrates that the presence of carbon dioxide facilitates the dissociation of oxygen from hemoglobin, thereby promoting the delivery of oxygen to tissue cells.

The kidneys are the main regulators of blood H.C.O 3 superscript minus concentration. The intercalated cells of the renal tubule can either form H.C.O 3 superscript minus and release it into the blood when the blood level is low (see Figure 27.10) or excrete excess H.C.O 3 superscript minus in the urine when the level in blood is too high. Changes in the blood level of H.C.O 3 superscript minus are considered later in this chapter in the section on acid-base balance.

Figure 27.10 summary: This figure consists of two schematic diagrams illustrating physiological processes within a kidney collecting duct. The first part depicts the mechanism of hydrogen ion secretion by an intercalated cell, showing the conversion of carbon dioxide and water into carbonic acid via carbonic anhydrase, which then dissociates into hydrogen ions and bicarbonate. The second part illustrates how secreted hydrogen ions are buffered within the tubule lumen by ammonia and phosphate. The diagrams show that hydrogen ions are actively transported into the lumen using energy from ATP, while bicarbonate is exchanged for chloride and absorbed into the peritubular capillary. It can be inferred that the intercalated cells play a critical role in acid-base balance by actively removing acid from the blood and regenerating new bicarbonate for systemic absorption, while luminal buffers prevent the urine from becoming excessively acidic.

Calcium

Because such a large amount of calcium is stored in bone, it is the most abundant mineral in the body. About 98% of the calcium in adults is located in the skeleton and teeth, where it is combined with phosphates to form a crystal lattice of mineral salts. In body fluids, calcium is mainly an extracellular cation ( Ca superscript 2 plus ). The normal concentration of free or unattached Ca superscript 2 plus in blood plasma is 4.5 to 5.5 mEq/liter. About the same amount of Ca superscript 2 plus is attached to various plasma proteins. Besides contributing to the hardness of bones and teeth, Ca superscript 2 plus plays important roles in blood clotting, neurotransmitter release, maintenance of muscle tone, and excitability of nervous and muscle tissue.

The most important regulator of Ca superscript 2 plus concentration in blood plasma is parathyroid hormone (P.T.H) (see Figure 18.13). A low level of Ca superscript 2 plus in blood plasma promotes release of more P.T.H, which stimulates osteoclasts in bone tissue to release calcium (and phosphate) from bone extracellular matrix. Thus, P.T.H increases bone resorption. Parathyroid hormone also enhances reabsorption of Ca superscript 2 plus from glomerular filtrate through renal tubule cells and back into blood, and increases production of calcitriol (the form of vitamin D that acts as a hormone), which in turn increases Ca superscript 2 plus absorption from food in the digestive canal. Recall that calcitonin (C.T) produced by the thyroid gland inhibits the activity of osteoclasts, accelerates Ca superscript 2 plus deposition into bones, and thus lowers blood Ca superscript 2 plus levels.

Phosphate

About 85 percent of the phosphate in adults is present as calcium phosphate salts, which are structural components of bone and teeth. The remaining 15 percent is ionized. Three phosphate ions ( H 2 P O 4 with a charge of minus 1, H P O 4 with a charge of minus 2, and P O 4 with a charge of minus 3) are important intracellular anions. At the normal pH of body fluids, H P O 4 with a charge of minus 2 is the most prevalent form.

Phosphates contribute about 100 mEq/liter of anions to intracellular fluid. H.P.O 4 superscript 2 minus is an important buffer of H^+ , both in body fluids and in the urine. Although some are “free,” most phosphate ions are covalently bound to organic molecules such as lipids (phospholipids), proteins, carbohydrates, nucleic acids (D.N.A and R.N.A), and adenosine triphosphate (A.T.P).

The normal blood plasma concentration of ionized phosphate is only 1.7 to 2.6 mEq/liter. The same two hormones that govern calcium homeostasis—parathyroid hormone (P.T.H) and calcitriol—also regulate the level of H.P.O 4 superscript 2 minus in blood plasma. P.T.H stimulates resorption of bone extracellular matrix by osteoclasts, which releases both phosphate and calcium ions. into the bloodstream. In the kidneys, however, P.T.H inhibits reabsorption of phosphate ions while stimulating reabsorption of calcium ions by renal tubular cells. Thus, P.T.H increases urinary excretion of phosphate and lowers blood phosphate level.

Calcitriol promotes absorption of both phosphates and calcium from the digestive canal. Fibroblast growth factor 23 (F.G.F 23) is a polypeptide paracrine (local hormone) that also helps regulate blood plasma levels of H P O 4 with a superscript of negative 2. This hormone decreases H P O 4 with a superscript of negative 2 blood levels by increasing H P O 4 with a superscript of negative 2 excretion by the kidneys and decreasing absorption of H P O 4 with a superscript of negative 2 by the digestive canal.

Magnesium

In adults, about 54% of the total body magnesium is part of bone matrix as magnesium salts. The remaining 46% occurs as magnesium ions ( Mg superscript 2 plus ) in intracellular fluid (45%) and extracellular fluid (1%). Mg superscript 2 plus is the second most common intracellular cation (35 mEq/liter). Functionally, Mg superscript 2 plus is a cofactor for certain enzymes needed for the metabolism of carbohydrates and proteins and for the sodium-potassium pump. Mg superscript 2 plus is essential for normal neuromuscular activity, synaptic transmission, and myocardial functioning. In addition, secretion of parathyroid hormone (P.T.H) depends on Mg superscript 2 plus .

Normal blood plasma Mg²⁺ concentration is low, only 1.3 to 2.1 mEq/liter. Several factors regulate the blood plasma level of Mg²⁺ by varying the rate at which it is excreted in the urine. The kidneys increase urinary excretion of Mg²⁺ in response to hypercalcemia, hypermagnesemia, increases in extracellular fluid volume, decreases in parathyroid hormone, and acidosis. The opposite conditions decrease renal excretion of Mg²⁺.

Table 27.2 describes the imbalances that result from the deficiency or excess of several electrolytes.

Table 27.2 summary: This table outlines various blood electrolyte imbalances, detailing the causes and clinical manifestations associated with both deficiency and excess of sodium, chloride, potassium, calcium, phosphate, and magnesium. It highlights how imbalances in these minerals lead to diverse physiological disruptions, ranging from neuromuscular issues like tetany and muscle weakness to severe cardiovascular and neurological complications such as cardiac arrhythmias, coma, and death.

People at risk for fluid and electrolyte imbalances include those who depend on others for fluid and food, such as infants, the elderly, and the hospitalized; individuals undergoing medical treatment that involves intravenous infusions, drainages or suctions, and urinary catheters; and people who receive diuretics, experience excessive fluid losses and require increased fluid intake, or experience fluid retention and have fluid restrictions. Finally, athletes and military personnel in extremely hot environments, postoperative individuals, severe burn or trauma cases, individuals with chronic diseases (congestive heart failure, diabetes, chronic obstructive lung disease, and cancer), people in confinement, and individuals with altered levels of consciousness who may be unable to communicate needs or respond to thirst are also subject to fluid and electrolyte imbalances.

Checkpoint

Image summary: This figure is a text-based image. It displays a single numerical value. The image presents a specific measurement or data point, indicating a precise quantitative value.

Acid-Base Balance

• Compare the roles of buffers, exhalation of carbon dioxide, and kidney excretion of H superscript plus in maintaining pH of body fluids.

• Describe the different types of acid–base imbalances.

From our discussion thus far, it should be clear that various ions play different roles that help maintain homeostasis. A major homeostatic challenge is keeping the H⁺ concentration (pH) of body fluids at an appropriate level. This task—the maintenance of acid-base balance—is of critical importance to normal cellular function.

For example, the three-dimensional shape of all body proteins, which enables them to perform specific functions, is very sensitive to pH changes. When the diet contains a large amount of protein, as is typical in North America, cellular metabolism produces more acids than bases, which tends to acidify the blood. Before proceeding with this section of the chapter, you may wish to review the discussion of acids, bases, and pH in Section 2.4.

In a healthy person, several mechanisms help maintain the pH of systemic arterial blood between 7.35 and 7.45. (A pH of 7.4 corresponds to a H⁺ concentration of 0.00004 mEq/liter = 40 nEq/liter.) Because metabolic reactions often produce a huge excess of H⁺, the lack of any mechanism for the disposal of H⁺ would cause H⁺ in body fluids to rise quickly to a lethal level. Homeostasis of H⁺ concentration within a narrow range is thus essential to survival. The removal of H⁺ from body fluids and its subsequent elimination from the body depend on the following three major mechanisms:

1. Buffer systems. Buffers act quickly to temporarily bind H⁺, removing the highly reactive, excess H⁺ from solution. Buffers thus raise pH of body fluids but do not remove H⁺ from the body.

2. Exhalation of carbon dioxide. By increasing the rate and depth of breathing, more carbon dioxide can be exhaled. Within minutes this reduces the level of carbonic acid in blood, which raises the blood pH (reduces blood H⁺ level).

3. Kidney excretion of H superscript plus . The slowest mechanism, but the only way to eliminate acids other than carbonic acid is through their excretion in urine.

We will examine each of these mechanisms in more detail in the following sections.

The Actions of Buffer Systems

Most buffer systems in the body consist of a weak acid and the salt of that acid, which functions as a weak base. Buffers prevent rapid, drastic changes in the pH of body fluids by converting strong acids and bases into weak acids and weak bases within fractions of a second. Strong acids lower pH more than weak acids because strong acids release H superscript plus more readily and thus contribute more free hydrogen ions. Similarly, strong bases raise pH more than weak ones. The principal buffer systems of the body fluids are the protein buffer system, the carbonic acid-bicarbonate buffer system, and the phosphate buffer system.

Protein Buffer System The protein buffer system is the most abundant buffer in intracellular fluid and blood plasma. For example, the protein hemoglobin is an especially good buffer within red blood cells, and albumin is the main protein buffer in blood plasma. Proteins are composed of amino acids, organic molecules that contain at least one carboxyl group (carboxyl) and at least one amino group (amino); these groups are the functional components of the protein buffer system. The free carboxyl group at one end of a protein acts like an acid by releasing H⁺ when pH rises; it dissociates as follows:

Math summary: This process describes the dissociation of an amino acid acting as an acid. The input molecule releases a hydrogen ion to produce a negatively charged carboxylate group and a free proton as the output.

The H⁺ is then able to react with any excess hydroxide in the solution to form water. The free amino group at the other end of a protein can act as a base by combining with H⁺ when pH falls, as follows:

Math summary: This process calculates the protonation of an amino acid. It takes an input amino group and a hydrogen ion to produce a positively charged ammonium group as the output.

So proteins can buffer both acids and bases. In addition to the terminal carboxyl and amino groups, side chains that can buffer H superscript plus are present on 7 of the 20 amino acids.

As we have already noted, the protein hemoglobin is an important buffer of H⁺ in red blood cells (see Figure 23.23). As blood flows through the systemic capillaries, carbon dioxide (C-O₂) passes from tissue cells into red blood cells, where it combines with water (H₂O) to form carbonic acid (H₂C-O₃). Once formed, H₂C-O₃ dissociates into H⁺ and H.C.O₃⁻. At the same time that C-O₂ is entering red blood cells, oxyhemoglobin (HbO₂) is giving up its oxygen to tissue cells. Reduced hemoglobin (deoxyhemoglobin) picks up most of the H⁺. For this reason, reduced hemoglobin usually is written as Hb–H. The following reactions summarize these relationships:

Carbonic Acid–Bicarbonate Buffer System The carbonic acid–bicarbonate buffer system is based on the bicarbonate ion (H.C.O₃⁻), which can act as a weak base, and carbonic acid (H₂C-O₃), which can act as a weak acid. As you have already learned, H.C.O₃⁻ is a significant anion in both intracellular and extracellular fluids (see Figure 27.8). Because the kidneys also synthesize new H.C.O₃⁻ and reabsorb filtered H.C.O₃⁻, this important buffer is not lost in the urine. If there is an excess of H⁺, the H.C.O₃⁻ can function as a weak base and remove the excess H⁺ as follows:

Math summary: This process calculates the chemical combination of a hydrogen ion and a bicarbonate ion. The input ions react to produce carbonic acid as the final output.

Then, H 2 C O 3 dissociates into water and carbon dioxide, and the C O 2 is exhaled from the lungs.

Conversely, if there is a shortage of H⁺, the H₂C-O₃ can function as a weak acid and provide H⁺ as follows:

Math summary: This process describes the chemical dissociation of carbonic acid. The input carbonic acid molecule breaks down to produce two outputs, a hydrogen ion and a bicarbonate ion.

At a pH of 7.4, H C O 3 minus concentration is about 24 mEq per liter and H 2 C O 3 concentration is about 1.2 millimoles per liter, so bicarbonate ions outnumber carbonic acid molecules by 20 to 1. Because C O 2 and H 2 O combine to form H 2 C O 3, this buffer system cannot protect against pH changes due to respiratory problems in which there is an excess or shortage of C O 2.

Phosphate Buffer System The phosphate buffer system acts via a mechanism similar to the one for the carbonic acid-bicarbonate buffer system. The components of the phosphate buffer system are the ions dihydrogen phosphate H 2 P O 4 with a charge of negative 1 and monohydrogen phosphate H P O 4 with a charge of negative 2. Recall that phosphates are major anions in intracellular fluid and minor ones in extracellular fluids (see Figure 27.8). The dihydrogen phosphate ion acts as a weak acid and is capable of buffering strong bases such as O H with a charge of negative 1, as follows:

Math summary: This chemical equation calculates the neutralization process where a strong base reacts with a weak acid. The input hydroxide ions combine with dihydrogen phosphate to produce water and monohydrogen phosphate as the final output.

The monohydrogen phosphate ion is capable of buffering the H superscript plus released by a strong acid such as hydrochloric acid (H.C.L) by acting as a weak base:

Math summary: This chemical equation represents a neutralization reaction where a strong acid provides hydrogen ions to a weak base. The process combines these inputs to produce a resulting weak acid.

Because the concentration of phosphates is highest in intracellular fluid, the phosphate buffer system is an important regulator of pH in the cytosol. It also acts to a smaller degree in extracellular fluids and buffers acids in urine. H 2 P O 4 with a charge of minus 1 is formed when excess H with a charge of plus 1 in the kidney tubule fluid combines with H P O 4 with a charge of minus 2 (see Figure 27.10). The H with a charge of plus 1 that becomes part of the H 2 P O 4 with a charge of minus 1 passes into the urine. This reaction is one way the kidneys help maintain blood pH by excreting H with a charge of plus 1 in the urine.

Exhalation of Carbon Dioxide

The simple act of breathing also plays an important role in maintaining the pH of body fluids. An increase in the carbon dioxide C O 2 concentration in body fluids increases H plus concentration and thus lowers the pH (makes body fluids more acidic). Because H 2 C O 3 can be eliminated by exhaling C O 2, it is called a volatile acid.

Conversely, a decrease in the C-O 2 concentration of body fluids raises the pH (makes body fluids more alkaline). This chemical interaction is illustrated by the following reversible reactions:

Math summary: This expression describes a reversible chemical equilibrium process. Carbon dioxide and water combine to form carbonic acid, which then dissociates into hydrogen ions and bicarbonate ions.

Changes in the rate and depth of breathing can alter the pH of body fluids within a couple of minutes. With increased breathing, more C-O 2 is exhaled. When C-O 2 levels decrease, the reaction is driven to the left, H superscript plus concentration falls, and blood pH increases. Doubling the breathing increases pH by about 0.23 units, from 7.4 to 7.63. If breathing is slower than normal, less carbon dioxide is exhaled. When C-O 2 levels increase, the reaction is driven to the right, the H superscript plus concentration increases, and blood pH decreases. Reducing breathing to one-quarter of normal lowers the pH by 0.4 units, from 7.4 to 7.0. These examples show the powerful effect of alterations in breathing on the pH of body fluids.

The pH of body fluids and the rate and depth of breathing interact via a negative feedback loop (Figure 27.9). When the blood acidity increases, the decrease in pH (increase in concentration of H⁺) is detected by central chemoreceptors in the medulla oblongata and peripheral chemoreceptors in the aortic and carotid bodies, both of which stimulate the dorsal respiratory group in the medulla oblongata. As a result, the diaphragm and other respiratory muscles contract more forcefully and frequently, so more C-O₂ is exhaled. As less H₂C-O₃ forms and fewer H⁺ are present, blood pH increases. When the response brings blood pH (H⁺ concentration) back to normal, there is a return to acid–base homeostasis. The same negative feedback loop operates if the blood level of C-O₂ increases. Breathing increases, which removes more C-O₂, reducing the H⁺ concentration and increasing the blood's pH.

Figure 27.9 summary: This figure is a flowchart depicting a biological feedback loop. It illustrates the process of negative feedback regulation of blood pH through the respiratory system, starting from an initial stimulus that disrupts homeostasis by decreasing blood pH, which is characterized by an increase in hydrogen ion concentration. The process follows a sequence where central chemoreceptors in the medulla oblongata and peripheral chemoreceptors in the aortic and carotid bodies detect the change and send nerve impulses to the control center, specifically the dorsal respiratory group in the medulla oblongata. This control center then sends output signals to the diaphragm, which acts as the effector. The resulting response involves the diaphragm contracting more forcefully and frequently to increase the exhalation of carbon dioxide. This leads to a decrease in hydrogen ion concentration and an increase in blood pH, effectively returning the system to homeostasis and inhibiting the original stimulus.

By contrast, if the pH of the blood increases, the respiratory center is inhibited and the rate and depth of breathing decrease. A decrease in the C-O 2 concentration of the blood has the same effect. When breathing decreases, C-O 2 accumulates in the blood so its H superscript plus concentration increases.

Kidney Excretion of H ^{+}

Metabolic reactions produce nonvolatile acids such as sulfuric acid at a rate of about 1 mEq of H superscript plus per day for every kilogram of body mass. The only way to eliminate this huge acid load is to excrete H superscript plus in the urine. Given the magnitude of these contributions to acid-base balance, it's not surprising that renal failure can quickly cause death.

As you learned in Chapter 26, cells in both the proximal convoluted tubules (P.C.T) and the collecting ducts of the kidneys secrete hydrogen ions into the tubular fluid. In the P.C.T, Na⁺-H⁺ antiporters secrete H⁺ as they reabsorb Na⁺ (see Figure 26.13). Even more important for regulation of pH of body fluids, however, are the intercalated cells of the collecting duct. The apical membranes of some intercalated cells include proton pumps (H⁺-A.T.P-ases) that secrete H⁺ into the tubular fluid (Figure 27.10). Intercalated cells can secrete H⁺ against a concentration gradient so effectively that urine can be up to 1000 times (3 pH units) more acidic than blood.

H.C.O₃⁻ produced by dissociation of H₂C-O₃ inside intercalated cells crosses the basolateral membrane by means of Cl⁻-H.C.O₃⁻ antiporters and then diffuses into peritubular capillaries (Figure 27.10a). The H.C.O₃⁻ that enters the blood in this way is new (not filtered). For this reason, blood leaving the kidney in the renal vein may have a higher H.C.O₃⁻ concentration than blood entering the kidney in the renal artery.

Interestingly, a second type of intercalated cell has proton pumps in its basolateral membrane and chloride minus bicarbonate antiporters in its apical membrane. These intercalated cells secrete bicarbonate and reabsorb hydrogen ions. Thus, the two types of intercalated cells help maintain the pH of body fluids in two ways—by excreting excess hydrogen ions when pH of body fluids is too low and by excreting excess bicarbonate when pH is too high.

Some H⁺ secreted into the tubular fluid of the collecting duct is buffered, but not by H.C.O₃⁻, most of which has been filtered and reabsorbed. Two other buffers combine with H⁺ in the collecting duct (Figure 27.10b). The most plentiful buffer in the tubular fluid of the collecting duct is H.P.O₄²⁻ (monohydrogen phosphate ion). In addition, a small amount of ammonia (ammonia) also is present. H⁺ combines with H.P.O₄²⁻ to form H₂P.O₄⁻ (dihydrogen phosphate ion) and with ammonia to form ammonium (ammonium ion). Because these ions cannot diffuse back into tubule cells, they are excreted in the urine.

Table 27.3 summarizes the mechanisms that maintain the pH of body fluids.

Table 27.3 summary: This table outlines the various biological mechanisms used to stabilize the pH of body fluids. It categorizes these into chemical buffer systems, such as proteins, phosphates, and the carbonic acid-bicarbonate system, which act in different compartments like the blood, intracellular fluid, and urine. Additionally, it describes the physiological roles of the respiratory system through carbon dioxide exhalation and the renal system through the secretion and reabsorption of ions to maintain acid-base balance.

Acid-Base Imbalances

The normal pH range of systemic arterial blood is between 7.35 (= 45 nEq of H⁺/liter) and 7.45 (= 35 nEq of H⁺/liter). Acidosis (or acidemia) is a condition in which blood pH is below 7.35; alkalosis (or alkalemia) is a condition in which blood pH is higher than 7.45.

Figure 27.10 Secretion of H⁺ by intercalated cells in the collecting duct. H.C.O₃⁻ = bicarbonate ion; C-O₂ = carbon dioxide; H₂O = water; H₂C-O₃ = carbonic acid; Cl⁻ = chloride ion; ammonia = ammonia; ammonium = ammonium ion; H.P.O₄²⁻ = monohydrogen phosphate ion; H₂P.O₄⁻ = dihydrogen phosphate ion.

Urine can be up to 1000 times more acidic than blood due to the operation of the proton pumps in the collecting ducts of the kidneys.

Key:

Proton pump (proton A.T.P-ase) in apical membrane H.C.O₃⁻–Cl⁻ antiporter in basolateral membrane ...▶ Diffusion Q What would be the effects of a drug that blocks the activity of carbonic anhydrase?

The major physiological effect of acidosis is depression of the central nervous system through depression of synaptic transmission. If the systemic arterial blood pH falls below 7, depression of the nervous system is so severe that the individual becomes disoriented, then comatose, and may die. Patients with severe acidosis usually die while in a coma. A major physiological effect of alkalosis, by contrast, is overexcitability in both the central nervous system and peripheral nerves. Neurons conduct impulses repetitively, even when not stimulated by normal stimuli; the results are nervousness, muscle spasms, and even convulsions and death.

A change in blood pH that leads to acidosis or alkalosis may be countered by compensation, the physiological response to an acid-base imbalance that acts to normalize arterial blood pH. Compensation may be either complete, if pH indeed is brought within the normal range, or partial, if systemic arterial blood pH is still lower than 7.35 or higher than 7.45. If a person has altered blood pH due to metabolic causes, hyperventilation or hypoventilation can help bring blood pH back toward the normal range; this form of compensation, termed respiratory compensation, occurs within minutes and reaches its maximum within hours. If, however, a person has altered blood pH due to respiratory causes, then renal compensation—changes in secretion of H⁺ and reabsorption of H.C.O₃⁻ by the kidney tubules—can help reverse the change. Renal compensation may begin in minutes, but it takes days to reach maximum effectiveness.

In the discussion that follows, note that both respiratory acidosis and respiratory alkalosis are disorders resulting from changes in the partial pressure of carbon dioxide (P carbon dioxide) in systemic arterial blood (normal range is 35 to 45 mmHg). By contrast, both metabolic acidosis and metabolic alkalosis are disorders resulting from changes in H.C.O 3 superscript minus concentration (normal range is 22 to 26 mEq/liter in systemic arterial blood).

Respiratory Acidosis The hallmark of respiratory acidosis is an abnormally high partial pressure of carbon dioxide in systemic arterial blood—above 45 mmHg. Inadequate exhalation of carbon dioxide causes the blood pH to drop. Any condition that decreases the movement of carbon dioxide from the blood to the pulmonary alveoli of the lungs to the atmosphere causes a buildup of carbon dioxide, H 2 carbon trioxide, and hydrogen ions. Such conditions include emphysema, pulmonary edema, injury to the respiratory center of the medulla oblongata, airway obstruction, or disorders of the muscles involved in breathing. If the respiratory problem is not too severe, the kidneys can help raise the blood pH into the normal range by increasing excretion of hydrogen ions and reabsorption of bicarbonate ions (renal compensation). The goal in treatment of respiratory acidosis is to increase the exhalation of carbon dioxide, as, for instance, by providing ventilation therapy. In addition, intravenous administration of bicarbonate ions may be helpful.

Respiratory Alkalosis In respiratory alkalosis, systemic arterial blood P C-O 2 falls below 35 mmHg. The cause of the drop in P C-O 2 and the resulting increase in pH is hyperventilation, which occurs in conditions that stimulate the dorsal respiratory group in the brain stem. Such conditions include oxygen deficiency due to high altitude or pulmonary disease, cerebrovascular accident (stroke), or severe anxiety. Again, renal compensation may bring blood pH into the normal range if the kidneys are able to decrease excretion of H^+ and reabsorption of H.C.O 3^-. Treatment of respiratory alkalosis is aimed at increasing the level of C-O 2 in the body. In cases where respiratory alkalosis is caused by severe anxiety, a simple treatment is to have the person inhale and exhale into a paper bag for a short period; as a result, the person inhales air containing a higher-than-normal concentration of C-O 2 .

Metabolic Acidosis In metabolic acidosis, the systemic arterial blood H.C.O 3 superscript minus level drops below 22 mEq/liter. Such a decline in this important buffer causes the blood pH to decrease. Three situations may lower the blood level of H.C.O 3 superscript minus : (1) actual loss of H.C.O 3 superscript minus , such as may occur with severe diarrhea or renal dysfunction; (2) accumulation of an acid other than carbonic acid, as may occur in ketosis (described in Clinical Connection: Ketosis in Section 25.4); or (3) failure of the kidneys to excrete H superscript plus from metabolism of dietary proteins. If the problem is not too severe, hyperventilation can help bring blood pH into the normal range (respiratory compensation). Treatment of metabolic acidosis consists of administering intravenous solutions of sodium bicarbonate and correcting the cause of the acidosis.

Metabolic Alkalosis In metabolic alkalosis, the systemic arterial blood H.C.O 3 superscript minus concentration is above 26 mEq/liter. A nonrespiratory loss of acid or excessive intake of alkaline drugs causes the blood pH to increase above 7.45. Excessive vomiting of gastric contents, which results in a substantial loss of hydrochloric acid, is probably the most frequent cause of metabolic alkalosis. Other causes include gastric suctioning, use of certain diuretics, endocrine disorders, excessive intake of alkaline drugs (antacids), and severe dehydration. Respiratory compensation through hypoventilation may bring blood pH into the normal range. Treatment of metabolic alkalosis consists of giving fluid solutions to correct Cl superscript minus , K superscript plus , and other electrolyte deficiencies plus correcting the cause of alkalosis.

Table 27.4 summarizes respiratory and metabolic acidosis and alkalosis.

Table 27.4 summary: This table outlines the definitions, common causes, and compensatory mechanisms for the four primary types of acid-base imbalances. It contrasts respiratory and metabolic conditions, noting that respiratory imbalances are driven by changes in carbon dioxide levels and compensated for by the kidneys, while metabolic imbalances are driven by bicarbonate levels and compensated for by changes in ventilation. In all cases, complete compensation restores the pH to a normal range while leaving the primary driver of the imbalance at an abnormal level.

Figure 27.20 summary: This figure is a schematic diagram. It illustrates the biological processes involved in the secretion and subsequent buffering of hydrogen ions within the urinary system. The illustration indicates that hydrogen ions are actively transported out of the blood and into the urine, where they are then neutralized by buffering agents to maintain physiological balance.

Clinical Connection

Diagnosis of Acid-Base Imbalances

The cause of an acid-base imbalance can often be pinpointed by careful evaluation of three factors in a sample of systemic arterial blood: pH, concentration of H.C.O 3 superscript minus , and P carbon dioxide . These three blood chemistry values are examined in the following four-step sequence:

1. Note whether the pH is high (alkalosis) or low (acidosis).

2. Decide which value— P C O 2 or H C O 3 with a superscript of minus—is out of the normal range and could be the cause of the p H change. For example, elevated p H could be caused by low P C O 2 or high H C O 3 with a superscript of minus.

3. If the cause is a change in P C O 2, the problem is respiratory; if the cause is a change in H C O 3 minus, the problem is metabolic.

4. Now look at the value that doesn't correspond with the observed pH change. If it is within its normal range, there is no compensation. If it is outside the normal range, compensation is occurring and partially correcting the pH imbalance.

Checkpoint

8. Explain how each of the following buffer systems helps to maintain the pH of body fluids: proteins, carbonic acid-bicarbonate buffers, and phosphates.

9. Define acidosis and alkalosis. Distinguish among respiratory and metabolic acidosis and alkalosis.

10. What are the principal physiological effects of acidosis and alkalosis?

27.4 Aging and Fluid, Electrolyte, and Acid-Base Homeostasis

Objective

• Describe the changes in fluid, electrolyte, and acid–base balance that may occur with aging.

There are significant differences between adults and infants, especially premature infants, with respect to fluid distribution, regulation of fluid and electrolyte balance, and acid-base homeostasis. Accordingly, infants experience more problems than adults in these areas. The differences are related to the following conditions:

• Proportion and distribution of water. A newborn's total body mass is about 75% water (and can be as high as 90% in a premature infant); an adult's total body mass is about 55 to 60% water. (The “adult” percentage is achieved at about 2 years of age.) Adults have twice as much water in I.C.F as E.C.F, but the opposite is true in premature infants. Because E.C.F is subject to more changes than I.C.F, rapid losses or gains of body water are much more critical in infants. Given that the rate of fluid intake and output is about seven times higher in infants than in adults, the slightest changes in fluid balance can result in severe abnormalities.

• Metabolic rate. The metabolic rate of infants is about double that of adults. This results in the production of more metabolic wastes and acids, which can lead to the development of acidosis in infants.

• Functional development of the kidneys. Infant kidneys are only about half as efficient in concentrating urine as those of adults. (Functional development is not complete until close to the end of the first month after birth.) As a result, the kidneys of newborns can neither concentrate urine nor rid the body of excess acids as effectively as those of adults.

• Body surface area. The ratio of body surface area to body volume of infants is about three times greater than that of adults. Water loss through the skin is significantly higher in infants than in adults.

• Breathing rate. The higher breathing rate of infants (about 30 to 80 times a minute) causes greater water loss from the lungs. Respiratory alkalosis may occur because greater ventilation eliminates more C-O₂ and lowers the P.C.O.2.

• Ion concentrations. Newborns have higher K⁺ and Cl⁻ concentrations than adults. This creates a tendency toward metabolic acidosis.

By comparison with children and younger adults, older adults often have an impaired ability to maintain fluid, electrolyte, and acid-base balance. With increasing age, many people have a decreased volume of intracellular fluid and decreased total body K⁺ due to declining skeletal muscle mass and increasing mass of adipose tissue (which contains very little water). Age-related decreases in respiratory and renal functioning may compromise acid-base balance by slowing the exhalation of C-O₂ and the excretion of excess acids in urine. Other kidney changes, such as decreased blood flow, decreased glomerular filtration rate, and reduced sensitivity to antidiuretic hormone, have an adverse effect on the ability to maintain fluid and electrolyte balance.

Due to a decrease in the number and efficiency of sweat glands, water loss from the skin declines with age. Because of these age-related changes, older adults are susceptible to several fluid and electrolyte disorders:

• Dehydration and hypernatremia often occur due to inadequate fluid intake or loss of more water than Na superscript plus in vomit, feces, or urine.

• Hyponatremia may occur due to inadequate intake of sodium with a positive charge; elevated loss of sodium with a positive charge in urine, vomit, or diarrhea; or impaired ability of the kidneys to produce dilute urine.

• Hypokalemia often occurs in older adults who chronically use laxatives to relieve constipation or who take K ^{+} -depleting diuretic drugs for treatment of hypertension or heart disease.

• Acidosis may occur due to impaired ability of the lungs and kidneys to compensate for acid-base imbalances. One cause of acidosis is decreased production of ammonia (ammonia) by renal tubule cells, which then is not available to

Chapter Review

Review

27.1 Fluid Compartments and Fluid Homeostasis

1. Body fluid includes water and dissolved solutes. About two-thirds of the body's fluid is located within cells and is called intracellular fluid. The other one-third, called extracellular fluid, includes interstitial fluid; blood plasma and lymph plasma; cerebrospinal fluid; digestive canal fluids; synovial fluid; fluids of the eyes and ears; pleural, pericardial, and peritoneal fluids; and glomerular filtrate.

2. Fluid balance means that the required amounts of water and solutes are present and are correctly proportioned among the various compartments.

3. An inorganic substance that dissociates into ions in solution is called an electrolyte.

4. Water is the largest single constituent in the body. It makes up 45 to 75% of total body mass, depending on age, gender, and the amount of adipose tissue present.

5. Daily water gain and loss are each about 2500 mL. Sources of water gain are ingested liquids and foods, and water produced by cellular respiration and dehydration synthesis reactions (metabolic water). Water is lost from the body via urination, evaporation from the skin surface, exhalation of water vapor, and defecation. In women, menstrual flow is an additional route for loss of body water.

6. Body water gain is regulated by adjusting the volume of water intake, mainly by drinking more or less fluid. The thirst center in the hypothalamus governs the urge to drink. Although increased amounts of water and solutes are lost through sweating and exhalation during exercise, loss of excess body water or excess solutes depends mainly on regulating excretion in the urine. The extent of urinary N-A-C-L loss is the main determinant of body fluid volume; the extent of urinary water loss is the main determinant of body fluid osmolarity. Table 27.1 summarizes the factors that regulate water gain and water loss in the body.

7. Angiotensin 2 and aldosterone reduce urinary loss of Na⁺ and thereby increase the volume of body fluids. A.N.P promotes natriuresis, elevated excretion of Na⁺, which decreases blood volume.

8. The major hormone that regulates water loss and thus body fluid osmolarity is antidiuretic hormone.

9. An increase in the osmolarity of interstitial fluid draws water out of cells, and they shrink slightly. A decrease in the osmolarity of interstitial fluid causes cells to swell. Most often a change in osmolarity is due to a change in the concentration of Na⁺, the dominant solute in interstitial fluid.

10. When a person consumes water faster than the kidneys can excrete it or when renal function is poor, the result may be water intoxication, in which cells swell dangerously.

combine with H⁺ and be excreted in urine as ammonium; another cause is reduced exhalation of C-O₂.

Checkpoint

11. Why do infants experience greater problems with fluid, electrolyte, and acid-base balance than adults?

27.2 Electrolytes in Body Fluids

1. Ions formed when electrolytes dissolve in body fluids control the osmosis of water between fluid compartments, help maintain acid-base balance, and carry electrical current.

2. The concentrations of cations and anions are expressed in units of milliequivalents/liter (mEq/liter). Blood plasma, interstitial fluid, and intracellular fluid contain varying types and amounts of ions.

3. Sodium ions (Na⁺) are the most abundant extracellular ions. They are involved in impulse transmission, muscle contraction, and fluid and electrolyte balance. Na⁺ level is controlled by aldosterone, antidiuretic hormone, and atrial natriuretic peptide.

4. Chloride ions (Cl⁻) are the major extracellular anions. They play a role in regulating osmotic pressure and forming H.C.L in gastric juice. Cl⁻ level is controlled indirectly by antidiuretic hormone and by processes that increase or decrease renal reabsorption of Na⁺.

5. Potassium ions (K⁺) are the most abundant cations in intracellular fluid. They play a key role in the resting membrane potential and action potential of neurons and muscle fibers; help maintain intracellular fluid volume; and contribute to regulation of pH. K⁺ level is controlled by aldosterone.

6. Bicarbonate ions ( H.C.O 3 superscript minus ) are the second most abundant anions in extracellular fluid. They are the most important buffer in blood plasma.

7. Calcium is the most abundant mineral in the body. Calcium salts are structural components of bones and teeth. Ca superscript 2 plus , which are principally extracellular cations, function in blood clotting, neurotransmitter release, and contraction of muscle. Ca superscript 2 plus level is controlled mainly by parathyroid hormone and calcitriol.

8. Phosphate ions ( H.2.P.O 4^-, H.P.O 4 superscript 2 minus , and P.O 4 superscript 3 minus ) are principally intracellular anions, and their salts are structural components of bones and teeth. They are also required for the synthesis of nucleic acids and A.T.P and participate in buffer reactions. Their level is controlled by parathyroid hormone and calcitriol.

9. Magnesium ions (Mg²⁺) are primarily intracellular cations. They act as cofactors in several enzyme systems.

10. Table 27.2 describes the imbalances that result from deficiency or excess of important body electrolytes.

27.3 Acid-Base Balance

1. The overall acid-base balance of the body is maintained by controlling the H⁺ concentration of body fluids, especially extracellular fluid.

2. The normal pH of systemic arterial blood is 7.35 to 7.45.

3. Homeostasis of pH is maintained by buffer systems, via exhalation of carbon dioxide, and via kidney excretion of H superscript plus and reabsorption of

H.C.O₃⁻. The important buffer systems include proteins, carbonic acid-bicarbonate buffers, and phosphates.

4. An increase in exhalation of carbon dioxide increases blood pH; a decrease in exhalation of C-O 2 decreases blood pH.

5. In the proximal convoluted tubules of the kidneys, Na⁺–H⁺ antiporters secrete H⁺ as they reabsorb Na⁺. In the collecting ducts of the kidneys, some intercalated cells reabsorb K⁺ and H.C.O₃⁻ and secrete H⁺; other intercalated cells secrete H.C.O₃⁻. In these ways, the kidneys can increase or decrease the pH of body fluids.

6. Table 27.3 summarizes the mechanisms that maintain pH of body fluids.

7. Acidosis is a systemic arterial blood pH below 7.35; its principal effect is depression of the central nervous system. Alkalosis is a systemic arterial blood pH above 7.45; its principal effect is overexcitability of the C.N.S.

8. Respiratory acidosis and alkalosis are disorders due to changes in blood P C O 2; metabolic acidosis and alkalosis are disorders associated with changes in blood H C O 3 with a negative charge concentration.

Critical Thinking Questions

1. Robin was in the early stages of pregnancy and has been vomiting excessively for several days. She became weak, was confused, and was taken to the emergency room. What do you suspect has happened to Robin's acid-base balance? How would her body attempt to compensate? What electrolytes would be affected by her vomiting, and how do her symptoms reflect those imbalances?

2. Henry is in the intensive care unit because he suffered a severe myocardial infarction three days ago. The lab reports the following values

Answers to Figure Questions

27.1 Blood plasma volume equals body mass times percent of body mass that is body fluid times proportion of body fluid that is E.C.F times proportion of E.C.F that is blood plasma times a conversion factor of 1 liter per kilogram. For males, blood plasma volume equals 60 kilograms times 0.60 times 1 third times 0.20 times 1 liter per kilogram equals 2.4 liters. Using similar calculations, female blood plasma volume is 2.2 liters.

27.2 Hyperventilation, vomiting, fever, and diuretics all increase fluid loss.

27.3 Osmoreceptors are receptors that detect changes in the osmolarity (concentration of dissolved solutes) of body fluids.

27.4 Alcohol inhibits secretion of A.D.H.

27.5 A.D.H is responsible for the water reabsorption that accompanies aldosterone-mediated Na⁺ reabsorption.

27.6 Overhydration would most likely stimulate the release of A.N.P.

9. Metabolic acidosis or alkalosis can be compensated by respiratory mechanisms (respiratory compensation); respiratory acidosis or alkalosis can be compensated by renal mechanisms (renal compensation). Table 27.4 summarizes the effects of respiratory and metabolic acidosis and alkalosis.

10. By examining systemic arterial blood pH, bicarbonate, and partial pressure of carbon dioxide values, it is possible to pinpoint the cause of an acid-base imbalance.

27.4 Aging and Fluid, Electrolyte, and Acid-Base Homeostasis

1. With increasing age, there is decreased intracellular fluid volume and decreased K superscript plus due to declining skeletal muscle mass.

2. Decreased kidney function with aging adversely affects fluid and electrolyte balance.

from an arterial blood sample: pH 7.30, bicarbonate minus equals 20 mEq/liter, partial pressure of carbon dioxide equals 32 mmHg. Diagnose Henry's acid-base status and decide whether compensation is occurring.

3. This summer, Sam is training for a marathon by running 10 miles a day. Describe changes in his fluid balance as he trains.

27.7 If a solution used for oral rehydration therapy contains a small amount of salt, both the salt and water are absorbed in the digestive canal, blood volume increases without a decrease in osmolarity, and water intoxication does not occur.

27.8 In E.C.F, the major cation is Na⁺, and the major anions are Cl⁻ and H.C.O₃⁻. In I.C.F, the major cation is K⁺, and the major anions are proteins and organic phosphates (for example, A.T.P).

27.9 Holding your breath causes blood pH to decrease slightly as C O 2 and H plus accumulate in the blood.

27.10 A carbonic anhydrase inhibitor reduces secretion of H⁺ into the urine and reduces reabsorption of Na⁺ and H.C.O₃⁻ into the blood. It has a diuretic effect and can cause acidosis (lowered pH of the blood) due to loss of H.C.O₃⁻ in the urine.

You have reached the end of the document.